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Protein

Ubiquitin carboxyl-terminal hydrolase 10

Gene

USP10

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Hydrolase that can remove conjugated ubiquitin from target proteins such as p53/TP53, BECN1, SNX3 and CFTR. 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. Following DNA damage, translocates to the nucleus and deubiquitinates p53/TP53, leading to regulate the p53/TP53-dependent DNA damage response. 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. 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. Does not deubiquitinate MDM2. Deubiquitinates CFTR in early endosomes, enhancing its endocytic recycling. Involved in a TANK-dependent negative feedback response to attenuate NF-kappaB 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).7 Publications

Catalytic activityi

Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).1 Publication

Enzyme regulationi

Specifically inhibited by spautin-1 (specific and potent autophagy inhibitor-1), a derivative of MBCQ that binds to USP10 and inhibits deubiquitinase activity. Regulated by PIK3C3/VPS34-containing complexes.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei424Nucleophile1
Active sitei749Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

  • cysteine-type endopeptidase activity Source: UniProtKB
  • ion channel binding Source: UniProtKB
  • p53 binding Source: UniProtKB
  • RNA binding Source: UniProtKB
  • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB
  • thiol-dependent ubiquitinyl hydrolase activity Source: UniProtKB

GO - Biological processi

  • autophagy Source: UniProtKB-KW
  • cellular response to DNA damage stimulus Source: UniProtKB
  • cellular response to interleukin-1 Source: UniProtKB
  • DNA damage response, signal transduction by p53 class mediator Source: UniProtKB
  • negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • protein deubiquitination Source: UniProtKB
  • regulation of autophagy Source: UniProtKB
  • translesion synthesis Source: Reactome
  • ubiquitin-dependent protein catabolic process Source: InterPro

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processAutophagy, DNA damage, DNA repair, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-5656169 Termination of translesion DNA synthesis
R-HSA-5689880 Ub-specific processing proteases

Protein family/group databases

MEROPSiC19.018

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase 10 (EC:3.4.19.121 Publication)
Alternative name(s):
Deubiquitinating enzyme 10
Ubiquitin thioesterase 10
Ubiquitin-specific-processing protease 10
Gene namesi
Name:USP10
Synonyms:KIAA0190
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000103194.15
HGNCiHGNC:12608 USP10
MIMi609818 gene
neXtProtiNX_Q14694

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endosome, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi42T → A: Abolishes phosphorylation by ATM; when associated with A-337. 1 Publication1
Mutagenesisi42T → E: Phospho-mimetic mutant that translocates to the nucleus in absence of genotoxic stress; when associated with D-337. 1 Publication1
Mutagenesisi337S → A: Abolishes phosphorylation by ATM; when associated with A-42. 1 Publication1
Mutagenesisi337S → D: Phospho-mimetic mutant that translocates to the nucleus in absence of genotoxic stress; when associated with E-42. 1 Publication1
Mutagenesisi424C → A: Abolishes de-ubiquitinating activity. 4 Publications1

Organism-specific databases

DisGeNETi9100
OpenTargetsiENSG00000103194
PharmGKBiPA37234

Chemistry databases

ChEMBLiCHEMBL3407323

Polymorphism and mutation databases

BioMutaiUSP10
DMDMi2501458

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000806292 – 798Ubiquitin carboxyl-terminal hydrolase 10Add BLAST797

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei24PhosphothreonineCombined sources1
Modified residuei42Phosphothreonine; by ATM1 Publication1
Modified residuei100PhosphothreonineCombined sources1
Modified residuei211PhosphoserineBy similarity1
Modified residuei226PhosphoserineCombined sources1
Modified residuei321PhosphoserineCombined sources1
Modified residuei337Phosphoserine; by ATM1 Publication1
Modified residuei365PhosphoserineCombined sources1
Modified residuei370PhosphoserineCombined sources1
Modified residuei547PhosphoserineCombined sources1
Modified residuei563PhosphoserineCombined sources1
Modified residuei576PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by ATM following DNA damage, leading to stablization and translocation it to the nucleus.1 Publication
Ubiquitinated. Deubiquitinated by USP13.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ14694
MaxQBiQ14694
PaxDbiQ14694
PeptideAtlasiQ14694
PRIDEiQ14694
ProteomicsDBi60132
60133 [Q14694-2]
60134 [Q14694-3]

