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Protein

Ubiquitin carboxyl-terminal hydrolase 10

Gene

Usp10

Organism
Rattus norvegicus (Rat)
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 sitei420NucleophilePROSITE-ProRule annotation1
Active sitei745Proton 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-RNO-5656169. Termination of translesion DNA synthesis.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 19

Organism-specific databases

RGDi1561965. 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_00003930002 – 794Ubiquitin carboxyl-terminal hydrolase 10Add BLAST793

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei24PhosphothreonineBy similarity1
Modified residuei99PhosphothreonineBy similarity1
Modified residuei209PhosphoserineBy similarity1
Modified residuei224PhosphoserineBy similarity1
Modified residuei316PhosphoserineBy similarity1
Modified residuei332Phosphoserine; by ATMBy similarity1
Modified residuei361PhosphoserineBy similarity1
Modified residuei366PhosphoserineBy similarity1
Modified residuei543PhosphoserineBy similarity1
Modified residuei568PhosphothreonineCombined sources1
Modified residuei572PhosphoserineCombined 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

PaxDbiQ3KR59.
PRIDEiQ3KR59.

PTM databases

iPTMnetiQ3KR59.
PhosphoSitePlusiQ3KR59.

Expressioni

Gene expression databases

BgeeiENSRNOG00000016509.
GenevisibleiQ3KR59. RN.

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

STRINGi10116.ENSRNOP00000022432.

Structurei

3D structure databases

ProteinModelPortaliQ3KR59.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini411 – 791USPAdd 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.
HOGENOMiHOG000285959.
HOVERGENiHBG059823.
InParanoidiQ3KR59.
KOiK11841.
OMAiGQEYQRI.
OrthoDBiEOG091G023X.
PhylomeDBiQ3KR59.
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]

Sequencei

Sequence statusi: Complete.

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

Q3KR59-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MALHNPQYIF GDFSPDEFNQ FFVTPRSSVE LPPYSGTQCG IQAEEELLDG
60 70 80 90 100
QEHQRIEFGV DEVIEPSDGL QRAPSYSISS TLNPQAPEFI LGCPTSKKTP
110 120 130 140 150
DDIEKDETYS SIDQYPASAL ALESSSNAEA ETLENDSGAG GLGQRERKKK
160 170 180 190 200
KKRPPGYYSY LKDGSEEGAS PAALVNGHAT SVGTNSEGVE DPEFMVDMLP
210 220 230 240 250
SVMPRTCDSP QNPMDLISDP VPDSPFPRTL GGDARTAGLP EGCRETDFEQ
260 270 280 290 300
PCLPTDNLLR TAVTQPNAGA DTTENLAVAN GKILESLGEG TAAANGVELH
310 320 330 340 350
TDESADLDPA KPESQSPPAE SALSVSGAIS ISQPAKSWAS LFHDSKPSSS
360 370 380 390 400
SPVAYVETKC SPPVPSPLAS EKQMEVKEGL VPVSEDPVAI KIAELLETVT
410 420 430 440 450
LVHKPVSLQP RGLINKGNWC YINATLQALV ACPPMYHLMK FIPLYSKVQR
460 470 480 490 500
PCTSTPMIDS FVRLMNEFTN MPVPPKPRQA LGDKIVRDIR PGAAFEPTYI
510 520 530 540 550
YRLLTVIKSS LSEKGRQEDA EEYLGFILNG LHEEMLSLKK LLSPTHEKHS
560 570 580 590 600
VSNGPGSHLI EDEELEDTGE GSEDEWEQVG PKNKTSVTRQ ADFVQTPITG
610 620 630 640 650
IFGGHIRSVV YQQSSKESAT LQPFFTLQLD IQSDKIRTVQ DALESLVARE
660 670 680 690 700
SVQGYTTKTK QEVEVSRRVT LEKLPPVLVL HLKRFVYEKT GGCQKLVKNI
710 720 730 740 750
EYPVDLEISR ELLSPGVKNK NFKCHRTYRL FAVVYHHGNS ATGGHYTTDV
760 770 780 790
FQIGLNGWLR IDDQTVKVIN QYQVVRPSAD RTAYLLYYRR VDLL
Length:794
Mass (Da):87,311
Last modified:November 8, 2005 - v1
Checksum:iF8D1A3D6C66D0926
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC105892 mRNA. Translation: AAI05893.1.
RefSeqiNP_001029318.1. NM_001034146.1.
UniGeneiRn.24862.

Genome annotation databases

EnsembliENSRNOT00000022432; ENSRNOP00000022432; ENSRNOG00000016509.
GeneIDi307905.
KEGGirno:307905.
UCSCiRGD:1561965. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC105892 mRNA. Translation: AAI05893.1.
RefSeqiNP_001029318.1. NM_001034146.1.
UniGeneiRn.24862.

3D structure databases

ProteinModelPortaliQ3KR59.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000022432.

Protein family/group databases

MEROPSiC19.018.

PTM databases

iPTMnetiQ3KR59.
PhosphoSitePlusiQ3KR59.

Proteomic databases

PaxDbiQ3KR59.
PRIDEiQ3KR59.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000022432; ENSRNOP00000022432; ENSRNOG00000016509.
GeneIDi307905.
KEGGirno:307905.
UCSCiRGD:1561965. rat.

Organism-specific databases

CTDi9100.
RGDi1561965. Usp10.

Phylogenomic databases

eggNOGiKOG1871. Eukaryota.
ENOG410XSIH. LUCA.
GeneTreeiENSGT00550000074994.
HOGENOMiHOG000285959.
HOVERGENiHBG059823.
InParanoidiQ3KR59.
KOiK11841.
OMAiGQEYQRI.
OrthoDBiEOG091G023X.
PhylomeDBiQ3KR59.
TreeFamiTF323203.

Enzyme and pathway databases

ReactomeiR-RNO-5656169. Termination of translesion DNA synthesis.

Miscellaneous databases

PROiQ3KR59.

Gene expression databases

BgeeiENSRNOG00000016509.
GenevisibleiQ3KR59. RN.

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_RAT
AccessioniPrimary (citable) accession number: Q3KR59
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 23, 2010
Last sequence update: November 8, 2005
Last modified: November 30, 2016
This is version 83 of the entry and version 1 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. Peptidase families
    Classification of peptidase families and list of entries
  2. 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.