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Q2HJE4

- UBP15_BOVIN

UniProt

Q2HJE4 - UBP15_BOVIN

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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

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.

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 – 2691Nucleophile By similarity
Active sitei862 – 8621Proton acceptor By similarity

GO - Molecular functioni

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

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
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

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

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine By similarity
Modified residuei932 – 9321Phosphoserine By similarity
Modified residuei936 – 9361Phosphoserine By similarity

Post-translational modificationi

Phosphorylated. Phosphorylation protects against ubiquitination and subsequent degradation by the proteasome 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.

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000037402.

Structurei

3D structure databases

ProteinModelPortaliQ2HJE4.
SMRiQ2HJE4. Positions 1-120.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini7 – 118112DUSP
Add
BLAST
Domaini260 – 904645USP
Add
BLAST

Sequence similaritiesi

Belongs to the peptidase C19 family.
Contains 1 DUSP domain.
Contains 1 USP domain.

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: September 3, 2014
This is version 68 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

Similar proteinsi