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OTUD5 is phosphorylated. 26 / 29
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sparser
"xref shows the overlaid 1 H- 15 N TROSY spectra of phosphorylated and non-phosphorylated DUBA, which display only minor differences."

sparser
"It is conceivable that also in the DDR, an upstream kinase phosphorylates OTUD5 to amplify DDR signaling through a similar positive feedback mechanism."

sparser
"Unlike other deubiquitinating enzymes, the phosphorylation of OTUD5 at a single residue (Ser177) is required for the activation of the enzyme [ xref ]."

sparser
"For instance, phosphorylation of OTUD5 catalytic domain induces conformational changes thereby promoting substrate binding and facilitating deubiquitination ( xref )."

sparser
"By comparing NMR and enzyme kinetics data among different forms of DUBA with low and high activities, we concluded that a two-state equilibrium that was present only in phosphorylated DUBA is important for DUBA activity."

sparser
"NMR analysis and crystal structures of apo-DUBA in both phosphorylated and unphosphorylated forms and of phospho-DUBA in complex with ubiquitin-aldehyde reveal the role of the phosphate in enzyme acti[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Consistent with previous NMR studies on the isoform 1 of DUBA ( xref ), the chemical shifts of only a few residues near S177, including G174, Y175 and E178, are perturbed in the phosphorylated DUBA."

sparser
"The phosphorylated DUBA displays essentially the same predicted secondary structure, which is in good agreement with the crystal structures of both non-phosphorylated DUBA in free form (PDB ID: 3PFY) and phosphorylated DUBA covalently linked to ubiquitin aldehyde (PDB ID: 3TMP)."

sparser
"Moreover, phosphorylated OTUD5 was more efficient than wild-type OTUD5 in removing the ubiquitin chain of TRIM25 (Fig.  xref , lane 2 versus lane 3)."

sparser
"Phosphorylation of the human deubiquitinase DUBA (OTUD5) at a single residue, Ser177, is both necessary and sufficient to activate the enzyme [23] ."

sparser
"In the second method, after phosphorylation modification, the conformation of DUBs changes only after binding to the substrate, such as the phosphorylated DUBA bound to Ub, which alters its conformation instead of the phosphorylated DUBA [ xref ]."

sparser
"This is somewhat reminiscent of the activation mechanism of DUBA/OTUD5 by phosphorylation, which also depends on a UIM, yet in the case of DUBA phosphorylation activates a relatively less chain-specific DUB ( xref )."

sparser
"The crystal structure of the catalytic domain of the phosphorylated DUBA (p-DUBA) conjugated to ubiquitin-aldehyde revealed that the interactions between the phosphate group and the two positively charged residues, R272 and K273, in the α6 helix lead to the enclosure of the C-terminal tail of ubiquitin ( xref ). xref NMR studies show that phosphorylation induces minimal structural changes in the apo state of DUBA, xref raising the question of whether modulation of conformational dynamics plays a role in DUBA activation."

sparser
"Here we show that phosphorylation of the human deubiquitinase DUBA (OTUD5) at a single residue, Ser177, is both necessary and sufficient to activate the enzyme."

sparser
"With genetic rescue experiments we demonstrate that DUBA phosphorylation and catalytic activity are crucial in vivo for DUBA function in spermatogenesis."

sparser
"To date, little is known about the kinases that phosphorylate OTUD5, apart from recent in vivo evidence that mTOR kinase promotes OTUD5 stability and activity via direct phosphorylation of multiple sites on OTUD5."

sparser
"It directly phosphorylates the Ser323/332/503 sites of OTUD5 and activates its DUB activity."

sparser
"To investigate whether we had selective fragment binders for either form of OTUD5, we validated both the inactive and activated forms, however we observed similar labelling for both states (Supplementary Fig.  xref ), supporting that OTUD5 phosphorylation does not alter the nucleophilicity of the catalytic cysteine."

sparser
"According to the crystal structure of phosphorylated DUBA (p-DUBA) conjugated to ubiquitin aldehyde, xref the mutations abolish the interactions between these two positively charged residues and the phosphate group in pS177 ( xref )."

sparser
"We have previously measured the backbone amide 1 H relaxation dispersion on DUBA in both phosphorylated and nonphosphorylated forms at 298 K. xref Here, we measured 1 H relaxation dispersion of both backbone amide and arginine side-chain N ε –H ε on phosphorylated DUBA at 290 K. The lower sample temperature was chosen to reduce the signal loss from solvent exchange."

sparser
"To assess the functional importance of arginines for which motions were detected, we performed activity assays on the R227A, R331A, and R294A mutants of phosphorylated DUBA, using the ubiquitin (Ub)–AMC substrate, where the fluorescent dye AMC was attached to the C-terminus of ubiquitin and can be cleaved by DUBs. xref contains the kinetics parameters."

sparser
"The crystal structure of the Ub-aldehyde complex with phosphorylated OTUD5 reveals a remarkable interaction between the phosphorylated Ser177 of OTUD5 and the guanidinium moiety of Arg74 of the bound ubiquitin showing that the phosphorylation is essential for the DUB activity [ xref ]."

sparser
"A recent study using NMR and enzymatic kinetics of different forms of OTUD5 confirmed that only the phosphorylated OTUD5 is important for the activity [ xref ]."

sparser
"Consistently, our work indicated that phosphorylated OTUD5 is particularly efficient at cleaving the ubiquitin chains of TRIM25."

sparser
"Therefore, modulating OTUD5 phosphorylation may be a promising strategy for tumor treatment."

sparser
"It was shown that the Ser177 site-phosphorylated OTUD5 protein was increased in response to T-cell antigen receptor (TCR) stimulation."