PTM databases

iPTMnetiQ14694
PhosphoSitePlusiQ14694

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Inductioni

Following DNA damage. Down-regulated in renal cell carcinomas.1 Publication

Gene expression databases

BgeeiENSG00000103194
CleanExiHS_USP10
ExpressionAtlasiQ14694 baseline and differential
GenevisibleiQ14694 HS

Organism-specific databases

HPAiHPA006731
HPA006749

Interactioni

Subunit structurei

Found in a deubiquitination complex with TANK, USP10 and ZC3H12A; this complex inhibits genotoxic stress- or interleukin-1-beta (IL1B)-mediated NF-kappaB activation by promoting IKBKG or TRAF6 deubiquitination (PubMed:25861989). Interacts with IKBKG; this interaction increases in response to DNA damage (PubMed:25861989). Interacts with TANK; this interaction increases in response to DNA damage (PubMed:25861989). Interacts with TRAF6; this interaction increases in response to DNA damage (PubMed:25861989). Interacts with ZC3H12A; this interaction increases in response to DNA damage (PubMed:25861989). Interacts with G3BP, which may regulate its function (PubMed:11439350). Interacts with p53/TP53 (PubMed:20096447). Interacts with SNX3 (PubMed:18632802). Interacts with CFTR (PubMed:19398555). Interacts with TBX21 (PubMed:24845384).6 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • ion channel binding Source: UniProtKB
  • p53 binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114554, 68 interactors
ELMiQ14694
IntActiQ14694, 29 interactors
MINTiQ14694
STRINGi9606.ENSP00000219473

Chemistry databases

BindingDBiQ14694

Structurei

3D structure databases

ProteinModelPortaliQ14694
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini415 – 795USPAdd BLAST381

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 100Interaction with p53/TP531 PublicationAdd BLAST99

Sequence similaritiesi

Belongs to the peptidase C19 family. USP10 subfamily.Curated

Phylogenomic databases

eggNOGiKOG1871 Eukaryota
ENOG410XSIH LUCA
GeneTreeiENSGT00550000074994
HOGENOMiHOG000285959
HOVERGENiHBG059823
InParanoidiQ14694
KOiK11841
OMAiGQEYQRI
OrthoDBiEOG091G023X
PhylomeDBiQ14694
TreeFamiTF323203

