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Q3KR59

- UBP10_RAT

UniProt

Q3KR59 - UBP10_RAT

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
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    • History
      Entry version 62 (01 Oct 2014)
      Sequence version 1 (08 Nov 2005)
      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 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. 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

    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

    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

    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: October 1, 2014
    This is version 62 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