USP2 affects AS1

| 103

USP2 binds AS1. 10 / 102

| 102

---

➶

sparser

"Also, the outcomes of transwell assays exhibited that USP2-AS1 silence successfully inhibited ovarian cancer cell migration to a great extent, which was abolished after inhibiting miR-520d-3p; and KIAA1522 depletion further reversed above phenomenon induced by miR-520d-3p inhibition ( xref )."

33122952

---

➶

sparser

"Taken together, we certified that USP2-AS1 promotes cell proliferation and migration by inhibiting miR-520d-3p in ovarian cancer."

33122952

---

➶

sparser

"LncRNA USP2-AS1 Promotes Hepatocellular Carcinoma Growth by Enhancing YBX1-Mediated HIF1α Protein Translation Under Hypoxia."

35692750

---

➶

sparser

"Patients with a higher level of USP2-AS1 suffered a poor prognosis."

36359803

---

➶

sparser

"Further, we observed that the decreased KIAA1522 expression resulting from depleted USP2-AS1 was reversed by miR-520d-3p inhibitor, while such recovery was counteracted in response to the absence of KIAA1522 ( xref )."

33122952

---

➶

sparser

"Therefore, loss-of-function assays were designed via transfecting sh-USP2-AS1#1 or sh-USP2-AS1#2 into A2780 and SKOV3 cells to effectively induce USP2-AS1 silence ( xref )."

33122952

---

➶

sparser

"The results of EdU assay showed that the suppression on ovarian cancer cell proliferation caused by the loss of USP2-AS1 was fully countervailed by miR-520d-3p reduction, while such reversion was then offset by KIAA1522 inhibition ( xref )."

33122952

---

➶

sparser

"It has been reported that some lncRNAs, such as ARHGEF7-AS2 , lnc-HLX-1 , lnc-EXPH5–2 , lnc-CH25H-2  and lnc-TDRP-3 , demonstrate differential expression in these two groups, and that other lncRNAs were subgroup-specific: lnc-CCL2–2 in the WNT subgroup, lnc-ABCE1–5 in the SHH subgroup, USP2-AS1 in group 3 and lnc-TBC1D16–3 in group 4 ( xref )."

34316694

---

➶

sparser

"Hypoxia-Regulated lncRNA USP2-AS1 Drives Head and Neck Squamous Cell Carcinoma Progression."

36359803

---

➶

sparser

"To expose the role of USP2-AS1 in ovarian cancer, data from GEPIA () was analyzed."

33122952

USP2 binds KIAA1522 and AS1. 1 / 1

| 1

---

➶

sparser

"To further reveal the connection among USP2-AS1, miR-520d-3p, and KIAA1522, rescue assays were again performed."

33122952

Ubiquitin affects USP2

| 3 27 52

Ubiquitin binds USP2.

| 19 41

Ubiquitin binds USP2. 10 / 61

| 14 37

---

➶

sparser

"Notably, both native ubiquitin and Ub-AMC bind to USP2 with monophasic kinetics."

23211065

---

➶

reach

"In the USP2 and ubiquitin complex the Finger domain is displaced outward to adopt the conformation observed in the other USP domains."

19243136

---

➶

sparser

"In summary, our data show that the ubiquitin core and the ubiquitin C terminus alone bind USP2 very weakly with affinities at best in the high micromolar range, while full-length ubiquitin inhibits USP2 with a K i of 2.8 mM."

16905103

---

➶

sparser

"In addition, a layer of ordered water molecules mediates key interactions between ubiquitin and USP2."

16905103

---

➶

sparser

"As observed for HAUSP xref and USP2 xref interactions with ubiquitin, a number of water molecules line the protein-protein interface including a loop of four ubiquitin residues (A46-Q49) that is involved in a number of polar interactions with the palm of PLpro ( xref )."

24854014

---

➶

reach

"The dashed lines indicate hydrophilic interactions between USP2 and 6TG or Ub."

29449607

---

➶

sparser

"Kinetic studies with peptidic substrates and truncated ubiquitin mutants show that neither the C-terminal peptide nor ubiquitin deletion mutants lacking the C-terminal residues bind to USP2 with detectable affinity."

16905103

---

➶

sparser

"In summary, our data show that the ubiquitin core and the ubiquitin C terminus alone bind USP2 very weakly with affinities at best in the high micromolar range, while full-length ubiquitin inhibits US[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

16905103

---

➶

sparser

"Overlay of the active site of human USP2-Ub complex (grey; PDB code: 2hd5) with that of USP2-Ub-6TG complex (USP2: cyan; Ub: yellow; 6TG: orange) (A) or that of USP2 C276S mutant (green) in complex with Ub (magenta) (B)."

29449607

---

➶

sparser

"Recombinant full-length human USP5/ISOT (residues 1–835) was purified from bacteria, inhibited with a ubiquitin-based suicide substrate and crystallized at 20 °C. A 2.8 Å resolution dataset was collected yielding a structure after phases were obtained by molecular replacement (covalent ubiquitin-USP2 complex (PDB code 2IBI) and the USP5 ZnF-UBP domain (PDB code 2G43)) with good crystallographic statistics ( xref )."

22283393

Ubiquitin binds USP2 and Asn221. 3 / 3

| 3

---

➶

reach

"In the USP2 and ubiquitin complex, Asn221 Ndelta is in close contact to one oxygen of the Gly76 carboxylate, while Asn218 Ndelta (" oxyanion hole ") interacts with the second C-terminal oxygen, an int[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

16905103

---

➶

reach

"In the USP2/ubiquitin complex, Asn221 Nd is in close contact to one oxygen of the Gly76 carboxylate, while Asn218 Nd (''oxyanion hole'') interacts with the second C-terminal oxygen, an interaction similar to the one observed in the USP7/ubiquitinaldehyde complex."

16905103

---

➶

reach

"In the USP2/ubiquitin complex, Asn221 Nδ is in close contact to one oxygen of the Gly76 carboxylate, while Asn218 Nδ (“oxyanion hole”) interacts with the second C-terminal oxygen, an interaction similar to the one observed in the USP7/ubiquitin-aldehyde complex."

16905103

Ubiquitin binds USP2 and Lys407. 2 / 2

| 2

---

➶

reach

"In the USP2 and ubiquitin complex, Nzeta of Lys407 occupies the same position as a solvent molecule in the USP7 and ubiquitin-aldehyde complex.The principles of protein protein interactions and the ro[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

16905103

---

➶

reach

"In the USP2/ubiquitin complex, Nz of Lys407 occupies the same position as a solvent molecule in the USP7/ubiquitin-aldehyde complex.The principles of protein-protein interactions and the role of water molecules in molecular recognition have been studied by various groups (Janin, 1997; Jones and Thornton, 1996; Larsen et al., 1998) ."

16905103

Ubiquitin binds USP14, USP2, and USP7. 2 / 2

| 2

---

➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

---

➶

sparser

"Only approximately 1000 Å 2 of the surface area of PL pro (640 Å 2 by the Ub core and 360 Å 2 by the Ub C-terminus) is buried in the interface, which is smaller than in the USP2-Ub (1900 Å 2 ; Supplementary Fig. S6b ), USP14-Ub aldehyde (1500 Å 2 ; Supplementary Fig. S6c ) and HAUSP-Ub aldehyde (1700 Å 2 ) complexes."

24531491

Ubiquitin binds USP2 and draT. 1 / 1

| 1

---

➶

sparser

"Upon treating ADPr-Ub with USP2, Ub was reactivated and formed UbcH5B~Ub ( xref )."

| PMC

Ubiquitin binds USP14, USP2, USP7, and CSH1. 1 / 1

| 1

---

➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

Ubiquitin inhibits USP2.

| 3 8 11

Ubiquitin inhibits USP2. 10 / 22

| 3 8 11

---

➶

reach

"While ubiquitin inhibits USP2 with a K i of 2.8 muM, mutants lacking residues Arg74-Gly75-Gly76 or Leu73-Arg74-Gly75-Gly76 affect the proteolytic activity of USP2 only marginally even at the highest i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

16905103

---

➶

reach

"USP2 is inhibited by ubiquitin with a K i of 2.8 mM, which is in the same range as the K i of 3 mM for the related enzyme USP5, also known as isopeptidase T (Dang et al., 1998) ."

16905103

---

➶

sparser

"While ubiquitin inhibits USP2 with a K of 2.8 μM, mutants lacking residues or affect the proteolytic activity of USP2 only marginally even at the highest inhibitor concentration."

16905103

---

➶

sparser

"Figure 4: USP2 Inhibition by Full-Length Ubiquitin and the C-Terminally Truncated Mutants, Ubiquitin 1-74 and 1-73 Residual enzymatic activity was determined at 22°C with ubiquitin-AMC as substrate."

16905103

---

➶

reach

"In summary, our data show that the ubiquitin core and the ubiquitin C terminus alone bind USP2 very weakly with affinities at best in the high micromolar range, while full-length ubiquitin inhibits US[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

16905103

---

➶

sparser

"In summary, our data show that the ubiquitin core and the ubiquitin C terminus alone bind USP2 very weakly with affinities at best in the high micromolar range, while full-length ubiquitin inhibits US[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

16905103

---

➶

eidos

"While ubiquitin inhibits USP2 with a Ki of 2.8 muM , mutants lacking residues Arg74-Gly75-Gly76 or Leu73-Arg74-Gly75-Gly76 affect the proteolytic activity of USP2 only marginally even at the highest inhibitor concentration ."

16905103

---

➶

eidos

"Figure 4 : USP2 Inhibition by Full-Length Ubiquitin and the C-Terminally Truncated Mutants , Ubiquitin 1-74 and 1-73 Residual enzymatic activity was determined at 22degreesC with ubiquitin-AMC as substrate ."

16905103

---

➶

reach

"USP2 is inhibited by ubiquitin with a K i of 2.8 muM, which is in the same range as the K i of 3 muM for the related enzyme USP5, also known as isopeptidase T (Dang et al., 1998)."

16905103

---

➶

sparser

"In summary, our data show that the ubiquitin core and the ubiquitin C terminus alone bind USP2 very weakly with affinities at best in the high micromolar range, while full-length ubiquitin inhibits USP2 with a Ki of 2.8 μM."

16905103

USP2 affects Ubiquitin

| 29 41

USP2 binds Ubiquitin.

| 19 41

Ubiquitin binds USP2. 10 / 61

| 14 37

---

➶

sparser

"Notably, both native ubiquitin and Ub-AMC bind to USP2 with monophasic kinetics."

23211065

---

➶

reach

"In the USP2 and ubiquitin complex the Finger domain is displaced outward to adopt the conformation observed in the other USP domains."

19243136

---

➶

sparser

"In summary, our data show that the ubiquitin core and the ubiquitin C terminus alone bind USP2 very weakly with affinities at best in the high micromolar range, while full-length ubiquitin inhibits USP2 with a K i of 2.8 mM."

16905103

---

➶

sparser

"In addition, a layer of ordered water molecules mediates key interactions between ubiquitin and USP2."

16905103

---

➶

sparser

"As observed for HAUSP xref and USP2 xref interactions with ubiquitin, a number of water molecules line the protein-protein interface including a loop of four ubiquitin residues (A46-Q49) that is involved in a number of polar interactions with the palm of PLpro ( xref )."

24854014

---

➶

reach

"The dashed lines indicate hydrophilic interactions between USP2 and 6TG or Ub."

29449607

---

➶

sparser

"Kinetic studies with peptidic substrates and truncated ubiquitin mutants show that neither the C-terminal peptide nor ubiquitin deletion mutants lacking the C-terminal residues bind to USP2 with detectable affinity."

16905103

---

➶

sparser

"In summary, our data show that the ubiquitin core and the ubiquitin C terminus alone bind USP2 very weakly with affinities at best in the high micromolar range, while full-length ubiquitin inhibits US[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

16905103

---

➶

sparser

"Overlay of the active site of human USP2-Ub complex (grey; PDB code: 2hd5) with that of USP2-Ub-6TG complex (USP2: cyan; Ub: yellow; 6TG: orange) (A) or that of USP2 C276S mutant (green) in complex with Ub (magenta) (B)."

29449607

---

➶

sparser

"Recombinant full-length human USP5/ISOT (residues 1–835) was purified from bacteria, inhibited with a ubiquitin-based suicide substrate and crystallized at 20 °C. A 2.8 Å resolution dataset was collected yielding a structure after phases were obtained by molecular replacement (covalent ubiquitin-USP2 complex (PDB code 2IBI) and the USP5 ZnF-UBP domain (PDB code 2G43)) with good crystallographic statistics ( xref )."

22283393

Ubiquitin binds USP2 and Asn221. 3 / 3

| 3

---

➶

reach

"In the USP2 and ubiquitin complex, Asn221 Ndelta is in close contact to one oxygen of the Gly76 carboxylate, while Asn218 Ndelta (" oxyanion hole ") interacts with the second C-terminal oxygen, an int[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

16905103

---

➶

reach

"In the USP2/ubiquitin complex, Asn221 Nd is in close contact to one oxygen of the Gly76 carboxylate, while Asn218 Nd (''oxyanion hole'') interacts with the second C-terminal oxygen, an interaction similar to the one observed in the USP7/ubiquitinaldehyde complex."

16905103

---

➶

reach

"In the USP2/ubiquitin complex, Asn221 Nδ is in close contact to one oxygen of the Gly76 carboxylate, while Asn218 Nδ (“oxyanion hole”) interacts with the second C-terminal oxygen, an interaction similar to the one observed in the USP7/ubiquitin-aldehyde complex."

16905103

Ubiquitin binds USP2 and Lys407. 2 / 2

| 2

---

➶

reach

"In the USP2 and ubiquitin complex, Nzeta of Lys407 occupies the same position as a solvent molecule in the USP7 and ubiquitin-aldehyde complex.The principles of protein protein interactions and the ro[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

16905103

---

➶

reach

"In the USP2/ubiquitin complex, Nz of Lys407 occupies the same position as a solvent molecule in the USP7/ubiquitin-aldehyde complex.The principles of protein-protein interactions and the role of water molecules in molecular recognition have been studied by various groups (Janin, 1997; Jones and Thornton, 1996; Larsen et al., 1998) ."

16905103

Ubiquitin binds USP14, USP2, and USP7. 2 / 2

| 2

---

➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

---

➶

sparser

"Only approximately 1000 Å 2 of the surface area of PL pro (640 Å 2 by the Ub core and 360 Å 2 by the Ub C-terminus) is buried in the interface, which is smaller than in the USP2-Ub (1900 Å 2 ; Supplementary Fig. S6b ), USP14-Ub aldehyde (1500 Å 2 ; Supplementary Fig. S6c ) and HAUSP-Ub aldehyde (1700 Å 2 ) complexes."

24531491

Ubiquitin binds USP2 and draT. 1 / 1

| 1

---

➶

sparser

"Upon treating ADPr-Ub with USP2, Ub was reactivated and formed UbcH5B~Ub ( xref )."

| PMC

Ubiquitin binds USP14, USP2, USP7, and CSH1. 1 / 1

| 1

---

➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

USP2 activates Ubiquitin.

| 6

USP2 activates Ubiquitin. 6 / 7

| 6

---

➶

reach

"At the molecular level, the simplest explanation for this result is that USP2 drives the Ub K48 -Imd molecules to the proteasome and/or ensures the removal of Ub K48 from Imd at the level of the proteasome, then allowing for Imd degradation by the proteasome machinery."

25027767

---

➶

reach

"As shown in XREF_FIG, USP2, a DUB that non specifically targets all ubiquitin linkages, completely reduced polyubiquitinated TLR2."

27805901

---

➶

reach

"Moreover, P5091 inhibits USP7-, but not USP2- or USP8 mediated cleavage of poly K48 linked ubiquitin chains (visualized by the presence or absence of mono-ubiquitin) (XREF_SUPPLEMENTARY)."

22975377

---

➶

reach

"In agreement with this interpretation, no cleavage was detected if USP2 was allowed to remove ubiquitin chains prior to DDI2-RAD23 incubation, showing that DDI2 requires the ubiquitin chain yet cleaves in the body of the NRF1 protein (Figure 4A, compare lanes 17–20 with 11–14)."

32521225

---

➶

reach

"USP2 promotes stabilization of cyclinD1 via direct interaction with cyclin D1 and antagonizes ubiquitin dependent degradation (Shan et al., 2009)."

26033248

---

➶

reach

"The specificity of SJB was confirmed by various experiments : first, we show that SJB potently and selectively block USP1 activity without inhibiting other DUBs (USP2/USP5/USP7/USP14/UCH37); second, SJB inhibited binding of USP1 with HA-Ub-VS probe, but it did not affect labeling of other DUBs with probe; and third, SJB inhibited USP1, but not USP2 or USP7, triggered cleavage of ubiquitin tetramer chains."

28270494

USP2 inhibits Ubiquitin.

| 3

USP2 inhibits Ubiquitin. 3 / 3

| 3

---

➶

reach

"Moreover, USP2 directly interacts with cyclin D1 and promotes its stabilization by antagonizing ubiquitin dependent degradation."

25972356

---

➶

reach

"The ubiquitin dependent proteolysis of cyclin D1 is antagonized by the deubiquitinating enzyme USP2, thus increasing cyclin D1 half-life."

30853938

---

➶

reach

"USP2 directly interacts with cyclin D1 and promotes its stabilization by antagonizing ubiquitin dependent degradation."

19917254

USP2 decreases the amount of Ubiquitin.

| 1

USP2 decreases the amount of Ubiquitin. 1 / 2

| 1

---

➶

reach

"Immunoblot analyses showed that USP2 treatment reduced the amount of associated ubiquitin by ~ 44% (XREF_FIG)."

26004230

USP2 affects UBD

| 8 13

USP2 binds UBD. 10 / 31

| 8 13

---

➶

reach

"This apparent dissociation constant was later used in calculating the individual microscopic binding rate constants in a proposed two-step process of diubiquitin binding to USP2 (vide infra)."

23211065

---

➶

sparser

"Binding of K48-linked IQF diubiquitin to USP2 under an equilibrium condition."

23211065

---

➶

sparser

"Nonetheless, the good agreement in the measured k 1 , k −1 for the native K48-linked diubiquitin and the K48-linked IQF diubiquitin support that the fluorophores on K48-linked IQF diubiquitin do not adversely affect USP2’s interaction with diubiquitin."

23211065

---

➶

sparser

"The binding interaction between USP2 and native K48-linked diubiquitin was also characterized using stopped-flow fluorescence analysis under the pre-steady-state condition."

23211065

---

➶

sparser

"We carried out stopped-flow fluorescence analyses of the binding of mono- and diubiquitin to an inactive USP2 mutant and unveiled interesting differences in the binding kinetics between the two substrates."

23211065

---

➶

reach

"Due to an extremely week fluorescence signal we were unable to determine the apparent dissociation constant of native K48 linked diubiquitin binding to C276A USP2 under an equilibrium condition, which prevented us from calculating the k 2 and k -2 of native diubiquitin binding to USP2."

23211065

---

➶

sparser

"We conducted stopped-flow fluorescence analyses of the binding of mono- and diubiquitin to an inactive USP2 mutant and unveiled interesting differences in the binding kinetics between the two substrates."

23211065

---

➶

sparser

"Binding was monitored by following the enhancement of TAMRA fluorescence upon the binding of K48-linked IQF diubiquitin substrate (25 nM) to USP2 (0-8 μM)."

23211065

---

➶

sparser

"The binding of native K48-linked diubiquitin to USP2 was again clearly biphasic ( xref )."

23211065

---

➶

sparser

"Stopped-flow fluorescence analysis was used to follow K48-linked IQF diubiquitin binding to USP2 under a pre-steady-state condition."

23211065

USP2 affects KMT2A

| 21

USP2 binds KMT2A. 10 / 21

| 21

---

➶

sparser

"The biological function of KMT2A-USP2 in ALL is still unclear."

35087776

---

➶

sparser

"The incidences of KMT2A-MLLT1 (0.6%), KMT2A-ELL (0.4%), KMT2A-MLLT6 (0.2%), and KMT2A-USP2 (0.2%) were all below 1%."

34135310

---

➶

sparser

"Other studies indicated that the number of MLL–USP2 fusions was underestimated, mainly because of the use of techniques that detect rearrangements occurring in the MLL breakpoint cluster region (BRC-1) only, although most translocations occur outside that area [ xref , xref ]."

32139316

---

➶

sparser

"According to this study, a customized PCR panel was developed for MLL-r evaluation in 109 pediatric patients and MLL-USP2 translocations were present in ~15% of all rearrangements [ xref , xref ]."

32139316

---

➶

sparser

"Notably, GATA2 outlier expression was found in patients with the KMT2A-USP2 fusion but not in other KMT2A rearranged patients with high expression of wild-type USP2 ( xref ), suggesting that GATA2 transcription was activated by the chimeric fusion protein as a whole."

35087776

---

➶

sparser

"Another 6 KMT2A fusions ( KMT2A-MLLT11 , KMT2A-SEPT5 , KMT2A-SEPT6 , KMT2A-MAML2 , KMT2A-MYO1F , KMT2A-USP2 ) fusions were detected in 1 case each."

34135310

---

➶

sparser

"Rare fusion genes were detected by RNA-seq, including 1 case of KMT2A-USP2 , 4 cases of Ph-like related fusion genes, 5 cases of MEF2D rearrangement, 5 cases of PAX5 rearrangement, 3 cases of ZNF384 rearrangement, as well as several fusion genes whose significance were not clear or had not been reported in children with leukemia."

36476892

---

➶

sparser

"Our results identifying GATA2 as a potentially novel target of the KMT2A-USP2 fusion might provide novel clues for understanding the function of this fusion."

35087776

---

➶

sparser

"Our data showed that in addition to the trans-activation of GATA2 by the KMT2A-USP2 fusion, a cis-activating mechanism is also involved in GATA2 dysregulation."

35087776

---

➶

sparser

"Further checking confirmed that these patients were the only two carrying this fusion in the cohort analyzed ( xref ), indicating that GATA2 could be trans-activated by KMT2A-USP2."

35087776

USP2 affects Cyclin

| 20

USP2 activates Cyclin.

| 8

USP2 activates Cyclin. 8 / 8

| 8

---

➶

reach

"Again, knockdown of USP2 in MCF-7 and PC3 cells significantly reduced the steady state levels of cyclin D1 protein (XREF_FIG, also in XREF_SUPPLEMENTARY) and also induced cell growth suppression (XREF_FIG)."

19917254

---

➶

reach

"Our results reveal that USP2 specifically modulates cyclin D1 function in vivo and demonstrate the importance of this regulation in human cancer cell growth."

19917254

---

➶

reach

"USP2 directly interacts with cyclin D1 to perform deubiquitylation and thereby antagonize proteasome-dependent degradation of cyclin D1."

32006569

---

➶

reach

"As expected, the half-life of cyclin D1 protein in MCF-7 cells was longer than that of other cancer lines such as HCT116; however, USP2 knockdown drastically reduced the cyclin D1 half-life from 60 to 20 minutes (XREF_FIG and XREF_SUPPLEMENTARY)."

19917254

---

➶

reach

"Pharmacological inhibition of USP2 accelerates cyclin D1 degradation and leads to cell cycle arrest in several cancer cell lines among which the HCT116 colon cancer cell line and MCF7 breast cancer cell line."

30853938

---

➶

reach

"APN can inhibit the expression of USP2 in tumor cells and promote the degradation of cyclin D1 [XREF_BIBR]."

33815885

---

➶

reach

"Although, USP-2, as a deubiquitinating enzyme, is well known to prevent degradation of cyclins, including cyclin A1 and cyclin D1 (Kim et al., 2012; Shan et al., 2009), no studies have been reported r[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

26033248

---

➶

reach

"The ubiquitin dependent proteolysis of cyclin D1 is antagonized by the deubiquitinating enzyme USP2, thus increasing cyclin D1 half-life."

30853938

USP2 deubiquitinates Cyclin.

| 5

USP2 deubiquitinates Cyclin on D1. 5 / 5

| 5

---

➶

reach

"reported that USP2 specifically deubiquitinates and stabilizes cyclin D1, whereas knockdown of this protease causes cyclin D1 degradation and growth arrest in cancer cells dependent on this cell cycle regulator."

22655236

---

➶

reach

"In particular, it has been recently shown that USP-2 deubiquitinates cyclin D1, prevents degradation, accumulates cyclin D1 and finally leads to cell cycle progression from G1 to S phase (Lee et al., [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

26033248

---

➶

reach

"Cyclin D1 ubiquitination is reversed by the deubiquitinases USP2 and USP22."

30853938

---

➶

reach

"Several compounds have been shown to suppress the activity of USP2, which can promote the deubiquitylation and stability of cyclin D1 [137]."

32006569

---

➶

reach

"In a screen of potential deubiquitination enzymes, Shan et al. identified USP2 to specifically deubiquitinate cyclin D1, preventing the degradation of cyclin D1, and leading to the accumulation of cyclin D1."

20160484

USP2 inhibits Cyclin.

| 3

USP2 inhibits Cyclin. 3 / 3

| 3

---

➶

reach

"The ubiquitin dependent proteolysis of cyclin D1 is antagonized by the deubiquitinating enzyme USP2, thus increasing cyclin D1 half-life."

30853938

---

➶

reach

"Based on our results, it is highly likely that USP-2 suppression by adiponectin enhanced proteasomal activity, thereby increasing cyclin D1 degradation, whereas enhancement in USP-2 expression by lept[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

26033248

---

➶

reach

"These data demonstrate that inactivation of USP2 downregulates the levels of endogenous cyclin D1 and suppresses cell growth by delaying G1/S progression."

19917254

USP2 increases the amount of Cyclin.

| 2

USP2 increases the amount of Cyclin. 2 / 2

| 2

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"Furthermore, the role of USP-2 induction in cyclin D1 expression was examined by gene silencing of USP-2."

26033248

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"We found that USP2 knockdown consistently downregulated cyclin D1 expression in multiple TNBC cells."

30918246

USP2 binds Cyclin.

| 2

Cyclin binds USP2 and D1. 2 / 2

| 2

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reach

"USP2 binds to Cyclin D1 and Mdm2 and induces their deubiquitination and stabilization, and its silencing causes downregulation of Cyclin D1 and Mdm2, leading to inhibiting cell proliferation."

20531303

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➶

reach

"By using co-immunoprecipitation approaches, we tried to determine whether elevation of O GlcNAcylation favors the binding of USP2 to cyclin D1, as described for BAP1 and PGC1alpha."

30853938

USP2 affects MDM2

4 1 1 | 6 2

USP2 binds MDM2.

4 1 | 1 2

USP2 binds MDM2. 8 / 9

4 1 | 1 2

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"Subsequent analysis demonstrated that USP2 can bind and deubiquitinate Mdm2."

32201366

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No evidence text available

17290220

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No evidence text available

17290220

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"USP2 binds to Cyclin D1 and Mdm2 and induces their deubiquitination and stabilization, and its silencing causes downregulation of Cyclin D1 and Mdm2, leading to inhibiting cell proliferation ( xref ; xref )."

20531303

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"Specifically, protein-protein interaction assays using the bacterial two-hybrid system showed that USP2 can deubiquitinate MDM2 and promotes p53 degradation, showing the association between USP2 and MDM2 (Stevenson et al., 2007)."

34539442

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No evidence text available

17290220

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17290220

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hprd

No evidence text available

17290220

USP2 deubiquitinates MDM2.

1 | 3

USP2 deubiquitinates MDM2. 4 / 4

1 | 3

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"USP2 deubiquitinates both MDM2 and MDMX [XREF_BIBR, XREF_BIBR] whereas USP4 deubiquitinates ARF-BP1 [XREF_BIBR], another ubiquitin ligase for p53, thus indirectly destabilizing p53 and inhibiting its function."

28035068

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reach

"Specifically, protein-protein interaction assays using the bacterial two-hybrid system showed that USP2 can deubiquitinate MDM2 and promotes p53 degradation, showing the association between USP2 and MDM2 (Stevenson et al., 2007)."

34539442

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reach

"USP2 deubiquitinates and stabilizes MDM2 thus inhibiting the proapoptotic activity of p53."

29479529

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ubibrowser

"Review"

28801249

USP2 decreases the amount of MDM2.

| 1

USP2 decreases the amount of MDM2. 1 / 3

| 1

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"Knockdown of USP2 decreases Mdm2 protein level and increases p53 transcriptional activity."

27351221

USP2 inhibits MDM2.

| 1

USP2 inhibits MDM2. 1 / 2

| 1

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➶

reach

"However, our Western blot assays demonstrated that depleting USP2 expression in multiple TNBC cells neither downregulated MDM2 nor upregulated p53 expression, suggesting that the MDM2 and p53 axis is not involved in USP2 's functions in CSCs."

30918246

UBC affects USP2

14 | 3

UBC binds USP2.

14 | 2

UBC binds USP2. 10 / 16

14 | 2

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No evidence text available

19373254

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No evidence text available

23287719

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28319114

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"In summary, our data show that the ubiquitin core and the ubiquitin C terminus alone bind USP2 very weakly with affinities at best in the high micromolar range, while full-length ubiquitin inhibits USP2 with a Ki of 2.8 μM.USP2 is one of 54 human members of the family of ubiquitin-specific proteases (USPs)."

16905103

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No evidence text available

23287719

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No evidence text available

16196087

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No evidence text available

20516210

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No evidence text available

26876099

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biogrid

No evidence text available

16905103

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No evidence text available

23211065

UBC inhibits USP2.

| 1

UBC bound to USP2 inhibits USP2. 1 / 1

| 1

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reach

"In summary, our data show that the ubiquitin core and the ubiquitin C terminus alone bind USP2 very weakly with affinities at best in the high micromolar range, while full-length ubiquitin inhibits USP2 with a K i of 2.8 mM.USP2 is one of 54 human members of the family of ubiquitin-specific proteases (USPs)."

16905103

USP2 affects apoptotic process

| 1 11 1

USP2 activates apoptotic process.

| 1 6

USP2 activates apoptotic process. 7 / 10

| 1 6

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"Our studies indicate that apoptosis can be modulated by peroxisomal import of USP2, resulting in its spatial separation from its target proteins in the cytosol and nucleus."

