UBP15_RAT
ID UBP15_RAT Reviewed; 952 AA.
AC Q9R085; E9PSP9;
DT 28-NOV-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 15;
DE EC=3.4.19.12 {ECO:0000269|PubMed:10880343};
DE AltName: Full=Deubiquitinating enzyme 15;
DE AltName: Full=Ubiquitin carboxyl-terminal hydrolase of 109 kDa;
DE AltName: Full=Ubiquitin thioesterase 15;
DE AltName: Full=Ubiquitin-specific-processing protease 15;
GN Name=Usp15; Synonyms=ubp109;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Skeletal muscle;
RX PubMed=10880343; DOI=10.1042/0264-6021:3490443;
RA Park K.C., Choi E.J., Min S.W., Chung S.S., Kim H., Suzuki T., Tanaka K.,
RA Chung C.H.;
RT "Tissue-specificity, functional characterization and subcellular
RT localization of a rat ubiquitin-specific processing protease, UBP109, whose
RT mRNA expression is developmentally regulated.";
RL Biochem. J. 349:443-453(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
CC -!- FUNCTION: Hydrolase that removes conjugated ubiquitin from target
CC proteins and regulates various pathways such as the TGF-beta receptor
CC signaling, NF-kappa-B and RNF41/NRDP1-PRKN pathways. Acts as a key
CC regulator of TGF-beta receptor signaling pathway, but the precise
CC mechanism is still unclear: according to a report, acts by promoting
CC deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2 and/or
CC SMAD3), thereby alleviating inhibition of R-SMADs and promoting
CC activation of TGF-beta target genes. According to another reports,
CC regulates the TGF-beta receptor signaling pathway by mediating
CC deubiquitination and stabilization of TGFBR1, leading to an enhanced
CC TGF-beta signal. Able to mediate deubiquitination of monoubiquitinated
CC substrates, 'Lys-27'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitin
CC chains. May also regulate gene expression and/or DNA repair through the
CC deubiquitination of histone H2B. Acts as an inhibitor of mitophagy by
CC counteracting the action of parkin (PRKN): hydrolyzes cleavage of 'Lys-
CC 48'- and 'Lys-63'-linked polyubiquitin chains attached by parkin on
CC target proteins such as MFN2, thereby reducing parkin's ability to
CC drive mitophagy. Acts as an associated component of COP9 signalosome
CC complex (CSN) and regulates different pathways via this association:
CC regulates NF-kappa-B by mediating deubiquitination of NFKBIA and
CC deubiquitinates substrates bound to VCP. Involved in endosome
CC organization by mediating deubiquitination of SQSTM1: ubiquitinated
CC SQSTM1 forms a molecular bridge that restrains cognate vesicles in the
CC perinuclear region and its deubiquitination releases target vesicles
CC for fast transport into the cell periphery. Acts as a negative
CC regulator of antifungal immunity by mediating 'Lys-27'-linked
CC deubiquitination of CARD9, thereby inactivating CARD9.
CC {ECO:0000250|UniProtKB:Q9Y4E8}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC residue protein attached to proteins as an intracellular targeting
CC signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:10880343};
CC -!- SUBUNIT: A homodimer structure has been reported; however it is unclear
CC whether the protein form a homodimer in vivo. Identified in a complex
CC with the COP9 signalosome complex (CSN). Interacts with SMAD1, SMAD2
CC and SMAD3; the interaction is direct. Forms a complex with SMURF2 and
CC SMAD7. Interacts with TGFBR1. Interacts with SART3; the interaction is
CC direct. May interact with RNF20 and RNF40. May interact with PRKN.
CC Interacts with INCA1. {ECO:0000250|UniProtKB:Q9Y4E8}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10880343}. Nucleus
CC {ECO:0000269|PubMed:10880343}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q9Y4E8}.
CC -!- TISSUE SPECIFICITY: Highly expressed in testis and spleen, and at lower
CC level in other tissues. {ECO:0000269|PubMed:10880343}.
CC -!- PTM: Phosphorylated. Phosphorylation protects against ubiquitination
CC and subsequent degradation by the proteasome.
CC {ECO:0000250|UniProtKB:Q9Y4E8}.
CC -!- PTM: Ubiquitinated, leading to degradation by the proteasome.
CC {ECO:0000250|UniProtKB:Q9Y4E8}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
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DR EMBL; AF106657; AAF14188.1; -; mRNA.
DR RefSeq; NP_660185.1; NM_145184.1.
DR AlphaFoldDB; Q9R085; -.
DR BMRB; Q9R085; -.
DR SMR; Q9R085; -.
DR BioGRID; 251185; 1.
DR IntAct; Q9R085; 1.
DR STRING; 10116.ENSRNOP00000034485; -.
DR MEROPS; C19.022; -.
DR iPTMnet; Q9R085; -.
DR PhosphoSitePlus; Q9R085; -.
DR jPOST; Q9R085; -.
DR PaxDb; Q9R085; -.
DR PRIDE; Q9R085; -.
DR GeneID; 171329; -.
DR KEGG; rno:171329; -.
DR CTD; 9958; -.
DR RGD; 628795; Usp15.
