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Protein

Ubiquitin carboxyl-terminal hydrolase 15

Gene

USP15

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: 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. May also regulate gene expression and/or DNA repair through the deubiquitination of histone H2B. 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 – 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

GO - Biological processi

  1. BMP signaling pathway Source: UniProtKB
  2. histone H2B conserved C-terminal lysine deubiquitination Source: UniProtKB
  3. monoubiquitinated protein deubiquitination Source: UniProtKB
  4. pathway-restricted SMAD protein phosphorylation Source: UniProtKB
  5. proteasome-mediated ubiquitin-dependent protein catabolic process Source: GO_Central
  6. protein deubiquitination Source: UniProtKB
  7. regulation of proteasomal protein catabolic process Source: GO_Central
  8. transforming growth factor beta receptor signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiREACT_281949. 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 Componenti: 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 – 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. Interacts with SART3; the interaction is direct. May interact with RNF20 and RNF40.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

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 223222Mediates interaction with SART3By similarityAdd
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.
OMAiIYVFEIA.
OrthoDBiEOG77Q4VW.
TreeFamiTF106276.

Family and domain databases

Gene3Di3.30.2230.10. 1 hit.
InterProiIPR006615. Pept_C19_DUSP.
IPR001394. Peptidase_C19_UCH.
IPR013792. RNA3'P_cycl/enolpyr_Trfase_a/b.
IPR028135. Ub_USP-typ.
IPR029071. Ubiquitin-rel_dom.
IPR018200. USP_CS.
IPR028889. USP_dom.
[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

« Hide

        10         20         30         40         50
MAEGGAADLD IQRSDIATLL KTSLRKGDTW YLVDSRWFKQ WKKYVGFDSW
60 70 80 90 100
DKYQMGDQNV YPGPIDNSGL LRDGDAQSLK EHLIDELDYI LLPTEGWNKL
110 120 130 140 150
VSWYTLMEGQ EPIARKVVEQ GMFVKHCKVE VYLTELKLCE NGNMNNVVTR
160 170 180 190 200
RFSKADTIDT IEKEIRKIFN IPDEKETRLW NKYMSNTFEP LNKPDSTIQD
210 220 230 240 250
AGLYQGQVLV IEQKNEDGTW PRGPSTPNVK NSNYCLPSYT AYKNYDYSEP
260 270 280 290 300
GRNNEQPGLC GLSNLGNTCF MNSAFQCLSN TPPLTEYFLN DKYQEELNFD
310 320 330 340 350
NPLGMRGEIA KSYAELIKQM WSGKYSYVTP RAFKTQVGRF APQFSGYQQQ
360 370 380 390 400
DCQELLAFLL DGLHEDLNRI RKKPYIQLKD ADGRPDKVVA EEAWENHLKR
410 420 430 440 450
NDSIIVDIFH GLFKSTLVCP ECAKISVTFD PFCYLTLPLP MKKERTLEVY
460 470 480 490 500
LVRMDPLTKP MQYKVVVPKI GNILDLCTAL SLLSGVPADK MIVTDIYNHR
510 520 530 540 550
FHRIFAMDEN LSSIMERDDI YVFEININRT EDTEHVIIPV CLREKFRHSS
560 570 580 590 600
YTHHTGSSLF GQPFLMAVPR NNTEDKLYNL LLVRMCRYVK ISTDTEDTEG
610 620 630 640 650
SLHCCKDQNI NGNGPNGIHE EGSPSEMETD EPDDESSQDQ ELPSENENSQ
660 670 680 690 700
SEDSVGGDND SENGLCTEET CRGQLTGHKK RLFTFQFNNL GNTDINYIKD
710 720 730 740 750
DTRHIRFDDR QLRLDERSFL ALDWDPDLKK RYFDENAAED FEKHESVEYK
760 770 780 790 800
PPKKPFVKLK DCIELFTTKE KLGAEDPWYC PNCKEHQQAT KKLDLWSLPP
810 820 830 840 850
VLVVHLKRFS YSRYMRDKLD TLVDFPINDL DMSEFLINPN AGPCRYNLIA
860 870 880 890 900
VSNHYGGMGG GHYTAFAKNK DDGKWYYFDD SSVSTASEDQ IVSKAAYVLF
910 920 930 940 950
YQRQDTFSGT GFFPLDRETK GASAATGIPL ESDEDSNDND NDIENENCMH

TN
Length:952
Mass (Da):109,442
Last modified:March 20, 2006 - v1
Checksum:iA4151AAE16BE8B53
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000037402.

Protein family/group databases

MEROPSiC19.022.

Proteomic databases

PRIDEiQ2HJE4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi9958.

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiREACT_281949. Downregulation of TGF-beta receptor signaling.

Miscellaneous databases

NextBioi20877322.

Family and domain databases

Gene3Di3.30.2230.10. 1 hit.
InterProiIPR006615. Pept_C19_DUSP.
IPR001394. Peptidase_C19_UCH.
IPR013792. RNA3'P_cycl/enolpyr_Trfase_a/b.
IPR028135. Ub_USP-typ.
IPR029071. Ubiquitin-rel_dom.
IPR018200. USP_CS.
IPR028889. USP_dom.
[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]
ProtoNetiSearch...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Hereford.
  2. NIH - Mammalian Gene Collection (MGC) project
    Submitted (AUG-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 27, 2012
Last sequence update: March 20, 2006
Last modified: March 31, 2015
This is version 74 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

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.