26484888

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reach

"Caspase dependent apoptosis caused by overexpression of USP2 was first described for USP2-2 [XREF_BIBR] but also for isoform 1 [XREF_BIBR]."

26484888

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reach

"Hence, the USP2 variants seem to cause the activation of apoptosis pathways by the specific stabilising of their RIP1 substrate.Based on the pro apoptotic effect when USP2c was targeted by RNAi, we fo[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

22659130

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"In vitro an artificial knockdown of USP2 inhibited actinomycin D/TNFalpha induced hepatocyte apoptosis, which was associated with elevated levels of the anti-apoptotic protein c-Flip (L/S) and a concomitant decrease of cellular levels of the ubiquitinligase Itch, a negative regulator of c-Flip."

19001362

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➶

eidos

"Significantly , siRNA knockdown of USP2 resulted in apoptosis , which could be reversed by overexpression of fatty acid synthase ( FAS ) ( 8) ."

20073038

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reach

"We have previously shown that the 41 kDa USP2 isoform induces apoptosis [3] and that the 69 kDa USP2a isoform mediates the apoptosis signal of the TNF receptor [5]."

22659130

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➶

reach

"Knockdown of USP2 did not increase cell apoptosis in Hut-78 cells compared to cells with control siRNA, further suggesting the pivotal role of p53 in USP2 function."

27351221

USP2 inhibits apoptotic process.

| 5 1

USP2 inhibits apoptotic process. 6 / 6

| 5 1

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reach

"Moreover, USP2 silencing enhanced apoptosis after PUVA treatment in MyLa2000 suggesting that USP2 enhanced therapeutic resistance."

27351221

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➶

reach

"Finally, the knockdown of USP2 in Hut-78 cells did not increase apoptosis after PUVA, in contrast to what was observed in MyLa2000 with intact p53."

27351221

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reach

"Stevenson, et al. showed that USP2 prevents cell apoptosis induced by stabilizing MDM2, in turn leading to p53 reduction XREF_BIBR, XREF_BIBR."

30918246

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➶

reach

"USP2 reduces cell apoptosis via p53 signaling."

27351221

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➶

sparser

"In vitro an artificial knockdown of USP2 inhibited actinomycin D/TNFalpha-induced hepatocyte apoptosis, which was associated with elevated levels of the anti-apoptotic protein c-Flip(L/S) and a concomitant decrease of cellular levels of the ubiquitinligase Itch, a negative regulator of c-Flip."

19001362

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➶

reach

"Here, we found that USP2 showed decreased expression in advanced CTCL compared with the early stage disease and blocked apoptosis in malignant p53 wt T-lymphocytes."

27351221

USP2 affects UBC

14 | 2

UBC binds USP2. 10 / 16

14 | 2

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biogrid

No evidence text available

19373254

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➶

biogrid

No evidence text available

23287719

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No evidence text available

28319114

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reach

"In summary, our data show that the ubiquitin core and the ubiquitin C terminus alone bind USP2 very weakly with affinities at best in the high micromolar range, while full-length ubiquitin inhibits USP2 with a Ki of 2.8 μM.USP2 is one of 54 human members of the family of ubiquitin-specific proteases (USPs)."

16905103

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biogrid

No evidence text available

23287719

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No evidence text available

16196087

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biogrid

No evidence text available

20516210

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biogrid

No evidence text available

26876099

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biogrid

No evidence text available

16905103

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biogrid

No evidence text available

23211065

USP2 affects PER1

1 | 10 5

USP2 binds PER1.

| 6 5

USP2 binds PER1. 10 / 11

| 6 5

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➶

sparser

"For example, USP2 binds directly to PER1 in order to regulate PER1 intracellular localization [ xref ]."

26473939

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reach

"USP2 can be coimmunoprecipitated with several clock proteins but directly interacts specifically with PER1 and deubiquitinates it."

23213472

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➶

sparser

"In our hands, whereas it forms a complex with several clock proteins, USP2 directly binds only to PER1 ( xref )."

25147498

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➶

reach

"For example, USP2 binds directly to PER1 in order to regulate PER1 intracellular localization [XREF_BIBR]."

26473939

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➶

reach

"These findings show that USP2 binds PER1 directly and indicate that the interaction of USP2 with the other clock proteins is indirect and possibly occurring within a complex that contains components known to participate in the main negative feedback loop of the circadian clock, including PER1."

23213472

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sparser

"These findings show that USP2 binds PER1 directly and indicate that the interaction of USP2 with the other clock proteins is indirect and possibly occurring within a complex that contains components known to participate in the main negative feedback loop of the circadian clock, including PER1."

23213472

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➶

sparser

"USP2 interacts directly with PER1."

23213472

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➶

sparser

"However, in vitro assays indicated that USP2 could only interact directly with PER1, suggesting that USP2 interacts with the other clock proteins by virtue of their being in a complex with PER1 ( xref )."

23213472

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➶

reach

"USP2 interacts directly with PER1."

23213472

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➶

reach

"However, in vitro assays indicated that USP2 could only interact directly with PER1, suggesting that USP2 interacts with the other clock proteins by virtue of their being in a complex with PER1 (XREF_FIG)."

23213472

USP2 deubiquitinates PER1.

1 | 3

USP2 deubiquitinates PER1. 4 / 4

1 | 3

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reach

"In light of the shorter half-life of USP2 (compared to that of PER1) (XREF_FIG) and of its rhythmic expression peaking almost simultaneously with that of PER1, the deubiquitination of PER1 by USP2 could be restricted to a specific circadian time and therefore be altering the function and/or localization of PER1 to fine tune the molecular clock in physiological conditions."

23213472

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ubibrowser

"Recently, we showed that the deubiquitinating enzyme ubiquitin-specific peptidase 2 (USP2) associates with clock proteins and deubiquitinates PERIOD1 (PER1) but does not affect its overall stability."

25238854

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➶

reach

"Deubiquitination of PER1 by USP2 does not stabilize it."

23213472

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➶

reach

"USP2 is essential to deubiquitinating PER1, CRY1 and CRY2 in vivo [54–57]."

32705594

USP2 ubiquitinates PER1.

| 1

USP2 leads to the ubiquitination of PER1. 1 / 1

| 1

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➶

reach

"We next tested whether USP2 could modulate the ubiquitination of PER1."

23213472

USP2 affects CCND1

4 1 | 9

USP2 binds CCND1.

4 | 9

USP2 binds CCND1. 10 / 15

4 | 9

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biogrid

No evidence text available

19917254

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➶

sparser

"USP2 directly interacts with cyclin D1 to perform deubiquitylation and thereby antagonize proteasome-dependent degradation of cyclin D1."

32006569

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biogrid

No evidence text available

19917254

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➶

sparser

"We next investigated whether USP2 can directly interact with cyclin D1 upon co-expression of both proteins in 293 cells."

19917254

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➶

sparser

"These data demonstrate a direct interaction between USP2 and cyclin D1."

19917254

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➶

sparser

"USP2 directly interacted with cyclin D1 and decreased polyubiquitination-dependent degradation [39]."

33530560

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➶

sparser

"Moreover, USP2 directly interacts with cyclin D1 and promotes its stabilization by antagonizing ubiquitin-dependent degradation."

25972356

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biogrid

No evidence text available

19917254

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biogrid

No evidence text available

19917254

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sparser

"USP2 directly interacted with cyclin D1 and decreased polyubiquitination-dependent degradation [ xref ]."

33530560

USP2 deubiquitinates CCND1.

1 |

USP2 deubiquitinates CCND1. 1 / 1

1 |

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ubibrowser

"Usp2 is a deubiquitination enzyme targeting various factors including CyclinD1 in cancer cells and PTH receptor 1 in osteoblasts."

26643174

USP7 affects USP2

| 5 9

USP2 binds USP7. 10 / 10

| 5 5

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➶

reach

"Indeed, the 76 ubiquitin Cα positions of the USP2 and USP7 complexes differ with an rmsd of only 0."

16905103

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➶

sparser

"It is possible that upon mutating Leu8 to Ala in Ub, the absence of the hydrophobic interaction shifts the conformation of the β1–β2 loop in Ub and reduced its binding to USP7 and USP2."

27501351

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➶

sparser

"Eleven of these water molecules are found at identical positions in the USP2 and USP7 complexes (Figure 2F)."

16905103

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➶

reach

"Indeed, the 76 ubiquitin Ca positions of the USP2 and USP7 complexes differ with an rmsd of only 0."

16905103

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➶

sparser

"Indeed, the 76 ubiquitin Ca positions of the USP2 and USP7 complexes differ with an rmsd of only 0.74 Å . This high structural similarity shows that the different protocols for the preparation of USP/ubiquitin complexes have no influence on the overall ubiquitin binding mode."

16905103

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➶

reach

"Eleven of these water molecules are found at identical positions in the USP2 and USP7 complexes (Figure 2F)."

16905103

---

➶

reach

"Eleven of these water molecules are found at identical positions in the USP2 and USP7 complexes."

16905103

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➶

sparser

"Figure 3: Substrate Binding Region of USP2 and USP7 (A) USP2/ubiquitin complex: the five C-terminal residues of ubiquitin, Leu-Arg-Leu-Gly-Gly, are shown as orange sticks."

16905103

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➶

reach

"Indeed, the 76 ubiquitin Calpha positions of the USP2 and USP7 complexes differ with an rmsd of only 0.74 A."

16905103

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➶

sparser

"Indeed, the 76 ubiquitin Cα positions of the USP2 and USP7 complexes differ with an rmsd of only 0.74 Å. This high structural similarity shows that the different protocols for the preparation of USP/ubiquitin complexes have no influence on the overall ubiquitin binding mode."

16905103

Ubiquitin binds USP14, USP2, and USP7. 2 / 2

| 2

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➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

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"Only approximately 1000 Å 2 of the surface area of PL pro (640 Å 2 by the Ub core and 360 Å 2 by the Ub C-terminus) is buried in the interface, which is smaller than in the USP2-Ub (1900 Å 2 ; Supplementary Fig. S6b ), USP14-Ub aldehyde (1500 Å 2 ; Supplementary Fig. S6c ) and HAUSP-Ub aldehyde (1700 Å 2 ) complexes."

24531491

UCHL3 binds USP14, USP2, and USP7. 1 / 1

| 1

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➶

sparser

"Binding of the C-terminal Ub segment in an extended conformation in the active-site cleft is a common feature of DUBs, as observed in the crystal structures of Ub derivatives in complex with UCH-L3, HAUSP, USP2, and USP14 (Hu et al., 2002, Hu et al., 2005, Misaghi et al., 2004, Renatus et al., 2006)."

17349955

Ubiquitin binds USP14, USP2, USP7, and CSH1. 1 / 1

| 1

---

➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

USP2 affects TWIST1

| 11 3

USP2 binds TWIST1.

| 3 3

TWIST1 binds USP2. 6 / 6

| 3 3

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➶

sparser

"We carried out a co-immunoprecipitation experiment and showed a strong interaction between endogenous USP2 and Twist in BT549 cells (Fig.  xref )."

30918246

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➶

reach

"We carried out a co-immunoprecipitation experiment and showed a strong interaction between endogenous USP2 and Twist in BT549 cells."

30918246

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➶

reach

"Further characterization of the interaction between USP2 and Twist uncovered that the N-terminal domain of USP2 mediates its binding to Twist."

30918246

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➶

sparser

"We demonstrate that TJP1 functions as a scaffold for the interaction between USP2 and TWIST1 and this may provide potential therapeutic targets in bladder cancer."

34782718

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➶

sparser

"Further characterization of the interaction between USP2 and Twist uncovered that the N-terminal domain of USP2 mediates its binding to Twist (Supplementary Figure  xref )."

30918246

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➶

reach

"We demonstrate that TJP1 functions as a scaffold for the interaction between USP2 and TWIST1 and this may provide potential therapeutic targets in bladder cancer."

34782718

USP2 activates TWIST1.

| 3

USP2 activates TWIST1. 3 / 3

| 3

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➶

reach

"In addition, USP2 activates Bmi1 and EMT by stabilizing Twist through removing ubiquitylation mediated by beta-transducin repeats containing proteins (beta-TrCP), a cellular E3 ubiquitin ligase."

32426267

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➶

reach

"Our work reveals that USP2 mediated Twist and Bmi1 pathway represents a cell-intrinsic mechanism crucial for CSC regulation besides EMT and provides pre-clinical evidence that targeting USP2 is indeed a promising approach for anti-CSC therapy."

30918246

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➶

reach

"Indeed, MG132 treatment reverted Twist downregulation mediated by USP2 depletion."

30918246

USP2 deubiquitinates TWIST1.

| 2

USP2 deubiquitinates TWIST1. 2 / 2

| 2

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➶

reach

"Furthermore, TJP1 recruited USP2, which deubiquitinated TWIST1, thereby protecting TWIST1 from proteasome-mediated protein degradation."

34782718

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➶

reach

"USP2 regulates Bmi1 and EMT by Twist stabilization and prevents Twist ubiquitination driven by beta-TrCP and subsequent proteasome mediated protein degradation."

30918246

USP2 decreases the amount of TWIST1.

| 2

Modified USP2 decreases the amount of TWIST1. 1 / 1

| 1

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➶

reach

"Western blot assays illustrated that ablating USP2 expression in BT549 and MDA-MB-157 cells considerably reduced protein expression of Twist as expected."

30918246

USP2-C276A decreases the amount of TWIST1. 1 / 1

| 1

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➶

reach

"Western blot and tumorsphere formation assays showed that the decreased Twist protein level and tumorspheres mediated by USP2 knockdown were rescued by WT but not the C276A mutant of USP2."

30918246

USP2 increases the amount of TWIST1.

| 1

Modified USP2 increases the amount of TWIST1. 1 / 1

| 1

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➶

reach

"Altogether, our study illustrates that USP2 overexpression in TNBC promotes Twist and Bmi1 expression, CSC expansion, cancer cell migration and tumor development."

30918246

USP2 affects LDLR

1 | 1 9

USP2 activates LDLR.

| 3

USP2 activates LDLR. 3 / 5

| 3

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➶

reach

"Conversely, loss of USP2 reduces LDLR protein in an IDOL dependent manner and limits LDL uptake."

26666640

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➶

reach

"USP2 not only interacts with and stabilises the sterol regulated E3-ligase IDOL but also rescues LDLR from lysosomal degradation, recalling the example of USP7 described in detail below 53."

28064438

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➶

reach

"USP2 promoting LDLR activity was not simply an artefact of overexpression, as convincingly demonstrated by the Usp2 siRNA experiments, which showed a 70% reduction in surface LDLR levels and a halving of LDL uptake."

26846634

USP2 deubiquitinates LDLR.

| 4

USP2 deubiquitinates LDLR. 4 / 4

| 4

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➶

reach

"The authors attempt to answer this question by introducing a tripartite complex model, in which USP2 interacts with LDLR at the plasma membrane in an IDOL dependent manner to deubiquitylate and stabilize both LDLR and IDOL."

26846634

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➶

reach

"Such a temporal expression pattern would leave little opportunity to alleviate the USP2 mediated antagonism of IDOL, and the tripartite complex model would imply that IDOL is constantly engaged in a futile reaction, in which its ubiquitylation of LDLR is immediately reversed by USP2."

26846634

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➶

reach

"We identify a tri and partite complex encompassing IDOL, USP2, and LDLR and demonstrate that in this context USP2 promotes deubiquitylation of the LDLR and prevents its degradation."

26666640

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➶

reach

"In summary, USP2 activity leads to the deubiquitylation and stabilization of cell surface LDLR in and IDOL dependent manner, but it remains uncertain exactly why such a phenomenon is accompanied by an extended IDOL protein half-life."

26846634

USP2 inhibits LDLR.

| 1 1

USP2 inhibits LDLR. 2 / 2

| 1 1

---

➶

eidos

"Both USP2-1 and USP2-4 deubiquitinate and stabilize IDOL , suggesting that USP2 promotes LDLR degradation [ 110 ] ."

33530560

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➶

reach

"Using a genetic screening approach, we identify the ubiquitin specific protease 2 (USP2) as a post-transcriptional regulator of IDOL mediated LDLR degradation."

26666640

USP2 binds LDLR.

1 | 1

USP2 binds LDLR. 2 / 2

1 | 1

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➶

biogrid

No evidence text available

26666640

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➶

reach

"The authors attempt to answer this question by introducing a tripartite complex model, in which USP2 interacts with LDLR at the plasma membrane in an IDOL dependent manner to deubiquitylate and stabilize both LDLR and IDOL."

26846634

USP2 affects Imd

| 13

USP2 binds Imd.

| 5

USP2 binds Imd. 5 / 5

| 5

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➶

reach

"USP2 interacts with Imd and promotes cleavage of Imd linked Ub K48."

25027767

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➶

reach

"Focusing on USP2 biochemical function, we show that USP2 binds to Imd and promotes the cleavage of Ub K48 chains from the protein in both cultured cells and flies."

25027767

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➶

reach

"Thus, the Imd and USP2 complex apparently binds more efficiently to the proteasome than do Imd or USP2 alone."

25027767

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➶

reach

"By using GST pull-down assays with GST tagged full length or truncated forms of USP2 (USP2-N-ter [AA :1-531] and USP2-C-ter [AA :475-856]), we finally showed that USP2 preferentially interacts with Imd through its non catalytic N-ter domain."

25027767

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➶

reach

"The control of Imd homeostasis by USP2 is associated with the hydrolysis of Imd linked K48-ubiquitin chains and the synergistic binding of USP2 and Imd to the proteasome, as evidenced by both mass-spectrometry analysis of USP2 partners and by co-immunoprecipitation experiments."

25027767

USP2 inhibits Imd.

| 4

USP2 inhibits Imd. 4 / 4

| 4

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➶

reach

"However, while USP2 also prevents excessive Imd dependent signalling in vivo, USP34 shows differential requirement depending on NF-kappaB target genes, in response to fly infection by either Gram positive or Gram negative bacteria."

25027767

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➶

reach

"However, while USP2 is also required to prevent excessive activation of the Imd pathway in infected flies, USP34 displays differential requirement depending on the antimicrobial peptide gene analysed : silencing Usp34 enhanced the activation of AttA, Drs and IM1."

25027767

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➶

reach

"We report here that USP2 and USP34 and Puf, in addition to the previously described USP36 and Scny, prevent inappropriate activation of Imd dependent immune signal in unchallenged conditions."

25027767

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➶

reach

"USP2 promotes Imd degradation by the proteasome."

25027767

USP2 deubiquitinates Imd.

| 2

USP2 deubiquitinates Imd. 2 / 2

| 2

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➶

reach

"USP2, for instance, deubiquitinates Imd, promoting its degradation."

32656090

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➶

reach

"Identifying USPs regulating immune signals in Drosophila : USP2 deubiquitinates Imd and promotes its degradation by interacting with the proteasome."

25027767

USP2 activates Imd.

| 2

USP2 activates Imd. 2 / 2

| 2

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➶

reach

"Surprisingly, USP2 also targets Imd for degradation, a function which, from our proteomic analysis of USP2 partners and subsequent co-immunoprecipitation experiments, likely occurs at the level of the proteasome."

25027767

---

➶

reach

"We further show that USP2 prevents the constitutive activation of signalling by promoting Imd proteasomal degradation."

25027767

USP2 affects cell population proliferation

| 10

USP2 activates cell population proliferation.

| 6

USP2 activates cell population proliferation. 6 / 8

| 6

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➶

reach

"In addition, USP2 inhibition suppressed CFs proliferation, collagen synthesis and cell cycle progression."

33314748

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➶

reach

"Mutations in the CYLD deubiquitinating enzyme leads to familial cylindromatosis XREF_BIBR and overexpression of USP2 has been reported to increase prostate cancer cell proliferation through the stabilization of fatty acid synthase XREF_BIBR."

21264218

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➶

reach

"USP2 promotes cell proliferation and metastasis in choroidal melanoma via stabilizing Snail."

37199836

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➶

reach

"USP2 promotes experimental colitis and bacterial infections by inhibiting the proliferation of myeloid cells and remodeling the extracellular matrix network."

37192862

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➶

reach

"These results suggest that USP-2 promotes cell proliferation pertinent to the features of human hepatic and breast cancers."

26033248

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"USP2 overexpression promoted proliferation and metastasis, and induced the EMT in CM cells in vitro, while specific inhibition of USP2 by ML364 produced the opposite effects."

37199836

USP2 inhibits cell population proliferation.

| 4

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"Ubiquitin-specific peptidase 2 overexpression inhibited clear cell renal cell carcinoma cell proliferation, migration, and invasion in vitro and in vivo ."

35152855

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"Ubiquitin-specific peptidase 2 inhibition promoted clear cell renal cell carcinoma cell proliferation, migration, and invasion."

35152855

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"USP2a overexpression in HepG2 and Huh 7 cells significantly increased cell proliferation while inhibition of USP2a activity by chemical inhibitor or stable knockout of USP2 by CRISPR markedly reduced cell proliferation."

37424823

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"Knockout or pharmacologic inhibition of USP2 promotes the proliferation of myeloid cells to activate IL-22 and IFNγ production of T cells."

37192862

USP2 affects TP53

| 2 10

USP2 inhibits TP53.

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"USP2 additionally prevents p53 signaling ."

33530560

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"Overexpression of USP2 was shown to reduce p53 stability, conversely suppression led to destabilisation of MDM2 and increased p53 level and activation (9)."

20073038

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"USP2 additionally prevents p53 signaling."

33530560

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"Since Mdm2 is responsible for p53 degradation, USP2 could negatively regulate the p53 pathway activity through up-regulation of Mdm2."

18755030

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"Overexpression of USP2 was also shown to reduce p53 stability [XREF_BIBR], and another de-ubiquitylase USP8 (also called UBPY) promotes epithelial growth factor receptor degradation [XREF_BIBR, XREF_BIBR, XREF_BIBR]."

25366495

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"To test whether USP2 could block p53 via Mdm2, we silenced USP2 and measured Mdm2 level by western blot in MyLa2000 cells after nutlin3a treatment."

27351221

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"Targeting USP2 regulation of VPRBP-mediated degradation of p53 and PD-L1 for cancer therapy."

37024504

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"We postulate that upregulation of USP2 antagonizes p53 effect via deubiquitination of Mdm2."

27351221

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"USP2a mediated enhanced stability of MDM2 abrogates p53 accumulation and its tumor suppressive functions."

34660907

USP2 activates TP53.

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"On the other hand , USP2 has also been shown to increase p53 in a hepatoma cell line ( HepG2 ) and a breast cancer cell line ( MCF7 ) after leptin stimulation [ 36 ] ."

33530560

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"USP2a mediated enhanced stability of MDM2 abrogates p53 accumulation and its tumor suppressive functions."

34660907

USP2 deubiquitinates TP53.

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| 1

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"Unlike USP7, USP2 does not deubiquitinate p53 (9)."

20073038

LEP affects USP2

| 11

LEP increases the amount of USP2.

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| 9

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"Based on our results, it is highly likely that USP-2 suppression by adiponectin enhanced proteasomal activity, thereby increasing cyclin D1 degradation, whereas enhancement in USP-2 expression by lept[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

26033248

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"Similarly, leptin also increased USP-2 protein expression in a dose- and time dependent manner in HepG2 cells and MCF-7 cells."

26033248

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"Although USP-2 seems to play a critical role in USP-2 expression modulated by adiponectin and leptin, the only little information regarding molecular mechanisms underlying USP-2 expression is availabl[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

26033248

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"Leptin increases expression of p53 and USP2 in HepG2 tumor Xenograft model."

27610035

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"Herein, we present the evidence that changes in USP-2 expression by adiponectin and leptin contribute to the regulation of cyclin D1 degradation by proteasomes that impacts cell cycle modulation in ca[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

26033248

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"In the present study, we clearly demonstrated that adiponectin and leptin modulates expression of USP-2 expression in the opposite manner, which in turn directly impacts cyclin D1 degradation (Figs. 3[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

26033248

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"Treatment with globular adiponectin (gAcrp) decreased, whereas leptin increased USP-2 expression both in human hepatoma and breast cancer cells."

26033248

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"As shown in Fig. 4C, transfection with siRNA targeting USP-2 significantly suppressed leptin induced cyclin D1 protein expression in HepG2 cells, suggesting that increase in USP-2 expression by leptin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

26033248

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"While it has been shown that USP2 is involved in the regulation of cancer growth and leptin induces USP2 expression, the functional role of USP2 in leptin induced p53 expression has not been explored."

27610035

LEP activates USP2.

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LEP activates USP2. 2 / 2

| 2

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"We next examined whether USP-2 modulation affects proteasomal activity in HepG2 cells treated with globular adiponectin and leptin."

26033248

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"We therefore next inquired the role of USP-2 in cyclin D1 expression in cancer cells treated with leptin."

26033248

USP2 affects MDM4

5 1 | 2 2

USP2 binds MDM4.

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"Ubiquitin-specific protease 2a (USP2a) is a deubiquitinating enzyme that protects MDM4 against degradation, so USP2-MDM4 interaction may be a key determinant of the malignant potential of human cancers."

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19838211

RAC binds USP2, EEF1A2, and MDM4. 1 / 1

| 1

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"In multivariate analysis high level of EEF1A2, pAKT, USP2 and MDM4 were clearly associated with a shorter patients' survival ( xref )."

24285179

USP2 deubiquitinates MDM4.

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"USP2 deubiquitinates both Mdm2 and MdmX."

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"MdmX, another target of Mdm2, is also deubiquitinated by USP2."

33621249

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"USP2 deubiquitinates both MDM2 and MDMX [XREF_BIBR, XREF_BIBR] whereas USP4 deubiquitinates ARF-BP1 [XREF_BIBR], another ubiquitin ligase for p53, thus indirectly destabilizing p53 and inhibiting its function."

28035068

USP2 affects KCNQ1

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"Coimmunoprecipitation assays suggested that USP2 can bind to KCNQ1 independently of the PY motif."

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22024150

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"Whether or not Nedd4-2 is coexpressed does not seem to influence the binding of USP2 to KCNQ1, as both USP2-45 and USP-69 bind equally well under the 2 conditions ( Figure 3 )."

22024150

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"Coimmunoprecipitation assays suggested that USP2 can bind to KCNQ1 independently of the PY motif."

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"A reduced level of ubiquitylation leads to an increased surface density of KCNQ1 channels and thereby explains the rescued current level observed in the functional experiments.Whether or not Nedd4-2 i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

22024150

USP2 activates KCNQ1.

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"Immunocytochemistry confirmed that USP2 restores the membrane localization of KCNQ1."

22024150

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"In contrast to previous observations with the ENaC, coexpression of the 2 isoforms of USP2 in the present study did not increase the KCNQ1 and KCNE1 mediated current in Xenopus oocytes per se."

22024150

USP2 inhibits KCNQ1.

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| 1

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"Having found that USP2 antagonized the Nedd4-2-mediated downregulation of KCNQ1, we aimed to test whether USP2 interacted directly with the channel."

22024150

USP2 increases the amount of KCNQ1.

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| 1

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"The catalytically inactive USP2 (CA) did not restore the KCNQ1 level."

22024150

USP2 affects FASN

6 1 | 2

USP2 binds FASN.

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"For example, USP-2 interacts and stabilizes fatty acid synthase which is overexpressed in prostate cancer cells (Graner et al., 2004) or causes murine double minute 2 (MDM2) accumulation and enhance M[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

26033248

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15050917

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USP2 activates FASN.

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"Usp2 enhances the stability of fatty acid synthase (FASN) by impeding proteasome-dependent degradation in human HCC (Calvisi et al., 2011; Kitamura and Hashimoto, 2021)."

34539442

USP2 deubiquitinates FASN.

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1 |

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"Here we show that the isopeptidase USP2a (ubiquitin-specific protease-2a) interacts with and stabilizes fatty acid synthase (FAS),?"

15050917

PER1 affects USP2

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"For example, USP2 binds directly to PER1 in order to regulate PER1 intracellular localization [ xref ]."

26473939

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"USP2 can be coimmunoprecipitated with several clock proteins but directly interacts specifically with PER1 and deubiquitinates it."

23213472

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"In our hands, whereas it forms a complex with several clock proteins, USP2 directly binds only to PER1 ( xref )."

25147498

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"For example, USP2 binds directly to PER1 in order to regulate PER1 intracellular localization [XREF_BIBR]."

26473939

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"These findings show that USP2 binds PER1 directly and indicate that the interaction of USP2 with the other clock proteins is indirect and possibly occurring within a complex that contains components known to participate in the main negative feedback loop of the circadian clock, including PER1."

23213472

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"These findings show that USP2 binds PER1 directly and indicate that the interaction of USP2 with the other clock proteins is indirect and possibly occurring within a complex that contains components known to participate in the main negative feedback loop of the circadian clock, including PER1."

23213472

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"USP2 interacts directly with PER1."

23213472

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"However, in vitro assays indicated that USP2 could only interact directly with PER1, suggesting that USP2 interacts with the other clock proteins by virtue of their being in a complex with PER1 ( xref )."

23213472

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"USP2 interacts directly with PER1."

23213472

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"However, in vitro assays indicated that USP2 could only interact directly with PER1, suggesting that USP2 interacts with the other clock proteins by virtue of their being in a complex with PER1 (XREF_FIG)."

23213472

USP2 affects cell cycle

| 3 6

USP2 activates cell cycle.

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| 3 5

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"USP2 inhibition causes cell cycle arrest in activated cardiac fibroblasts ."

33314748

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"Taken together, these results demonstrate that USP2 mediated cell cycle control occurs primarily through its effect on cyclin D1, regardless of p53 status."

19917254

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"USP2 modulates cell cycle progression, and therefore carcinogenesis, via the deubiquitination of cyclins and Aurora-A."

33530560

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"USP2 modulates cell cycle progression , and therefore carcinogenesis , via the deubiquitination of cyclins and Aurora-A ."

33530560

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"To test this hypothesis, we first examined cell cycle distribution in cells treated with control versus USP2 siRNAs."

19917254

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"In addition, USP2 inhibition suppressed CFs proliferation, collagen synthesis and cell cycle progression."

33314748

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"In addition , USP2 inhibition suppressed CFs proliferation , collagen synthesis and cell cycle progression ."

