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Protein

Ubiquitin carboxyl-terminal hydrolase 10

Gene

Usp10

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.By similarity

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).By similarity

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 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei418NucleophilePROSITE-ProRule annotation1
Active sitei743Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Autophagy, DNA damage, DNA repair, Ubl conjugation pathway

Enzyme and pathway databases

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

Protein family/group databases

MEROPSiC19.018.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase 10 (EC:3.4.19.12By similarity)
Alternative name(s):
Deubiquitinating enzyme 10
Ubiquitin thioesterase 10
Ubiquitin-specific-processing protease 10
Gene namesi
Name:Usp10
Synonyms:Kiaa0190, Ode-1, Uchrp
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:894652. Usp10.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity
  • Early endosome By similarity

  • Note: Cytoplasmic in normal conditions (By similarity). After DNA damage, translocates to the nucleus following phosphorylation by ATM (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endosome, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000806302 – 792Ubiquitin carboxyl-terminal hydrolase 10Add BLAST791

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei24PhosphothreonineBy similarity1
Modified residuei208PhosphoserineCombined sources1
Modified residuei223PhosphoserineCombined sources1
Modified residuei314PhosphoserineBy similarity1
Modified residuei330Phosphoserine; by ATMBy similarity1
Modified residuei359PhosphoserineCombined sources1
Modified residuei364PhosphoserineBy similarity1
Modified residuei541PhosphoserineBy similarity1
Modified residuei566PhosphothreonineCombined sources1
Modified residuei570PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by ATM following DNA damage, leading to stablization and translocation it to the nucleus.By similarity
Ubiquitinated. Deubiquitinated by USP13 (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP52479.
PaxDbiP52479.
PeptideAtlasiP52479.
PRIDEiP52479.

PTM databases

iPTMnetiP52479.
PhosphoSitePlusiP52479.

Expressioni

Gene expression databases

BgeeiENSMUSG00000031826.
CleanExiMM_USP10.
ExpressionAtlasiP52479. baseline and differential.
GenevisibleiP52479. MM.

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. Interacts with IKBKG; this interaction increases in response to DNA damage. Interacts with TANK; this interaction increases in response to DNA damage. Interacts with TRAF6; this interaction increases in response to DNA damage. Interacts with ZC3H12A; this interaction increases in response to DNA damage. Interacts with G3BP, which may regulate its function. Interacts with p53/TP53, SNX3 and CFTR.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204424. 4 interactors.
IntActiP52479. 4 interactors.
MINTiMINT-1870263.
STRINGi10090.ENSMUSP00000123590.

Structurei

3D structure databases

ProteinModelPortaliP52479.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini409 – 789USPAdd BLAST381

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 99Interaction with p53/TP53By similarityAdd BLAST98

Sequence similaritiesi

Belongs to the peptidase C19 family. USP10 subfamily.Curated
Contains 1 USP domain.Curated

Phylogenomic databases

eggNOGiKOG1871. Eukaryota.
ENOG410XSIH. LUCA.
GeneTreeiENSGT00550000074994.
HOVERGENiHBG059823.
InParanoidiP52479.
KOiK11841.
OMAiGQEYQRI.
OrthoDBiEOG091G023X.
PhylomeDBiP52479.
TreeFamiTF323203.

Family and domain databases

InterProiIPR009818. Ataxin-2_C.
IPR001394. Peptidase_C19_UCH.
IPR028767. USP10.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PANTHERiPTHR24006:SF69. PTHR24006:SF69. 3 hits.
PfamiPF07145. PAM2. 1 hit.
PF00443. UCH. 1 hit.
[Graphical view]
PROSITEiPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P52479-1) [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
MALHNPQYIF GDFSPDEFNQ FFVTPRSSVE LPPYSGTLCS IQAEDELPDG
60 70 80 90 100
QEHQRIEFGV DEVIEPSEGL PPTPSYSISS TLNPQAPEFI LGCTTSKKIP
110 120 130 140 150
EAVEKDETYS SIDQYPASAL ALESNSNAEA ETLENDSGAG GLGQRERKKK
160 170 180 190 200
KKRPPGYYSY LKDGGEDSAS PATLVNGHAT SVGTSGEAVE DAEFMDVLPP
210 220 230 240 250
VMPRTCDSPQ NPVDFISGPV PDSPFPRTLG GDARTAGLCE GCHEADFEQP
260 270 280 290 300
CLPADSLLRT AGTQPYVGTD TTENFAVANG KILESPGEDT AANGAELHTD
310 320 330 340 350
EGADLDPAKP ESQSPPAESA LSASGAIPIS QPAKSWASLF HDSKPSASSP
360 370 380 390 400
MAYVETKCSP PVPSPLASEK QMEVKEGLVP VSEDPVAIKI AELLETVTLI
410 420 430 440 450
HKPVSLQPRG LINKGNWCYI NATLQALVAC PPMYHLMKFI PLYSKVQRPC
460 470 480 490 500
TSTPMIDSFV RLMNEFTNMP VPPKPRQALG DKIVRDIRPG AAFEPTYIYR
510 520 530 540 550
LLTVIKSSLS EKGRQEDAEE YLGFILNGLH EEMLSLKKLL SPTHEKHSVS
560 570 580 590 600
NGPRSDLIED EELEDTGKGS EDEWEQVGPK NKTSITRQAD FVQTPITGIF
610 620 630 640 650
GGHIRSVVYQ QSSKESATLQ LFFTLQLDIQ SDKIRTVQDA LESLVARESV
660 670 680 690 700
QGYTTKTKQE VEVSRRVTLE KLPPVLVLHL KRFVYEKTGG CQKLVKNIDY
710 720 730 740 750
PVDLEISREL LSPGIKNKNF KCQRTYRLFA VVYHHGNSAT GGHYTTDVFQ
760 770 780 790
IGLNGWLRID DQTVKVINQY QVVKPPADRT AYLLYYRRVD LL
Length:792
Mass (Da):87,022
Last modified:March 23, 2010 - v3
Checksum:i02D07A8194215D09
GO
Isoform 2 (identifier: P52479-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     49-49: D → DA

