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A5PJS6

- UBP10_BOVIN

UniProt

A5PJS6 - UBP10_BOVIN

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Protein
Ubiquitin carboxyl-terminal hydrolase 10
Gene
USP10
Organism
Bos taurus (Bovine)
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 sitei426 – 4261Nucleophile By similarity
Active sitei751 – 7511Proton 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 thiolesterase activity Source: UniProtKB
  5. ubiquitin-specific protease activity Source: UniProtKB
Complete GO annotation...

GO - Biological processi

  1. DNA damage response, signal transduction by p53 class mediator Source: UniProtKB
  2. DNA repair Source: UniProtKB-KW
  3. autophagy 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

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
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
ProteomesiUP000009136: Chromosome 18

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 – 800799Ubiquitin carboxyl-terminal hydrolase 10
PRO_0000392999Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine By similarity
Modified residuei24 – 241Phosphothreonine By similarity
Modified residuei337 – 3371Phosphoserine; by ATM By similarity
Modified residuei367 – 3671Phosphoserine By similarity
Modified residuei372 – 3721Phosphoserine By similarity
Modified residuei565 – 5651Phosphoserine By similarity
Modified residuei578 – 5781Phosphoserine 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

PRIDEiA5PJS6.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000012432.

Structurei

3D structure databases

ProteinModelPortaliA5PJS6.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini417 – 797381USP
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 10099Interaction with p53/TP53 By similarity
Add
BLAST

Sequence similaritiesi

Contains 1 USP domain.

Phylogenomic databases

eggNOGiCOG5533.
GeneTreeiENSGT00550000074994.
HOGENOMiHOG000285959.
HOVERGENiHBG059823.
InParanoidiA5PJS6.
KOiK11841.
OMAiGQEYQRI.
OrthoDBiEOG7Z69BX.
TreeFamiTF323203.

Family and domain databases

InterProiIPR009818. Ataxin-2_C.
IPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR028889. UCH/PAN2.
IPR028767. USP10.
[Graphical view]
PANTHERiPTHR24006:SF69. PTHR24006:SF69. 1 hit.
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.

A5PJS6-1 [UniParc]FASTAAdd to Basket

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MALRSPQYIF GDFSPDEFNQ FFVTPRASVE LPPYGGTVLC GAQAADDLPD    50
GHDYQRIEFG VNEVIEPSDT LPRTPNYSIS STLNPQAPEF ILSCTTSKKL 100
PDDIDKEVNY SSANCQYPGP ALALDGGSPA EAEALENDGV SGGLGQRERK 150
KKKKRPPGYY SYLKDGGEGG PSAEALVNGH AGPAVSNSVG AEDTDLMGDV 200
PTAGTPRTWG SPQDATDFVS DAGPAGAFPG ALDGGARTAG QLEGCPGADS 250
EASCLPAEAG RDTLLRTAVA QPSVGTDTTE NLGVTNGQIL ESLGEGTAAN 300
GVELHTVESS DSDPAKAESA PPPADAPASA AGTVPASQPA KSWASLFHDS 350
KPSSSSLPVV SVETKYSPPA TSPLVSEKQA EVKEGLVPVS EDPVAIKIAE 400
LLENVTLIHK PVSLQPRGLI NKGNWCYINA TLQALVACPP MYHLMKLIPL 450
YSKVQRPCTS TPMIDSFVRL MNEFTNMPVP PKPRQALGDK IVRDIRPGAA 500
FEPTYIYRLL TVIKSSLSEK GRQEDAEEYL GFILNGLHEE MLNLKKLLSP 550
NNDKLTISNG PKSHSVNEDE QEEPGEGSED EWEQVGPRNK TSVTRQADFV 600
QTPITGIFGG HIRSVVYQQS SKESATLQPF FTLQLDIQSD KIRTVQDALE 650
SLVARESVQG YTTKTRQEVE ISRRVTLEKL PPVLVLHLKR FVYEKTGGCQ 700
KLIKNIEYPV DLEISKELLS PGVKNKNFKC HRTYRLFAVV YHHGSSATGG 750
HYTTDVFQIG LNGWLRIDDQ TVKVVSQQQV VRPAAERTAY LLYYRRVDLL 800
Length:800
Mass (Da):86,532
Last modified:July 10, 2007 - v1
Checksum:i16B8045CABAE6AED
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
BC142223 mRNA. Translation: AAI42224.1.
RefSeqiNP_001092394.1. NM_001098924.1.
UniGeneiBt.27346.

Genome annotation databases

EnsembliENSBTAT00000012432; ENSBTAP00000012432; ENSBTAG00000009446.
GeneIDi510164.
KEGGibta:510164.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
BC142223 mRNA. Translation: AAI42224.1 .
RefSeqi NP_001092394.1. NM_001098924.1.
UniGenei Bt.27346.

3D structure databases

ProteinModelPortali A5PJS6.
ModBasei Search...

Protein-protein interaction databases

STRINGi 9913.ENSBTAP00000012432.

Proteomic databases

PRIDEi A5PJS6.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSBTAT00000012432 ; ENSBTAP00000012432 ; ENSBTAG00000009446 .
GeneIDi 510164.
KEGGi bta:510164.

Organism-specific databases

CTDi 9100.

Phylogenomic databases

eggNOGi COG5533.
GeneTreei ENSGT00550000074994.
HOGENOMi HOG000285959.
HOVERGENi HBG059823.
InParanoidi A5PJS6.
KOi K11841.
OMAi GQEYQRI.
OrthoDBi EOG7Z69BX.
TreeFami TF323203.

Miscellaneous databases

NextBioi 20869309.

Family and domain databases

InterProi IPR009818. Ataxin-2_C.
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 PF07145. PAM2. 1 hit.
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. NIH - Mammalian Gene Collection (MGC) project
    Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Hereford.
    Tissue: Fetal skin.

Entry informationi

Entry nameiUBP10_BOVIN
AccessioniPrimary (citable) accession number: A5PJS6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 23, 2010
Last sequence update: July 10, 2007
Last modified: April 16, 2014
This is version 49 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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