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"Within this group, Usp2 activates Wnt signaling [17]; Rab35 is a GTPase that regulates phosphoinositides and F-actin on endosomes [18]; Grtp1 is a Rab-GAP with broad specificity [19]; and Casp6 regula[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

30302405

USP2 inhibits cell cycle.

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| 1

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"Strikingly, ectopic overexpression of cyclin D1 in USP2-knockdown cells effectively reverses the changes in cell cycle distribution caused by USP2 knockdown (XREF_FIG)."

19917254

MDM2 affects USP2

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"Subsequent analysis demonstrated that USP2 can bind and deubiquitinate Mdm2."

32201366

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No evidence text available

17290220

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"USP2 binds to Cyclin D1 and Mdm2 and induces their deubiquitination and stabilization, and its silencing causes downregulation of Cyclin D1 and Mdm2, leading to inhibiting cell proliferation ( xref ; xref )."

20531303

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"Specifically, protein-protein interaction assays using the bacterial two-hybrid system showed that USP2 can deubiquitinate MDM2 and promotes p53 degradation, showing the association between USP2 and MDM2 (Stevenson et al., 2007)."

34539442

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17290220

USP2 affects TRAF2

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22659130

MDM4 affects USP2

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"Ubiquitin-specific protease 2a (USP2a) is a deubiquitinating enzyme that protects MDM4 against degradation, so USP2-MDM4 interaction may be a key determinant of the malignant potential of human cancers."

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19838211

RAC binds USP2, EEF1A2, and MDM4. 1 / 1

| 1

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"In multivariate analysis high level of EEF1A2, pAKT, USP2 and MDM4 were clearly associated with a shorter patients' survival ( xref )."

24285179

USP2 affects EGFR

1 | 1

USP2 inhibits EGFR.

| 1

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| 1

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"USP2 has also been shown to localise to endosomes and negatively regulate EGFR down-regulation 52."

28064438

USP2 binds EGFR.

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22370483

USP2 affects CRY1

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USP2 deubiquitinates CRY1.

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"In addition to PER1 and BMAL1, USP2 deubiquitinates CRY1 in cultured cells in response to a serum shock, and in the mouse liver, Usp2 knockdown increases CRY ubiquitination and decreases CRY1 protein levels."

25147498

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"USP2a protein deubiquitinates and stabilizes the circadian protein CRY1 in response to inflammatory signals."

22669941

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"USP2 is essential to deubiquitinating PER1, CRY1 and CRY2 in vivo [54–57]."

32705594

USP2 binds CRY1.

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22669941

USP2 decreases the amount of CRY1.

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| 1

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"In addition to PER1 and BMAL1, USP2 deubiquitinates CRY1 in cultured cells in response to a serum shock, and in the mouse liver, Usp2 knockdown increases CRY ubiquitination and decreases CRY1 protein levels."

25147498

USP2 affects CLOCK

| 7

USP2 activates CLOCK.

| 6

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| 6

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"By its action on the ubiquitination status of PER1, and possibly other clock proteins it interacts with, USP2 appears to exert a broad function, modulating both SCN central clock function (as seen by effects on both period length and response to photic stimuli) as well as peripheral clocks (as exemplified by our observations in embryonic fibroblasts)."

23213472

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"Apart from its functions within the clock, USP2 also mediates clock output."

33621249

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"Thus, the USP2 deubiquitinating enzyme modulates the two major features of clock function - its intrinsic circadian rhythm and its capacity to respond to external cues."

23213472

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"The ability of USP2 to modulate these central functions of the clock suggested that it acts on the molecular clock machinery."

23213472

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"USP2 may also mediate the response of the clock to inflammation, as the expression of the gene is increased in response to TNFalpha treatment, and CRY1 protein induction in response to this cytokine is abrogated when Usp2 expression is knocked down."

25147498

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"Our group showed that USP2 modulates the response of the clock to light [XREF_BIBR]."

33621249

USP2 decreases the amount of CLOCK.

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| 1

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"We show that USP2 acts as an integral component of the circadian clock through deubiquitination of PER1, and that Usp2 gene deletion in mice leads to altered circadian behavior and expression of core clock components."

23213472

TRAF6 affects USP2

5 | 1

TRAF6 binds USP2.

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TRAF6 binds USP2. 5 / 6

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No evidence text available

23264041

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23264041

TRAF6 activates USP2.

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| 1

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"TRAF6 and NF-kappaB Are Not Targets of USP2 in LPS Stimulated HL-60 Cells."

29138532

PTH affects USP2

| 1 6

PTH activates USP2.

| 1 3

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| 1 3

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"USP2 was found to be stimulated by PTH in the bone."

30123285

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"Together, these results demonstrate that UBP41, an ubiquitin specific protease, is selectively upregulated in bone by the osteotropic agents PTH, PTHrP, and PGE2, possibly via the PKA and cAMP pathway."

11948679

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"A further study revealed that PTH ( 1-34 ) could upregulate the expression of USP2 and promote PTHR deubiquitination as well as stabilization [ 108 ] ."

30123285

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"In contrast, PTH (7-34) does not increase USP2."

21898592

PTH increases the amount of USP2.

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| 3

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"A further study revealed that PTH (1-34) could upregulate the expression of USP2 and promote PTHR deubiquitination as well as stabilization [108]."

30123285

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"Parathyroid hormone (hPTH 1-38) stimulates the expression of UBP41, an ubiquitin specific protease, in bone."

11948679

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"PTH (1-31), which stimulates intracellular cAMP, and PTHrP (1-34) both induced UBP41 mRNA expression; whereas PTH analogs (3-34) and (7-34), that do not stimulate cAMP, had no effect on UBP41 expression."

11948679

ML364 affects USP2

| 7

ML364 inhibits USP2.

| 5

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| 5

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"We demonstrated that pharmacological inhibition of USP2 by ML364 prominently reduced the formation of TNBC tumorspheres in a dose dependent fashion."

30918246

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"In support of this notion, USP2 inhibition by ML364 led to a dose dependent reduction in Twist and Bmi1 expression."

30918246

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➶

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"USP2 overexpression promoted proliferation and metastasis, and induced the EMT in CM cells in vitro, while specific inhibition of USP2 by ML364 produced the opposite effects."

37199836

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➶

reach

"Given that ML364 inhibits USP2, we next investigated the role of USP2 in antithrombin turnover."

34324733

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"Moreover, USP2 inhibition by ML364 considerably enhanced the cytotoxicity of doxorubicin or paclitaxel in multiple TNBC cell models."

30918246

ML364 binds USP2.

| 2

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| 2

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"ML364 directly binds to USP2 and selectively inhibits its enzymatic activity 31."

30918246

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"Direct binding of ML364 to USP2 was demonstrated using microscale thermophoresis."

27681596

FASN affects USP2

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15050917

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15050917

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"For example, USP-2 interacts and stabilizes fatty acid synthase which is overexpressed in prostate cancer cells (Graner et al., 2004) or causes murine double minute 2 (MDM2) accumulation and enhance M[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

26033248

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15050917

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15050917

ADIPOQ affects USP2

| 1 6

ADIPOQ increases the amount of USP2.

| 5

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| 5

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"It would be interesting to examine the role of AMPK and JAK and STAT signaling in the modulation of USP-2 expression by adiponectin and leptin for the future study.Cyclin D1, an important regulator of[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

26033248

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"Although USP-2 seems to play a critical role in USP-2 expression modulated by adiponectin and leptin, the only little information regarding molecular mechanisms underlying USP-2 expression is availabl[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

26033248

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"Herein, we present the evidence that changes in USP-2 expression by adiponectin and leptin contribute to the regulation of cyclin D1 degradation by proteasomes that impacts cell cycle modulation in ca[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

26033248

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"In the present study, we clearly demonstrated that adiponectin and leptin modulates expression of USP-2 expression in the opposite manner, which in turn directly impacts cyclin D1 degradation (Figs. 3[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

26033248

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"As expected from our microarray data, adiponectin did not trigger elevated transcript levels of TR2, CASP1 and USP2 in MCF-7 breast cancer cells, but a significantly reduced USP2 expression by approximately 60%."

18827813

ADIPOQ decreases the amount of USP2.

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| 1

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"As expected from our microarray data, adiponectin did not trigger elevated transcript levels of TR2, CASP1 and USP2 in MCF-7 breast cancer cells, but a significantly reduced USP2 expression by approximately 60%."

18827813

ADIPOQ activates USP2.

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ADIPOQ activates USP2. 1 / 1

| 1

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➶

eidos

"On the other hand , adiponectin induces USP2 in mammary epithelial cells ( Treeck et al ., 2008 ) ."

31353872

2,3,7,8-tetrachlorodibenzodioxine affects USP2

7 |

2,3,7,8-tetrachlorodibenzodioxine decreases the amount of USP2.

4 |

2,3,7,8-tetrachlorodibenzodioxine decreases the amount of USP2. 4 / 4

4 |

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No evidence text available

21724226

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No evidence text available

17942748

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ctd

No evidence text available

21215274

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ctd

No evidence text available

19490992

2,3,7,8-tetrachlorodibenzodioxine increases the amount of USP2.

3 |

2,3,7,8-tetrachlorodibenzodioxine increases the amount of USP2. 3 / 3

3 |

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ctd

No evidence text available

19770486

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ctd

No evidence text available

28433925

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➶

ctd

No evidence text available

19465110

Catenin affects USP2

| 6

USP2 binds catenin. 6 / 6

| 6

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sparser

"Furthermore, USP2 interacted with β‐catenin, thereby regulating its deubiquitination and stabilization in CFs."

33314748

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➶

sparser

"As expected, we found that USP2 notably interacted with β‐catenin in CFs (Figure xref )."

33314748

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➶

sparser

"To investigate the potential interaction between β‐catenin and USP2, co‐immunoprecipitation (Co‐IP) was performed."

33314748

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➶

sparser

"As expected, USP2 interacted with β‐catenin, and regulated its ubiquitination and degradation in CFs."

33314748

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sparser

"However, inhibiting the Wnt /β‐catenin canonical pathway and down‐regulating β‐catenin can achieve the aim of improving the ventricular remodelling. xref Actually, one of the major mechanisms of β‐catenin regulation is ubiquitination, beside which DUBs, such as USP47, USP20, and USP2, have also been shown to deubiquitinate and stabilize β‐catenin directly. xref , xref , xref In this study, β‐catenin was down‐regulated by USP2 inhibition, which prompted us to assess the interaction between USP2 and β‐catenin."

33314748

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"To further detect the interaction between β‐catenin and USP2, Co‐IP was performed."

33314748

USP2 affects TRAF6

5 |

TRAF6 binds USP2. 5 / 6

5 |

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No evidence text available

23264041

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No evidence text available

25416956

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biogrid

No evidence text available

20622874

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biogrid

No evidence text available

23264041

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biogrid

No evidence text available

23264041

USP2 affects RIPK1

1 4 1 |

USP2 binds RIPK1.

4 |

RIPK1 binds USP2. 4 / 4

4 |

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biogrid

No evidence text available

22659130

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biogrid

No evidence text available

22179575

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biogrid

No evidence text available

22179575

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biogrid

No evidence text available

22179575

USP2 deubiquitinates RIPK1.

1 1 |

USP2 deubiquitinates RIPK1 on K377. 1 / 1

1 |

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biopax:reactome

No evidence text available

USP2 deubiquitinates RIPK1. 1 / 1

1 |

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ubibrowser

"?We have found that the ubiquitin-specific protease USP2a has a pivotal role in the decision for cell death or survival by the TNFR1 complex. This enzyme is a novel component of the TNFR1 complex that is recruited upon ligand binding and controls the signalling activity of the TNFR1-interacting protein RIP1 by removing its K63-linked ubiquitin chains.?"

22179575

USP2 affects Proteasome

| 6

USP2 inhibits Proteasome.

| 2

USP2 inhibits Proteasome. 2 / 2

| 2

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reach

"Usp2 enhances the stability of fatty acid synthase (FASN) by impeding proteasome-dependent degradation in human HCC (Calvisi et al., 2011; Kitamura and Hashimoto, 2021)."

34539442

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➶

reach

"Ubiquitin specific protease-2 (USP-2), a deubiquitinating enzyme, is known to impair proteasome induced degradation of cyclin D1, a critical cell cycle regulator."

26033248

USP2 binds Proteasome.

| 2

Proteasome binds USP2. 2 / 2

| 2

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reach

"Taken together, our data suggest that USP2 and Imd synergistically bind to the proteasome and that USP2 contributes to Imd degradation at the proteasome level."

25027767

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➶

reach

"USP2 and Imd synergistically interact with the proteasome."

25027767

USP2 activates Proteasome.

| 2

USP2 activates Proteasome. 2 / 2

| 2

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reach

"USP2 directly interacts with cyclin D1 to perform deubiquitylation and thereby antagonize proteasome-dependent degradation of cyclin D1."

32006569

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reach

"At the molecular level, the simplest explanation for this result is that USP2 drives the Ub K48 -Imd molecules to the proteasome and/or ensures the removal of Ub K48 from Imd at the level of the proteasome, then allowing for Imd degradation by the proteasome machinery."

25027767

USP2 affects PEX5

1 | 3 1

USP2 binds PEX5. 5 / 6

1 | 3 1

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"The results of the two-hybrid analysis indicate that the interaction between USP2 and PEX5 depends on the quality of the PTS1 and is significantly increased by conversion of the sequence."

26484888

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reach

"The results of the two-hybrid analysis indicate that the interaction between USP2 and PEX5 depends on the quality of the PTS1 and is significantly increased by conversion of the sequence."

26484888

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➶

reach

"Taking into account that USP2 interacts with the import receptor PEX5, deubiquitination of monoubiquitinated PEX5 could have been a peroxisome related function of the enzyme."

26484888

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reach

"By mammalian two-hybrid analysis, a clear binding between PEX5 and USP2 was observed, whereas no interaction was detected when the PTS1-sequence is deleted (DeltaSRM) (XREF_FIG)."

26484888

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biogrid

No evidence text available

26484888

USP2 affects PDZD3

| 3

USP2 binds PDZD3. 3 / 6

| 3

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sparser

"We observed that USP2-45 interacts with NHERF4 ( xref ) and endogenous Clathrin Heavy Chain (CLH) ( xref ), whereas the non-circadian isoform USP2-69 does not."

26756164

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sparser

"Accordingly, USP2-45 interacts with NHERF4 and endogenous Clathrin Heavy Chain (CLH) in transfected HEK293 cells ( xref )."

26756164

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sparser

"Finally, USP2-45 interacts in vitro with NHERF4 and endogenous Clathrin Heavy Chain."

26756164

USP2 affects MYLIP

1 | 4

USP2 deubiquitinates MYLIP.

| 2

USP2 deubiquitinates MYLIP. 2 / 2

| 2

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reach

"In summary, USP2 activity leads to the deubiquitylation and stabilization of cell surface LDLR in and IDOL dependent manner, but it remains uncertain exactly why such a phenomenon is accompanied by an extended IDOL protein half-life."

26846634

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"The authors attempt to answer this question by introducing a tripartite complex model, in which USP2 interacts with LDLR at the plasma membrane in an IDOL dependent manner to deubiquitylate and stabilize both LDLR and IDOL."

26846634

USP2 binds MYLIP.

1 |

USP2 binds MYLIP. 1 / 2

1 |

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biogrid

No evidence text available

26666640

USP2 activates MYLIP.

| 2

USP2 activates MYLIP. 2 / 2

| 2

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reach

"As expected of an interacting DUB, USP2 decreased the ubiquitylation and increased the protein stability of IDOL."

26846634

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reach

"Such a temporal expression pattern would leave little opportunity to alleviate the USP2 mediated antagonism of IDOL, and the tripartite complex model would imply that IDOL is constantly engaged in a futile reaction, in which its ubiquitylation of LDLR is immediately reversed by USP2."

26846634

USP2 affects AURKA

5 1 |

USP2 binds AURKA.

5 |

AURKA binds USP2. 5 / 5

5 |

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No evidence text available

21890637

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biogrid

No evidence text available

21890637

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biogrid

No evidence text available

21890637

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biogrid

No evidence text available

21890637

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biogrid

No evidence text available

21890637

USP2 deubiquitinates AURKA.

1 |

USP2 deubiquitinates AURKA. 1 / 1

1 |

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ubibrowser

"In various cancers, including prostate cancer and ovarian carcinoma, upregulation of USP2 leads to an increase in the levels of deubiquitinated substrates such as fatty acid synthase, MDM2, cyclin D1 and Aurora-A."

29449607

TWIST1 affects USP2

| 3 3

TWIST1 binds USP2. 6 / 6

| 3 3

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sparser

"We carried out a co-immunoprecipitation experiment and showed a strong interaction between endogenous USP2 and Twist in BT549 cells (Fig.  xref )."

30918246

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reach

"We carried out a co-immunoprecipitation experiment and showed a strong interaction between endogenous USP2 and Twist in BT549 cells."

30918246

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reach

"Further characterization of the interaction between USP2 and Twist uncovered that the N-terminal domain of USP2 mediates its binding to Twist."

30918246

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sparser

"We demonstrate that TJP1 functions as a scaffold for the interaction between USP2 and TWIST1 and this may provide potential therapeutic targets in bladder cancer."

34782718

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sparser

"Further characterization of the interaction between USP2 and Twist uncovered that the N-terminal domain of USP2 mediates its binding to Twist (Supplementary Figure  xref )."

30918246

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reach

"We demonstrate that TJP1 functions as a scaffold for the interaction between USP2 and TWIST1 and this may provide potential therapeutic targets in bladder cancer."

34782718

PEX5 affects USP2

1 | 3 1

USP2 binds PEX5. 5 / 6

1 | 3 1

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➶

sparser

"The results of the two-hybrid analysis indicate that the interaction between USP2 and PEX5 depends on the quality of the PTS1 and is significantly increased by conversion of the sequence."

26484888

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➶

reach

"The results of the two-hybrid analysis indicate that the interaction between USP2 and PEX5 depends on the quality of the PTS1 and is significantly increased by conversion of the sequence."

26484888

---

➶

reach

"Taking into account that USP2 interacts with the import receptor PEX5, deubiquitination of monoubiquitinated PEX5 could have been a peroxisome related function of the enzyme."

26484888

---

➶

reach

"By mammalian two-hybrid analysis, a clear binding between PEX5 and USP2 was observed, whereas no interaction was detected when the PTS1-sequence is deleted (DeltaSRM) (XREF_FIG)."

26484888

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biogrid

No evidence text available

26484888

PDZD3 affects USP2

| 3

USP2 binds PDZD3. 3 / 6

| 3

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➶

sparser

"We observed that USP2-45 interacts with NHERF4 ( xref ) and endogenous Clathrin Heavy Chain (CLH) ( xref ), whereas the non-circadian isoform USP2-69 does not."

26756164

---

➶

sparser

"Accordingly, USP2-45 interacts with NHERF4 and endogenous Clathrin Heavy Chain (CLH) in transfected HEK293 cells ( xref )."

26756164

---

➶

sparser

"Finally, USP2-45 interacts in vitro with NHERF4 and endogenous Clathrin Heavy Chain."

26756164

KCNQ1 affects USP2

2 | 2 2

USP2 binds KCNQ1. 6 / 6

2 | 2 2

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reach

"Coimmunoprecipitation assays suggested that USP2 can bind to KCNQ1 independently of the PY motif."

22024150

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No evidence text available

22024150

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sparser

"Whether or not Nedd4-2 is coexpressed does not seem to influence the binding of USP2 to KCNQ1, as both USP2-45 and USP-69 bind equally well under the 2 conditions ( Figure 3 )."

22024150

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sparser

"Coimmunoprecipitation assays suggested that USP2 can bind to KCNQ1 independently of the PY motif."

22024150

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biogrid

No evidence text available

22024150

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reach

"A reduced level of ubiquitylation leads to an increased surface density of KCNQ1 channels and thereby explains the rescued current level observed in the functional experiments.Whether or not Nedd4-2 i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

22024150

JUN affects USP2

6 |

JUN decreases the amount of USP2. 6 / 6

6 |

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biopax:msigdb

No evidence text available

---

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biopax:msigdb

No evidence text available

---

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biopax:msigdb

No evidence text available

---

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biopax:msigdb

No evidence text available

---

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biopax:msigdb

No evidence text available

---

➶

biopax:msigdb

No evidence text available

Monoubiquitin affects USP2

| 4 1

USP2 binds monoubiquitin. 5 / 5

| 4 1

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reach

"While a simple one-step binding of monoubiquitin to USP2 was observed, a biphasic binding was evident for diubiquitin."

23211065

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sparser

"Kinetics of monoubiquitin binding to USP2."

23211065

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reach

"Kinetics of monoubiquitin binding to USP2."

23211065

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➶

reach

"As a support of this notion, the binding of monoubiquitin to the USP2 catalytic core is monophasic and lacks a conformational change step following the bimolecular binding step."

23211065

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➶

reach

"Here we developed two methods to follow the binding of monoubiquitin to USP2 catalytic core."

23211065

Benzo[a]pyrene affects USP2

5 |

Benzo[a]pyrene increases the amount of USP2. 5 / 5

5 |

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ctd

No evidence text available

27195522

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ctd

No evidence text available

19770486

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ctd

No evidence text available

21569818

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ctd

No evidence text available

20106945

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ctd

No evidence text available

27858113

USP2 affects monoubiquitin

| 4 1

USP2 binds monoubiquitin. 5 / 5

| 4 1

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➶

reach

"While a simple one-step binding of monoubiquitin to USP2 was observed, a biphasic binding was evident for diubiquitin."

23211065

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sparser

"Kinetics of monoubiquitin binding to USP2."

23211065

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➶

reach

"Kinetics of monoubiquitin binding to USP2."

23211065

---

➶

reach

"As a support of this notion, the binding of monoubiquitin to the USP2 catalytic core is monophasic and lacks a conformational change step following the bimolecular binding step."

23211065

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➶

reach

"Here we developed two methods to follow the binding of monoubiquitin to USP2 catalytic core."

23211065

USP2 affects epithelial to mesenchymal transition

| 1 4

USP2 activates epithelial to mesenchymal transition.

| 1 2

USP2 activates epithelial to mesenchymal transition. 3 / 3

| 1 2

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➶

eidos

"In addition , USP2 activates Bmi1 and EMT by stabilizing Twist through removing ubiquitylation mediated by beta-transducin repeats-containing proteins ( beta-TrCP ) , a cellular E3 ubiquitin ligase ( 104 ) ."

32426267

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➶

reach

"In addition, USP2 activates Bmi1 and EMT by stabilizing Twist through removing ubiquitylation mediated by beta-transducin repeats containing proteins (beta-TrCP), a cellular E3 ubiquitin ligase."

32426267

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➶

reach

"USP2 overexpression promoted proliferation and metastasis, and induced the EMT in CM cells in vitro, while specific inhibition of USP2 by ML364 produced the opposite effects."

37199836

USP2 inhibits epithelial to mesenchymal transition.

| 2

USP2 inhibits epithelial to mesenchymal transition. 2 / 2

| 2

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➶

reach

"Ubiquitin-specific peptidase 2 inhibits epithelial-mesenchymal transition in clear cell renal cell carcinoma metastasis by downregulating the NF-κB pathway."

35152855

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➶

reach

"Ubiquitin-specific peptidase 2-mediated inhibition of epithelial-mesenchymal transition in clear cell renal cell carcinoma cells is dependent on the nuclear factor-κB pathway."

35152855

USP2 affects Neoplasm Invasiveness

| 5

USP2 inhibits Neoplasm Invasiveness.

| 3

USP2 inhibits Neoplasm Invasiveness. 3 / 3

| 3

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➶

reach

"Ubiquitin-specific peptidase 2 inhibition promoted clear cell renal cell carcinoma cell proliferation, migration, and invasion."

35152855

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➶

reach

"Functional experiments suggested USP2 inhibited lung cancer cell invasion and migration by reducing ARID2 protein degradation."

36567903

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➶

reach

"Ubiquitin-specific peptidase 2 overexpression inhibited clear cell renal cell carcinoma cell proliferation, migration, and invasion in vitro and in vivo ."

35152855

USP2 activates Neoplasm Invasiveness.

| 2

USP2 activates Neoplasm Invasiveness. 2 / 2

| 2

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➶

reach

"USP2 promotes cell migration and invasion in triple negative breast cancer cell lines."

25687182

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➶

reach

"In breast cancer, overexpression of USP2 in TNBC cell lines MDA-MB-468 and MDA-MB-231 enhances migration and invasion with the elevated MMP2 protein level."

28279784

USP2 affects MMP2

1 | 3

USP2 increases the amount of MMP2.

| 1

USP2 increases the amount of MMP2. 1 / 2

| 1

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➶

reach

"This study also showed that USP2 upregulates MMP2 expression and induces the motility and invasiveness of TNBC cells [XREF_BIBR]; however, it remains unknown whether MMP2 is a direct substrate of USP2."

27844253

USP2 deubiquitinates MMP2.

1 | 1

USP2 leads to the deubiquitination of MMP2. 2 / 2

1 | 1

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➶

reach

"It has been proven that USP2 promotes breast cancer metastasis by deubiquitinating MMP2 XREF_BIBR."

33123271

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➶

ubibrowser

"Review"

28279784

USP2 decreases the amount of MMP2.

| 1

USP2 decreases the amount of MMP2. 1 / 1

| 1

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➶

reach

"Silencing of USP2 expression decreased migration and invasion in LM2-4175 and SCP46 cells in association with the downregulation of matrix metalloproteinase-2 (MMP2) expression, whereas overexpression of USP2 in MDA-MB-468 and MDA-MB-231 cells enhanced migration and invasion and upregulated the expression of MMP2."

25687182

MEF2A affects USP2

5 |

MEF2A decreases the amount of USP2. 5 / 5

5 |

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➶

biopax:msigdb

No evidence text available

---

➶

biopax:msigdb

No evidence text available

---

➶

biopax:msigdb

No evidence text available

---

➶

biopax:msigdb

No evidence text available

---

➶

biopax:msigdb

No evidence text available

Imd affects USP2

| 5

USP2 binds Imd. 5 / 5

| 5

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➶

reach

"USP2 interacts with Imd and promotes cleavage of Imd linked Ub K48."

25027767

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➶

reach

"Focusing on USP2 biochemical function, we show that USP2 binds to Imd and promotes the cleavage of Ub K48 chains from the protein in both cultured cells and flies."

25027767

---

➶

reach

"Thus, the Imd and USP2 complex apparently binds more efficiently to the proteasome than do Imd or USP2 alone."

25027767

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➶

reach

"By using GST pull-down assays with GST tagged full length or truncated forms of USP2 (USP2-N-ter [AA :1-531] and USP2-C-ter [AA :475-856]), we finally showed that USP2 preferentially interacts with Imd through its non catalytic N-ter domain."

25027767

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➶

reach

"The control of Imd homeostasis by USP2 is associated with the hydrolysis of Imd linked K48-ubiquitin chains and the synergistic binding of USP2 and Imd to the proteasome, as evidenced by both mass-spectrometry analysis of USP2 partners and by co-immunoprecipitation experiments."

25027767

AURKA affects USP2

5 |

AURKA binds USP2. 5 / 5

5 |

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biogrid

No evidence text available

21890637

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➶

biogrid

No evidence text available

21890637

---

➶

biogrid

No evidence text available

21890637

---

➶

biogrid

No evidence text available

21890637

---

➶

biogrid

No evidence text available

21890637

Valproic acid affects USP2

4 |

Valproic acid increases the amount of USP2.

3 |

Valproic acid increases the amount of USP2. 3 / 3

3 |

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ctd

No evidence text available

21427059

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➶

ctd

No evidence text available

29154799

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ctd

No evidence text available

23179753

Valproic acid decreases the amount of USP2.

1 |

Valproic acid decreases the amount of USP2. 1 / 1

1 |

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➶

ctd

No evidence text available

24935251

Tioguanine affects USP2

| 3 1

Tioguanine inhibits USP2. 4 / 4

| 3 1

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➶

eidos

"( C ) Noncompetitive inhibition of USP2 by 6TG ."

29449607

---

➶

eidos

"Slow-binding inhibition of USP2 by 6TG ."

29449607

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➶

sparser

"Previous studies indicated that 6-TG could non-competitively inhibit human USP2 ( xref ) thus plays a critical role in tumor cells survival."

33194583

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➶

eidos

"Overall , the ternary complex structure of USP2-Ub-6TG suggests the existence of an enzyme-substrate-inhibitor ( ESI ) complex and confirms the noncompetitive mechanism of USP2 inhibition by 6TG ."

29449607

USP7 affects USP14

| 4

Ubiquitin binds USP14, USP2, and USP7. 2 / 2

| 2

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➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

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➶

sparser

"Only approximately 1000 Å 2 of the surface area of PL pro (640 Å 2 by the Ub core and 360 Å 2 by the Ub C-terminus) is buried in the interface, which is smaller than in the USP2-Ub (1900 Å 2 ; Supplementary Fig. S6b ), USP14-Ub aldehyde (1500 Å 2 ; Supplementary Fig. S6c ) and HAUSP-Ub aldehyde (1700 Å 2 ) complexes."

24531491

UCHL3 binds USP14, USP2, and USP7. 1 / 1

| 1

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➶

sparser

"Binding of the C-terminal Ub segment in an extended conformation in the active-site cleft is a common feature of DUBs, as observed in the crystal structures of Ub derivatives in complex with UCH-L3, HAUSP, USP2, and USP14 (Hu et al., 2002, Hu et al., 2005, Misaghi et al., 2004, Renatus et al., 2006)."

17349955

Ubiquitin binds USP14, USP2, USP7, and CSH1. 1 / 1

| 1

---

➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

USP2 affects cell growth

| 3

USP2 activates cell growth.

| 2

USP2 activates cell growth. 2 / 3

| 2

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➶

reach

"To completely exclude the possibility that the cell growth repression induced by USP2 knockdown is p53 dependent, we performed the same experiments in isogenic p53 knockout cells (HCT116 p53-/-)."

19917254

---

➶

reach

"Again, knockdown of USP2 in MCF-7 and PC3 cells significantly reduced the steady state levels of cyclin D1 protein (XREF_FIG, also in XREF_SUPPLEMENTARY) and also induced cell growth suppression (XREF_FIG)."

