ID   UBP15_BOVIN             Reviewed;         952 AA.
AC   Q2HJE4;
DT   28-NOV-2012, integrated into UniProtKB/Swiss-Prot.
DT   21-MAR-2006, sequence version 1.
DT   24-JAN-2024, entry version 122.
DE   RecName: Full=Ubiquitin carboxyl-terminal hydrolase 15;
DE            EC=3.4.19.12 {ECO:0000250|UniProtKB:Q9Y4E8};
DE   AltName: Full=Deubiquitinating enzyme 15;
DE   AltName: Full=Ubiquitin thioesterase 15;
DE   AltName: Full=Ubiquitin-specific-processing protease 15;
GN   Name=USP15;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Hereford;
RX   PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42;
RA   Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C., Puiu D.,
RA   Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G.,
RA   Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.;
RT   "A whole-genome assembly of the domestic cow, Bos taurus.";
RL   Genome Biol. 10:R42.01-R42.10(2009).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Uterus;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
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:0000250|UniProtKB:Q9Y4E8};
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:0000250|UniProtKB:Q9Y4E8}. Nucleus
CC       {ECO:0000250|UniProtKB:Q9Y4E8}. Mitochondrion
CC       {ECO:0000250|UniProtKB:Q9Y4E8}.
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; DAAA02013374; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; DAAA02013375; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; DAAA02013376; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; DAAA02013377; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; DAAA02013378; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC105521; AAI05522.1; -; mRNA.
DR   RefSeq; NP_001039895.1; NM_001046430.2.
DR   AlphaFoldDB; Q2HJE4; -.
DR   BMRB; Q2HJE4; -.
DR   SMR; Q2HJE4; -.
DR   STRING; 9913.ENSBTAP00000064906; -.
DR   MEROPS; C19.022; -.
DR   PaxDb; 9913-ENSBTAP00000037402; -.
DR   Ensembl; ENSBTAT00000078328.1; ENSBTAP00000056662.1; ENSBTAG00000010428.6.
DR   GeneID; 538284; -.
DR   KEGG; bta:538284; -.
DR   CTD; 9958; -.
DR   VEuPathDB; HostDB:ENSBTAG00000010428; -.
DR   VGNC; VGNC:36713; USP15.
DR   eggNOG; KOG1870; Eukaryota.
DR   GeneTree; ENSGT00940000154932; -.
DR   HOGENOM; CLU_001060_7_1_1; -.
DR   InParanoid; Q2HJE4; -.
DR   TreeFam; TF106276; -.
DR   Reactome; R-BTA-5689880; Ub-specific processing proteases.
DR   Proteomes; UP000009136; Chromosome 5.
DR   Bgee; ENSBTAG00000010428; Expressed in spermatid and 108 other cell types or tissues.
DR   ExpressionAtlas; Q2HJE4; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB.
DR   GO; GO:0030509; P:BMP signaling pathway; 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:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:1990167; P:protein K27-linked deubiquitination; ISS:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0140673; P:transcription elongation-coupled chromatin remodeling; ISS:UniProtKB.
DR   CDD; cd02674; Peptidase_C19R; 1.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 2.
DR   Gene3D; 3.30.2230.10; DUSP-like; 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   PANTHER; PTHR21646; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR   PANTHER; PTHR21646:SF28; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 15; 1.
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; SSF54001; Cysteine proteinases; 1.
DR   SUPFAM; SSF143791; DUSP-like; 1.
DR   SUPFAM; SSF55205; EPT/RTPC-like; 1.
DR   SUPFAM; SSF54236; Ubiquitin-like; 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   2: Evidence at transcript 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_0000420489"
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          598..666
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        604..618
FT                   /note="Polar residues"
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..666
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         226
FT                   /note="Phosphothreonine"
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;  109442 MW;  A4151AAE16BE8B53 CRC64;
     MAEGGAADLD IQRSDIATLL KTSLRKGDTW YLVDSRWFKQ WKKYVGFDSW DKYQMGDQNV
     YPGPIDNSGL LRDGDAQSLK EHLIDELDYI LLPTEGWNKL VSWYTLMEGQ EPIARKVVEQ
     GMFVKHCKVE VYLTELKLCE NGNMNNVVTR RFSKADTIDT IEKEIRKIFN IPDEKETRLW
     NKYMSNTFEP LNKPDSTIQD AGLYQGQVLV IEQKNEDGTW PRGPSTPNVK NSNYCLPSYT
     AYKNYDYSEP GRNNEQPGLC GLSNLGNTCF MNSAFQCLSN TPPLTEYFLN DKYQEELNFD
     NPLGMRGEIA KSYAELIKQM WSGKYSYVTP RAFKTQVGRF APQFSGYQQQ DCQELLAFLL
     DGLHEDLNRI RKKPYIQLKD ADGRPDKVVA EEAWENHLKR NDSIIVDIFH GLFKSTLVCP
     ECAKISVTFD PFCYLTLPLP MKKERTLEVY LVRMDPLTKP MQYKVVVPKI GNILDLCTAL
     SLLSGVPADK MIVTDIYNHR FHRIFAMDEN LSSIMERDDI YVFEININRT EDTEHVIIPV
     CLREKFRHSS YTHHTGSSLF GQPFLMAVPR NNTEDKLYNL LLVRMCRYVK ISTDTEDTEG
     SLHCCKDQNI NGNGPNGIHE EGSPSEMETD EPDDESSQDQ ELPSENENSQ SEDSVGGDND
     SENGLCTEET CRGQLTGHKK RLFTFQFNNL GNTDINYIKD DTRHIRFDDR QLRLDERSFL
     ALDWDPDLKK RYFDENAAED FEKHESVEYK PPKKPFVKLK DCIELFTTKE KLGAEDPWYC
     PNCKEHQQAT KKLDLWSLPP VLVVHLKRFS YSRYMRDKLD TLVDFPINDL DMSEFLINPN
     AGPCRYNLIA VSNHYGGMGG GHYTAFAKNK DDGKWYYFDD SSVSTASEDQ IVSKAAYVLF
     YQRQDTFSGT GFFPLDRETK GASAATGIPL ESDEDSNDND NDIENENCMH TN
//