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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 transcript 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 (By similarity).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).

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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei420 – 4201NucleophilePROSITE-ProRule annotation
Active sitei745 – 7451Proton acceptorPROSITE-ProRule annotation

GO - Molecular functioni

  1. cysteine-type endopeptidase activity Source: UniProtKB
  2. ion channel binding Source: UniProtKB
  3. p53 binding Source: UniProtKB
  4. poly(A) RNA binding Source: Ensembl
  5. ubiquitin-specific protease activity Source: UniProtKB
  6. ubiquitin thiolesterase activity Source: UniProtKB

GO - Biological processi

  1. autophagy Source: UniProtKB-KW
  2. DNA damage response, signal transduction by p53 class mediator Source: UniProtKB
  3. DNA repair Source: UniProtKB-KW
  4. proteasome-mediated ubiquitin-dependent protein catabolic process Source: GO_Central
  5. protein deubiquitination Source: UniProtKB
  6. regulation of autophagy Source: UniProtKB
  7. regulation of proteasomal protein catabolic process Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Autophagy, DNA damage, DNA repair, Ubl conjugation pathway

Protein family/group databases

MEROPSiC19.018.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase 10 (EC:3.4.19.12)
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
ProteomesiUP000002494: Chromosome 19

Organism-specific databases

RGDi1561965. Usp10.

Subcellular locationi

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

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. early endosome Source: UniProtKB
  3. intermediate filament cytoskeleton Source: Ensembl
  4. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endosome, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 794793Ubiquitin carboxyl-terminal hydrolase 10PRO_0000393000Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei24 – 241PhosphothreonineBy similarity
Modified residuei99 – 991PhosphothreonineBy similarity
Modified residuei224 – 2241PhosphoserineBy similarity
Modified residuei332 – 3321Phosphoserine; by ATMBy similarity
Modified residuei361 – 3611PhosphoserineBy similarity
Modified residuei366 – 3661PhosphoserineBy similarity
Modified residuei572 – 5721PhosphoserineBy similarity

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

PhosphoSiteiQ3KR59.

Expressioni

Gene expression databases

GenevestigatoriQ3KR59.

Interactioni

Subunit structurei

Interacts with G3BP, which may regulate its function. Interacts with p53/TP53, SNX3 and CFTR (By similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000022432.

Structurei

3D structure databases

ProteinModelPortaliQ3KR59.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini411 – 791381USPAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 9998Interaction with p53/TP53By similarityAdd
BLAST

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiCOG5533.
GeneTreeiENSGT00550000074994.
HOGENOMiHOG000285959.
HOVERGENiHBG059823.
InParanoidiQ3KR59.
KOiK11841.
OMAiGQEYQRI.
OrthoDBiEOG7Z69BX.
PhylomeDBiQ3KR59.
TreeFamiTF323203.

Family and domain databases

InterProiIPR001394. Peptidase_C19_UCH.
IPR028767. USP10.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PANTHERiPTHR24006:SF69. PTHR24006:SF69. 1 hit.
PfamiPF00443. 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

PhosphoSiteiQ3KR59.

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

eggNOGiCOG5533.
GeneTreeiENSGT00550000074994.
HOGENOMiHOG000285959.
HOVERGENiHBG059823.
InParanoidiQ3KR59.
KOiK11841.
OMAiGQEYQRI.
OrthoDBiEOG7Z69BX.
PhylomeDBiQ3KR59.
TreeFamiTF323203.

Miscellaneous databases

NextBioi658066.
PROiQ3KR59.

Gene expression databases

GenevestigatoriQ3KR59.

Family and domain databases

InterProiIPR001394. Peptidase_C19_UCH.
IPR028767. USP10.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PANTHERiPTHR24006:SF69. PTHR24006:SF69. 1 hit.
PfamiPF00443. UCH. 1 hit.
[Graphical view]
PROSITEiPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Spleen.

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: February 4, 2015
This is version 65 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

External Data

Dasty 3

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 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.