19917254

USP2 inhibits cell growth.

| 1

USP2 inhibits cell growth. 1 / 1

| 1

---

➶

reach

"These data demonstrate that inactivation of USP2 downregulates the levels of endogenous cyclin D1 and suppresses cell growth by delaying G1/S progression."

19917254

USP2 affects antithrombin

| 4

USP2 binds antithrombin.

| 2

USP2 binds antithrombin. 2 / 2

| 2

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➶

reach

"To determine the potential interaction of USP2 and antithrombin, we performed immunoprecipitation and immunoblotting experiments, which revealed that the endogenous USP2 isoform (USP2a) interacted with antithrombin in HepG2 and SMMC7721 cells (Figure 5A,B)."

34324733

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➶

reach

"We further found that USP2 interacted with antithrombin and regulated antithrombin expression, showing that overexpression of USP2 inhibits the ubiquitination and proteasomal clearance of antithrombin, whereas pharmacological inhibition or siRNA mediated knockdown of USP2 downregulates antithrombin."

34324733

USP2 deubiquitinates antithrombin.

| 1

USP2 deubiquitinates antithrombin. 1 / 1

| 1

---

➶

reach

"3.5 | USP2 deubiquitinates and stabilizes antithrombin."

34324733

USP2 activates antithrombin.

| 1

USP2 activates antithrombin. 1 / 1

| 1

---

➶

reach

"Moreover, USP2 knockdown accelerated antithrombin turnover (Figure 5F) and increased total polyubiquitinated and K48-linked polyubiquitinated forms of antithrombin (Figure 5G)."

34324733

USP2 affects USP14

| 4

Ubiquitin binds USP14, USP2, and USP7. 2 / 2

| 2

---

➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

---

➶

sparser

"Only approximately 1000 Å 2 of the surface area of PL pro (640 Å 2 by the Ub core and 360 Å 2 by the Ub C-terminus) is buried in the interface, which is smaller than in the USP2-Ub (1900 Å 2 ; Supplementary Fig. S6b ), USP14-Ub aldehyde (1500 Å 2 ; Supplementary Fig. S6c ) and HAUSP-Ub aldehyde (1700 Å 2 ) complexes."

24531491

UCHL3 binds USP14, USP2, and USP7. 1 / 1

| 1

---

➶

sparser

"Binding of the C-terminal Ub segment in an extended conformation in the active-site cleft is a common feature of DUBs, as observed in the crystal structures of Ub derivatives in complex with UCH-L3, HAUSP, USP2, and USP14 (Hu et al., 2002, Hu et al., 2005, Misaghi et al., 2004, Renatus et al., 2006)."

17349955

Ubiquitin binds USP14, USP2, USP7, and CSH1. 1 / 1

| 1

---

➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

USP2 affects Neoplasm Metastasis

| 1 3

USP2 activates Neoplasm Metastasis.

| 1 2

USP2 activates Neoplasm Metastasis. 3 / 3

| 1 2

---

➶

reach

"USP2 promotes cell proliferation and metastasis in choroidal melanoma via stabilizing Snail."

37199836

---

➶

eidos

"USP2 promotes cell proliferation and metastasis in choroidal melanoma via stabilizing Snail ."

37199836

---

➶

reach

"USP2 overexpression promoted proliferation and metastasis, and induced the EMT in CM cells in vitro, while specific inhibition of USP2 by ML364 produced the opposite effects."

37199836

USP2 inhibits Neoplasm Metastasis.

| 1

USP2 inhibits Neoplasm Metastasis. 1 / 1

| 1

---

➶

reach

"Ubiquitin-specific peptidase 2 inhibits epithelial-mesenchymal transition in clear cell renal cell carcinoma metastasis by downregulating the NF-κB pathway."

35152855

USP2 affects NEDD4L

| 4

USP2 inhibits NEDD4L.

| 2

USP2 inhibits NEDD4L. 2 / 2

| 2

---

➶

reach

"The biochemical experiments show an augmented surface expression and reduced ubiquitylation level of KCNQ1 when catalytically active USP2 is coexpressed with Nedd4-2, suggesting that USP2 may counter [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

22024150

---

➶

reach

"In cells coexpressing USP2-45/-69, the amount of ubiquitylated KCNQ1 was significantly decreased and the total amount of KCNQ1 was increased, demonstrating that USP2 antagonizes the effect of Nedd4-2 [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

22024150

USP2 activates NEDD4L.

| 2

USP2 activates NEDD4L. 2 / 2

| 2

---

➶

reach

"However, coexpression of USP2 together with Nedd4-2 and KCNQ1 augments the binding efficiency of Nedd4-2, indicating that either both USP2-45 and USP-69 stabilize the binding to the KCNQ1 protein or N[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

22024150

---

➶

reach

"Interestingly, Nedd4-2 coimmunoprecipitation with wild-type KCNQ1 was increased when USP2 was coexpressed, suggesting that USP2 may augment the binding of Nedd4-2 to the channel complex."

22024150

USP2 affects KRT15

3 1 |

USP2 binds KRT15. 4 / 4

3 1 |

---

➶

biogrid

No evidence text available

16189514

---

➶

hprd

No evidence text available

16189514

---

➶

biogrid

No evidence text available

25416956

---

➶

biogrid

No evidence text available

16189514

USP2 affects FAS

1 | 2 1

USP2 binds FAS.

| 2 1

FAS binds USP2. 3 / 3

| 2 1

---

➶

sparser

"In 2004, Graner and colleagues showed that USP2 binds to and stabilizes FAS [ xref ], a protein known to be upregulated in many cancers including prostate cancer [ xref ]."

33621249

---

➶

reach

"In prostate cancer cells, USP2 interacts with and stabilizes FAS, which is often over-expressed in biologically aggressive human tumors."

18755030

---

➶

reach

"In 2004, Graner and colleagues showed that USP2 binds to and stabilizes FAS [XREF_BIBR], a protein known to be upregulated in many cancers including prostate cancer [XREF_BIBR]."

33621249

USP2 deubiquitinates FAS.

1 |

USP2 deubiquitinates FAS. 1 / 1

1 |

---

➶

ubibrowser

"USP2a can also deubiquitinate Fas preventing apoptosis in PCa"

25121098

USP2 affects DLL1

| 4

USP2 binds DLL1. 4 / 4

| 4

---

➶

sparser

"These results suggest that USP2-45 binding to α 2 δ-1 promotes the de-ubiquitylation of both Ca v 1.2 and α 2 δ-1 subunits, in order to regulate the expression of Ca v 1.2 channels at the plasma membrane."

25366495

---

➶

sparser

"In addition, the binding of USP2-45 to α 2 δ-1 may disrupt the chaperone role of this subunit towards Ca v 1.2, leading to the reduction of Ca v 1.2 surface expression."

25366495

---

➶

sparser

"This result suggests that the first critical event is the binding of USP2-45 to the auxiliary α 2 δ-1 subunit which may act as an anchor allowing for USP2-45 to de-ubiquitylate Ca v 1.2 channels."

25366495

---

➶

sparser

"Though the reason for this peculiarity is presently unknown, it may lie in the fact that the USP2-45 binding to Ca V α 2 δ-1 might disrupt the chaperone role of the auxiliary subunit, leading to a reduction of the Ca V 1.2α 1 pore-forming subunit trafficked to the plasma membrane [ xref ]."

28957379

USP14 affects USP7

| 4

Ubiquitin binds USP14, USP2, and USP7. 2 / 2

| 2

---

➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

---

➶

sparser

"Only approximately 1000 Å 2 of the surface area of PL pro (640 Å 2 by the Ub core and 360 Å 2 by the Ub C-terminus) is buried in the interface, which is smaller than in the USP2-Ub (1900 Å 2 ; Supplementary Fig. S6b ), USP14-Ub aldehyde (1500 Å 2 ; Supplementary Fig. S6c ) and HAUSP-Ub aldehyde (1700 Å 2 ) complexes."

24531491

UCHL3 binds USP14, USP2, and USP7. 1 / 1

| 1

---

➶

sparser

"Binding of the C-terminal Ub segment in an extended conformation in the active-site cleft is a common feature of DUBs, as observed in the crystal structures of Ub derivatives in complex with UCH-L3, HAUSP, USP2, and USP14 (Hu et al., 2002, Hu et al., 2005, Misaghi et al., 2004, Renatus et al., 2006)."

17349955

Ubiquitin binds USP14, USP2, USP7, and CSH1. 1 / 1

| 1

---

➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

TP53 affects USP2

| 4

TP53 activates USP2.

| 3

TP53 activates USP2. 3 / 3

| 3

---

➶

reach

"USP2 is upregulated by PUVA and a p53 activator, nutlin3a."

27351221

---

➶

reach

"It would be interesting to investigate whether USP2 aggravates the resistance to other therapeutic modalities, such as ionizing radiation or ultraviolet B. Mechanistically we were able to demonstrate that the activation of p53 upregulated USP2."

27351221

---

➶

reach

"These results suggested that activated p53 increased USP2, which in turn counteracted the pro apoptotic activity of p53, forming a negative feedback loop."

27351221

TP53 inhibits USP2.

| 1

TP53 inhibits USP2. 1 / 1

| 1

---

➶

reach

"Interestingly, leptin induced increase in p53 expression was significantly suppressed by gene silencing of USP2 in both HepG2 and MCF-7 cells (XREF_FIG), suggesting the crucial role of USP2 and probably modulation of ubiquitination in leptin induced p53 expression."

27610035

STAT1 affects USP2

1 2 |

STAT1 binds USP2.

2 |

STAT1 binds USP2. 2 / 3

2 |

---

➶

biogrid

No evidence text available

27434509

---

➶

biogrid

No evidence text available

27434509

STAT1 decreases the amount of USP2.

1 |

STAT1 decreases the amount of USP2. 1 / 1

1 |

---

➶

biopax:msigdb

No evidence text available

RIPK1 affects USP2

4 |

RIPK1 binds USP2. 4 / 4

4 |

---

➶

biogrid

No evidence text available

22659130

---

➶

biogrid

No evidence text available

22179575

---

➶

biogrid

No evidence text available

22179575

---

➶

biogrid

No evidence text available

22179575

PUVA affects USP2

| 4

PUVA increases the amount of USP2.

| 2

PUVA increases the amount of USP2. 2 / 2

| 2

---

➶

reach

"PUVA caused a significant (P < 0.01) upregulation of USP2 mRNA expression already after 8 hours with an even stronger increase after 24 and 48 hours post-treatment."

27351221

---

➶

reach

"More importantly, PUVA did not upregulate USP2 mRNA expression in Hut-78 cells and only slightly in SeAx cells."

27351221

PUVA activates USP2.

| 2

PUVA activates USP2. 2 / 2

| 2

---

➶

reach

"We propose that a negative regulatory loop in which USP2 is induced by PUVA via p53 increases cell resistance to apoptosis via deubiquitination of Mdm2."

27351221

---

➶

reach

"USP2 is upregulated by PUVA and a p53 activator, nutlin3a."

27351221

KRT15 affects USP2

3 1 |

USP2 binds KRT15. 4 / 4

3 1 |

---

➶

biogrid

No evidence text available

16189514

---

➶

hprd

No evidence text available

16189514

---

➶

biogrid

No evidence text available

25416956

---

➶

biogrid

No evidence text available

16189514

DLL1 affects USP2

| 4

USP2 binds DLL1. 4 / 4

| 4

---

➶

sparser

"These results suggest that USP2-45 binding to α 2 δ-1 promotes the de-ubiquitylation of both Ca v 1.2 and α 2 δ-1 subunits, in order to regulate the expression of Ca v 1.2 channels at the plasma membrane."

25366495

---

➶

sparser

"In addition, the binding of USP2-45 to α 2 δ-1 may disrupt the chaperone role of this subunit towards Ca v 1.2, leading to the reduction of Ca v 1.2 surface expression."

25366495

---

➶

sparser

"This result suggests that the first critical event is the binding of USP2-45 to the auxiliary α 2 δ-1 subunit which may act as an anchor allowing for USP2-45 to de-ubiquitylate Ca v 1.2 channels."

25366495

---

➶

sparser

"Though the reason for this peculiarity is presently unknown, it may lie in the fact that the USP2-45 binding to Ca V α 2 δ-1 might disrupt the chaperone role of the auxiliary subunit, leading to a reduction of the Ca V 1.2α 1 pore-forming subunit trafficked to the plasma membrane [ xref ]."

28957379

Pirinixic acid affects USP2

3 |

Pirinixic acid decreases the amount of USP2.

2 |

Pirinixic acid decreases the amount of USP2. 2 / 2

2 |

---

➶

ctd

No evidence text available

23811191

---

➶

ctd

No evidence text available

19710929

Pirinixic acid activates USP2.

1 |

Pirinixic acid activates USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

19710929

GAcrp affects USP2

| 3

GAcrp decreases the amount of USP2.

| 2

GAcrp decreases the amount of USP2. 2 / 2

| 2

---

➶

reach

"As depicted in Fig. 1C and 1D, gAcrp significantly decreased USP-2 protein levels in a dose- and time dependent manner."

26033248

---

➶

reach

"Similarly, gAcrp decreased USP-2 protein levels in a time dependent manner in MCF-7 cells."

26033248

GAcrp activates USP2.

| 1

GAcrp activates USP2. 1 / 1

| 1

---

➶

reach

"Therefore, we examined the relationship between USP-2 and cyclin D1 in cancer cells treated with gAcrp."

26033248

Antithrombin affects USP2

| 3

Antithrombin binds USP2.

| 2

USP2 binds antithrombin. 2 / 2

| 2

---

➶

reach

"To determine the potential interaction of USP2 and antithrombin, we performed immunoprecipitation and immunoblotting experiments, which revealed that the endogenous USP2 isoform (USP2a) interacted with antithrombin in HepG2 and SMMC7721 cells (Figure 5A,B)."

34324733

---

➶

reach

"We further found that USP2 interacted with antithrombin and regulated antithrombin expression, showing that overexpression of USP2 inhibits the ubiquitination and proteasomal clearance of antithrombin, whereas pharmacological inhibition or siRNA mediated knockdown of USP2 downregulates antithrombin."

34324733

Antithrombin activates USP2.

| 1

Antithrombin activates USP2. 1 / 1

| 1

---

➶

reach

"Given that ML364 inhibits USP2, we next investigated the role of USP2 in antithrombin turnover."

34324733

ZEB1 affects USP2

3 |

ZEB1 decreases the amount of USP2. 3 / 3

3 |

---

➶

biopax:msigdb

No evidence text available

---

➶

biopax:msigdb

No evidence text available

---

➶

biopax:msigdb

No evidence text available

Ubiquitin affects USP7

| 3

Ubiquitin binds USP14, USP2, and USP7. 2 / 2

| 2

---

➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

---

➶

sparser

"Only approximately 1000 Å 2 of the surface area of PL pro (640 Å 2 by the Ub core and 360 Å 2 by the Ub C-terminus) is buried in the interface, which is smaller than in the USP2-Ub (1900 Å 2 ; Supplementary Fig. S6b ), USP14-Ub aldehyde (1500 Å 2 ; Supplementary Fig. S6c ) and HAUSP-Ub aldehyde (1700 Å 2 ) complexes."

24531491

Ubiquitin binds USP14, USP2, USP7, and CSH1. 1 / 1

| 1

---

➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

Ubiquitin affects Asn221

| 3

Ubiquitin binds USP2 and Asn221. 3 / 3

| 3

---

➶

reach

"In the USP2 and ubiquitin complex, Asn221 Ndelta is in close contact to one oxygen of the Gly76 carboxylate, while Asn218 Ndelta (" oxyanion hole ") interacts with the second C-terminal oxygen, an int[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

16905103

---

➶

reach

"In the USP2/ubiquitin complex, Asn221 Nd is in close contact to one oxygen of the Gly76 carboxylate, while Asn218 Nd (''oxyanion hole'') interacts with the second C-terminal oxygen, an interaction similar to the one observed in the USP7/ubiquitinaldehyde complex."

16905103

---

➶

reach

"In the USP2/ubiquitin complex, Asn221 Nδ is in close contact to one oxygen of the Gly76 carboxylate, while Asn218 Nδ (“oxyanion hole”) interacts with the second C-terminal oxygen, an interaction similar to the one observed in the USP7/ubiquitin-aldehyde complex."

16905103

Ub-AMC affects USP2

| 3

USP2 binds Ub-AMC. 3 / 3

| 3

---

➶

reach

"Notably, both native ubiquitin and Ub-AMC bind to USP2 with monophasic kinetics."

23211065

---

➶

reach

"We also determined the equilibrium binding constant of Ub-AMC binding to USP2 by measuring the decrease in Ub-AMC fluorescence in the presence of increasing concentrations of C276A USP2."

23211065

---

➶

reach

"Binding of Ub-AMC to USP2 under an equilibrium condition."

23211065

USP7 affects Ubiquitin

| 3

Ubiquitin binds USP14, USP2, and USP7. 2 / 2

| 2

---

➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

---

➶

sparser

"Only approximately 1000 Å 2 of the surface area of PL pro (640 Å 2 by the Ub core and 360 Å 2 by the Ub C-terminus) is buried in the interface, which is smaller than in the USP2-Ub (1900 Å 2 ; Supplementary Fig. S6b ), USP14-Ub aldehyde (1500 Å 2 ; Supplementary Fig. S6c ) and HAUSP-Ub aldehyde (1700 Å 2 ) complexes."

24531491

Ubiquitin binds USP14, USP2, USP7, and CSH1. 1 / 1

| 1

---

➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

USP25 affects USP2

| 2 1

USP2 binds USP25. 3 / 3

| 2 1

---

➶

sparser

"We found that Ubvs that bind to USP2 or USP21 contain a remarkably similar core functional epitope, or &quot;hot spot,&quot; consisting mainly of positions that are conserved as the wild type sequence, but also some positions that prefer mutant sequences."

27436899

---

➶

reach

"We first screened a panel of DUBs and found that both USP2 and USP21 bound to endogenous SKP2, but only USP2 deubiquitylated and stabilized SKP2 protein."

34425107

---

➶

reach

"In the USP2 and USP21 complex structure, the side chain of Ub Lys48 does not occupy the nearby pocket on USP (see XREF_FIG)."

27501351

USP2 affects proteolysis

| 3

USP2 inhibits proteolysis. 3 / 3

| 3

---

➶

reach

"Seventh, alcohol induced dramatic reduction of USP2, the major deubiquitinating enzyme may provide mechanistic perspectives underlying caveolar protein depletion and/or degradation as USP2 depletion has been documented to significantly enhance protein degradation."

20053519

---

➶

reach

"Knockdown of USP2 or USP14 accelerated protein degradation of TNF-alpha, and abolished the effect of miR-124 on TNF-alpha protein stability."

27063215

---

➶

reach

"The ubiquitin dependent proteolysis of cyclin D1 is antagonized by the deubiquitinating enzyme USP2, thus increasing cyclin D1 half-life."

30853938

USP2 affects inflammatory response

| 2

USP2 activates inflammatory response.

| 1

USP2 activates inflammatory response. 1 / 2

| 1

---

➶

reach

"USP2 may also mediate the response of the clock to inflammation, as the expression of the gene is increased in response to TNFalpha treatment, and CRY1 protein induction in response to this cytokine is abrogated when Usp2 expression is knocked down."

25147498

USP2 inhibits inflammatory response.

| 1

USP2 inhibits inflammatory response. 1 / 1

| 1

---

➶

reach

"Macrophage USP2 may therefore selectively prevent age- and/or adiposity related chronic inflammation and subsequent insulin resistance."

28956020

USP2 affects cytokine production

| 3

USP2 inhibits cytokine production. 3 / 3

| 3

---

➶

reach

"In LPS stimulated macrophage like cell line J774.1, the knockdown of USP2 promoted cytokine production, whereas the ectopic expression of USP2 repressed cytokine production."

33138315

---

➶

reach

"USP2a, a 69-kDa splice variant of USP2, also known as USP9 and UBP41, negatively regulates NF-kappaB activation and proinflammatory cytokine production by interacting with TRAF6."

33138315

---

➶

reach

"In this study, we demonstrated that USP2KD promotes 25 of 104 cytokines in macrophage like cells after LPS stimulation, while ectopic expression of USP2 represses most cytokine production following this stimulation."

29138532

USP2 affects Ub-AMC

| 3

USP2 binds Ub-AMC. 3 / 3

| 3

---

➶

reach

"Notably, both native ubiquitin and Ub-AMC bind to USP2 with monophasic kinetics."

23211065

---

➶

reach

"We also determined the equilibrium binding constant of Ub-AMC binding to USP2 by measuring the decrease in Ub-AMC fluorescence in the presence of increasing concentrations of C276A USP2."

23211065

---

➶

reach

"Binding of Ub-AMC to USP2 under an equilibrium condition."

23211065

USP2 affects USP25

| 2 1

USP2 binds USP25. 3 / 3

| 2 1

---

➶

sparser

"We found that Ubvs that bind to USP2 or USP21 contain a remarkably similar core functional epitope, or &quot;hot spot,&quot; consisting mainly of positions that are conserved as the wild type sequence, but also some positions that prefer mutant sequences."

27436899

---

➶

reach

"We first screened a panel of DUBs and found that both USP2 and USP21 bound to endogenous SKP2, but only USP2 deubiquitylated and stabilized SKP2 protein."

34425107

---

➶

reach

"In the USP2 and USP21 complex structure, the side chain of Ub Lys48 does not occupy the nearby pocket on USP (see XREF_FIG)."

27501351

USP2 affects USP2

| 2

USP2 activates USP2.

| 1

USP2 activates USP2. 1 / 2

| 1

---

➶

reach

"On the other hand, a defect of peroxisomal protein import or even release of USP2 from defective peroxisomes because of cell injury or dysfunction would increase the cytosolic pool of USP2, which might contribute to the initiation of apoptosis."

26484888

USP2 inhibits USP2.

| 1

USP2 inhibits USP2. 1 / 1

| 1

---

➶

reach

"In summary, our data show that the ubiquitin core and the ubiquitin C terminus alone bind USP2 very weakly with affinities at best in the high micromolar range, while full-length ubiquitin inhibits USP2 with a K i of 2.8 mM.USP2 is one of 54 human members of the family of ubiquitin-specific proteases (USPs)."

16905103

USP2 affects TRIM27

2 | 1

USP2 binds TRIM27.

2 |

USP2 binds TRIM27. 2 / 2

2 |

---

➶

biogrid

No evidence text available

25416956

---

➶

biogrid

No evidence text available

23105109

USP2 activates TRIM27.

| 1

USP2 activates TRIM27. 1 / 1

| 1

---

➶

reach

"Importantly, when RFP was immunoprecipitated in the presence of NEM and then treated with the deubiquitinating enzyme Usp2 the slower migrating band was lost in both RFP and HA western blots (XREF_FIG, lane 12), confirming that " JMD-Ub " was ubiquitinated."

22693575

USP2 affects TBK1

1 | 1

USP2 binds TBK1.

1 |

TBK1 binds USP2. 1 / 2

1 |

---

➶

biogrid

No evidence text available

25070846

USP2 activates TBK1.

| 1

USP2 activates TBK1. 1 / 1

| 1

---

➶

eidos

"Additionally , USP2 modulates TBK1 to attenuate signaling along the RIGI , cGAS / STING , and TRIF pathways ."

33530560

USP2 affects STAT1

2 |

STAT1 binds USP2. 2 / 3

2 |

---

➶

biogrid

No evidence text available

27434509

---

➶

biogrid

No evidence text available

27434509

USP2 affects SLC22A2

| 3

USP2 activates SLC22A2. 3 / 3

| 3

---

➶

reach

"USP2 Modulates Oct-1 and Oct-2 in LPS Stimulated HL-60 Cells."

29138532

---

➶

reach

"Overexpression of USP2 did not cause modification of the K48 linked polyubiquitination of Oct-2 protein, suggesting that USP2 is unlikely to modulate Oct-2 digestion in a direct manner."

29138532

---

➶

reach

"Therefore, USP2 potentiates nuclear accumulation of Oct-1 and Oct-2 proteins."

29138532

USP2 affects SKP2

| 1 2

SKP2 binds USP2. 3 / 3

| 1 2

---

➶

reach

"We first screened a panel of DUBs and found that both USP2 and USP21 bound to endogenous SKP2, but only USP2 deubiquitylated and stabilized SKP2 protein."

34425107

---

➶

sparser

"Mechanistically, USP2 bound to SKP2 via the leucine-rich repeat (LRR) substrate-binding domain on SKP2 to disrupt the SKP2-substrate binding, leading to stabilization of both SKP2 and these substrates."

34425107

---

➶

sparser

"Our study revealed a new mechanism of the cross-talk among the E3-DUB-substrates and its potential implication in targeting the USP2-SKP2 axis for cancer therapy."

34425107

USP2 affects SCNN1G

2 1 |

USP2 binds SCNN1G.

2 |

SCNN1G binds USP2. 2 / 2

2 |

---

➶

biogrid

No evidence text available

18701608

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➶

biogrid

No evidence text available

21478478

USP2 deubiquitinates SCNN1G.

1 |

USP2 deubiquitinates SCNN1G. 1 / 1

1 |

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➶

ubibrowser

"The surface expression of ENaC components is directed by the ubiquitination of ENaC by NEDD4L, an ENaC-specific E3 ubiquitin ligase, and is regulated by the deubiquitination of ENaC by USP2.?"

20090362

USP2 affects SCNN1A

3 |

SCNN1A binds USP2. 3 / 3

3 |

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➶

biogrid

No evidence text available

18701608

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➶

biogrid

No evidence text available

18701608

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➶

biogrid

No evidence text available

21478478

USP2 affects Neoplastic Stem Cells

| 3

USP2 activates Neoplastic Stem Cells. 1 / 1

| 1

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➶

reach

"Since our study is the first to uncover USP2 's novel function in CSCs, future studies will be needed to delineate the contribution of cyclin D1 to USP2 mediated CSC expansion in TNBC."

30918246

Modified USP2 activates Neoplastic Stem Cells. 1 / 1

| 1

---

➶

reach

"Altogether, our study illustrates that USP2 overexpression in TNBC promotes Twist and Bmi1 expression, CSC expansion, cancer cell migration and tumor development."

30918246

Mutated USP2 activates Neoplastic Stem Cells. 1 / 1

| 1

---

➶

reach

"Moreover, the enzymatically inactive mutant of USP2 failed to promote CSC renewal, suggesting that the CSC promoting effect mediated by USP2 depends on its deubiquitinase activity."

30918246

USP2 affects NFkappaB

| 2

USP2 inhibits NFkappaB. 2 / 3

| 2

---

➶

reach

"The ubiquitin #specific proteases system 2 (USP2) stabilizes the ubiquitin-E3-ligase ITCH and lowers NF-kappaB basal activity, which leads to reduced c-FLIP mRNA production; proteasomal degradation of c- FLIP isoforms is also elevated by its negative regulator proteasome ITCH [XREF_BIBR]."

32352084

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➶

reach

"USP2a, a 69-kDa splice variant of USP2, also known as USP9 and UBP41, negatively regulates NF-kappaB activation and proinflammatory cytokine production by interacting with TRAF6."

33138315

USP2 affects MALT1

3 |

USP2 binds MALT1. 3 / 3

3 |

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➶

biogrid

No evidence text available

28052131

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➶

biogrid

No evidence text available

23264041

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➶

biogrid

No evidence text available

23264041

USP2 affects ERBB2

1 | 2

USP2 binds ERBB2. 3 / 3

1 | 2

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➶

biogrid

No evidence text available

19436748

---

➶

sparser

"Additionally, in the subsequent co-immunoprecipitation analysis to examine the association of USP2 with ErbB2, USP2 was readily pulled down by immunoprecipitated ErbB2 especially in cells treated with 17-AAG, suggesting stronger association between USP2 and ubiquitylated ErbB2 (Fig.  xref )."

32327714

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➶

sparser

"USP2 associates with internalized ErbB2 and prevents its lysosomal sorting and degradation via exerting deubiquitylase activity."

32327714

USP2 affects E2F4

| 3

USP2 binds E2F4. 3 / 3

| 3

---

➶

sparser

"In clinical gastric cancer specimens, both USP2 and E2F4 were upregulated and associated with poor outcome of patients."

35253629

---

➶

sparser

"Therapeutic targeting of the USP2-E2F4 axis inhibits autophagic machinery essential for zinc homeostasis in cancer progression."

35253629

---

➶

sparser

"These findings indicate that therapeutic targeting of the USP2-E2F4 axis inhibits autophagic machinery essential for zinc homeostasis in cancer progression."

35253629

USP2 affects BMI1

| 1 1 1

USP2 activates BMI1. 3 / 3

| 1 1 1

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➶

sparser

"In addition, USP2 activates Bmi1 and EMT by stabilizing Twist through removing ubiquitylation mediated by beta-transducin repeats-containing proteins (β-TrCP), a cellular E3 ubiquitin ligase ( xref )."

32426267

---

➶

eidos

"In addition , USP2 activates Bmi1 and EMT by stabilizing Twist through removing ubiquitylation mediated by beta-transducin repeats-containing proteins ( beta-TrCP ) , a cellular E3 ubiquitin ligase ( 104 ) ."

32426267

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➶

reach

"In addition, USP2 activates Bmi1 and EMT by stabilizing Twist through removing ubiquitylation mediated by beta-transducin repeats containing proteins (beta-TrCP), a cellular E3 ubiquitin ligase."

32426267

USP2 affects Asn221

| 3

Ubiquitin binds USP2 and Asn221. 3 / 3

| 3

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➶

reach

"In the USP2 and ubiquitin complex, Asn221 Ndelta is in close contact to one oxygen of the Gly76 carboxylate, while Asn218 Ndelta (" oxyanion hole ") interacts with the second C-terminal oxygen, an int[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

16905103

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➶

reach

"In the USP2/ubiquitin complex, Asn221 Nd is in close contact to one oxygen of the Gly76 carboxylate, while Asn218 Nd (''oxyanion hole'') interacts with the second C-terminal oxygen, an interaction similar to the one observed in the USP7/ubiquitinaldehyde complex."

16905103

---

➶

reach

"In the USP2/ubiquitin complex, Asn221 Nδ is in close contact to one oxygen of the Gly76 carboxylate, while Asn218 Nδ (“oxyanion hole”) interacts with the second C-terminal oxygen, an interaction similar to the one observed in the USP7/ubiquitin-aldehyde complex."