Family and domain databases

InterProiView protein in InterPro
IPR009818 Ataxin-2_C
IPR038765 Papain_like_cys_pep_sf
IPR001394 Peptidase_C19_UCH
IPR018200 USP_CS
IPR028889 USP_dom
PfamiView protein in Pfam
PF07145 PAM2, 1 hit
PF00443 UCH, 1 hit
SUPFAMiSSF54001 SSF54001, 1 hit
PROSITEiView protein in PROSITE
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q14694-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MALHSPQYIF GDFSPDEFNQ FFVTPRSSVE LPPYSGTVLC GTQAVDKLPD
60 70 80 90 100
GQEYQRIEFG VDEVIEPSDT LPRTPSYSIS STLNPQAPEF ILGCTASKIT
110 120 130 140 150
PDGITKEASY GSIDCQYPGS ALALDGSSNV EAEVLENDGV SGGLGQRERK
160 170 180 190 200
KKKKRPPGYY SYLKDGGDDS ISTEALVNGH ANSAVPNSVS AEDAEFMGDM
210 220 230 240 250
PPSVTPRTCN SPQNSTDSVS DIVPDSPFPG ALGSDTRTAG QPEGGPGADF
260 270 280 290 300
GQSCFPAEAG RDTLSRTAGA QPCVGTDTTE NLGVANGQIL ESSGEGTATN
310 320 330 340 350
GVELHTTESI DLDPTKPESA SPPADGTGSA SGTLPVSQPK SWASLFHDSK
360 370 380 390 400
PSSSSPVAYV ETKYSPPAIS PLVSEKQVEV KEGLVPVSED PVAIKIAELL
410 420 430 440 450
ENVTLIHKPV SLQPRGLINK GNWCYINATL QALVACPPMY HLMKFIPLYS
460 470 480 490 500
KVQRPCTSTP MIDSFVRLMN EFTNMPVPPK PRQALGDKIV RDIRPGAAFE
510 520 530 540 550
PTYIYRLLTV NKSSLSEKGR QEDAEEYLGF ILNGLHEEML NLKKLLSPSN
560 570 580 590 600
EKLTISNGPK NHSVNEEEQE EQGEGSEDEW EQVGPRNKTS VTRQADFVQT
610 620 630 640 650
PITGIFGGHI RSVVYQQSSK ESATLQPFFT LQLDIQSDKI RTVQDALESL
660 670 680 690 700
VARESVQGYT TKTKQEVEIS RRVTLEKLPP VLVLHLKRFV YEKTGGCQKL
710 720 730 740 750
IKNIEYPVDL EISKELLSPG VKNKNFKCHR TYRLFAVVYH HGNSATGGHY
760 770 780 790
TTDVFQIGLN GWLRIDDQTV KVINQYQVVK PTAERTAYLL YYRRVDLL
Length:798
Mass (Da):87,134
Last modified:November 1, 1997 - v2
Checksum:iE6BA77E2B5CE2B3F
GO
Isoform 2 (identifier: Q14694-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MCSKDTVLSVCALYWRKGIQSHTPLIGAWRRGKQREQPEDRGVPMKRAA

Show »
Length:846
Mass (Da):92,597
Checksum:i01C2CD6FC3709AE4
GO
Isoform 3 (identifier: Q14694-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-6: MALHSP → MPWLPSPGIG

Note: No experimental confirmation available.
Show »
Length:802
Mass (Da):87,533
Checksum:iCBA33D0F268AEF5A
GO

Sequence cautioni

The sequence CAD97644 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti108A → V in BAG61546 (PubMed:14702039).Curated1
Sequence conflicti263T → A in BAG61546 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_015859200M → V1 PublicationCorresponds to variant dbSNP:rs1862792Ensembl.1
Natural variantiVAR_015860203S → P1 PublicationCorresponds to variant dbSNP:rs2326391Ensembl.1
Natural variantiVAR_015861204V → L1 PublicationCorresponds to variant dbSNP:rs1812061Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0388681 – 6MALHSP → MPWLPSPGIG in isoform 3. 1 Publication6
Alternative sequenceiVSP_0388691M → MCSKDTVLSVCALYWRKGIQ SHTPLIGAWRRGKQREQPED RGVPMKRAA in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D80012 mRNA Translation: BAA11507.1
AK299618 mRNA Translation: BAG61546.1
AK315570 mRNA Translation: BAG37945.1
AL162049 mRNA Translation: CAB82392.2
BX537402 mRNA Translation: CAD97644.1 Different initiation.
AC009116 Genomic DNA No translation available.
AC025280 Genomic DNA No translation available.
BC000263 mRNA Translation: AAH00263.1
CCDSiCCDS45537.1 [Q14694-1]
CCDS62004.1 [Q14694-3]
RefSeqiNP_001259004.1, NM_001272075.1 [Q14694-3]
NP_005144.2, NM_005153.2 [Q14694-1]
UniGeneiHs.136778

Genome annotation databases

EnsembliENST00000219473; ENSP00000219473; ENSG00000103194 [Q14694-1]
ENST00000570191; ENSP00000457411; ENSG00000103194 [Q14694-3]
GeneIDi9100
KEGGihsa:9100
UCSCiuc002fii.4 human [Q14694-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiUBP10_HUMAN
AccessioniPrimary (citable) accession number: Q14694
Secondary accession number(s): B2RDJ8
, B4DS84, Q9BWG7, Q9NSL7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: June 20, 2018
This is version 179 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

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