Show »
Length:793
Mass (Da):87,093
Checksum:iAC67428E5DBC3D9F
GO

Sequence cautioni

The sequence BAC97893 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti72P → R in AAH07134 (PubMed:15489334).Curated1
Sequence conflicti101E → D in AAH07134 (PubMed:15489334).Curated1
Sequence conflicti293N → S in AAH07134 (PubMed:15489334).Curated1
Sequence conflicti347A → S in AAH07134 (PubMed:15489334).Curated1
Sequence conflicti448R → G in BAE34291 (PubMed:16141072).Curated1
Sequence conflicti472P → T in BAE32139 (PubMed:16141072).Curated1
Sequence conflicti528G → R in BAE38053 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03887049D → DA in isoform 2. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D84096 mRNA. Translation: BAA12220.1.
AK129083 mRNA. Translation: BAC97893.1. Different initiation.
AK153675 mRNA. Translation: BAE32139.1.
AK157970 mRNA. Translation: BAE34291.1.
AK165156 mRNA. Translation: BAE38053.1.
AK172443 mRNA. Translation: BAE43006.1.
CH466525 Genomic DNA. Translation: EDL11620.1.
BC007134 mRNA. Translation: AAH07134.1.
CCDSiCCDS40495.1. [P52479-2]
CCDS80938.1. [P52479-1]
RefSeqiNP_001297559.1. NM_001310630.1. [P52479-1]
NP_033488.1. NM_009462.2. [P52479-2]
UniGeneiMm.256910.
Mm.421337.

Genome annotation databases

EnsembliENSMUST00000108988; ENSMUSP00000104616; ENSMUSG00000031826. [P52479-1]
ENSMUST00000144458; ENSMUSP00000123590; ENSMUSG00000031826. [P52479-2]
GeneIDi22224.
KEGGimmu:22224.
UCSCiuc009nqn.1. mouse. [P52479-2]
uc009nqo.1. mouse. [P52479-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D84096 mRNA. Translation: BAA12220.1.
AK129083 mRNA. Translation: BAC97893.1. Different initiation.
AK153675 mRNA. Translation: BAE32139.1.
AK157970 mRNA. Translation: BAE34291.1.
AK165156 mRNA. Translation: BAE38053.1.
AK172443 mRNA. Translation: BAE43006.1.
CH466525 Genomic DNA. Translation: EDL11620.1.
BC007134 mRNA. Translation: AAH07134.1.
CCDSiCCDS40495.1. [P52479-2]
CCDS80938.1. [P52479-1]
RefSeqiNP_001297559.1. NM_001310630.1. [P52479-1]
NP_033488.1. NM_009462.2. [P52479-2]
UniGeneiMm.256910.
Mm.421337.

3D structure databases

ProteinModelPortaliP52479.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204424. 4 interactors.
IntActiP52479. 4 interactors.
MINTiMINT-1870263.
STRINGi10090.ENSMUSP00000123590.

Protein family/group databases

MEROPSiC19.018.

PTM databases

iPTMnetiP52479.
PhosphoSitePlusiP52479.

Proteomic databases

MaxQBiP52479.
PaxDbiP52479.
PeptideAtlasiP52479.
PRIDEiP52479.

Protocols and materials databases

DNASUi22224.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000108988; ENSMUSP00000104616; ENSMUSG00000031826. [P52479-1]
ENSMUST00000144458; ENSMUSP00000123590; ENSMUSG00000031826. [P52479-2]
GeneIDi22224.
KEGGimmu:22224.
UCSCiuc009nqn.1. mouse. [P52479-2]
uc009nqo.1. mouse. [P52479-1]

Organism-specific databases

CTDi9100.
MGIiMGI:894652. Usp10.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG1871. Eukaryota.
ENOG410XSIH. LUCA.
GeneTreeiENSGT00550000074994.
HOVERGENiHBG059823.
InParanoidiP52479.
KOiK11841.
OMAiGQEYQRI.
OrthoDBiEOG091G023X.
PhylomeDBiP52479.
TreeFamiTF323203.

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiUsp10. mouse.
PROiP52479.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031826.
CleanExiMM_USP10.
ExpressionAtlasiP52479. baseline and differential.
GenevisibleiP52479. MM.

Family and domain databases

InterProiIPR009818. Ataxin-2_C.
IPR001394. Peptidase_C19_UCH.
IPR028767. USP10.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PANTHERiPTHR24006:SF69. PTHR24006:SF69. 3 hits.
PfamiPF07145. PAM2. 1 hit.
PF00443. UCH. 1 hit.
[Graphical view]
PROSITEiPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUBP10_MOUSE
AccessioniPrimary (citable) accession number: P52479
Secondary accession number(s): Q3T9L4
, Q3TNN5, Q3TZB8, Q3U5E0, Q6ZQG9, Q91VY7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: March 23, 2010
Last modified: November 2, 2016
This is version 141 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.