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Q2HJE4

- UBP15_BOVIN

UniProt

Q2HJE4 - UBP15_BOVIN

Protein

Ubiquitin carboxyl-terminal hydrolase 15

Gene

USP15

Organism
Bos taurus (Bovine)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 69 (01 Oct 2014)
      Sequence version 1 (21 Mar 2006)
      Previous versions | rss
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    Functioni

    Hydrolase that removes conjugated ubiquitin from target proteins and regulates various pathways such as the TGF-beta receptor signaling and NF-kappa-B pathways. Acts as a key regulator of TGF-beta receptor signaling pathway, but the precise mechanism is still unclear: according to a report, acts by promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and promoting activation of TGF-beta target genes. According to another reports, regulates the TGF-beta receptor signaling pathway by mediating deubiquitination and stabilization of TGFBR1, leading to an enhanced TGF-beta signal. Able to mediate deubiquitination of monoubiquitinated substrates as well as 'Lys-48'-linked polyubiquitin chains, protecting them against proteasomal degradation. Acts as an associated component of COP9 signalosome complex (CSN) and regulates different pathways via this association: regulates NF-kappa-B by mediating deubiquitination of NFKBIA and deubiquitinates substrates bound to VCP 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).

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei269 – 2691NucleophilePROSITE-ProRule annotation
    Active sitei862 – 8621Proton acceptorPROSITE-ProRule annotation

    GO - Molecular functioni

    1. cysteine-type endopeptidase activity Source: UniProtKB
    2. ubiquitin-specific protease activity Source: UniProtKB
    3. ubiquitin thiolesterase activity Source: UniProtKB

    GO - Biological processi

    1. BMP signaling pathway Source: UniProtKB
    2. monoubiquitinated protein deubiquitination Source: UniProtKB
    3. pathway-restricted SMAD protein phosphorylation Source: UniProtKB
    4. protein deubiquitination Source: UniProtKB
    5. transforming growth factor beta receptor signaling pathway Source: UniProtKB
    6. ubiquitin-dependent protein catabolic process Source: InterPro

    Keywords - Molecular functioni

    Hydrolase, Protease, Thiol protease

    Keywords - Biological processi

    Ubl conjugation pathway

    Enzyme and pathway databases

    ReactomeiREACT_225632. Downregulation of TGF-beta receptor signaling.

    Protein family/group databases

    MEROPSiC19.022.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Ubiquitin carboxyl-terminal hydrolase 15 (EC:3.4.19.12)
    Alternative name(s):
    Deubiquitinating enzyme 15
    Ubiquitin thioesterase 15
    Ubiquitin-specific-processing protease 15
    Gene namesi
    Name:USP15
    OrganismiBos taurus (Bovine)
    Taxonomic identifieri9913 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
    ProteomesiUP000009136: Chromosome 5

    Subcellular locationi

    Cytoplasm By similarity. Nucleus By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 952951Ubiquitin carboxyl-terminal hydrolase 15PRO_0000420489Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanineBy similarity
    Modified residuei932 – 9321PhosphoserineBy similarity
    Modified residuei936 – 9361PhosphoserineBy similarity

    Post-translational modificationi

    Phosphorylated. Phosphorylation protects against ubiquitination and subsequent degradation by the proteasome By similarity.By similarity
    Ubiquitinated, leading to degradation by the proteasome.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiQ2HJE4.

    Interactioni

    Subunit structurei

    Identified in a complex with the COP9 signalosome complex (CSN). Interacts with SMAD1, SMAD2 and SMAD3; the interaction is direct. Forms a complex with SMURF2 and SMAD7. Interacts with TGFBR1 By similarity.By similarity

    Protein-protein interaction databases

    STRINGi9913.ENSBTAP00000037402.