DR eggNOG; KOG1870; Eukaryota.
DR InParanoid; Q9R085; -.
DR OrthoDB; 1283205at2759; -.
DR PhylomeDB; Q9R085; -.
DR Reactome; R-RNO-5689880; Ub-specific processing proteases.
DR PRO; PR:Q9R085; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:1990380; F:Lys48-specific deubiquitinase activity; ISO:RGD.
DR GO; GO:0046332; F:SMAD binding; ISO:RGD.
DR GO; GO:0005160; F:transforming growth factor beta receptor binding; ISO:RGD.
DR GO; GO:0061649; F:ubiquitin modification-dependent histone binding; ISO:RGD.
DR GO; GO:0030509; P:BMP signaling pathway; ISS:UniProtKB.
DR GO; GO:0035616; P:histone H2B conserved C-terminal lysine deubiquitination; ISS:UniProtKB.
DR GO; GO:0035520; P:monoubiquitinated protein deubiquitination; ISS:UniProtKB.
DR GO; GO:1905035; P:negative regulation of antifungal innate immune response; ISS:UniProtKB.
DR GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; ISS:UniProtKB.
DR GO; GO:1900246; P:positive regulation of RIG-I signaling pathway; ISO:RGD.
DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
DR GO; GO:1990167; P:protein K27-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR Gene3D; 3.30.2230.10; -; 1.
DR InterPro; IPR035927; DUSP-like_sf.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR006615; Pept_C19_DUSP.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR013792; RNA3'P_cycl/enolpyr_Trfase_a/b.
DR InterPro; IPR028135; Ub_USP-typ.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR InterPro; IPR029346; USP_C.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR Pfam; PF06337; DUSP; 1.
DR Pfam; PF14836; Ubiquitin_3; 1.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF14533; USP7_C2; 1.
DR SMART; SM00695; DUSP; 1.
DR SUPFAM; SSF143791; SSF143791; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF55205; SSF55205; 1.
DR PROSITE; PS51283; DUSP; 1.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Hydrolase; Mitochondrion; Nucleus; Phosphoprotein;
KW Protease; Reference proteome; Thiol protease; Ubl conjugation;
KW Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E8"
FT CHAIN 2..952
FT /note="Ubiquitin carboxyl-terminal hydrolase 15"
FT /id="PRO_0000420490"
FT DOMAIN 7..118
FT /note="DUSP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00613"
FT DOMAIN 260..904
FT /note="USP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT REGION 2..223
FT /note="Mediates interaction with SART3"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E8"
FT REGION 597..665
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 923..952
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 626..641
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 642..665
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 269
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT ACT_SITE 862
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E8"
FT MOD_RES 573
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8R5H1"
FT MOD_RES 932
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E8"
FT MOD_RES 936
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E8"
SQ SEQUENCE 952 AA; 109255 MW; 6BE7449FD93CF658 CRC64;
MAEGGAADLD TQRSDIATLL KTSLRKGDTW YLVDSRWFKQ WKKYVGFDSW DKYQMGDQNV
YPGPIDNSGL LKDGDAQSLK EHLIDELDYI LLPTEGWNKL VSWYTLMEGQ EPIARKVVEQ
GMFVKHCKVE VYLTELKLCE NGNMNNVVTR RFSKADTIDT IEKEIRKIFN IPDEKEARLW
NKYMSNTFEP LNKPDSTIQD AGLYQGQVLV IEQKNEDGTW PRGPSAPNVK NSNYCLPSYT
AYKNYDYSEP GRNNEQPGLC GLSNLGNTCF MNSAIQCLSN TPPLTEYFLN DKYQEELNFD
NPLGMRGEIA KSYAELIKQM WSGKFSYVTP RAFKTQVGRF APQFSGYQQQ DCQELLAFLL
DGLHEDLNRI RKKPYIQLKD ADGRPDKVVA EEAWENHLKR NDSIIVDIFH GLFKSTLVCP
ECAKISVTFD PFCYLTLPLP MKKERSLEVY LVRMDPLAKP MQYKVIVPKI GNILDLCTAL
SALSGVPADK MIVTDIYNHR FHRIFAMDEN LSSIMERDDI YVFEININRT EDTEHVVIPV
CLREKFRHSS YTHHTGSSLF GQPFLMAVPR NNTEDKLYNL LLLRMCRYVK MSTETEETDG
PLRCCEDQNI NGNGPNGIHE EGSPSEMETD EPDDESSQDQ ELPSENENSQ SEDSVGGDND
SENGLCTEET CKGRLTGHKK RLFTFQFNNL GNTDINYIKD DTRHIRFDDR QLRLDERSFL
ALDWDPDLKK RYFDENAAED FEKHESVEYK PPKRPFVKLK DCIELFTTKE KLGAEDPWYC
PNCKEHQQAT KKLDLWSLPP VLVVHLKRFS YSRYMRDKLD TLVDFPISDL DMSEFLINPN
AGPCRYNLIA VSNHYGGMGG GHYTAFAKNK DDGKWYYFDD SSVSSASEDQ IVSKAAYVLF
YQRQDTFSGT GFFPLDRETK GASAATGVPL ESDEDSNDND NDLENENCMH TN