16905103

USP14 affects Ubiquitin

| 3

Ubiquitin binds USP14, USP2, and USP7. 2 / 2

| 2

---

➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

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➶

sparser

"Only approximately 1000 Å 2 of the surface area of PL pro (640 Å 2 by the Ub core and 360 Å 2 by the Ub C-terminus) is buried in the interface, which is smaller than in the USP2-Ub (1900 Å 2 ; Supplementary Fig. S6b ), USP14-Ub aldehyde (1500 Å 2 ; Supplementary Fig. S6c ) and HAUSP-Ub aldehyde (1700 Å 2 ) complexes."

24531491

Ubiquitin binds USP14, USP2, USP7, and CSH1. 1 / 1

| 1

---

➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

TNF affects USP2

| 2 1

TNF activates USP2.

| 2

TNF activates USP2. 2 / 2

| 2

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➶

reach

"Our results indicate that TNFalpha induced USP2 down-regulation is an effective cytoprotective mechanism in hepatocytes."

19001362

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➶

reach

"Here we investigated the role of TNFalpha induced down-modulation of the de-ubiquitinating enzyme USP2 for hepatocyte survival."

19001362

TNF binds USP2.

| 1

TNF binds USP2, CFLAR, and PRH1. 1 / 1

| 1

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➶

sparser

"In vitro an artificial knockdown of USP2 inhibited actinomycin D/TNFalpha-induced hepatocyte apoptosis, which was associated with elevated levels of the anti-apoptotic protein c-Flip(L/S) and a concomitant decrease of cellular levels of the ubiquitinligase Itch, a negative regulator of c-Flip."

19001362

TFDP1 affects USP2

3 |

TFDP1 decreases the amount of USP2. 3 / 3

3 |

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➶

biopax:msigdb

No evidence text available

---

➶

biopax:msigdb

No evidence text available

---

➶

biopax:msigdb

No evidence text available

TCF3 affects USP2

3 |

TCF3 decreases the amount of USP2. 3 / 3

3 |

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➶

biopax:msigdb

No evidence text available

---

➶

biopax:msigdb

No evidence text available

---

➶

biopax:msigdb

No evidence text available

SKP2 affects USP2

| 1 2

SKP2 binds USP2. 3 / 3

| 1 2

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➶

reach

"We first screened a panel of DUBs and found that both USP2 and USP21 bound to endogenous SKP2, but only USP2 deubiquitylated and stabilized SKP2 protein."

34425107

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➶

sparser

"Mechanistically, USP2 bound to SKP2 via the leucine-rich repeat (LRR) substrate-binding domain on SKP2 to disrupt the SKP2-substrate binding, leading to stabilization of both SKP2 and these substrates."

34425107

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➶

sparser

"Our study revealed a new mechanism of the cross-talk among the E3-DUB-substrates and its potential implication in targeting the USP2-SKP2 axis for cancer therapy."

34425107

SCNN1A affects USP2

3 |

SCNN1A binds USP2. 3 / 3

3 |

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➶

biogrid

No evidence text available

18701608

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➶

biogrid

No evidence text available

18701608

---

➶

biogrid

No evidence text available

21478478

MYC affects USP2

2 | 1

MYC decreases the amount of USP2.

2 |

MYC decreases the amount of USP2. 2 / 2

2 |

---

➶

biopax:msigdb

No evidence text available

---

➶

biopax:msigdb

No evidence text available

MYC activates USP2.

| 1

MYC activates USP2. 1 / 1

| 1

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➶

sparser

"C-Myc-activated USP2-AS1 suppresses senescence and promotes tumor progression via stabilization of E2F1 mRNA."

34707111

MALT1 affects USP2

3 |

USP2 binds MALT1. 3 / 3

3 |

---

➶

biogrid

No evidence text available

28052131

---

➶

biogrid

No evidence text available

23264041

---

➶

biogrid

No evidence text available

23264041

FAS affects USP2

| 2 1

FAS binds USP2. 3 / 3

| 2 1

---

➶

sparser

"In 2004, Graner and colleagues showed that USP2 binds to and stabilizes FAS [ xref ], a protein known to be upregulated in many cancers including prostate cancer [ xref ]."

33621249

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➶

reach

"In prostate cancer cells, USP2 interacts with and stabilizes FAS, which is often over-expressed in biologically aggressive human tumors."

18755030

---

➶

reach

"In 2004, Graner and colleagues showed that USP2 binds to and stabilizes FAS [XREF_BIBR], a protein known to be upregulated in many cancers including prostate cancer [XREF_BIBR]."

33621249

ERBB2 affects USP2

1 | 2

USP2 binds ERBB2. 3 / 3

1 | 2

---

➶

biogrid

No evidence text available

19436748

---

➶

sparser

"Additionally, in the subsequent co-immunoprecipitation analysis to examine the association of USP2 with ErbB2, USP2 was readily pulled down by immunoprecipitated ErbB2 especially in cells treated with 17-AAG, suggesting stronger association between USP2 and ubiquitylated ErbB2 (Fig.  xref )."

32327714

---

➶

sparser

"USP2 associates with internalized ErbB2 and prevents its lysosomal sorting and degradation via exerting deubiquitylase activity."

32327714

E2F4 affects USP2

| 3

USP2 binds E2F4. 3 / 3

| 3

---

➶

sparser

"In clinical gastric cancer specimens, both USP2 and E2F4 were upregulated and associated with poor outcome of patients."

35253629

---

➶

sparser

"Therapeutic targeting of the USP2-E2F4 axis inhibits autophagic machinery essential for zinc homeostasis in cancer progression."

35253629

---

➶

sparser

"These findings indicate that therapeutic targeting of the USP2-E2F4 axis inhibits autophagic machinery essential for zinc homeostasis in cancer progression."

35253629

Dietary Fats affects USP2

3 |

Dietary Fats increases the amount of USP2. 3 / 3

3 |

---

➶

ctd

No evidence text available

30120929

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➶

ctd

No evidence text available

19467301

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➶

ctd

No evidence text available

28433925

CRY1 affects USP2

3 |

USP2 binds CRY1. 3 / 3

3 |

---

➶

biogrid

No evidence text available

22669941

---

➶

biogrid

No evidence text available

22669941

---

➶

biogrid

No evidence text available

22669941

CLOCK affects USP2

| 3

CLOCK activates USP2. 3 / 3

| 3

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➶

reach

"However, the free running period (tau), a key intrinsic characteristic of the central circadian clock, was significantly increased in Usp2 KO mice (XREF_FIG; XREF_TABLE) (also reproduced in an additional group of mice, data not shown), suggesting the involvement of USP2 in the molecular clockwork."

23213472

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➶

reach

"This suggests a scenario in USP2 -/- mice in which increased turnover of BMAL1 coincides with increased CLOCK and BMAL1 driven gene expression in the USP2 -/- SCN."

21966515

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➶

reach

"The circadian rhythm of Usp2 is blunted in Clock mutant and Bmal1 KO mice, and the Usp2 promoter is activated by CLOCK and BMAL1, indicating that Usp2 is a direct target of these transcription factors."

25147498

Asn221 affects Ubiquitin

| 3

Ubiquitin binds USP2 and Asn221. 3 / 3

| 3

---

➶

reach

"In the USP2 and ubiquitin complex, Asn221 Ndelta is in close contact to one oxygen of the Gly76 carboxylate, while Asn218 Ndelta (" oxyanion hole ") interacts with the second C-terminal oxygen, an int[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

16905103

---

➶

reach

"In the USP2/ubiquitin complex, Asn221 Nd is in close contact to one oxygen of the Gly76 carboxylate, while Asn218 Nd (''oxyanion hole'') interacts with the second C-terminal oxygen, an interaction similar to the one observed in the USP7/ubiquitinaldehyde complex."

16905103

---

➶

reach

"In the USP2/ubiquitin complex, Asn221 Nδ is in close contact to one oxygen of the Gly76 carboxylate, while Asn218 Nδ (“oxyanion hole”) interacts with the second C-terminal oxygen, an interaction similar to the one observed in the USP7/ubiquitin-aldehyde complex."

16905103

Tetraphene affects USP2

2 |

Tetraphene increases the amount of USP2. 2 / 2

2 |

---

➶

ctd

No evidence text available

27858113

---

➶

ctd

No evidence text available

26377693

Tetrachloromethane affects USP2

2 |

Tetrachloromethane decreases the amount of USP2. 2 / 2

2 |

---

➶

ctd

No evidence text available

27339419

---

➶

ctd

No evidence text available

31150632

Succimer affects USP2

2 |

Succimer decreases the amount of USP2. 2 / 2

2 |

---

➶

ctd

No evidence text available

26378955

---

➶

ctd

No evidence text available

21641980

Sodium arsenite affects USP2

2 |

Sodium arsenite increases the amount of USP2.

1 |

Sodium arsenite increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

17879257

Sodium arsenite decreases the amount of USP2.

1 |

Sodium arsenite decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

22714537

Reactive oxygen species affects USP2

| 1 1

Reactive oxygen species inhibits USP2. 2 / 2

| 1 1

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➶

sparser

"While USP2 was readily inhibited by ROS, the activity of AMSH was unaffected, even in the presence of STAM, the binding partner and catalytic activator of AMSH ( xref )."

23219552

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➶

reach

"While USP2 was readily inhibited by ROS, the activity of AMSH was unaffected, even in the presence of STAM, the binding partner and catalytic activator of AMSH (XREF_FIG)."

23219552

Phenylmercury acetate affects USP2

2 |

Phenylmercury acetate decreases the amount of USP2. 2 / 2

2 |

---

➶

ctd

No evidence text available

27188386

---

➶

ctd

No evidence text available

26272509

Phenobarbital affects USP2

2 |

Phenobarbital increases the amount of USP2. 2 / 2

2 |

---

➶

ctd

No evidence text available

19482888

---

➶

ctd

No evidence text available

19270015

Magnetite nanoparticle affects USP2

2 |

Magnetite nanoparticle decreases the amount of USP2. 2 / 2

2 |

---

➶

ctd

No evidence text available

21641980

---

➶

ctd

No evidence text available

26378955

Lipopolysaccharide affects USP2

| 1 1

Lipopolysaccharide inhibits USP2.

| 1

Lipopolysaccharide inhibits USP2. 1 / 1

| 1

---

➶

eidos

"LPS suppressed the expression of USP2 in macrophages ( human myeloid HL-60 cell line ) [ 21 ] ."

32963492

Lipopolysaccharide decreases the amount of USP2.

| 1

Lipopolysaccharide decreases the amount of USP2. 1 / 1

| 1

---

➶

reach

"LPS and Pam3CSK4 Repress the Expression of USP2 Splice Variants in Macrophages."

29138532

Full-length ubiquitin affects USP2

| 2

Full-length ubiquitin inhibits USP2. 2 / 2

| 2

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➶

eidos

"In summary , our data show that the ubiquitin core and the ubiquitin C terminus alone bind USP2 very weakly with affinities at best in the high micromolar range , while full-length ubiquitin inhibits USP2 with a Ki of 2.8 muM ."

16905103

---

➶

eidos

"In summary , our data show that the ubiquitin core and the ubiquitin C terminus alone bind USP2 very weakly with affinities at best in the high micromolar range , while full-length ubiquitin inhibits USP2 with a K i of 2.8 mM ."

16905103

Ezogabine affects USP2

| 2

Ezogabine increases the amount of USP2. 2 / 2

| 2

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➶

reach

"Indeed, we found that retigabine (8 mg/kg) significantly increased the protein levels of USP2 in hippocampal CA1 area of stressed rats."

29501527

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➶

reach

"On the other hand, the expression and coexpression of GluA1 and USP2 in hippocampal CA1 area were down-regulated after acute stress, and increased by retigabine treatment."

29501527

Epithelial sodium channel affects USP2

| 2

USP2 binds epithelial sodium channel. 2 / 2

| 2

---

➶

sparser

"The interaction of Usp2-45 with ENaC exogenously expressed in HEK293 cells was tested by coimmunoprecipitation."

21478478

---

➶

sparser

"Here, in HEK293 cells stably transfected with ENaC, Usp2-45 interacted with ENaC, leading to deubiquitylation of the channel and stimulation of ENaC activity >20-fold."

18701608

Disulfiram affects USP2

| 1 1

Disulfiram inhibits USP2. 2 / 2

| 1 1

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➶

reach

"Disulfiram and 6-Thioguanine synergistically inhibit the enzymatic activities of USP2 and USP21."

33582217

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➶

sparser

"In addition, we also observed a synergistic inhibition of USP2 and USP21 by disulfiram and 6-Thioguanine (6TG), a clinical drug for acute myeloid leukemia."

33582217

Cisplatin affects USP2

1 |

Cisplatin decreases the amount of USP2. 1 / 2

1 |

---

➶

ctd

No evidence text available

27392435

Chrysene affects USP2

2 |

Chrysene increases the amount of USP2. 2 / 2

2 |

---

➶

ctd

No evidence text available

26377693

---

➶

ctd

No evidence text available

27858113

Carbon nanotube affects USP2

2 |

Carbon nanotube decreases the amount of USP2. 2 / 2

2 |

---

➶

ctd

No evidence text available

25554681

---

➶

ctd

No evidence text available

25620056

Bisphenol A affects USP2

2 |

Bisphenol A decreases the amount of USP2. 2 / 2

2 |

---

➶

ctd

No evidence text available

31715268

---

➶

ctd

No evidence text available

26063408

Benzo[b]fluoranthene affects USP2

2 |

Benzo[b]fluoranthene increases the amount of USP2. 2 / 2

2 |

---

➶

ctd

No evidence text available

26377693

---

➶

ctd

No evidence text available

27858113

Aflatoxin B1 affects USP2

2 |

Aflatoxin B1 demethylates USP2.

1 |

Aflatoxin B1 demethylates USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

27153756

Aflatoxin B1 decreases the amount of USP2.

1 |

Aflatoxin B1 decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

19770486

Ubiquitin affects Lys407

| 2

Ubiquitin binds USP2 and Lys407. 2 / 2

| 2

---

➶

reach

"In the USP2 and ubiquitin complex, Nzeta of Lys407 occupies the same position as a solvent molecule in the USP7 and ubiquitin-aldehyde complex.The principles of protein protein interactions and the ro[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

16905103

---

➶

reach

"In the USP2/ubiquitin complex, Nz of Lys407 occupies the same position as a solvent molecule in the USP7/ubiquitin-aldehyde complex.The principles of protein-protein interactions and the role of water molecules in molecular recognition have been studied by various groups (Janin, 1997; Jones and Thornton, 1996; Larsen et al., 1998) ."

16905103

USP2 affects transcription, DNA-templated

| 1 1

USP2 activates transcription, DNA-templated. 2 / 2

| 1 1

---

➶

reach

"We next investigated whether USP2 activates transcription of the cytokine genes by modifying chromatin accessibility after TLR stimulation."

29138532

---

➶

sparser

"We next investigated whether USP2 activates transcription of the cytokine genes by modifying chromatin accessibility after TLR stimulation."

29138532

USP2 affects reactive oxygen species

| 2

USP2 inhibits reactive oxygen species.

| 1

USP2 inhibits reactive oxygen species. 1 / 1

| 1

---

➶

reach

"USP2 overexpression suppressed the degree of cardiac hypertrophy (decreased ANP, BNP, and β-MHC mRNA levels, cell surface area, and ratio of protein/DNA), calcium overload (decreased Ca 2+ concentration and t-CaMKⅡ and p-CaMKⅡ, and increased SERCA2), and mitochondrial dysfunction (decreased MDA and ROS and increased MFN1, ATP, MMP, and complex Ⅰ and II) both in vitro and in vivo."

37100191

USP2 decreases the amount of reactive oxygen species.

| 1

USP2 decreases the amount of reactive oxygen species. 1 / 1

| 1

---

➶

reach

"The USP2 selective inhibitor ML364 also increased the levels of mitochondrial ROS, and modulated the membranepotential and morphology of the mitochondria."

31353872

USP2 affects glucose

| 2

USP2 decreases the amount of glucose. 2 / 2

| 2

---

➶

reach

"These results indicate hypothalamic USP2 attenuates perturbations in blood glucose levels by modifying the ROS-AMPK-sympathetic nerve axis."

35504726

---

➶

reach

"Administration of a USP2-selective inhibitor, ML364 (20 ng/head), into the VMH elicited a rapid increase in the circulating glucose level in male mice, suggesting USP2 has a suppressive role on glucose mobilization."

35504726

USP2 affects epithelial sodium channel

| 2

USP2 binds epithelial sodium channel. 2 / 2

| 2

---

➶

sparser

"The interaction of Usp2-45 with ENaC exogenously expressed in HEK293 cells was tested by coimmunoprecipitation."

21478478

---

➶

sparser

"Here, in HEK293 cells stably transfected with ENaC, Usp2-45 interacted with ENaC, leading to deubiquitylation of the channel and stimulation of ENaC activity >20-fold."

18701608

USP2 affects doxorubicin

| 2

USP2 inhibits doxorubicin. 2 / 2

| 2

---

➶

reach

"Moreover, USP2 inhibition by ML364 considerably enhanced the cytotoxicity of doxorubicin or paclitaxel in multiple TNBC cell models."

30918246

---

➶

reach

"In light of the vital role of USP2 in CSC regulation, we sought to determine whether USP2 inhibition increases TNBC sensitivity to doxorubicin and paclitaxel."

30918246

USP2 affects calcium(2+)

| 2

USP2 inhibits calcium(2+). 2 / 2

| 2

---

➶

reach

"In summary, we found that the inactivation of Usp2 in mouse and of its orthologue CG14619 in Drosophila does not affect the circadian free running period, but impairs bodily Ca 2+ homeostasis in both species, especially in dietary Ca 2+ absorption in mouse small intestine."

26756164

---

➶

reach

"USP2 overexpression suppressed the degree of cardiac hypertrophy (decreased ANP, BNP, and β-MHC mRNA levels, cell surface area, and ratio of protein/DNA), calcium overload (decreased Ca 2+ concentration and t-CaMKⅡ and p-CaMKⅡ, and increased SERCA2), and mitochondrial dysfunction (decreased MDA and ROS and increased MFN1, ATP, MMP, and complex Ⅰ and II) both in vitro and in vivo."

37100191

USP2 affects USP8

| 1 1

USP2 inhibits USP8.

| 1

USP2 inhibits USP8. 1 / 1

| 1

---

➶

reach

"Overexpression of USP2 was also shown to reduce p53 stability [XREF_BIBR], and another de-ubiquitylase USP8 (also called UBPY) promotes epithelial growth factor receptor degradation [XREF_BIBR, XREF_BIBR, XREF_BIBR]."

25366495

USP2 binds USP8.

| 1

USP2 binds USP8 and KCNN4. 1 / 1

| 1

---

➶

sparser

"Channel-DUB interactions were verified after 90 min as there were notable interactions of KCa3.1 with USP2 and USP8 and a weaker association with AMSH (associated molecule with the SH3 domain of STAM; Figure xref )."

22615701

USP2 affects TNFRSF1A

2 |

TNFRSF1A binds USP2. 2 / 2

2 |

---

➶

biogrid

No evidence text available

22179575

---

➶

biogrid

No evidence text available

22179575

USP2 affects SMAD7

| 1 1

USP2 deubiquitinates SMAD7.

| 1

USP2 leads to the deubiquitination of SMAD7. 1 / 1

| 1

---

➶

reach

"Specifically, USP2 interacted with SMAD7 and prevented SMAD7 ubiquitination."

35332268

USP2 binds SMAD7.

| 1

USP2 binds SMAD7. 1 / 1

| 1

---

➶

sparser

"Specifically, USP2 interacted with SMAD7 and prevented SMAD7 ubiquitination."

35332268

USP2 affects SLC22A1

| 2

USP2 activates SLC22A1. 2 / 2

| 2

---

➶

reach

"Therefore, USP2 potentiates nuclear accumulation of Oct-1 and Oct-2 proteins."

29138532

---

➶

reach

"USP2 Modulates Oct-1 and Oct-2 in LPS Stimulated HL-60 Cells."

29138532

USP2 affects PTH1R

| 1

USP2 inhibits PTH1R. 1 / 2

| 1

---

➶

reach

"Furthermore, overexpression of USP2 in ROS cells rescued PTHR degradation induced by PTH (7-34) (XREF_FIG)."

21898592

USP2 affects PTH

| 2

USP2 activates PTH. 2 / 2

| 2

---

➶

reach

"Overexpression of USP2 prevented PTH (7-34)-induced PTHR degradation."

21898592

---

➶

reach

"Recently, research data have demonstrated that USP2 is necessary for PTH (1-34) to induce osteoblast proliferation [109]."

30123285

USP2 affects NFKB2

1 1 |

USP2 binds NFKB2. 2 / 2

1 1 |

---

➶

hprd

No evidence text available

14743216

---

➶

biogrid

No evidence text available

14743216

USP2 affects ML364

| 2

USP2 binds ML364. 2 / 2

| 2

---

➶

reach

"ML364 directly binds to USP2 and selectively inhibits its enzymatic activity 31."

30918246

---

➶

reach

"Direct binding of ML364 to USP2 was demonstrated using microscale thermophoresis."

27681596

USP2 affects Lys407

| 2

Ubiquitin binds USP2 and Lys407. 2 / 2

| 2

---

➶

reach

"In the USP2 and ubiquitin complex, Nzeta of Lys407 occupies the same position as a solvent molecule in the USP7 and ubiquitin-aldehyde complex.The principles of protein protein interactions and the ro[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

16905103

---

➶

reach

"In the USP2/ubiquitin complex, Nz of Lys407 occupies the same position as a solvent molecule in the USP7/ubiquitin-aldehyde complex.The principles of protein-protein interactions and the role of water molecules in molecular recognition have been studied by various groups (Janin, 1997; Jones and Thornton, 1996; Larsen et al., 1998) ."

16905103

USP2 affects IRAK1

| 1 1

USP2 binds IRAK1.

| 1

USP2 binds IRAK1. 1 / 1

| 1

---

➶

sparser

"The slower migrating forms of IRAK1 were more abundant at 10 min and could be converted to the unmodified form of IRAK1 by USP2 CD in a NEM-sensitive manner."

18724939

USP2 activates IRAK1.

| 1

USP2 activates IRAK1. 1 / 1

| 1

---

➶

reach

"In the case of IRAK1, the " disappearance " of the protein from cell extracts (XREF_FIG B, left panel) could be fully reversed when immunoprecipitated IRAK1 was treated with USP2 plus phage lambda-phosphatase (lambda-PPase) (XREF_FIG B, right panel)."

26325464

USP2 affects INS

| 2

USP2 inhibits INS. 2 / 2

| 2

---

➶

reach

"Our current cellular experiments suggest that macrophage USP2 inhibits the insulin resistance of myocytes in an adipocyte dependent manner."

28956020

---

➶

reach

"Macrophage USP2 may therefore selectively prevent age- and/or adiposity related chronic inflammation and subsequent insulin resistance."

28956020

USP2 affects HOOK2

1 1 |

USP2 binds HOOK2. 2 / 2

1 1 |

---

➶

hprd

No evidence text available

16189514

---

➶

biogrid

No evidence text available

16189514

USP2 affects GRIA

| 2

USP2 increases the amount of GRIA.

| 1

USP2 increases the amount of GRIA. 1 / 1

| 1

---

➶

reach

"Given the same type of deubiquitinating enzyme (USP46) is able to deubiquitinate AMPA receptors, and knockdown of USP46 elevated AMPA receptor ubiquitination and reduced AMPA receptor expression in hi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

29501527

USP2 deubiquitinates GRIA.

| 1

USP2 leads to the deubiquitination of GRIA. 1 / 1

| 1

---

➶

reach

"Given the same type of deubiquitinating enzyme (USP46) is able to deubiquitinate AMPA receptors, and knockdown of USP46 elevated AMPA receptor ubiquitination and reduced AMPA receptor expression in hi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

29501527

USP2 affects GATA2

| 2

USP2 activates GATA2. 2 / 2

| 2

---

➶

sparser

"Although patient SJINF066 was an infant (9-month-old) and SJBALL021549_D1 was a 9-year-old child, the expression levels of GATA2 in these two cases were comparable, indicating that trans-activation of GATA2 by KMT2A-USP2 is not influenced by age but rather by the function of this fusion."

35087776

---

➶

sparser

"Further checking confirmed that these patients were the only two carrying this fusion in the cohort analyzed ( xref ), indicating that GATA2 could be trans-activated by KMT2A-USP2."

35087776

USP2 affects D1

| 2

Cyclin binds USP2 and D1. 2 / 2

| 2

---

➶

reach

"USP2 binds to Cyclin D1 and Mdm2 and induces their deubiquitination and stabilization, and its silencing causes downregulation of Cyclin D1 and Mdm2, leading to inhibiting cell proliferation."

20531303

---

➶

reach

"By using co-immunoprecipitation approaches, we tried to determine whether elevation of O GlcNAcylation favors the binding of USP2 to cyclin D1, as described for BAP1 and PGC1alpha."

30853938

USP2 affects Cell Survival

| 2

USP2 activates Cell Survival. 2 / 2

| 2

---

➶

reach

"Knockdown or inhibition of USP2 alone was found to reduce TNBC cell viability."

30918246

---

➶

reach

"USP2 knockdown decreases MyLa2000 cell viability after PUVA by 50% but not Hut-78, suggesting that the function of USP2 in CTCL cells is p53 dependent."

27351221

USP2 affects Carcinoma, Renal Cell

| 2

USP2 inhibits Carcinoma, Renal Cell. 2 / 2

| 2

---

➶

reach

"Ubiquitin-specific peptidase 2 inhibition promoted clear cell renal cell carcinoma cell proliferation, migration, and invasion."

35152855

---

➶

reach

"Ubiquitin-specific peptidase 2-mediated inhibition of epithelial-mesenchymal transition in clear cell renal cell carcinoma cells is dependent on the nuclear factor-κB pathway."

35152855

USP2 affects CTNNB1

| 1 1

USP2 binds CTNNB1. 2 / 2

| 1 1

---

➶

reach

"Furthermore, USP2 interacted with beta-catenin, thereby regulating its deubiquitination and stabilization in CFs."

33314748

---

➶

sparser

"Furthermore, USP2 interacted with β-catenin, thereby regulating its deubiquitination and stabilization in CFs."

33314748

USP2 affects CFLAR

| 1 1

USP2 inhibits CFLAR.

| 1

USP2 inhibits CFLAR. 1 / 1

| 1

---

➶

eidos

"Compared to its parental cells , the sorafenib-resistant clones express lower levels of USP2 , which presumably caused the aforementioned increase in cFLIP levels and decrease in ITCH levels [ 13,81 ] ."

33530560

USP2 binds CFLAR.

| 1

TNF binds USP2, CFLAR, and PRH1. 1 / 1

| 1

---

➶

sparser

"In vitro an artificial knockdown of USP2 inhibited actinomycin D/TNFalpha-induced hepatocyte apoptosis, which was associated with elevated levels of the anti-apoptotic protein c-Flip(L/S) and a concomitant decrease of cellular levels of the ubiquitinligase Itch, a negative regulator of c-Flip."

19001362

USP2 affects CCDC85B

1 1 |

USP2 binds CCDC85B. 2 / 2

1 1 |

---

➶

biogrid

No evidence text available

16189514

---

➶

hprd

No evidence text available

16189514

USP2 affects CARD11

2 |

USP2 binds CARD11. 2 / 2

2 |

---

➶

biogrid

No evidence text available

23264041

---

➶

biogrid

No evidence text available

23264041

USP2 affects Bacterial Infections

| 1 1

USP2 activates Bacterial Infections. 2 / 2

| 1 1

---

➶

eidos

"USP2 promotes experimental colitis and bacterial infections by inhibiting the proliferation of myeloid cells and remodeling the extracellular matrix network ."

37192862

---

➶

reach

"USP2 promotes experimental colitis and bacterial infections by inhibiting the proliferation of myeloid cells and remodeling the extracellular matrix network."

37192862

USP2 affects BRCA1

2 |

BRCA1 binds USP2. 2 / 2

2 |

---

➶

biogrid

No evidence text available

23105109

---

➶

biogrid

No evidence text available

22990118

USP2 affects BEND5

1 1 |

USP2 binds BEND5. 2 / 2

1 1 |

---

➶

hprd

No evidence text available

16189514

---

➶

biogrid

No evidence text available

16189514

USP2 affects BEGAIN

1 1 |

USP2 binds BEGAIN. 2 / 2

1 1 |

---

➶

biogrid

No evidence text available

16189514

---

➶

hprd

No evidence text available

16189514

USP2 affects ASAH1

| 1

USP2 activates ASAH1. 1 / 2

| 1

---

➶

reach

"USP2 siRNA decreased ACDase protein, whereas USP2 overexpression increased ACDase protein of LNCaP cells."

25888580

USP2 affects APP

2 |

USP2 binds APP. 2 / 2

2 |

---

➶

biogrid

No evidence text available

21832049

---

➶

biogrid

No evidence text available

21244100

USP14 affects USP2, USP7, and Ubiquitin

| 2

Ubiquitin binds USP14, USP2, and USP7. 2 / 2

| 2

---

➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

---

➶

sparser

"Only approximately 1000 Å 2 of the surface area of PL pro (640 Å 2 by the Ub core and 360 Å 2 by the Ub C-terminus) is buried in the interface, which is smaller than in the USP2-Ub (1900 Å 2 ; Supplementary Fig. S6b ), USP14-Ub aldehyde (1500 Å 2 ; Supplementary Fig. S6c ) and HAUSP-Ub aldehyde (1700 Å 2 ) complexes."

