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A5PJS6

- UBP10_BOVIN

UniProt

A5PJS6 - UBP10_BOVIN

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
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    • History
      Entry version 50 (01 Oct 2014)
      Sequence version 1 (10 Jul 2007)
      Previous versions | rss
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    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 sitei426 – 4261NucleophilePROSITE-ProRule annotation
    Active sitei751 – 7511Proton 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. 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

    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.By similarity

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Cytoplasm, Endosome, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 800799Ubiquitin carboxyl-terminal hydrolase 10PRO_0000392999Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanineBy similarity
    Modified residuei24 – 241PhosphothreonineBy similarity
    Modified residuei337 – 3371Phosphoserine; by ATMBy similarity
    Modified residuei367 – 3671PhosphoserineBy similarity
    Modified residuei372 – 3721PhosphoserineBy similarity
    Modified residuei565 – 5651PhosphoserineBy similarity
    Modified residuei578 – 5781PhosphoserineBy 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

    PRIDEiA5PJS6.

    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

    STRINGi9913.ENSBTAP00000012432.

    Structurei

    3D structure databases

    ProteinModelPortaliA5PJS6.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

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

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni2 – 10099Interaction 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.
    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...
    MobiDBi 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: October 1, 2014
    This is version 50 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