Search Results

Overview

Uniprot IDQ14694
Protein NameUbiquitin carboxyl-terminal hydrolase 10
Gene NameUSP10
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
512 YRLLTVNKSSLSEKG
552 LLSPSNEKLTISNGP
662 SVQGYTTKTKQEVEI
664 QGYTTKTKQEVEISR
693 LKRFVYEKTGGCQKL

Function

Hydrolase that can remove conjugated ubiquitin from target proteins such as p53/TP53, RPS2/us5, RPS3/us3, RPS10/eS10, BECN1, SNX3 and CFTR (PubMed:11439350, PubMed:18632802, PubMed:31981475). Acts as an essential regulator of p53/TP53 stability: in unstressed cells, specifically deubiquitinates p53/TP53 in the cytoplasm, leading to counteract MDM2 action and stabilize p53/TP53 (PubMed:20096447). Following DNA damage, translocates to the nucleus and deubiquitinates p53/TP53, leading to regulate the p53/TP53-dependent DNA damage response (PubMed:20096447). Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes (PubMed:21962518). In turn, PIK3C3/VPS34-containing complexes regulate USP10 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13 (PubMed:21962518). Does not deubiquitinate MDM2 (PubMed:20096447). Plays a key role in 40S ribosome subunit recycling when a ribosome has stalled during translation: acts both by inhibiting formation of stress granules, which store stalled translation pre-initiation complexes, and mediating deubiquitination of 40S ribosome subunits (PubMed:27022092, PubMed:31981475, PubMed:34348161, PubMed:34469731). Acts as a negative regulator of stress granules formation by lowering G3BP1 and G3BP2 valence, thereby preventing G3BP1 and G3BP2 ability to undergo liquid-liquid phase separation (LLPS) and assembly of stress granules (PubMed:11439350, PubMed:27022092, PubMed:32302570). Promotes 40S ribosome subunit recycling following ribosome dissociation in response to ribosome stalling by mediating deubiquitination of 40S ribosomal proteins RPS2/us5, RPS3/us3 and RPS10/eS10, thereby preventing their degradation by the proteasome (PubMed:31981475, PubMed:34348161, PubMed:34469731). Part of a ribosome quality control that takes place when ribosomes have stalled during translation initiation (iRQC): USP10 acts by removing monoubiquitination of RPS2/us5 and RPS3/us3, promoting 40S ribosomal subunit recycling (PubMed:34469731). Deubiquitinates CFTR in early endosomes, enhancing its endocytic recycling (PubMed:19398555). Involved in a TANK-dependent negative feedback response to attenuate NF-kappa-B activation via deubiquitinating IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage (PubMed:25861989). Deubiquitinates TBX21 leading to its stabilization (PubMed:24845384). Plays a negative role in the RLR signaling pathway upon RNA virus infection by blocking the RIGI-mediated MAVS activation. Mechanistically, removes the unanchored 'Lys-63'-linked polyubiquitin chains of MAVS to inhibit its aggregation, essential for its activation (PubMed:37582970)

Protein Sequence

10 MALHSPQYIF 20 GDFSPDEFNQ 30 FFVTPRSSVE 40 LPPYSGTVLC 50 GTQAVDKLPD 60 GQEYQRIEFG 70 VDEVIEPSDT 80 LPRTPSYSIS 90 STLNPQAPEF 100 ILGCTASKIT 110 PDGITKEASY 120 GSIDCQYPGS 130 ALALDGSSNV 140 EAEVLENDGV 150 SGGLGQRERK 160 KKKKRPPGYY 170 SYLKDGGDDS 180 ISTEALVNGH 190 ANSAVPNSVS 200 AEDAEFMGDM 210 PPSVTPRTCN 220 SPQNSTDSVS 230 DIVPDSPFPG 240 ALGSDTRTAG 250 QPEGGPGADF 260 GQSCFPAEAG 270 RDTLSRTAGA 280 QPCVGTDTTE 290 NLGVANGQIL 300 ESSGEGTATN 310 GVELHTTESI 320 DLDPTKPESA 330 SPPADGTGSA 340 SGTLPVSQPK 350 SWASLFHDSK 360 PSSSSPVAYV 370 ETKYSPPAIS 380 PLVSEKQVEV 390 KEGLVPVSED 400 PVAIKIAELL 410 ENVTLIHKPV 420 SLQPRGLINK 430 GNWCYINATL 440 QALVACPPMY 450 HLMKFIPLYS 460 KVQRPCTSTP 470 MIDSFVRLMN 480 EFTNMPVPPK 490 PRQALGDKIV 500 RDIRPGAAFE 510 PTYIYRLLTV 520 NKSSLSEKGR 530 QEDAEEYLGF 540 ILNGLHEEML 550 NLKKLLSPSN 560 EKLTISNGPK 570 NHSVNEEEQE 580 EQGEGSEDEW 590 EQVGPRNKTS 600 VTRQADFVQT 610 PITGIFGGHI 620 RSVVYQQSSK 630 ESATLQPFFT 640 LQLDIQSDKI 650 RTVQDALESL 660 VARESVQGYT 670 TKTKQEVEIS 680 RRVTLEKLPP 690 VLVLHLKRFV 700 YEKTGGCQKL 710 IKNIEYPVDL 720 EISKELLSPG 730 VKNKNFKCHR 740 TYRLFAVVYH 750 HGNSATGGHY 760 TTDVFQIGLN 770 GWLRIDDQTV 780 KVINQYQVVK 790 PTAERTAYLL YYRRVDLL

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0022626 cytosolic ribosome
Cellular Component GO:0005769 early endosome
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0032991 protein-containing complex
Molecular Function GO:0004843 cysteine-type deubiquitinase activity
Molecular Function GO:0004197 cysteine-type endopeptidase activity
Molecular Function GO:0140678 molecular function inhibitor activity
Molecular Function GO:0002039 p53 binding
Molecular Function GO:0003723 RNA binding
Molecular Function GO:0044325 transmembrane transporter binding
Biological Process GO:0006914 autophagy
Biological Process GO:0071347 cellular response to interleukin-1
Biological Process GO:0006974 DNA damage response
Biological Process GO:0030330 DNA damage response, signal transduction by p53 class mediator
Biological Process GO:0006281 DNA repair
Biological Process GO:0045087 innate immune response
Biological Process GO:0035520 monoubiquitinated protein deubiquitination
Biological Process GO:0043124 negative regulation of canonical NF-kappaB signal transduction
Biological Process GO:0062030 negative regulation of stress granule assembly
Biological Process GO:0016579 protein deubiquitination
Biological Process GO:0006508 proteolysis
Biological Process GO:0010506 regulation of autophagy
Biological Process GO:0031647 regulation of protein stability
Biological Process GO:0072344 rescue of stalled cytosolic ribosome
Biological Process GO:0019985 translesion synthesis

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[3] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[4] Chao L, Xu Y, Yang Y, Ao X, Liang J. Identification of lactylation-related biomarkers for diagnosis, prognosis, and treatment responsiveness in triple-negative breast cancer.. World J Surg Oncol 24(1):77. 2026 Jan 22. PMID: 41566505.

[5] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.