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Q3KR59

- UBP10_RAT

UniProt

Q3KR59 - UBP10_RAT

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Protein

Ubiquitin carboxyl-terminal hydrolase 10

Gene
Usp10
Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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.

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei420 – 4201Nucleophile By similarity
Active sitei745 – 7451Proton acceptor By similarity

GO - Molecular functioni

  1. cysteine-type endopeptidase activity Source: UniProtKB
  2. ion channel binding Source: UniProtKB
  3. p53 binding Source: UniProtKB
  4. ubiquitin-specific protease activity Source: UniProtKB
  5. 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. protein deubiquitination Source: UniProtKB
  5. regulation of autophagy Source: UniProtKB
  6. ubiquitin-dependent protein catabolic process Source: InterPro
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.

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 – 11Removed By similarity
Chaini2 – 794793Ubiquitin carboxyl-terminal hydrolase 10PRO_0000393000Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine By similarity
Modified residuei24 – 241Phosphothreonine By similarity
Modified residuei99 – 991Phosphothreonine By similarity
Modified residuei224 – 2241Phosphoserine By similarity
Modified residuei332 – 3321Phosphoserine; by ATM By similarity
Modified residuei361 – 3611Phosphoserine By similarity
Modified residuei366 – 3661Phosphoserine By similarity
Modified residuei572 – 5721Phosphoserine By 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.

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.

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000022432.

Structurei

3D structure databases

ProteinModelPortaliQ3KR59.

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/TP53 By similarityAdd
BLAST

Sequence similaritiesi

Contains 1 USP domain.

Phylogenomic databases

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

Family and domain databases

InterProiIPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR028889. UCH/PAN2.
IPR028767. USP10.
[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

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MALHNPQYIF GDFSPDEFNQ FFVTPRSSVE LPPYSGTQCG IQAEEELLDG    50
QEHQRIEFGV DEVIEPSDGL QRAPSYSISS TLNPQAPEFI LGCPTSKKTP 100
DDIEKDETYS SIDQYPASAL ALESSSNAEA ETLENDSGAG GLGQRERKKK 150
KKRPPGYYSY LKDGSEEGAS PAALVNGHAT SVGTNSEGVE DPEFMVDMLP 200
SVMPRTCDSP QNPMDLISDP VPDSPFPRTL GGDARTAGLP EGCRETDFEQ 250
PCLPTDNLLR TAVTQPNAGA DTTENLAVAN GKILESLGEG TAAANGVELH 300
TDESADLDPA KPESQSPPAE SALSVSGAIS ISQPAKSWAS LFHDSKPSSS 350
SPVAYVETKC SPPVPSPLAS EKQMEVKEGL VPVSEDPVAI KIAELLETVT 400
LVHKPVSLQP RGLINKGNWC YINATLQALV ACPPMYHLMK FIPLYSKVQR 450
PCTSTPMIDS FVRLMNEFTN MPVPPKPRQA LGDKIVRDIR PGAAFEPTYI 500
YRLLTVIKSS LSEKGRQEDA EEYLGFILNG LHEEMLSLKK LLSPTHEKHS 550
VSNGPGSHLI EDEELEDTGE GSEDEWEQVG PKNKTSVTRQ ADFVQTPITG 600
IFGGHIRSVV YQQSSKESAT LQPFFTLQLD IQSDKIRTVQ DALESLVARE 650
SVQGYTTKTK QEVEVSRRVT LEKLPPVLVL HLKRFVYEKT GGCQKLVKNI 700
EYPVDLEISR ELLSPGVKNK NFKCHRTYRL FAVVYHHGNS ATGGHYTTDV 750
FQIGLNGWLR IDDQTVKVIN QYQVVRPSAD RTAYLLYYRR VDLL 794
Length:794
Mass (Da):87,311
Last modified:November 8, 2005 - v1
Checksum:iF8D1A3D6C66D0926
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
BC105892 mRNA. Translation: AAI05893.1 .
RefSeqi NP_001029318.1. NM_001034146.1.
UniGenei Rn.24862.

3D structure databases

ProteinModelPortali Q3KR59.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10116.ENSRNOP00000022432.

Protein family/group databases

MEROPSi C19.018.

PTM databases

PhosphoSitei Q3KR59.

Proteomic databases

PaxDbi Q3KR59.
PRIDEi Q3KR59.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000022432 ; ENSRNOP00000022432 ; ENSRNOG00000016509 .
GeneIDi 307905.
KEGGi rno:307905.
UCSCi RGD:1561965. rat.

Organism-specific databases

CTDi 9100.
RGDi 1561965. Usp10.

Phylogenomic databases

eggNOGi COG5533.
GeneTreei ENSGT00550000074994.
HOGENOMi HOG000285959.
HOVERGENi HBG059823.
InParanoidi Q3KR59.
KOi K11841.
OMAi GQEYQRI.
OrthoDBi EOG7Z69BX.
PhylomeDBi Q3KR59.
TreeFami TF323203.

Miscellaneous databases

NextBioi 658066.
PROi Q3KR59.

Gene expression databases

Genevestigatori Q3KR59.

Family and domain databases

InterProi IPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR028889. UCH/PAN2.
IPR028767. USP10.
[Graphical view ]
PANTHERi PTHR24006:SF69. PTHR24006:SF69. 1 hit.
Pfami PF00443. UCH. 1 hit.
[Graphical view ]
PROSITEi PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: April 16, 2014
This is version 61 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

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