24531491

TRIM27 affects USP2

2 |

USP2 binds TRIM27. 2 / 2

2 |

---

➶

biogrid

No evidence text available

25416956

---

➶

biogrid

No evidence text available

23105109

TNFRSF1A affects USP2

2 |

TNFRSF1A binds USP2. 2 / 2

2 |

---

➶

biogrid

No evidence text available

22179575

---

➶

biogrid

No evidence text available

22179575

TGFBR2 affects USP2

2 |

TGFBR2 phosphorylates USP2 on S225. 1 / 1

1 |

---

➶

biopax:phosphositeplus

No evidence text available

TGFBR2 phosphorylates USP2 on S207. 1 / 1

1 |

---

➶

biopax:phosphositeplus

No evidence text available

TBK1 affects USP2

1 |

TBK1 binds USP2. 1 / 2

1 |

---

➶

biogrid

No evidence text available

25070846

SRC affects USP2

2 |

SRC phosphorylates USP2 on S225. 1 / 1

1 |

---

➶

biopax:phosphositeplus

No evidence text available

SRC phosphorylates USP2 on S207. 1 / 1

1 |

---

➶

biopax:phosphositeplus

No evidence text available

SJB3-019A affects USP2

| 1 1

SJB3-019A inhibits USP2. 2 / 2

| 1 1

---

➶

reach

"Interestingly, USP2 and USP8, which were both inhibited by SJB3-019A in a previous report, were also inhibited by 42% and 68%, respectively, in our evaluation."

| PMC

---

➶

eidos

"Interestingly , USP2 and USP8 , which were both inhibited by SJB3-019A in a previous report , were also inhibited by 42 % and 68 % , respectively , in our evaluation ."

| PMC

SCNN1G affects USP2

2 |

SCNN1G binds USP2. 2 / 2

2 |

---

➶

biogrid

No evidence text available

18701608

---

➶

biogrid

No evidence text available

21478478

Proteasome affects USP2

| 2

Proteasome binds USP2. 2 / 2

| 2

---

➶

reach

"Taken together, our data suggest that USP2 and Imd synergistically bind to the proteasome and that USP2 contributes to Imd degradation at the proteasome level."

25027767

---

➶

reach

"USP2 and Imd synergistically interact with the proteasome."

25027767

PPARGC1A affects USP2

| 1 1

PPARGC1A increases the amount of USP2.

| 1

PPARGC1A increases the amount of USP2. 1 / 1

| 1

---

➶

reach

"In primary hepatocytes, the expression of Usp2 was strongly stimulated by PGC-1alpha."

26332966

PPARGC1A binds USP2.

| 1

USP2 binds PPARGC1A. 1 / 1

| 1

---

➶

sparser

"Further experiment showed that there was an interaction between USP2 and the transcription coactivator—PGC-1α which is related with various liver fasting reactions."

29230097

NFKB2 affects USP2

1 1 |

USP2 binds NFKB2. 2 / 2

1 1 |

---

➶

hprd

No evidence text available

14743216

---

➶

biogrid

No evidence text available

14743216

NFIL3 affects USP2

2 |

NFIL3 decreases the amount of USP2. 2 / 2

2 |

---

➶

biopax:msigdb

No evidence text available

---

➶

biopax:msigdb

No evidence text available

N-ethylmaleimide affects USP2

| 2

N-ethylmaleimide inhibits USP2. 2 / 2

| 2

---

➶

sparser

"As expected, NEM inhibited USP2, USP7, and SENP2 with EC50 values of 1.9 ± 0.2 mM, 1.4 ± 0.07 mM, and 1.3 ± 0.2 mM, respectively (Fig. 5A–C)."

18424514

---

➶

sparser

"As expected, NEM inhibited USP2, USP7, and SENP2 with EC 50 values of 1.9 6 0.2 mM, 1.4 6 0.07 mM, and 1.3 6 0.2 mM, respectively ( Fig. 5A-C) ."

18424514

MYOD1 affects USP2

2 |

MYOD1 decreases the amount of USP2. 2 / 2

2 |

---

➶

biopax:msigdb

No evidence text available

---

➶

biopax:msigdb

No evidence text available

MYLIP affects USP2

1 |

USP2 binds MYLIP. 1 / 2

1 |

---

➶

biogrid

No evidence text available

26666640

MECOM affects USP2

2 |

MECOM decreases the amount of USP2. 2 / 2

2 |

---

➶

biopax:msigdb

No evidence text available

---

➶

biopax:msigdb

No evidence text available

Lys407 affects Ubiquitin

| 2

Ubiquitin binds USP2 and Lys407. 2 / 2

| 2

---

➶

reach

"In the USP2 and ubiquitin complex, Nzeta of Lys407 occupies the same position as a solvent molecule in the USP7 and ubiquitin-aldehyde complex.The principles of protein protein interactions and the ro[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

16905103

---

➶

reach

"In the USP2/ubiquitin complex, Nz of Lys407 occupies the same position as a solvent molecule in the USP7/ubiquitin-aldehyde complex.The principles of protein-protein interactions and the role of water molecules in molecular recognition have been studied by various groups (Janin, 1997; Jones and Thornton, 1996; Larsen et al., 1998) ."

16905103

LDLR affects USP2

1 | 1

USP2 binds LDLR. 2 / 2

1 | 1

---

➶

biogrid

No evidence text available

26666640

---

➶

reach

"The authors attempt to answer this question by introducing a tripartite complex model, in which USP2 interacts with LDLR at the plasma membrane in an IDOL dependent manner to deubiquitylate and stabilize both LDLR and IDOL."

26846634

HOOK2 affects USP2

1 1 |

USP2 binds HOOK2. 2 / 2

1 1 |

---

➶

hprd

No evidence text available

16189514

---

➶

biogrid

No evidence text available

16189514

EGFR affects USP2

1 |

USP2 binds EGFR. 1 / 2

1 |

---

➶

biogrid

No evidence text available

22370483

E2F1 affects USP2

2 |

E2F1 decreases the amount of USP2. 2 / 2

2 |

---

➶

biopax:msigdb

No evidence text available

---

➶

biopax:msigdb

No evidence text available

D1 affects USP2

| 2

Cyclin binds USP2 and D1. 2 / 2

| 2

---

➶

reach

"USP2 binds to Cyclin D1 and Mdm2 and induces their deubiquitination and stabilization, and its silencing causes downregulation of Cyclin D1 and Mdm2, leading to inhibiting cell proliferation."

20531303

---

➶

reach

"By using co-immunoprecipitation approaches, we tried to determine whether elevation of O GlcNAcylation favors the binding of USP2 to cyclin D1, as described for BAP1 and PGC1alpha."

30853938

CTNNB1 affects USP2

| 1 1

USP2 binds CTNNB1. 2 / 2

| 1 1

---

➶

reach

"Furthermore, USP2 interacted with beta-catenin, thereby regulating its deubiquitination and stabilization in CFs."

33314748

---

➶

sparser

"Furthermore, USP2 interacted with β-catenin, thereby regulating its deubiquitination and stabilization in CFs."

33314748

CCDC85B affects USP2

1 1 |

USP2 binds CCDC85B. 2 / 2

1 1 |

---

➶

biogrid

No evidence text available

16189514

---

➶

hprd

No evidence text available

16189514

CARD11 affects USP2

2 |

USP2 binds CARD11. 2 / 2

2 |

---

➶

biogrid

No evidence text available

23264041

---

➶

biogrid

No evidence text available

23264041

BRCA1 affects USP2

2 |

BRCA1 binds USP2. 2 / 2

2 |

---

➶

biogrid

No evidence text available

23105109

---

➶

biogrid

No evidence text available

22990118

BEND5 affects USP2

1 1 |

USP2 binds BEND5. 2 / 2

1 1 |

---

➶

hprd

No evidence text available

16189514

---

➶

biogrid

No evidence text available

16189514

BEGAIN affects USP2

1 1 |

USP2 binds BEGAIN. 2 / 2

1 1 |

---

➶

biogrid

No evidence text available

16189514

---

➶

hprd

No evidence text available

16189514

Angiotensin-2 affects USP2

| 1 1

Angiotensin-2 inhibits USP2.

| 1

Angiotensin-2 inhibits USP2. 1 / 1

| 1

---

➶

eidos

"Our experiments revealed that Ang II induced USP2 downregulation in the in vitro and in vivo models ."

37100191

Angiotensin-2 activates USP2.

| 1

Angiotensin-2 activates USP2. 1 / 1

| 1

---

➶

reach

"Our experiments revealed that Ang II induced USP2 downregulation in the in vitro and in vivo models."

37100191

ATF2 affects USP2

2 |

ATF2 decreases the amount of USP2. 2 / 2

2 |

---

➶

biopax:msigdb

No evidence text available

---

➶

biopax:msigdb

No evidence text available

ARNTL affects USP2

| 2

ARNTL activates USP2. 2 / 2

| 2

---

➶

reach

"The circadian rhythm of Usp2 is blunted in Clock mutant and Bmal1 KO mice, and the Usp2 promoter is activated by CLOCK and BMAL1, indicating that Usp2 is a direct target of these transcription factors."

25147498

---

➶

reach

"This suggests a scenario in USP2 -/- mice in which increased turnover of BMAL1 coincides with increased CLOCK and BMAL1 driven gene expression in the USP2 -/- SCN."

21966515

APP affects USP2

2 |

USP2 binds APP. 2 / 2

2 |

---

➶

biogrid

No evidence text available

21832049

---

➶

biogrid

No evidence text available

21244100

17alpha-ethynylestradiol affects USP2

2 |

17alpha-ethynylestradiol increases the amount of USP2.

1 |

17alpha-ethynylestradiol increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

17942748

17alpha-ethynylestradiol decreases the amount of USP2.

1 |

17alpha-ethynylestradiol decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

17942748

1,2-dichloroethane affects USP2

2 |

1,2-dichloroethane decreases the amount of USP2. 2 / 2

2 |

---

➶

ctd

No evidence text available

28189721

---

➶

ctd

No evidence text available

28960355

2,2',4,4'-tetrabromodiphenyl ether affects USP2

2 |

2,2',4,4'-tetrabromodiphenyl ether decreases the amount of USP2. 2 / 2

2 |

---

➶

ctd

No evidence text available

20056577

---

➶

ctd

No evidence text available

27291303

Ubiquitin Ki muM is same Ki muM related enzyme USP5 known affects USP2

| 1

Ubiquitin Ki muM is same Ki muM related enzyme USP5 known inhibits USP2. 1 / 1

| 1

---

➶

eidos

"USP2 is inhibited by ubiquitin with a Ki of 2.8 muM , which is in the same range as the Ki of 3 muM for the related enzyme USP5 , also known as isopeptidase T ( Dang et al ., 1998 ) ."

16905103

Tumour necrosis factor alpha affects USP2

| 1

Tumour necrosis factor alpha inhibits USP2. 1 / 1

| 1

---

➶

reach

"However, tumour necrosis factor alpha (TNFalpha) has been reported to downregulate a USP2 isoform in hepatocytes 8, so possibly, USP2 inhibited degradation of LDLR is a pathway that is affected in inflammatory conditions."

26846634

Triacetylcellulose affects USP2

| 1

Triacetylcellulose inhibits USP2. 1 / 1

| 1

---

➶

eidos

"Transverse aortic construction ( TAC ) , which mimics cardiac pressure overload , has clearly been shown to downregulate USP2 in cardiac muscle [ 133 ] ."

33530560

Tamoxifen affects USP2

1 |

Tamoxifen increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

25123088

Sunitinib affects USP2

1 |

Sunitinib decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

31533062

Sulfone affects USP2

| 1

Sulfone binds USP2. 1 / 1

| 1

---

➶

reach

"Interestingly, both approaches found that USP2, USP5, and USP7 were DUBs; however, Catic and colleagues reported that USP2 and USP5 also bound to ISG15-vinyl sulfone, suggesting that they had deISGylating activity as well as DUB activity."

18424514

Streptozocin affects USP2

1 |

Streptozocin increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

25905778

Serpentine asbestos affects USP2

1 |

Serpentine asbestos decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

24160326

Schizandrin B affects USP2

1 |

Schizandrin B decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

31150632

SandostatinLAR affects USP2

1 |

SandostatinLAR decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

17210224

Rosiglitazone affects USP2

1 |

Rosiglitazone increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

21515302

Resveratrol affects USP2

1 |

Resveratrol increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

25905778

Potassium dichromate affects USP2

1 |

Potassium dichromate increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

23608068

Nitrosobenzylmethylamine affects USP2

1 |

Nitrosobenzylmethylamine increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

17616710

Nickel sulfate affects USP2

1 |

Nickel sulfate decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

22714537

Nickel atom affects USP2

1 |

Nickel atom decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

24768652

Movement residue Asp575 affects USP2

| 1

Movement residue Asp575 inhibits USP2. 1 / 1

| 1

---

➶

eidos

"Accordingly , the movement of residue Asp575 following 6TG binding also results in the inhibition of USP2 ."

29449607

MiR-17 affects USP2

| 1

MiR-17 decreases the amount of USP2. 1 / 1

| 1

---

➶

reach

"Among the different DUBs (USP14, USP2 and PSMD13) modulated by miR-17 in RNA sequencing data, our results in RASFs lysates confirmed that miR-17 suppressed the expression of PSMD13 and USP2 in TNF-alpha-stimulated RASFs."

27534557

Lipopolysaccharide, E coli O55-B5 affects USP2

1 |

Lipopolysaccharide, E coli O55-B5 increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

28134560

Leflunomide affects USP2

1 |

Leflunomide increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

24136188

Ketamine affects USP2

1 |

Ketamine increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

20080153

Jinfukang affects USP2

1 |

Jinfukang decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

27392435

Isotretinoin affects USP2

1 |

Isotretinoin decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

20436886

Inflammatory activation mesangial cells affects USP2

| 1

Inflammatory activation mesangial cells activates USP2. 1 / 1

| 1

---

➶

eidos

"Concordantly , the expression of USP2 protein was potentiated in cultured mesangial cells by IL-1beta , anti-thymocyte serum ( ATS ) , and ATS with fresh human serum , indicating that inflammatory activation of mesangial cells elicits USP2 expression ."

33530560

Hsa-miR-9500 affects USP2

1 |

Hsa-miR-9500 decreases the amount of USP2. 1 / 1

1 |

---

➶

biopax:mirtarbase

No evidence text available

27292025

Hsa-miR-6501-3p affects USP2

1 |

Hsa-miR-6501-3p decreases the amount of USP2. 1 / 1

1 |

---

➶

biopax:mirtarbase

No evidence text available

27292025

Hsa-miR-493-5p affects USP2

1 |

Hsa-miR-493-5p decreases the amount of USP2. 1 / 1

1 |

---

➶

biopax:mirtarbase

No evidence text available

24374217

Hsa-miR-4700-5p affects USP2

1 |

Hsa-miR-4700-5p decreases the amount of USP2. 1 / 1

1 |

---

➶

biopax:mirtarbase

No evidence text available

27292025

Hsa-miR-4668-5p affects USP2

1 |

Hsa-miR-4668-5p decreases the amount of USP2. 1 / 1

1 |

---

➶

biopax:mirtarbase

No evidence text available

27292025

Hsa-miR-4667-5p affects USP2

1 |

Hsa-miR-4667-5p decreases the amount of USP2. 1 / 1

1 |

---

➶

biopax:mirtarbase

No evidence text available

27292025

Hsa-let-7f-5p affects USP2

1 |

Hsa-let-7f-5p decreases the amount of USP2. 1 / 1

1 |

---

➶

biopax:mirtarbase

No evidence text available

23622248

Halofuginone affects USP2

1 |

Halofuginone decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

17180598

HPTH 1-38 affects USP2

| 1

HPTH 1-38 increases the amount of USP2. 1 / 1

| 1

---

➶

reach

"Parathyroid hormone (hPTH 1-38) stimulates the expression of UBP41, an ubiquitin specific protease, in bone."

11948679

Established anti-cancer drugs affects USP2

| 1

Established anti-cancer drugs inhibits USP2. 1 / 1

| 1

---

➶

eidos

"Furthermore , other reports have demonstrated that previously established anti-cancer drugs inhibit USP2 activity ."

33530560

Entinostat affects USP2

1 |

Entinostat increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

27188386

Endosulfan affects USP2

1 |

Endosulfan decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

29391264

DraT affects Ubiquitin

| 1

Ubiquitin binds USP2 and draT. 1 / 1

| 1

---

➶

sparser

"Upon treating ADPr-Ub with USP2, Ub was reactivated and formed UbcH5B~Ub ( xref )."

| PMC

Doxorubicin affects USP2

1 |

Doxorubicin decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

29803840

Dorsomorphin affects USP2

1 |

Dorsomorphin decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

27188386

Dipeptide affects USP2

| 1

Dipeptide binds USP2. 1 / 1

| 1

---

➶

reach

"This is surprising, as, in the USP2/ubiquitin complex structure, the Gly75-Gly76 dipeptide binds into a narrow channel formed by the highly conserved residue Gln293 and is engaged in five potential H bond interactions."

16905103

Dimethylarsinic acid affects USP2

1 |

Dimethylarsinic acid increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

17720352

Decabromodiphenyl ether affects USP2

1 |

Decabromodiphenyl ether increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

23640034

Copper(II) sulfate affects USP2

1 |

Copper(II) sulfate decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

18579281

Choline affects USP2

1 |

Choline decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

20938992

Chloroquine affects USP2

1 |

Chloroquine increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

28134560

Cannabidiol affects USP2

1 |

Cannabidiol decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

21542829

Bis(2-ethylhexyl) phthalate affects USP2

1 |

Bis(2-ethylhexyl) phthalate increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

28433925

Atrazine affects USP2

1 |

Atrazine increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

22378314

Arsenite(3-) affects USP2

1 |

Arsenite(3-) methylates USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

23974009

Amiodarone affects USP2

1 |

Amiodarone increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

19774075

Aldrin affects USP2

1 |

Aldrin decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

18579281

Actein affects USP2

1 |

Actein decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

29969672

ZIC2 affects USP2

1 |

ZIC2 decreases the amount of USP2. 1 / 1

1 |

---

➶

biopax:msigdb

No evidence text available

ZAP70 affects USP2

1 |

USP2 binds ZAP70. 1 / 1

1 |

---

➶

biogrid

No evidence text available

26936881

YLL039C affects USP2

1 |

USP2 binds YLL039C. 1 / 1

1 |

---

➶

biogrid

No evidence text available

24997605

YAP1 affects USP2

| 1

USP2 binds YAP1, YAP1, and Delta-actitoxin-Avd1a. 1 / 1

| 1

---

➶

sparser

"Another study illustrated that LINC01559, lncRNA B4GALT1-AS1, and lncRNA USP2-AS1, a Yes-associated protein 1 (YAP1)-binding lncRNA, can interact with YAP proteins, hinder YAP phosphorylation, recruit YAP to the nucleus, and trigger the expression of downstream target genes to accelerate tumor progression ( xref – xref )."

35071016

VPS52 affects USP2

1 |

VPS52 binds USP2. 1 / 1

1 |

---

➶

biogrid

No evidence text available

25416956

VCAM1 affects USP2

1 |

USP2 binds VCAM1. 1 / 1

1 |

---

➶

biogrid

No evidence text available

26337389

Ubiquitin affects draT

| 1

Ubiquitin binds USP2 and draT. 1 / 1

| 1

---

➶

sparser

"Upon treating ADPr-Ub with USP2, Ub was reactivated and formed UbcH5B~Ub ( xref )."

| PMC

Ubiquitin affects CSH1

| 1

Ubiquitin binds USP14, USP2, USP7, and CSH1. 1 / 1

| 1

---

➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

Ub core affects USP2

| 1

USP2 binds 1-72 and Ub core. 1 / 1

| 1

---

➶

reach

"In fact, the different truncated forms of the Ub core (residues 1-71, 1-72, and 1-73) and the various short peptides of the C-terminus of Ub (residues 72-76 and 68-76) alone bind USP2 weakly 35, suggesting that both interactions are required simultaneously for appropriate binding of Ub."

28536428

USP8 affects USP2

| 1

USP2 binds USP8 and KCNN4. 1 / 1

| 1

---

➶

sparser

"Channel-DUB interactions were verified after 90 min as there were notable interactions of KCa3.1 with USP2 and USP8 and a weaker association with AMSH (associated molecule with the SH3 domain of STAM; Figure xref )."

22615701

USP7 affects UCHL3

| 1

UCHL3 binds USP14, USP2, and USP7. 1 / 1

| 1

---

➶

sparser

"Binding of the C-terminal Ub segment in an extended conformation in the active-site cleft is a common feature of DUBs, as observed in the crystal structures of Ub derivatives in complex with UCH-L3, HAUSP, USP2, and USP14 (Hu et al., 2002, Hu et al., 2005, Misaghi et al., 2004, Renatus et al., 2006)."

17349955

USP7 affects CSH1

| 1

Ubiquitin binds USP14, USP2, USP7, and CSH1. 1 / 1

| 1

---

➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

USP5 affects USP2

| 1

USP2 binds USP5 and ISG15. 1 / 1

| 1

---

➶

sparser

"Interestingly, both approaches found that USP2, USP5, and USP7 were DUBs; however, Catic and colleagues reported that USP2 and USP5 also bound to ISG15-vinyl sulfone, suggesting that they had deISGylating activity as well as DUB activity."

18424514

USP21-Ub 39 affects USP2

| 1

USP2 binds USP21-Ub 39. 1 / 1

| 1

---

➶

reach

"The structural modelling of USP21-Ub 39 and USP2-Ub complexes 35 in which Ub has been replaced by the NEDD8 equivalent residues at positions 4, 12, and 14 results in steric clashes and charge repulsion between their interaction surfaces."

28536428

USP21 affects USP2

1 |

USP2 binds USP21. 1 / 1

1 |

---

➶

biogrid

No evidence text available

22626734

USP2 affects β-MHC mRNA

| 1

USP2 increases the amount of β-MHC mRNA. 1 / 1

| 1

---

➶

reach

"USP2 overexpression suppressed the degree of cardiac hypertrophy (decreased ANP, BNP, and β-MHC mRNA levels, cell surface area, and ratio of protein/DNA), calcium overload (decreased Ca 2+ concentration and t-CaMKⅡ and p-CaMKⅡ, and increased SERCA2), and mitochondrial dysfunction (decreased MDA and ROS and increased MFN1, ATP, MMP, and complex Ⅰ and II) both in vitro and in vivo."

37100191

USP2 affects ubiquitinated beta-catenin

| 1

USP2 inhibits ubiquitinated beta-catenin. 1 / 1

| 1

---

➶

eidos

"Interestingly , USP2 inhibition markedly elevated the amounts of ubiquitinated beta-catenin , suggesting USP2 as a DUB for beta-catenin , capable of reversing beta-catenin ubiquitination , thereby stabilizing the beta-catenin protein ( Figure 6G , H ) ."

33314748

USP2 affects transmembrane G protein-coupled receptor

| 1

USP2 activates transmembrane G protein-coupled receptor. 1 / 1

| 1

---

➶

reach

"Within this group, Usp2 activates Wnt signaling [17]; Rab35 is a GTPase that regulates phosphoinositides and F-actin on endosomes [18]; Grtp1 is a Rab-GAP with broad specificity [19]; and Casp6 regula[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

30302405

USP2 affects t-CaMKⅡ

| 1

USP2 activates t-CaMKⅡ. 1 / 1

| 1

---

➶

reach

"USP2 overexpression suppressed the degree of cardiac hypertrophy (decreased ANP, BNP, and β-MHC mRNA levels, cell surface area, and ratio of protein/DNA), calcium overload (decreased Ca 2+ concentration and t-CaMKⅡ and p-CaMKⅡ, and increased SERCA2), and mitochondrial dysfunction (decreased MDA and ROS and increased MFN1, ATP, MMP, and complex Ⅰ and II) both in vitro and in vivo."

37100191

USP2 affects surface ion channels intestinal epithelial cells

| 1

USP2 activates surface ion channels intestinal epithelial cells. 1 / 1

| 1

---

➶

eidos

"USP2 also has the potential to promote surface expression of ion channels in renal and intestinal epithelial cells ."

33530560

USP2 affects sulfone

| 1

Sulfone binds USP2. 1 / 1

| 1

---

➶

reach

"Interestingly, both approaches found that USP2, USP5, and USP7 were DUBs; however, Catic and colleagues reported that USP2 and USP5 also bound to ISG15-vinyl sulfone, suggesting that they had deISGylating activity as well as DUB activity."

18424514

USP2 affects sufficient ATP

| 1

USP2 activates sufficient ATP. 1 / 1

| 1

---

➶

eidos

"In the present study , we demonstrated that USP2 contributes to the generation of sufficient ATP by OXPHOS in myoblasts ."

31353872

USP2 affects stability tumor-associated proteins

| 1

USP2 activates stability tumor-associated proteins. 1 / 1

| 1

---

➶

eidos

"In particular , since USP2 modulates the stability of critical tumor-associated proteins such as cyclin D1 , Mdm2 , and FASN , great efforts have been made to establish a USP2-targeting anticancer drug ."

33530560

USP2 affects signaling

| 1

USP2 activates signaling. 1 / 1

| 1

---

➶

sparser

"Within this group, Usp2 activates Wnt signaling ; Rab35 is a GTPase that regulates phosphoinositides and F-actin on endosomes ; Grtp1 is a Rab-GAP with broad specificity ; and Casp6 regulates B cell a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

30302405

USP2 affects regulation of mitochondrial membrane potential

| 1

USP2 activates regulation of mitochondrial membrane potential. 1 / 1

| 1

---

➶

reach

"In addition, macrophage Usp2 ablation led to a decrease in the sperm population exhibiting high intracellular pH, calcium influx, and mitochondrial membrane potential."

33104844

USP2 affects regulation of cell cycle

| 1

USP2 activates regulation of cell cycle. 1 / 1

| 1

---

➶

eidos

"Since leptin and adiponectin have opposite effects on USP2 expression in these cells , USP2 likely contributes to cell cycle regulation via adipokines [ 41 ] ."

33530560

USP2 affects pro-degradation HSP90 ErbB2 respective therapeutic windows

| 1

USP2 activates pro-degradation HSP90 ErbB2 respective therapeutic windows. 1 / 1

| 1

---

➶

eidos

"Through promoting ErbB2 ubiquitylation , USP2 inhibitor is expected to augment the pro-degradation effects of HSP90 inhibitors toward ErbB2 within their respective therapeutic windows , thus eliciting potent anti-tumor effects with tolerable adverse side effects , which warrants further investigations and clinical evaluations ."

32327714

USP2 affects polyubiquitination PER1

| 1

USP2 inhibits polyubiquitination PER1. 1 / 1

| 1

---

➶

eidos

"Interestingly , neither cycloheximide nor MG132 affected the stability of PER1 , indicating that USP2 reduced the polyubiquitination of PER1 without significantly modifying its stability [ 86 ] ."

33530560

USP2 affects polyubiquitin chain

| 1

USP2 activates polyubiquitin chain. 1 / 1

| 1

---

➶

reach

"It is possible that USP2 deficiency caused aberrant digestion of the polyubiquitin chain, resulting in remarkably reduced Oct-2 in the nucleus."

29138532

USP2 affects oxidative phosphorylation C2C12 myoblasts Insufficient supply glucose

| 1

USP2 activates oxidative phosphorylation C2C12 myoblasts Insufficient supply glucose. 1 / 1

| 1

---

➶

eidos

"Usp2 deficiency suppressed oxidative phosphorylation in C2C12 myoblasts Insufficient supply of glucose is known to repress proliferation and differentiation but not migration of C2C12 cells ( Topman et al ., 2012 ; Elkalaf et al ., 2013 ) ."

31353872

USP2 affects nuclear accumulation STATs

| 1

USP2 activates nuclear accumulation STATs. 1 / 1

| 1

---

➶

eidos

"Moreover , USP2 stimulates nuclear accumulation of STATs , which promotes antiviral activity in cells ."

33530560

USP2 affects molecular clock

| 1

USP2 activates molecular clock. 1 / 1

| 1

---

➶

eidos

"As previously mentioned , USP2 modulates the molecular clock in the SCN by regulating BMAL1 stability , and presumably alters neuroendocrine activity [ 87 ] ."

33530560

USP2 affects mitophagy-triggering malfunction

| 1

USP2 inhibits mitophagy-triggering malfunction. 1 / 1

| 1

---

➶

eidos

"Collectively , these observations indicate that USP2 might prevent mitophagy-triggering malfunction in the mitochondrium ."

31353872

USP2 affects mitochondria fission

| 1

USP2 inhibits mitochondria fission. 1 / 1

| 1

---

➶

eidos

"In addition , the present study demonstrated that lack of USP2 caused mitochondria fission ."

31353872

USP2 affects miR-124

| 1

USP2 inhibits miR-124. 1 / 1

| 1

---

➶

reach

"Knockdown of USP2 or USP14 accelerated protein degradation of TNF-alpha, and abolished the effect of miR-124 on TNF-alpha protein stability."

27063215

USP2 affects lipopolysaccharide

| 1

USP2 inhibits lipopolysaccharide. 1 / 1

| 1

---

➶

reach

"USP2 Knockdown (KD) Promotes LPS Elicited Cytokine Production in Macrophage Like HL-60 Cells."

29138532

USP2 affects larger key molecules

| 1

USP2 activates larger key molecules. 1 / 1

| 1

---

➶

eidos

"The ectopic expression of USP2 has been shown to deubiquitinate an enormous number of proteins in cultured cells [ 46 ] , and USP2 potentially modulates a far larger number of key molecules that determine physiological responses ."

33530560

USP2 affects keratinocyte differentiation

| 1

USP2 inhibits keratinocyte differentiation. 1 / 1

| 1

---

➶

reach

"A decrease in USP2 expression reduces the keratinocyte proliferation rate and increases the keratinocyte differentiation, demonstrated by a rise in the mRNA expression level of differentiation markers (keratin 1410 and involucrin)."

32140356

USP2 affects induction TNF-alpha-elicited proinflammatory cytokines

| 1

USP2 activates induction TNF-alpha-elicited proinflammatory cytokines. 1 / 1

| 1

---

➶

eidos

"These results indicate that USP2 mediates the induction of TNF-alpha-elicited proinflammatory cytokines by activating NF-kappaB ."

33530560

USP2 affects histone accessibility

| 1

USP2 inhibits histone accessibility. 1 / 1

| 1

---

➶

eidos

"Coinciding with these actions , USP2 knockdown increased histone accessibility , suggesting that USP2 epigenetically impedes the expression of adipose inflammation-associated genes ."