    Structurei

    3D structure databases

    ProteinModelPortaliQ2HJE4.
    SMRiQ2HJE4. Positions 1-120.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini7 – 118112DUSPPROSITE-ProRule annotationAdd
    BLAST
    Domaini260 – 904645USPAdd
    BLAST

    Sequence similaritiesi

    Belongs to the peptidase C19 family.Curated
    Contains 1 DUSP domain.PROSITE-ProRule annotation
    Contains 1 USP domain.Curated

    Phylogenomic databases

    eggNOGiCOG5560.
    GeneTreeiENSGT00670000097750.
    HOGENOMiHOG000264375.
    HOVERGENiHBG000864.
    InParanoidiQ2HJE4.
    KOiK11835.
    OMAiRYVKTCT.
    OrthoDBiEOG77Q4VW.
    TreeFamiTF106276.

    Family and domain databases

    Gene3Di3.30.2230.10. 1 hit.
    InterProiIPR006615. Pept_C19_DUSP.
    IPR018200. Pept_C19ubi-hydrolase_C_CS.
    IPR001394. Peptidase_C19_UCH.
    IPR013792. RNA3'P_cycl/enolpyr_Trfase_a/b.
    IPR028135. Ub_USP-typ.
    IPR029071. Ubiquitin-rel_dom.
    IPR028889. UCH/PAN2.
    [Graphical view]
    PfamiPF06337. DUSP. 1 hit.
    PF14836. Ubiquitin_3. 1 hit.
    PF00443. UCH. 1 hit.
    [Graphical view]
    SMARTiSM00695. DUSP. 1 hit.
    [Graphical view]
    SUPFAMiSSF143791. SSF143791. 1 hit.
    SSF54236. SSF54236. 1 hit.
    SSF55205. SSF55205. 1 hit.
    PROSITEiPS51283. DUSP. 1 hit.
    PS00972. 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.

    Q2HJE4-1 [UniParc]FASTAAdd to Basket

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    MAEGGAADLD IQRSDIATLL KTSLRKGDTW YLVDSRWFKQ WKKYVGFDSW    50
    DKYQMGDQNV YPGPIDNSGL LRDGDAQSLK EHLIDELDYI LLPTEGWNKL 100
    VSWYTLMEGQ EPIARKVVEQ GMFVKHCKVE VYLTELKLCE NGNMNNVVTR 150
    RFSKADTIDT IEKEIRKIFN IPDEKETRLW NKYMSNTFEP LNKPDSTIQD 200
    AGLYQGQVLV IEQKNEDGTW PRGPSTPNVK NSNYCLPSYT AYKNYDYSEP 250
    GRNNEQPGLC GLSNLGNTCF MNSAFQCLSN TPPLTEYFLN DKYQEELNFD 300
    NPLGMRGEIA KSYAELIKQM WSGKYSYVTP RAFKTQVGRF APQFSGYQQQ 350
    DCQELLAFLL DGLHEDLNRI RKKPYIQLKD ADGRPDKVVA EEAWENHLKR 400
    NDSIIVDIFH GLFKSTLVCP ECAKISVTFD PFCYLTLPLP MKKERTLEVY 450
    LVRMDPLTKP MQYKVVVPKI GNILDLCTAL SLLSGVPADK MIVTDIYNHR 500
    FHRIFAMDEN LSSIMERDDI YVFEININRT EDTEHVIIPV CLREKFRHSS 550
    YTHHTGSSLF GQPFLMAVPR NNTEDKLYNL LLVRMCRYVK ISTDTEDTEG 600
    SLHCCKDQNI NGNGPNGIHE EGSPSEMETD EPDDESSQDQ ELPSENENSQ 650
    SEDSVGGDND SENGLCTEET CRGQLTGHKK RLFTFQFNNL GNTDINYIKD 700
    DTRHIRFDDR QLRLDERSFL ALDWDPDLKK RYFDENAAED FEKHESVEYK 750
    PPKKPFVKLK DCIELFTTKE KLGAEDPWYC PNCKEHQQAT KKLDLWSLPP 800
    VLVVHLKRFS YSRYMRDKLD TLVDFPINDL DMSEFLINPN AGPCRYNLIA 850
    VSNHYGGMGG GHYTAFAKNK DDGKWYYFDD SSVSTASEDQ IVSKAAYVLF 900
    YQRQDTFSGT GFFPLDRETK GASAATGIPL ESDEDSNDND NDIENENCMH 950
    TN 952
    Length:952
    Mass (Da):109,442
    Last modified:March 21, 2006 - v1
    Checksum:iA4151AAE16BE8B53
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    DAAA02013374 Genomic DNA. No translation available.
    DAAA02013375 Genomic DNA. No translation available.
    DAAA02013376 Genomic DNA. No translation available.
    DAAA02013377 Genomic DNA. No translation available.
    DAAA02013378 Genomic DNA. No translation available.
    BC105521 mRNA. Translation: AAI05522.1.
    RefSeqiNP_001039895.1. NM_001046430.2.
    UniGeneiBt.29017.

