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Protein

Ubiquitin carboxyl-terminal hydrolase 15

Gene

USP15

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: -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, NF-kappa-B and RNF41/NRDP1-PRKN 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 inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes cleavage of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains attached by parkin on target proteins such as MFN2, thereby reducing parkin's ability to drive mitophagy. 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. Involved in endosome organization by mediating deubiquitination of SQSTM1: ubiquitinated SQSTM1 forms a molecular bridge that restrains cognate vesicles in the perinuclear region and its deubiquitination releases target vesicles for fast transport into the cell periphery.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).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei269NucleophilePROSITE-ProRule annotation1
Active sitei862Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-BTA-5689880 Ub-specific processing proteases

Protein family/group databases

MEROPSiC19.022

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase 15 (EC:3.4.19.12By similarity)
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
Proteomesi
  • UP000009136 Componenti: Chromosome 5

Organism-specific databases

VGNCiVGNC:36713 USP15

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00004204892 – 952Ubiquitin carboxyl-terminal hydrolase 15Add BLAST951

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei226PhosphothreonineBy similarity1
Modified residuei573PhosphothreonineBy similarity1
Modified residuei932PhosphoserineBy similarity1
Modified residuei936PhosphoserineBy similarity1

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

PaxDbiQ2HJE4
PRIDEiQ2HJE4

Expressioni

Gene expression databases

BgeeiENSBTAG00000010428

Interactioni

Subunit structurei

A homodimer structure has been reported; however it is unclear whether the protein form a homodimer in vivo. 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. May interact with PRKN.By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000037402

Structurei

3D structure databases

ProteinModelPortaliQ2HJE4
SMRiQ2HJE4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini7 – 118DUSPPROSITE-ProRule annotationAdd BLAST112
Domaini260 – 904USPPROSITE-ProRule annotationAdd BLAST645

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 223Mediates interaction with SART3By similarityAdd BLAST222

Sequence similaritiesi

Belongs to the peptidase C19 family.Curated

Phylogenomic databases

eggNOGiKOG1870 Eukaryota
COG5560 LUCA
GeneTreeiENSGT00670000097750
HOGENOMiHOG000264375
HOVERGENiHBG000864
InParanoidiQ2HJE4
KOiK21343
OMAiCTEETCK
OrthoDBiEOG091G0157
TreeFamiTF106276

Family and domain databases

InterProiView protein in InterPro
IPR035927 DUSP-like_sf
IPR006615 Pept_C19_DUSP
IPR001394 Peptidase_C19_UCH
IPR013792 RNA3'P_cycl/enolpyr_Trfase_a/b
IPR028135 Ub_USP-typ
IPR029071 Ubiquitin-like_domsf
IPR028134 USP4
IPR029346 USP_C
IPR018200 USP_CS
IPR028889 USP_dom
PANTHERiPTHR43913 PTHR43913, 2 hits
PfamiView protein in Pfam
PF06337 DUSP, 1 hit
PF14836 Ubiquitin_3, 1 hit
PF00443 UCH, 1 hit
PF14533 USP7_C2, 1 hit
SMARTiView protein in SMART
SM00695 DUSP, 1 hit
SUPFAMiSSF143791 SSF143791, 1 hit
SSF54236 SSF54236, 1 hit
SSF55205 SSF55205, 1 hit
PROSITEiView protein in PROSITE
PS51283 DUSP, 1 hit
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit

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 21, 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

Similar proteinsi

Entry informationi

Entry nameiUBP15_BOVIN
AccessioniPrimary (citable) accession number: Q2HJE4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2012
Last sequence update: March 21, 2006
Last modified: March 28, 2018
This is version 94 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health