33530560

USP2 affects extracellular matrix

| 1

USP2 activates extracellular matrix. 1 / 1

| 1

---

➶

reach

"In addition, knockout of USP2 in myeloid cells inhibits the production of pro-inflammatory cytokines to relieve the dysregulation of extracellular matrix (ECM) network and promote the gut epithelial integrity after DSS treatment."

37192862

USP2 affects draT

| 1

Ubiquitin binds USP2 and draT. 1 / 1

| 1

---

➶

sparser

"Upon treating ADPr-Ub with USP2, Ub was reactivated and formed UbcH5B~Ub ( xref )."

| PMC

USP2 affects dipeptide

| 1

Dipeptide binds USP2. 1 / 1

| 1

---

➶

reach

"This is surprising, as, in the USP2/ubiquitin complex structure, the Gly75-Gly76 dipeptide binds into a narrow channel formed by the highly conserved residue Gln293 and is engaged in five potential H bond interactions."

16905103

USP2 affects development Ang II-induced cardiac fibroblasts activation

| 1

USP2 activates development Ang II-induced cardiac fibroblasts activation. 1 / 1

| 1

---

➶

eidos

"In summary , the above findings suggested that USP2 contributes to the development of Ang II-induced cardiac fibroblasts activation in vitro , which is associated with beta-catenin deubiquitination and stabilization , and may be related to increased cyclin D1 ."

33314748

USP2 affects detection

| 1

USP2 activates detection. 1 / 1

| 1

---

➶

eidos

"Use of USP2 improves detection as shown for RIPK1 ( Fig. 1E ) ."

34106523

USP2 affects degradation

| 1

USP2 inhibits degradation. 1 / 1

| 1

---

➶

sparser

"However, tumour necrosis factor α (TNFα) has been reported to downregulate a USP2 isoform in hepatocytes xref , so possibly, USP2-inhibited degradation of LDLR is a pathway that is affected in inflammatory conditions."

26846634

USP2 affects cytokines microbicide peptides

| 1

USP2 inhibits cytokines microbicide peptides. 1 / 1

| 1

---

➶

eidos

"In contrast , USP2 has also been suggested to attenuate the production of cytokines and microbicide peptides by perturbing the OCT1 / 2 , NF-kappaB , and IRF3 pathways ."

33530560

USP2 affects cytokines anti-viral proteins

| 1

USP2 activates cytokines anti-viral proteins. 1 / 1

| 1

---

➶

eidos

"Some reports have demonstrated that USP2 stimulates the production of cytokines and anti-viral proteins through NF-kappaB and STAT1-dependent mechanisms ."

33530560

USP2 affects content cell surface

| 1

USP2 activates content cell surface. 1 / 1

| 1

---

➶

eidos

"Thus , USP2 has the potential to increase EGFR content on the cell surface ."

33530560

USP2 affects collagen biosynthetic process

| 1

USP2 activates collagen biosynthetic process. 1 / 1

| 1

---

➶

eidos

"In addition , USP2 inhibition suppressed CFs proliferation , collagen synthesis and cell cycle progression ."

33314748

USP2 affects clock output

| 1

USP2 activates clock output. 1 / 1

| 1

---

➶

eidos

"Apart from its functions within the clock , USP2 also mediates clock output ."

33621249

USP2 affects circadian rhythm

| 1

USP2 activates circadian rhythm. 1 / 1

| 1

---

➶

reach

"Thus, the USP2 deubiquitinating enzyme modulates the two major features of clock function - its intrinsic circadian rhythm and its capacity to respond to external cues."

23213472

USP2 affects cellular metabolic process

| 1

USP2 activates cellular metabolic process. 1 / 1

| 1

---

➶

reach

"mi125b-related FGFR2 and USP2 pathways may contribute to only small arms for miRNA125b underlying cellular metabolism, as shown in Figure 2."

32140356

USP2 affects cell

| 1

USP2 activates cell. 1 / 1

| 1

---

➶

eidos

"USP2 promotes cell proliferation and metastasis in choroidal melanoma via stabilizing Snail ."

37199836

USP2 affects cell G1 phase cells

| 1

USP2 activates cell G1 phase cells. 1 / 1

| 1

---

➶

eidos

"Phenotypic experiments showed that depletion of USP2 impairs cell proliferation as well as progression through G1 phase in cells whose growth depends on cyclin D1 ."

32201366

USP2 affects cardiac remodeling

| 1

USP2 inhibits cardiac remodeling. 1 / 1

| 1

---

➶

eidos

"Therefore , USP2 may attenuate cardiac remodeling during pressure overload by disrupting the signaling processes ."

33530560

USP2 affects autophagy

| 1

USP2 activates autophagy. 1 / 1

| 1

---

➶

eidos

"Collectively , USP2 potentially modulates autophagy and ERS by altering the abundance of cFLIP ."

33530560

USP2 affects assess interaction

| 1

USP2 inhibits assess interaction. 1 / 1

| 1

---

➶

eidos

"20 , 38 , 39 In this study , beta-catenin was down-regulated by USP2 inhibition , which prompted us to assess the interaction between USP2 and beta-catenin ."

33314748

USP2 affects alpha-induced apoptosis

| 1

USP2 activates alpha-induced apoptosis. 1 / 1

| 1

---

➶

eidos

"In addition to cancer cells , USP2 has been also postulated to modulate tumor necrosis factor ( TNF ) alpha-induced apoptosis in hepatocytes ."

33530560

USP2 affects adipose inflammation-associated

| 1

USP2 inhibits adipose inflammation-associated. 1 / 1

| 1

---

➶

eidos

"Coinciding with these actions , USP2 knockdown increased histone accessibility , suggesting that USP2 epigenetically impedes the expression of adipose inflammation-associated genes ."

33530560

USP2 affects acute respiratory syndrome coronavirus papain-like protease

| 1

USP2 activates acute respiratory syndrome coronavirus papain-like protease. 1 / 1

| 1

---

➶

eidos

"Meanwhile , drug specificity should be taken into consideration , because many chemical inhibitors have unexpected molecular targets [ 159 ] ; for example , a recent paper reported that a USP2 blocker also inhibits severe acute respiratory syndrome coronavirus 2 papain-like protease [ 160 ] ."

33530560

USP2 affects accumulation reactive oxygen species mitochondria dysfunction intracellular ATP decrement C2C12 myoblasts Regulation Oxidative Phosphorylation

| 1

USP2 activates accumulation reactive oxygen species mitochondria dysfunction intracellular ATP decrement C2C12 myoblasts Regulation Oxidative Phosphorylation. 1 / 1

| 1

---

➶

eidos

"Inhibition of ubiquitin-specific protease 2 causes accumulation of reactive oxygen species , mitochondria dysfunction , and intracellular ATP decrement in C2C12 myoblasts Regulation of Oxidative Phosphorylation by USP2 M. Hashimoto et al ."

31353872

USP2 affects abundance Na H exchange regulatory cofactor

| 1

USP2 inhibits abundance Na H exchange regulatory cofactor. 1 / 1

| 1

---

➶

eidos

"Proteomics data from the intestine revealed that the lack of USP2 strongly increased the abundance of Na + / H + exchange regulatory cofactor 4 ( NHERF4 ) [ 90 ] , which is a known regulator of a calcium ion channel [ 91 ] ."

33530560

USP2 affects ZAP70

1 |

USP2 binds ZAP70. 1 / 1

1 |

---

➶

biogrid

No evidence text available

26936881

USP2 affects YLL039C

1 |

USP2 binds YLL039C. 1 / 1

1 |

---

➶

biogrid

No evidence text available

24997605

USP2 affects YAP1

| 1

USP2 binds YAP1, YAP1, and Delta-actitoxin-Avd1a. 1 / 1

| 1

---

➶

sparser

"Another study illustrated that LINC01559, lncRNA B4GALT1-AS1, and lncRNA USP2-AS1, a Yes-associated protein 1 (YAP1)-binding lncRNA, can interact with YAP proteins, hinder YAP phosphorylation, recruit YAP to the nucleus, and trigger the expression of downstream target genes to accelerate tumor progression ( xref – xref )."

35071016

USP2 affects Wnt

| 1

USP2 activates Wnt. 1 / 1

| 1

---

➶

reach

"Within this group, Usp2 activates Wnt signaling [17]; Rab35 is a GTPase that regulates phosphoinositides and F-actin on endosomes [18]; Grtp1 is a Rab-GAP with broad specificity [19]; and Casp6 regula[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

30302405

USP2 affects VPS52

1 |

VPS52 binds USP2. 1 / 1

1 |

---

➶

biogrid

No evidence text available

25416956

USP2 affects VCAM1

1 |

USP2 binds VCAM1. 1 / 1

1 |

---

➶

biogrid

No evidence text available

26337389

USP2 affects Ubiquitin, and draT

| 1

Ubiquitin binds USP2 and draT. 1 / 1

| 1

---

➶

sparser

"Upon treating ADPr-Ub with USP2, Ub was reactivated and formed UbcH5B~Ub ( xref )."

| PMC

USP2 affects Ub core

| 1

USP2 binds 1-72 and Ub core. 1 / 1

| 1

---

➶

reach

"In fact, the different truncated forms of the Ub core (residues 1-71, 1-72, and 1-73) and the various short peptides of the C-terminus of Ub (residues 72-76 and 68-76) alone bind USP2 weakly 35, suggesting that both interactions are required simultaneously for appropriate binding of Ub."

28536428

USP2 affects Ub chain

| 1

USP2 activates Ub chain. 1 / 1

| 1

---

➶

reach

"No significant inhibitory effect of SJB was noted in USP7 or USP2 mediated Ub chain disassembly (XREF_SUPPLEMENTARY)."

28270494

USP2 affects USP5

| 1

USP2 binds USP5 and ISG15. 1 / 1

| 1

---

➶

sparser

"Interestingly, both approaches found that USP2, USP5, and USP7 were DUBs; however, Catic and colleagues reported that USP2 and USP5 also bound to ISG15-vinyl sulfone, suggesting that they had deISGylating activity as well as DUB activity."

18424514

USP2 affects USP21-Ub 39

| 1

USP2 binds USP21-Ub 39. 1 / 1

| 1

---

➶

reach

"The structural modelling of USP21-Ub 39 and USP2-Ub complexes 35 in which Ub has been replaced by the NEDD8 equivalent residues at positions 4, 12, and 14 results in steric clashes and charge repulsion between their interaction surfaces."

28536428

USP2 affects USP21

1 |

USP2 binds USP21. 1 / 1

1 |

---

➶

biogrid

No evidence text available

22626734

USP2 affects USP2 activation

| 1

USP2 inhibits USP2 activation. 1 / 1

| 1

---

➶

eidos

"Because USP2 gene was transcriptionally activated in splenic B-lymphocytes in response to stimulation with IL-4 , the role of USP2 in lymphocyte activation may not be restricted to T-lymphocytes , but may also encompass B-lymphocytes [ 147 ] ."

33530560

USP2 affects UCHL3

| 1

UCHL3 binds USP14, USP2, and USP7. 1 / 1

| 1

---

➶

sparser

"Binding of the C-terminal Ub segment in an extended conformation in the active-site cleft is a common feature of DUBs, as observed in the crystal structures of Ub derivatives in complex with UCH-L3, HAUSP, USP2, and USP14 (Hu et al., 2002, Hu et al., 2005, Misaghi et al., 2004, Renatus et al., 2006)."

17349955

USP2 affects TRIM9

1 |

USP2 binds TRIM9. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

USP2 affects TRIM74

1 |

USP2 binds TRIM74. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

USP2 affects TRIM63

1 |

USP2 binds TRIM63. 1 / 1

1 |

---

➶

biogrid

No evidence text available

22626734

USP2 affects TRIM54

1 |

USP2 binds TRIM54. 1 / 1

1 |

---

➶

biogrid

No evidence text available

22626734

USP2 affects TRIM5

1 |

USP2 binds TRIM5. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

USP2 affects TRIM35

1 |

USP2 binds TRIM35. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

USP2 affects TRIM23

1 |

USP2 binds TRIM23. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

USP2 affects TRIM21

1 |

TRIM21 binds USP2. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

USP2 affects TRAF6 HEK293 cells IL-1beta SeV

| 1

USP2 inhibits TRAF6 HEK293 cells IL-1beta SeV. 1 / 1

| 1

---

➶

eidos

"Because USP2 deficiency leads to elevated TRAF6 levels in HEK293 cells independently of IL-1beta or SeV stimulation , USP2 may therefore repress TRAF6 / NF-kappaB signaling during the steady state ."

33530560

USP2 affects TNFR1 complex

| 1

USP2 inhibits TNFR1 complex. 1 / 1

| 1

---

➶

eidos

"Moreover , USP2 deficiency also caused a prolonged formation of the TNFR1 complex I with concomitant decrements of TNFR1 complex II and cleaved caspase-8 [ 77 ] ."

33530560

USP2 affects TNF

| 1

TNF binds USP2, CFLAR, and PRH1. 1 / 1

| 1

---

➶

sparser

"In vitro an artificial knockdown of USP2 inhibited actinomycin D/TNFalpha-induced hepatocyte apoptosis, which was associated with elevated levels of the anti-apoptotic protein c-Flip(L/S) and a concomitant decrease of cellular levels of the ubiquitinligase Itch, a negative regulator of c-Flip."

19001362

USP2 affects TNF receptor

| 1

USP2 activates TNF receptor. 1 / 1

| 1

---

➶

reach

"We have previously shown that the 41 kDa USP2 isoform induces apoptosis [3] and that the 69 kDa USP2a isoform mediates the apoptosis signal of the TNF receptor [5]."

22659130

USP2 affects TNBC

| 1

USP2 activates TNBC. 1 / 1

| 1

---

➶

reach

"We demonstrated that pharmacological inhibition of USP2 by ML364 prominently reduced the formation of TNBC tumorspheres in a dose dependent fashion."

30918246

USP2 affects TCR

| 1

USP2 activates TCR. 1 / 1

| 1

---

➶

eidos

"USP2 appears to mediate TCR signaling , because its knockdown suppressed TCR activation-provoked phosphorylation of IkappaBalpha and subsequent IL-2 production [ 145 ] ."

33530560

USP2 affects TCN1

| 1

TCN1 binds USP2. 1 / 1

| 1

---

➶

reach

"Here, we identify the USP2 (ubiquitin specific peptidase 2)-VPRBP (viral protein R binding protein) axis as an important pathway for p53 regulation."

37024504

USP2 affects Spermatozoa

| 1

USP2 activates Spermatozoa. 1 / 1

| 1

---

➶

eidos

"Given that sperm isolated from wild-type mice maintained motility even in PBS , USP2 therefore enables sperm to sustain hyperactive motility with a minimal supply of nutrients and ions ."

33530560

USP2 affects SSX

| 1

USP2 inhibits SSX. 1 / 1

| 1

---

➶

reach

"USP2 mediated removal of H2A K119Ub disrupted SSX peptide hybridization to Barr bodies specifically and without affecting its overall nuclear staining pattern, consistent with the general ability of SSX to bind unmodified nucleosomes via its acidic patch binding region."

32747783

USP2 affects SIRT1

1 |

USP2 deubiquitinates SIRT1. 1 / 1

1 |

---

➶

ubibrowser

"Review"

29142505

USP2 affects Rab-GAP

| 1

USP2 activates Rab-GAP. 1 / 1

| 1

---

➶

reach

"Within this group, Usp2 activates Wnt signaling [17]; Rab35 is a GTPase that regulates phosphoinositides and F-actin on endosomes [18]; Grtp1 is a Rab-GAP with broad specificity [19]; and Casp6 regula[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

30302405

USP2 affects RRP15

1 |

USP2 binds RRP15. 1 / 1

1 |

---

➶

biogrid

No evidence text available

19615732

USP2 affects RNF166

1 |

USP2 binds RNF166. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

USP2 affects RNF144B

1 |

USP2 binds RNF144B. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

USP2 affects RNF126

1 |

USP2 binds RNF126. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

USP2 affects RNF125

1 |

USP2 binds RNF125. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

USP2 affects RBCK1

1 |

USP2 binds RBCK1. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

USP2 affects RAD18

1 |

USP2 binds RAD18. 1 / 1

1 |

---

➶

biogrid

No evidence text available

25023518

USP2 affects RAC

| 1

RAC binds USP2, EEF1A2, and MDM4. 1 / 1

| 1

---

➶

sparser

"In multivariate analysis high level of EEF1A2, pAKT, USP2 and MDM4 were clearly associated with a shorter patients' survival ( xref )."

24285179

USP2 affects Polyubiquitin

| 1

USP2 inhibits Polyubiquitin 1 / 1

| 1

---

➶

reach

"However, when we repeated the PABPC1 IP with the addition of the nonspecific deubiquitinating enzyme USP2, which was sufficient to eliminate poly-ubiquitin, we saw no change in the PABPC1 interactome (fig."

34739326

USP2 affects PRKAA1

1 |

USP2 binds PRKAA1. 1 / 1

1 |

---

➶

biogrid

No evidence text available

16306228

USP2 affects PRH1

| 1

TNF binds USP2, CFLAR, and PRH1. 1 / 1

| 1

---

➶

sparser

"In vitro an artificial knockdown of USP2 inhibited actinomycin D/TNFalpha-induced hepatocyte apoptosis, which was associated with elevated levels of the anti-apoptotic protein c-Flip(L/S) and a concomitant decrease of cellular levels of the ubiquitinligase Itch, a negative regulator of c-Flip."

19001362

USP2 affects PPARGC1A

| 1

USP2 binds PPARGC1A. 1 / 1

| 1

---

➶

sparser

"Further experiment showed that there was an interaction between USP2 and the transcription coactivator—PGC-1α which is related with various liver fasting reactions."

29230097

USP2 affects POU5F1

| 1

USP2 binds POU5F1. 1 / 1

| 1

---

➶

sparser

"In contrast to negligible differences in NF- κ B binding activity between USP2 KD and control cells, we found a slight increase in Oct binding activity in USP2-deficient conditions."

29138532

USP2 affects PERIOD1

| 1

USP2 deubiquitinates PERIOD1. 1 / 1

| 1

---

➶

reach

"Recently, we showed that the deubiquitinating enzyme ubiquitin specific peptidase 2 (USP2) associates with clock proteins and deubiquitinates PERIOD1 (PER1) but does not affect its overall stability."

25238854

USP2 affects PALB2

1 |

USP2 binds PALB2. 1 / 1

1 |

---

➶

biogrid

No evidence text available

26649820

USP2 affects Neoplasms

| 1

USP2 activates Neoplasms. 1 / 1

| 1

---

➶

reach

"USP2a mediated enhanced stability of MDM2 abrogates p53 accumulation and its tumor suppressive functions."

34660907

USP2 affects NXF1

1 |

USP2 binds NXF1. 1 / 1

1 |

---

➶

biogrid

No evidence text available

22658674

USP2 affects NR3C2

| 1

USP2 binds NR3C2. 1 / 1

| 1

---

➶

sparser

"The association of MR with USP2-45 or TSG101 as well as MR ubiquitylation state were determined by immunoprecipitation and immunoblotting."

23548632

USP2 affects NFKBIA

| 1

USP2 leads to the dephosphorylation of NFKBIA. 1 / 1

| 1

---

➶

reach

"AMSH, OTULIN and USP2, but not Otubain-1, inhibited the phosphorylation of IkappaBalpha induced by Tax (XREF_FIG), indicating that generation of both K63 and M1 chains is essential for Tax induced IKK activation."

28103322

USP2 affects NF-kappaB basal

| 1

USP2 inhibits NF-kappaB basal. 1 / 1

| 1

---

➶

eidos

"The ubiquitin #specific proteases system 2 ( USP2 ) stabilizes the ubiquitin-E3-ligase ITCH and lowers NF-kappaB basal activity , which leads to reduced c-FLIP mRNA production ; proteasomal degradation of c - FLIP isoforms is also elevated by its negative regulator proteasome ITCH [ 31 ] ."

32352084

USP2 affects NEFL

1 |

USP2 binds NEFL. 1 / 1

1 |

---

➶

biogrid

No evidence text available

25416956

USP2 affects NANOG

| 1

USP2 binds NANOG. 1 / 1

| 1

---

➶

reach

"In contrast, the binding between Nanog and USP2 was much weaker than that between Nanog and USP21 (XREF_SUPPLEMENTARY)."

27886188

USP2 affects Myoblasts

| 1

USP2 activates Myoblasts. 1 / 1

| 1

---

➶

eidos

"It can , therefore , be concluded that depletion of USP2 decreases proliferation of myoblasts ."

31353872

USP2 affects MYC

| 1

USP2 increases the amount of MYC. 1 / 1

| 1

---

➶

reach

"The deubiquitinating enzyme USP2 has been found to enhance MYC levels through the modulation of specific subsets of microRNAs in prostate cancer [XREF_BIBR]."

29511348

USP2 affects MTUS2

1 |

USP2 binds MTUS2. 1 / 1

1 |

---

➶

biogrid

No evidence text available

25416956

USP2 affects MOV10

1 |

USP2 binds MOV10. 1 / 1

1 |

---

➶

biogrid

No evidence text available

22658674

USP2 affects MNCb-0190

1 |

USP2 binds MNCb-0190. 1 / 1

1 |

---

➶

biogrid

No evidence text available

14686789

USP2 affects MFN2

| 1

USP2 binds MFN2. 1 / 1

| 1

---

➶

sparser

"Mechanically, USP2 interacted with MFN2 and improved the protein level of MFN2 through deubiquitination."

37100191

USP2 affects MFN1

| 1

USP2 inhibits MFN1. 1 / 1

| 1

---

➶

reach

"USP2 overexpression suppressed the degree of cardiac hypertrophy (decreased ANP, BNP, and β-MHC mRNA levels, cell surface area, and ratio of protein/DNA), calcium overload (decreased Ca 2+ concentration and t-CaMKⅡ and p-CaMKⅡ, and increased SERCA2), and mitochondrial dysfunction (decreased MDA and ROS and increased MFN1, ATP, MMP, and complex Ⅰ and II) both in vitro and in vivo."

37100191

USP2 affects MAP3K7

1 |

USP2 binds MAP3K7. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23264041

USP2 affects MAP3K2

1 |

USP2 binds MAP3K2. 1 / 1

1 |

---

➶

biogrid

No evidence text available

24975362

USP2 affects LZTS2

1 |

USP2 binds LZTS2. 1 / 1

1 |

---

➶

biogrid

No evidence text available

25416956

USP2 affects LRSAM1

1 |

USP2 binds LRSAM1. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

USP2 affects LRIG1

| 1

USP2 binds LRIG1. 1 / 1

| 1

---

➶

reach

"As shown in XREF_FIG, USP8, but not USP2, indeed interacted with LRIG1."

24828152

USP2 affects LNX2

1 |

USP2 binds LNX2. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

USP2 affects LMNA

1 |

USP2 binds LMNA. 1 / 1

1 |

---

➶

biogrid

No evidence text available

24623722

USP2 affects LHX4

1 |

USP2 binds LHX4. 1 / 1

1 |

---

➶

biogrid

No evidence text available

25416956

USP2 affects LDL uptake cultured hepatocytes

| 1

USP2 activates LDL uptake cultured hepatocytes. 1 / 1

| 1

---

➶

eidos

"In agreement , USP2 increased surface LDLR levels and promoted LDL uptake in cultured hepatocytes [ 110 ] ."

33530560

USP2 affects Kv7.2/7.3 channels-Nedd4-2

| 1

USP2 binds Kv7.2/7.3 channels-Nedd4-2. 1 / 1

| 1

---

➶

reach

"Hence, USP2 potentially binds to Kv7.2/7.3 channels-Nedd4-2 and regulate the expression of Kv7.2/7.3 channels in the brain tissues."

29501527

USP2 affects KRT40

1 |

USP2 binds KRT40. 1 / 1

1 |

---

➶

biogrid

No evidence text available

25416956

USP2 affects KIFC3

1 |

USP2 binds KIFC3. 1 / 1

1 |

---

➶

biogrid

No evidence text available

25416956

USP2 affects KIAA1522

| 1

USP2 binds KIAA1522 and AS1. 1 / 1

| 1

---

➶

sparser

"To further reveal the connection among USP2-AS1, miR-520d-3p, and KIAA1522, rescue assays were again performed."

33122952

USP2 affects KCNN4

| 1

USP2 binds USP8 and KCNN4. 1 / 1

| 1

---

➶

sparser

"Channel-DUB interactions were verified after 90 min as there were notable interactions of KCa3.1 with USP2 and USP8 and a weaker association with AMSH (associated molecule with the SH3 domain of STAM; Figure xref )."

22615701

USP2 affects KCNE1

| 1

USP2 activates KCNE1. 1 / 1

| 1

---

➶

reach

"In contrast to previous observations with the ENaC, coexpression of the 2 isoforms of USP2 in the present study did not increase the KCNQ1 and KCNE1 mediated current in Xenopus oocytes per se."

22024150

USP2 affects K63-linked polyubiquitination TRAF2

| 1

USP2 inhibits K63-linked polyubiquitination TRAF2. 1 / 1

| 1

---

➶

eidos

"On the contrary , USP2 knockdown augmented the K63-linked polyubiquitination of both RIP1 and TRAF2 [ 77 ] ."

33530560

USP2 affects Interferon

| 1

USP2 inhibits Interferon. 1 / 1

| 1

---

➶

reach

"Knockout or pharmacologic inhibition of USP2 promotes the proliferation of myeloid cells to activate IL-22 and IFNγ production of T cells."

37192862

USP2 affects ISG15

| 1

USP2 binds USP5 and ISG15. 1 / 1

| 1

---

➶

sparser

"Interestingly, both approaches found that USP2, USP5, and USP7 were DUBs; however, Catic and colleagues reported that USP2 and USP5 also bound to ISG15-vinyl sulfone, suggesting that they had deISGylating activity as well as DUB activity."

18424514

USP2 affects INSRbeta-GFP

| 1

USP2 activates INSRbeta-GFP. 1 / 1

| 1

---

➶

reach

"The INSRbeta or INSRbeta-GFP immunoprecipitates treated with USP2 enzyme were analysed for INSRbeta or INSRbeta-GFP."

27577745

USP2 affects INSRbeta

| 1

USP2 activates INSRbeta. 1 / 1

| 1

---

➶

reach

"The INSRbeta or INSRbeta-GFP immunoprecipitates treated with USP2 enzyme were analysed for INSRbeta or INSRbeta-GFP."

27577745

USP2 affects IL32

| 1

USP2 deubiquitinates IL32. 1 / 1

| 1

---

➶

reach

"USP2 deubiquitinated and stabilized tAIF, thus promoting AIF mediated cell death."

21293491

USP2 affects IL22

| 1

USP2 inhibits IL22. 1 / 1

| 1

---

➶

reach

"Knockout or pharmacologic inhibition of USP2 promotes the proliferation of myeloid cells to activate IL-22 and IFNγ production of T cells."

37192862

USP2 affects IL17RA

| 1

USP2 inhibits IL17RA. 1 / 1

| 1

---

➶

reach

"Recently, deubiquitinases USP2 and A20 were identified to mediate feedback inhibition of IL-17R signaling (Liu et al., 2009; Zhong et al., 2012; Garg et al., 2013)."

25202827

USP2 affects IKBKG

1 |

USP2 binds IKBKG. 1 / 1

1 |

---

➶

biogrid

No evidence text available

14695475

USP2 affects Hydrogen-Ion Concentration

| 1

USP2 activates Hydrogen-Ion Concentration. 1 / 1

| 1

---

➶

reach

"In addition, macrophage Usp2 ablation led to a decrease in the sperm population exhibiting high intracellular pH, calcium influx, and mitochondrial membrane potential."

33104844

USP2 affects HSD1 mRNA

| 1

USP2 activates HSD1 mRNA. 1 / 1

| 1

---

➶

reach

"Hepatic overexpression of USP2 increases HSD1 mRNA and protein levels, leading to the induction of gluconeogenic genes as well as several other glucocorticoid targets, whereas RNAi knockdown of USP2 significantly lowers HSD1 gene expression in the liver."

22447855

USP2 affects H2AC20

1 |

USP2 binds H2AC20. 1 / 1

1 |

---

➶

biogrid

No evidence text available

26507658

USP2 affects Glioblastoma

| 1

USP2 inhibits Glioblastoma. 1 / 1

| 1

---

➶

reach

"Loss of deubiquitylase USP2 triggers development of glioblastoma via TGF-β signaling."

35332268

USP2 affects EcR-B1-USP-1

| 1

USP2 inhibits EcR-B1-USP-1. 1 / 1

| 1

---

➶

reach

"When cell extracts were used, the EcR-B1 and USP-2 heterodimer showed no binding to EcRE1, and the presence of excess USP-2 prevented the binding of EcR-B1-USP-1 to this element."

10373539

USP2 affects EcR-B1

| 1

USP2 binds EcR-B1. 1 / 1

| 1

---

➶

reach

"When cell extracts were used, the EcR-B1 and USP-2 heterodimer showed no binding to EcRE1, and the presence of excess USP-2 prevented the binding of EcR-B1-USP-1 to this element."

10373539

USP2 affects EcR-A

| 1

USP2 binds EcR-A. 1 / 1

| 1

---

➶

reach

"Proliferation and differentiation processes of midgut stem cells are carried out via EcR-A and USP-2 heterodimer complex."

27620558

USP2 affects EcR

| 1

USP2 increases the amount of EcR. 1 / 1

| 1

---

➶

reach

"Usp 2, a protein null, does not activate EcR transcription."

11804781

USP2 affects ERBB2-associated physiological events

| 1

USP2 activates ERBB2-associated physiological events. 1 / 1

| 1

---

➶

eidos

"Given that ERBB2 is not only involved in tumorigenesis , but also in physiological events such as neural repair [ 63 ] , USP2 may also modulate ERBB2-associated physiological events ."

33530560

USP2 affects ENaC

| 1

Modified USP2 leads to the deubiquitination of ENaC. 1 / 1

| 1

---

➶

reach

"Likewise, overexpression of USP2 causes decreased ubiquitination of ENaC and increases its activity at the plasma membrane."

21332354

USP2 affects EEF1A2

| 1

RAC binds USP2, EEF1A2, and MDM4. 1 / 1

| 1

---

➶

sparser

"In multivariate analysis high level of EEF1A2, pAKT, USP2 and MDM4 were clearly associated with a shorter patients' survival ( xref )."