    Genome annotation databases

    EnsembliENSBTAT00000037574; ENSBTAP00000037402; ENSBTAG00000010428.
    GeneIDi538284.
    KEGGibta:538284.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    DAAA02013374 Genomic DNA. No translation available.
    DAAA02013375 Genomic DNA. No translation available.
    DAAA02013376 Genomic DNA. No translation available.
    DAAA02013377 Genomic DNA. No translation available.
    DAAA02013378 Genomic DNA. No translation available.
    BC105521 mRNA. Translation: AAI05522.1 .
    RefSeqi NP_001039895.1. NM_001046430.2.
    UniGenei Bt.29017.

    3D structure databases

    ProteinModelPortali Q2HJE4.
    SMRi Q2HJE4. Positions 1-120.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9913.ENSBTAP00000037402.

    Protein family/group databases

    MEROPSi C19.022.

    Proteomic databases

    PRIDEi Q2HJE4.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSBTAT00000037574 ; ENSBTAP00000037402 ; ENSBTAG00000010428 .
    GeneIDi 538284.
    KEGGi bta:538284.

    Organism-specific databases

    CTDi 9958.

    Phylogenomic databases

    eggNOGi COG5560.
    GeneTreei ENSGT00670000097750.
    HOGENOMi HOG000264375.
    HOVERGENi HBG000864.
    InParanoidi Q2HJE4.
    KOi K11835.
    OMAi RYVKTCT.
    OrthoDBi EOG77Q4VW.
    TreeFami TF106276.

    Enzyme and pathway databases

    Reactomei REACT_225632. Downregulation of TGF-beta receptor signaling.

    Miscellaneous databases

    NextBioi 20877322.

    Family and domain databases

    Gene3Di 3.30.2230.10. 1 hit.
    InterProi IPR006615. Pept_C19_DUSP.
    IPR018200. Pept_C19ubi-hydrolase_C_CS.
    IPR001394. Peptidase_C19_UCH.
    IPR013792. RNA3'P_cycl/enolpyr_Trfase_a/b.
    IPR028135. Ub_USP-typ.
    IPR029071. Ubiquitin-rel_dom.
    IPR028889. UCH/PAN2.
    [Graphical view ]
    Pfami PF06337. DUSP. 1 hit.
    PF14836. Ubiquitin_3. 1 hit.
    PF00443. UCH. 1 hit.
    [Graphical view ]
    SMARTi SM00695. DUSP. 1 hit.
    [Graphical view ]
    SUPFAMi SSF143791. SSF143791. 1 hit.
    SSF54236. SSF54236. 1 hit.
    SSF55205. SSF55205. 1 hit.
    PROSITEi PS51283. DUSP. 1 hit.
    PS00972. USP_1. 1 hit.
    PS00973. USP_2. 1 hit.
    PS50235. USP_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: Hereford.
    2. NIH - Mammalian Gene Collection (MGC) project
      Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: Hereford.
      Tissue: Uterus.

    Entry informationi

    Entry nameiUBP15_BOVIN
    AccessioniPrimary (citable) accession number: Q2HJE4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 28, 2012
    Last sequence update: March 21, 2006
    Last modified: October 1, 2014
    This is version 69 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