24285179

USP2 affects Delta-actitoxin-Avd1a

| 1

USP2 binds YAP1, YAP1, and Delta-actitoxin-Avd1a. 1 / 1

| 1

---

➶

sparser

"Another study illustrated that LINC01559, lncRNA B4GALT1-AS1, and lncRNA USP2-AS1, a Yes-associated protein 1 (YAP1)-binding lncRNA, can interact with YAP proteins, hinder YAP phosphorylation, recruit YAP to the nucleus, and trigger the expression of downstream target genes to accelerate tumor progression ( xref – xref )."

35071016

USP2 affects DCAF1

| 1

USP2 binds DCAF1. 1 / 1

| 1

---

➶

sparser

"Interestingly, the USP2-VPRBP axis also regulates PD-L1 (programmed death-ligand 1) expression."

37024504

USP2 affects Cystic Fibrosis

| 1

USP2 activates Cystic Fibrosis. 1 / 1

| 1

---

➶

eidos

"In addition , USP2 inhibition suppressed CFs proliferation , collagen synthesis and cell cycle progression ."

33314748

USP2 affects Collagen

| 1

USP2 activates Collagen. 1 / 1

| 1

---

➶

reach

"In addition, USP2 inhibition suppressed CFs proliferation, collagen synthesis and cell cycle progression."

33314748

USP2 affects Colitis

| 1

USP2 activates Colitis. 1 / 1

| 1

---

➶

reach

"USP2 promotes experimental colitis and bacterial infections by inhibiting the proliferation of myeloid cells and remodeling the extracellular matrix network."

37192862

USP2 affects CYCD1-1

| 1

USP2 activates CYCD1-1. 1 / 1

| 1

---

➶

reach

"USP2 promotes stabilization of cyclinD1 via direct interaction with cyclin D1 and antagonizes ubiquitin dependent degradation (Shan et al., 2009)."

26033248

USP2 affects CSH1

| 1

Ubiquitin binds USP14, USP2, USP7, and CSH1. 1 / 1

| 1

---

➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

USP2 affects CRYL1

| 1

USP2 leads to the deubiquitination of CRYL1. 1 / 1

| 1

---

➶

reach

"In addition to PER1 and BMAL1, USP2 deubiquitinates CRY1 in cultured cells in response to a serum shock, and in the mouse liver, Usp2 knockdown increases CRY ubiquitination and decreases CRY1 protein levels."

25147498

USP2 affects CRY2

| 1

USP2 deubiquitinates CRY2. 1 / 1

| 1

---

➶

reach

"USP2 is essential to deubiquitinating PER1, CRY1 and CRY2 in vivo [54–57]."

32705594

USP2 affects CD274

| 1

USP2 inhibits CD274. 1 / 1

| 1

---

➶

reach

"Targeting USP2 regulation of VPRBP-mediated degradation of p53 and PD-L1 for cancer therapy."

37024504

USP2 affects CCNA1

1 |

USP2 binds CCNA1. 1 / 1

1 |

---

➶

biogrid

No evidence text available

22370483

USP2 affects CCDC57

1 |

USP2 binds CCDC57. 1 / 1

1 |

---

➶

biogrid

No evidence text available

25416956

USP2 affects CCDC36

1 |

USP2 binds CCDC36. 1 / 1

1 |

---

➶

biogrid

No evidence text available

25416956

USP2 affects CACNA2D2

1 |

USP2 binds CACNA2D2. 1 / 1

1 |

---

➶

biogrid

No evidence text available

25366495

USP2 affects BHR3 gene

| 1

USP2 inhibits BHR3 gene. 1 / 1

| 1

---

➶

reach

"Therefore high USP-2 expression in mature midgut cells during late prepupal stage probably inhibits BHR3 gene activation through this process."

27620558

USP2 affects BAP1

1 |

USP2 binds BAP1. 1 / 1

1 |

---

➶

biogrid

No evidence text available

24703950

USP2 affects Apoptosis

1 |

USP2 inhibits Apoptosis. 1 / 1

1 |

---

➶

bel

"Further, USP2a is androgen-regulated and overexpressed in prostate cancer, and its functional inactivation results in decreased FAS protein and enhanced apoptosis"

15050917

USP2 affects Ang II-induced

| 1

USP2 activates Ang II-induced. 1 / 1

| 1

---

➶

eidos

"To determine whether USP2 inhibition may reverse the effects of Ang II-induced proliferation , CFs were administered various ML364 amounts for distinct times , followed by the MTS assay ."

33314748

USP2 affects Amelogenesis imperfecta nephrocalcinosis

| 1

USP2 activates Amelogenesis imperfecta nephrocalcinosis. 1 / 1

| 1

---

➶

eidos

"Collectively , USP2 potentially modulates autophagy and ERS by altering the abundance of cFLIP ."

33530560

USP2 affects ATP

| 1

USP2 inhibits ATP. 1 / 1

| 1

---

➶

reach

"USP2 overexpression suppressed the degree of cardiac hypertrophy (decreased ANP, BNP, and β-MHC mRNA levels, cell surface area, and ratio of protein/DNA), calcium overload (decreased Ca 2+ concentration and t-CaMKⅡ and p-CaMKⅡ, and increased SERCA2), and mitochondrial dysfunction (decreased MDA and ROS and increased MFN1, ATP, MMP, and complex Ⅰ and II) both in vitro and in vivo."

37100191

USP2 affects ARNTL

| 1

USP2 activates ARNTL. 1 / 1

| 1

---

➶

reach

"USP2 increased the stability of BMAL1, an important regulator of circadian rhythms that was linked to regulating hepatic USP2 expression in the study by Molusky et al.."

22517656

USP2 affects ARIH2

| 1

USP2 deubiquitinates ARIH2. 1 / 1

| 1

---

➶

reach

"Indeed, USP2 but not heat inactivated USP2 depleted the slower migrating, and hence ubiquitylated, form of TRIAD1 (XREF_FIG E)."

30587576

USP2 affects ARID2

| 1

USP2 binds ARID2. 1 / 1

| 1

---

➶

sparser

"Co-IP assays were designed to validate USP2-ARID2 protein interaction."

36567903

USP2 affects 1-72

| 1

USP2 binds 1-72 and Ub core. 1 / 1

| 1

---

➶

reach

"In fact, the different truncated forms of the Ub core (residues 1-71, 1-72, and 1-73) and the various short peptides of the C-terminus of Ub (residues 72-76 and 68-76) alone bind USP2 weakly 35, suggesting that both interactions are required simultaneously for appropriate binding of Ub."

28536428

USP14 affects UCHL3

| 1

UCHL3 binds USP14, USP2, and USP7. 1 / 1

| 1

---

➶

sparser

"Binding of the C-terminal Ub segment in an extended conformation in the active-site cleft is a common feature of DUBs, as observed in the crystal structures of Ub derivatives in complex with UCH-L3, HAUSP, USP2, and USP14 (Hu et al., 2002, Hu et al., 2005, Misaghi et al., 2004, Renatus et al., 2006)."

17349955

USP14 affects CSH1

| 1

Ubiquitin binds USP14, USP2, USP7, and CSH1. 1 / 1

| 1

---

➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

UCHL3 affects USP7

| 1

UCHL3 binds USP14, USP2, and USP7. 1 / 1

| 1

---

➶

sparser

"Binding of the C-terminal Ub segment in an extended conformation in the active-site cleft is a common feature of DUBs, as observed in the crystal structures of Ub derivatives in complex with UCH-L3, HAUSP, USP2, and USP14 (Hu et al., 2002, Hu et al., 2005, Misaghi et al., 2004, Renatus et al., 2006)."

17349955

Transverse aortic construction affects USP2

| 1

Transverse aortic construction inhibits USP2. 1 / 1

| 1

---

➶

eidos

"Transverse aortic construction ( TAC ) , which mimics cardiac pressure overload , has clearly been shown to downregulate USP2 in cardiac muscle [ 133 ] ."

33530560

TRIM9 affects USP2

1 |

USP2 binds TRIM9. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

TRIM74 affects USP2

1 |

USP2 binds TRIM74. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

TRIM63 affects USP2

1 |

USP2 binds TRIM63. 1 / 1

1 |

---

➶

biogrid

No evidence text available

22626734

TRIM54 affects USP2

1 |

USP2 binds TRIM54. 1 / 1

1 |

---

➶

biogrid

No evidence text available

22626734

TRIM5 affects USP2

1 |

USP2 binds TRIM5. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

TRIM35 affects USP2

1 |

USP2 binds TRIM35. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

TRIM23 affects USP2

1 |

USP2 binds TRIM23. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

TRIM21 affects USP2

1 |

TRIM21 binds USP2. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

TNF affects PRH1

| 1

TNF binds USP2, CFLAR, and PRH1. 1 / 1

| 1

---

➶

sparser

"In vitro an artificial knockdown of USP2 inhibited actinomycin D/TNFalpha-induced hepatocyte apoptosis, which was associated with elevated levels of the anti-apoptotic protein c-Flip(L/S) and a concomitant decrease of cellular levels of the ubiquitinligase Itch, a negative regulator of c-Flip."

19001362

TFAP4 affects USP2

1 |

TFAP4 decreases the amount of USP2. 1 / 1

1 |

---

➶

biopax:msigdb

No evidence text available

TCN1 affects USP2

| 1

TCN1 binds USP2. 1 / 1

| 1

---

➶

reach

"Here, we identify the USP2 (ubiquitin specific peptidase 2)-VPRBP (viral protein R binding protein) axis as an important pathway for p53 regulation."

37024504

STAT4 affects USP2

1 |

STAT4 decreases the amount of USP2. 1 / 1

1 |

---

➶

biopax:msigdb

No evidence text available

SMAD7 affects USP2

| 1

USP2 binds SMAD7. 1 / 1

| 1

---

➶

sparser

"Specifically, USP2 interacted with SMAD7 and prevented SMAD7 ubiquitination."

35332268

SMAD4 affects USP2

1 |

SMAD4 decreases the amount of USP2. 1 / 1

1 |

---

➶

biopax:msigdb

No evidence text available

SGI-1027 affects USP2

| 1

SGI-1027 inhibits USP2. 1 / 1

| 1

---

➶

reach

"Moreover, we demonstrated that the DNMT3A inhibitor SGI-1027 induced USP2, suppressed TGF-β signaling and GBM development."

35332268

Ritodrine affects USP2

1 |

Ritodrine increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

23370008

RRP15 affects USP2

1 |

USP2 binds RRP15. 1 / 1

1 |

---

➶

biogrid

No evidence text available

19615732

RNF166 affects USP2

1 |

USP2 binds RNF166. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

RNF144B affects USP2

1 |

USP2 binds RNF144B. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

RNF126 affects USP2

1 |

USP2 binds RNF126. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

RNF125 affects USP2

1 |

USP2 binds RNF125. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

RBCK1 affects USP2

1 |

USP2 binds RBCK1. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

RAD18 affects USP2

1 |

USP2 binds RAD18. 1 / 1

1 |

---

➶

biogrid

No evidence text available

25023518

RAC affects USP2

| 1

RAC binds USP2, EEF1A2, and MDM4. 1 / 1

| 1

---

➶

sparser

"In multivariate analysis high level of EEF1A2, pAKT, USP2 and MDM4 were clearly associated with a shorter patients' survival ( xref )."

24285179

RA-9 affects USP2

| 1

RA-9 inhibits USP2. 1 / 1

| 1

---

➶

reach

"RA-9, a chalcone derivative with a structure similar to b-AP15, was reported to inhibit proteasomal DUBs [XREF_BIBR] as well as UCHL1, UCHL3, USP2, USP5, and USP8 [XREF_BIBR]."

29039082

Pam3CSK4 affects USP2

| 1

Pam3CSK4 decreases the amount of USP2. 1 / 1

| 1

---

➶

reach

"LPS and Pam3CSK4 Repress the Expression of USP2 Splice Variants in Macrophages."

29138532

PTS1 sequence -SRM affects USP2

| 1

PTS1 sequence -SRM activates USP2. 1 / 1

| 1

---

➶

reach

"In this context, it is noteworthy that endogenous USP2 is targeted to peroxisomes by a unique PTS1 sequence -SRM, which shows a weaker interaction with the cycling PTS1 import receptor PEX5, in comparison to the common PTS1 signal -SKL (XREF_FIG)."

26484888

PTC-209 affects USP2

1 |

PTC-209 increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

31023824

PRKAA1 affects USP2

1 |

USP2 binds PRKAA1. 1 / 1

1 |

---

➶

biogrid

No evidence text available

16306228

PRH1 affects USP2

| 1

TNF binds USP2, CFLAR, and PRH1. 1 / 1

| 1

---

➶

sparser

"In vitro an artificial knockdown of USP2 inhibited actinomycin D/TNFalpha-induced hepatocyte apoptosis, which was associated with elevated levels of the anti-apoptotic protein c-Flip(L/S) and a concomitant decrease of cellular levels of the ubiquitinligase Itch, a negative regulator of c-Flip."

19001362

PPAR affects USP2

| 1

PPAR increases the amount of USP2. 1 / 1

| 1

---

➶

reach

"USP2 expression was induced by counter-regulatory hormones and the peroxisome proliferator activated receptor coactivator 1alpha (PGC-1alpha), which all strongly activate gluconeogenesis (XREF_FIG)."

22517656

POU5F1 affects USP2

| 1

USP2 binds POU5F1. 1 / 1

| 1

---

➶

sparser

"In contrast to negligible differences in NF- κ B binding activity between USP2 KD and control cells, we found a slight increase in Oct binding activity in USP2-deficient conditions."

29138532

PALB2 affects USP2

1 |

USP2 binds PALB2. 1 / 1

1 |

---

➶

biogrid

No evidence text available

26649820

USP2 is modified

| 1

USP2 is phosphorylated. 1 / 1

| 1

---

➶

sparser

"Western blotting showed that supernatant from USP2 KD cells repressed insulin-elicited phosphorylation of Akt in 3T3-L1 cells significantly more than media from control HL-60 cells ( xref A)."

28956020

NXF1 affects USP2

1 |

USP2 binds NXF1. 1 / 1

1 |

---

➶

biogrid

No evidence text available

22658674

NR3C2 affects USP2

| 1

USP2 binds NR3C2. 1 / 1

| 1

---

➶

sparser

"The association of MR with USP2-45 or TSG101 as well as MR ubiquitylation state were determined by immunoprecipitation and immunoblotting."

23548632

NFkappaB affects USP2

| 1

NFkappaB activates USP2. 1 / 1

| 1

---

➶

reach

"TRAF6 and NF-kappaB Are Not Targets of USP2 in LPS Stimulated HL-60 Cells."

29138532

NEFL affects USP2

1 |

USP2 binds NEFL. 1 / 1

1 |

---

➶

biogrid

No evidence text available

25416956

NDRG1 affects USP2

| 1

NDRG1 inhibits USP2. 1 / 1

| 1

---

➶

reach

"Remarkably, many deregulated genes in the tumor-free, transduced livers are associated with p53 signaling, thus, bearing the following evidence of p53 activation : (i) upregulation of the p53 targets,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

23982166

NANOG affects USP2

| 1

USP2 binds NANOG. 1 / 1

| 1

---

➶

reach

"In contrast, the binding between Nanog and USP2 was much weaker than that between Nanog and USP21 (XREF_SUPPLEMENTARY)."

27886188

N-nitrosodiethylamine affects USP2

1 |

N-nitrosodiethylamine decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

19638242

N-benzylpiperazine affects USP2

1 |

N-benzylpiperazine decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

26821219

MYCN affects USP2

1 |

MYCN decreases the amount of USP2. 1 / 1

1 |

---

➶

biopax:msigdb

No evidence text available

MYB affects USP2

1 |

MYB decreases the amount of USP2. 1 / 1

1 |

---

➶

biopax:msigdb

No evidence text available

MTUS2 affects USP2

1 |

USP2 binds MTUS2. 1 / 1

1 |

---

➶

biogrid

No evidence text available

25416956

MOV10 affects USP2

1 |

USP2 binds MOV10. 1 / 1

1 |

---

➶

biogrid

No evidence text available

22658674

MNCb-0190 affects USP2

1 |

USP2 binds MNCb-0190. 1 / 1

1 |

---

➶

biogrid

No evidence text available

14686789

MM-589 affects USP2

1 |

MM-589 increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

31023824

MFN2 affects USP2

| 1

USP2 binds MFN2. 1 / 1

| 1

---

➶

sparser

"Mechanically, USP2 interacted with MFN2 and improved the protein level of MFN2 through deubiquitination."

37100191

MEIS1 affects USP2

1 |

MEIS1 decreases the amount of USP2. 1 / 1

1 |

---

➶

biopax:msigdb

No evidence text available

MDM4 affects RAC

| 1

RAC binds USP2, EEF1A2, and MDM4. 1 / 1

| 1

---

➶

sparser

"In multivariate analysis high level of EEF1A2, pAKT, USP2 and MDM4 were clearly associated with a shorter patients' survival ( xref )."

24285179

MAP3K7 affects USP2

1 |

USP2 binds MAP3K7. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23264041

MAP3K2 affects USP2

1 |

USP2 binds MAP3K2. 1 / 1

1 |

---

➶

biogrid

No evidence text available

24975362

LZTS2 affects USP2

1 |

USP2 binds LZTS2. 1 / 1

1 |

---

➶

biogrid

No evidence text available

25416956

LRSAM1 affects USP2

1 |

USP2 binds LRSAM1. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

LRIG1 affects USP2

| 1

USP2 binds LRIG1. 1 / 1

| 1

---

➶

reach

"As shown in XREF_FIG, USP8, but not USP2, indeed interacted with LRIG1."

24828152

LNX2 affects USP2

1 |

USP2 binds LNX2. 1 / 1

1 |

---

➶

biogrid

No evidence text available

23105109

LMNA affects USP2

1 |

USP2 binds LMNA. 1 / 1

1 |

---

➶

biogrid

No evidence text available

24623722

LHX4 affects USP2

1 |

USP2 binds LHX4. 1 / 1

1 |

---

➶

biogrid

No evidence text available

25416956

Kv7.2/7.3 channels-Nedd4-2 affects USP2

| 1

USP2 binds Kv7.2/7.3 channels-Nedd4-2. 1 / 1

| 1

---

➶

reach

"Hence, USP2 potentially binds to Kv7.2/7.3 channels-Nedd4-2 and regulate the expression of Kv7.2/7.3 channels in the brain tissues."

29501527

KRT40 affects USP2

1 |

USP2 binds KRT40. 1 / 1

1 |

---

➶

biogrid

No evidence text available

25416956

KIFC3 affects USP2

1 |

USP2 binds KIFC3. 1 / 1

1 |

---

➶

biogrid

No evidence text available

25416956

KIAA1522 affects USP2

| 1

USP2 binds KIAA1522 and AS1. 1 / 1

| 1

---

➶

sparser

"To further reveal the connection among USP2-AS1, miR-520d-3p, and KIAA1522, rescue assays were again performed."

33122952

KCNN4 affects USP8

| 1

USP2 binds USP8 and KCNN4. 1 / 1

| 1

---

➶

sparser

"Channel-DUB interactions were verified after 90 min as there were notable interactions of KCa3.1 with USP2 and USP8 and a weaker association with AMSH (associated molecule with the SH3 domain of STAM; Figure xref )."

22615701

ISG15 affects USP5

| 1

USP2 binds USP5 and ISG15. 1 / 1

| 1

---

➶

sparser

"Interestingly, both approaches found that USP2, USP5, and USP7 were DUBs; however, Catic and colleagues reported that USP2 and USP5 also bound to ISG15-vinyl sulfone, suggesting that they had deISGylating activity as well as DUB activity."

18424514

IRF7 affects USP2

1 |

IRF7 decreases the amount of USP2. 1 / 1

1 |

---

➶

biopax:msigdb

No evidence text available

IRAK1 affects USP2

| 1

USP2 binds IRAK1. 1 / 1

| 1

---

➶

sparser

"The slower migrating forms of IRAK1 were more abundant at 10 min and could be converted to the unmodified form of IRAK1 by USP2 CD in a NEM-sensitive manner."

18724939

IKBKG affects USP2

1 |

USP2 binds IKBKG. 1 / 1

1 |

---

➶

biogrid

No evidence text available

14695475

HLF affects USP2

1 |

HLF decreases the amount of USP2. 1 / 1

1 |

---

➶

biopax:msigdb

No evidence text available

H2AC20 affects USP2

1 |

USP2 binds H2AC20. 1 / 1

1 |

---

➶

biogrid

No evidence text available

26507658

Full-Length Ubiquitin affects USP2

| 1

Full-Length Ubiquitin inhibits USP2. 1 / 1

| 1

---

➶

eidos

"Figure 4 : USP2 Inhibition by Full-Length Ubiquitin and the C-Terminally Truncated Mutants , Ubiquitin 1-74 and 1-73 Residual enzymatic activity was determined at 22degreesC with ubiquitin-AMC as substrate ."

16905103

FOXJ2 affects USP2

1 |

FOXJ2 decreases the amount of USP2. 1 / 1

1 |

---

➶

biopax:msigdb

No evidence text available

EcR-B1 affects USP2

| 1

USP2 binds EcR-B1. 1 / 1

| 1

---

➶

reach

"When cell extracts were used, the EcR-B1 and USP-2 heterodimer showed no binding to EcRE1, and the presence of excess USP-2 prevented the binding of EcR-B1-USP-1 to this element."

10373539

EcR-A affects USP2

| 1

USP2 binds EcR-A. 1 / 1

| 1

---

➶

reach

"Proliferation and differentiation processes of midgut stem cells are carried out via EcR-A and USP-2 heterodimer complex."

27620558

EcR affects USP2

| 1

EcR increases the amount of USP2. 1 / 1

| 1

---

➶

reach

"Usp 2, a protein null, does not activate EcR transcription."

11804781

ESRRA affects USP2

1 |

ESRRA decreases the amount of USP2. 1 / 1

1 |

---

➶

biopax:msigdb

No evidence text available

EGR1 affects USP2

| 1

EGR1 inhibits USP2. 1 / 1

| 1

---

➶

reach

"Remarkably, many deregulated genes in the tumor-free, transduced livers are associated with p53 signaling, thus, bearing the following evidence of p53 activation : (i) upregulation of the p53 targets,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

23982166

EEF1A2 affects USP2

| 1

RAC binds USP2, EEF1A2, and MDM4. 1 / 1

| 1

---

➶

sparser

"In multivariate analysis high level of EEF1A2, pAKT, USP2 and MDM4 were clearly associated with a shorter patients' survival ( xref )."

24285179

Delta-actitoxin-Avd1a affects YAP1

| 1

USP2 binds YAP1, YAP1, and Delta-actitoxin-Avd1a. 1 / 1

| 1

---

➶

sparser

"Another study illustrated that LINC01559, lncRNA B4GALT1-AS1, and lncRNA USP2-AS1, a Yes-associated protein 1 (YAP1)-binding lncRNA, can interact with YAP proteins, hinder YAP phosphorylation, recruit YAP to the nucleus, and trigger the expression of downstream target genes to accelerate tumor progression ( xref – xref )."

35071016

DUB inhibitor affects USP2

| 1

DUB inhibitor inhibits USP2. 1 / 1

| 1

---

➶

reach

"Importantly, comparable EC50 values were obtained for the inhibition of USP2 by the specific DUB inhibitor Ub-ald as detected by Ub-PLA2/NBD C6-HPC or Ub-AMC, illustrating that the Ub-PLA2 assay is appropriate for screening for inhibitors of isopeptidases (Fig. 4)."

18424514

DDIT4 affects USP2

| 1

DDIT4 inhibits USP2. 1 / 1

| 1

---

➶

reach

"Remarkably, many deregulated genes in the tumor-free, transduced livers are associated with p53 signaling, thus, bearing the following evidence of p53 activation : (i) upregulation of the p53 targets,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

23982166

DCAF1 affects USP2

| 1

USP2 binds DCAF1. 1 / 1

| 1

---

➶

sparser

"Interestingly, the USP2-VPRBP axis also regulates PD-L1 (programmed death-ligand 1) expression."

37024504

Calcium, Dietary affects USP2

1 |

Calcium, Dietary increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

26756164

CSH1 affects Ubiquitin

| 1

Ubiquitin binds USP14, USP2, USP7, and CSH1. 1 / 1

| 1

---

➶

sparser

"Here, we compare the structure of the PL pro -Ub complex with those of the USP2-Ub (PDB entry 2hd5; Renatus et al., 2006) , USP14-Ub aldehyde (PDB entry 2ayo; Hu et al., 2005) and HAUSP-Ub aldehyde (PDB entry 1nbf; Hu et al., 2002) complexes ( Supplementary Fig. S6 )."

24531491

CRY affects USP2

| 1

CRY ubiquitinates USP2. 1 / 1

| 1

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➶

sparser

"In addition to PER1 and BMAL1, USP2 deubiquitinates CRY1 in cultured cells in response to a serum shock, and in the mouse liver, Usp2 knockdown increases CRY ubiquitination and decreases CRY1 protein levels ( xref )."

25147498

CREB1 affects USP2

1 |

CREB1 decreases the amount of USP2. 1 / 1

1 |

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➶

biopax:msigdb

No evidence text available

CFLAR affects USP2

| 1

TNF binds USP2, CFLAR, and PRH1. 1 / 1

| 1

---

➶

sparser

"In vitro an artificial knockdown of USP2 inhibited actinomycin D/TNFalpha-induced hepatocyte apoptosis, which was associated with elevated levels of the anti-apoptotic protein c-Flip(L/S) and a concomitant decrease of cellular levels of the ubiquitinligase Itch, a negative regulator of c-Flip."

19001362

CEBPA affects USP2

1 |

CEBPA decreases the amount of USP2. 1 / 1

1 |

---

➶

biopax:msigdb

No evidence text available

CDKN1A affects USP2

| 1

CDKN1A inhibits USP2. 1 / 1

| 1

---

➶

reach

"Remarkably, many deregulated genes in the tumor-free, transduced livers are associated with p53 signaling, thus, bearing the following evidence of p53 activation : (i) upregulation of the p53 targets,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

23982166

CCNA1 affects USP2

1 |

USP2 binds CCNA1. 1 / 1

1 |

---

➶

biogrid

No evidence text available

22370483

CCDC57 affects USP2

1 |

USP2 binds CCDC57. 1 / 1

1 |

---

➶

biogrid

No evidence text available

25416956

CCDC36 affects USP2

1 |

USP2 binds CCDC36. 1 / 1

1 |

---

➶

biogrid

No evidence text available

25416956

CACNA2D2 affects USP2

1 |

USP2 binds CACNA2D2. 1 / 1

1 |

---

➶

biogrid

No evidence text available

25366495

Benzo[k]fluoranthene affects USP2

1 |

Benzo[k]fluoranthene increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

26377693

BMP3 affects USP2

| 1

BMP3 inhibits USP2. 1 / 1

| 1

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➶

reach

"These data indicate that MXD3 direct transcriptional regulation could account for both phenotypes described in this paper, namely proliferation (upregulation of putative direct targets IRF4, FBL, HTR1B) and growth arrest and apoptosis (upregulation of RUNX1T1 and BMP3; downregulation of USP2 and MYCL1) as shown in XREF_TABLE."

22808009

BAP1 affects USP2

1 |

USP2 binds BAP1. 1 / 1

1 |

---

➶

biogrid

No evidence text available

24703950

Antirheumatic Agents affects USP2

1 |

Antirheumatic Agents decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

24449571

ATM affects USP2

| 1

ATM phosphorylates USP2. 1 / 1

| 1

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sparser

"Phosphorylation of two critical residues in the N terminus of USP2 by ATM is required for its recruitment to DSBs and its interaction with RECQL4."

36436562

ATF6 affects USP2

1 |

ATF6 decreases the amount of USP2. 1 / 1

1 |

---

➶

biopax:msigdb

No evidence text available

ATF4 affects USP2

1 |

ATF4 decreases the amount of USP2. 1 / 1

1 |

---

➶

biopax:msigdb

No evidence text available

ASAH1 affects USP2

| 1

ASAH1 increases the amount of USP2. 1 / 1

| 1

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➶

reach

"Thus, ACDase regulation by androgen in androgen sensitive LNCaP cells is mainly due to its prolonged protein half-life by androgen stimulated USP2 expression."

25888580

AS1 affects KIAA1522, and USP2

| 1

USP2 binds KIAA1522 and AS1. 1 / 1

| 1

---

➶

sparser

"To further reveal the connection among USP2-AS1, miR-520d-3p, and KIAA1522, rescue assays were again performed."

33122952

ARID2 affects USP2

| 1

USP2 binds ARID2. 1 / 1

| 1

---

➶

sparser

"Co-IP assays were designed to validate USP2-ARID2 protein interaction."

36567903

ANPEP affects USP2

| 1

ANPEP decreases the amount of USP2. 1 / 1

| 1

---

➶

reach

"APN can inhibit the expression of USP2 in tumor cells and promote the degradation of cyclin D1 [XREF_BIBR]."

33815885

A-83-01 affects USP2

1 |

A-83-01 increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

31023824

2-hydroxypropanoic acid affects USP2

1 |

2-hydroxypropanoic acid decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

30851411

1H-pyrazole affects USP2

1 |

1H-pyrazole decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

17945193

1-72 affects Ub core

| 1

USP2 binds 1-72 and Ub core. 1 / 1

| 1

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reach

"In fact, the different truncated forms of the Ub core (residues 1-71, 1-72, and 1-73) and the various short peptides of the C-terminus of Ub (residues 72-76 and 68-76) alone bind USP2 weakly 35, suggesting that both interactions are required simultaneously for appropriate binding of Ub."

28536428

1,4-bis(2-(3,5-dichloropyridyloxy))benzene affects USP2

1 |

1,4-bis(2-(3,5-dichloropyridyloxy))benzene decreases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

21354444

N-(2-(1,1'-bicyclopropyl)-2-ylphenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide affects USP2

1 |

N-(2-(1,1'-bicyclopropyl)-2-ylphenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide increases the amount of USP2. 1 / 1

1 |

---

➶

ctd

No evidence text available

29244179