ID   UBP15_XENTR             Reviewed;         982 AA.
AC   F6Z5C0; B2GUK6; F6ZNA0;
DT   28-NOV-2012, integrated into UniProtKB/Swiss-Prot.
DT   28-NOV-2012, sequence version 2.
DT   03-AUG-2022, entry version 60.
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   Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX   NCBI_TaxID=8364;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=20431018; DOI=10.1126/science.1183670;
RA   Hellsten U., Harland R.M., Gilchrist M.J., Hendrix D., Jurka J.,
RA   Kapitonov V., Ovcharenko I., Putnam N.H., Shu S., Taher L., Blitz I.L.,
RA   Blumberg B., Dichmann D.S., Dubchak I., Amaya E., Detter J.C., Fletcher R.,
RA   Gerhard D.S., Goodstein D., Graves T., Grigoriev I.V., Grimwood J.,
RA   Kawashima T., Lindquist E., Lucas S.M., Mead P.E., Mitros T., Ogino H.,
RA   Ohta Y., Poliakov A.V., Pollet N., Robert J., Salamov A., Sater A.K.,
RA   Schmutz J., Terry A., Vize P.D., Warren W.C., Wells D., Wills A.,
RA   Wilson R.K., Zimmerman L.B., Zorn A.M., Grainger R., Grammer T.,
RA   Khokha M.K., Richardson P.M., Rokhsar D.S.;
RT   "The genome of the Western clawed frog Xenopus tropicalis.";
RL   Science 328:633-636(2010).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Embryo;
RG   NIH - Xenopus Gene Collection (XGC) project;
RL   Submitted (APR-2008) 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 and NF-kappa-B pathways. Acts as a key regulator of TGF-beta
CC       receptor signaling pathway, but the precise mechanism is still unclear:
CC       according to a report, acts by promoting deubiquitination of
CC       monoubiquitinated R-SMADs, thereby alleviating inhibition of R-SMADs
CC       and promoting activation of TGF-beta target genes. According to another
CC       reports, regulates the TGF-beta receptor signaling pathway by mediating
CC       deubiquitination and stabilization of tgfbr1, leading to an enhanced
CC       TGF-beta signal. May also regulate gene expression and/or DNA repair
CC       through the deubiquitination of histone H2B. Involved in endosome
CC       organization by mediating deubiquitination of rnf26 target(s),
CC       releasing vesicles that are restrained in the perinuclear region.
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   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9Y4E8}. Nucleus
CC       {ECO:0000250|UniProtKB:Q9Y4E8}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=F6Z5C0-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=F6Z5C0-2; Sequence=VSP_044519;
CC   -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
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DR   EMBL; AAMC01103598; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AAMC01103599; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AAMC01103600; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AAMC01103601; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC166318; AAI66318.1; -; mRNA.
DR   RefSeq; NP_001121498.1; NM_001128026.1.
DR   RefSeq; XP_012814097.1; XM_012958643.2. [F6Z5C0-1]
DR   RefSeq; XP_012814098.1; XM_012958644.2. [F6Z5C0-2]
DR   AlphaFoldDB; F6Z5C0; -.
DR   SMR; F6Z5C0; -.
DR   STRING; 8364.ENSXETP00000061641; -.
DR   MEROPS; C19.022; -.
DR   Ensembl; ENSXETT00000066127; ENSXETP00000061641; ENSXETG00000021472.
DR   GeneID; 100158604; -.
DR   KEGG; xtr:100158604; -.
DR   CTD; 9958; -.
DR   Xenbase; XB-GENE-1008519; usp15.
DR   eggNOG; KOG1870; Eukaryota.
DR   InParanoid; F6Z5C0; -.
DR   OrthoDB; 1283205at2759; -.
DR   Reactome; R-XTR-5689880; Ub-specific processing proteases.
DR   Proteomes; UP000008143; Chromosome 3.
DR   Proteomes; UP000790000; Unplaced.
DR   Bgee; ENSXETG00000021472; Expressed in heart and 12 other tissues.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
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:0035616; P:histone H2B conserved C-terminal lysine deubiquitination; ISS:UniProtKB.
DR   GO; GO:0035520; P:monoubiquitinated protein deubiquitination; ISS:UniProtKB.
DR   GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; ISS:UniProtKB.
DR   GO; GO:0016579; P:protein 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; 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   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   Alternative splicing; Cytoplasm; Hydrolase; Nucleus; Protease;
KW   Reference proteome; Thiol protease; Ubl conjugation pathway.
FT   CHAIN           1..982
FT                   /note="Ubiquitin carboxyl-terminal hydrolase 15"
FT                   /id="PRO_0000420491"
FT   DOMAIN          7..118
FT                   /note="DUSP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00613"
FT   DOMAIN          288..933
FT                   /note="USP"
FT   REGION          623..695
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          950..982
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        654..669
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        670..695
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        297
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   ACT_SITE        891
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   VAR_SEQ         227..256
FT                   /note="KSSGIPNFSTLPKISPSSLSNNYNNFNSRI -> N (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_044519"
FT   CONFLICT        626
FT                   /note="N -> I (in Ref. 2; AAI66318)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        978..982
FT                   /note="CMHTN -> YLEKL (in Ref. 2; AAI66318)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   982 AA;  112689 MW;  2B4F415FE1199C24 CRC64;
     MAEGGVVDLE TQRSEVSALL KTPLRRGDTW YLIDSRWFKQ WKKYVGFDSW DKYQMGDQNV
     YPGPIDNSGL LKDTDTQSLK EHLIDELDYI LLPTEGWNKL VSWYSVVESQ QPIARKVVEQ
     GMFVKHCKVE VYLTELKLCE NGNMNNVVTR RFSKADTIDM IEKEMRTIFS IPDEKETRLW
     NKYMSNTFEP LNKPESTIQD AGLYQGQMLV IEQKNQEGQW PRGSMPKSSG IPNFSTLPKI
     SPSSLSNNYN NFNSRIMKNS NYCLPSYAAY KNYEYSEPGR HNEQPGLCGL SNLGNTCFMN
     SAIQCLSNTP PLTEYFLNDK YQDELNMDNP LGMRGEIAKS YAELIKQMWS GKYSYVTPRA
     FKTQVGRFAP QFSGYQQQDC QELLAFLLDG LHEDLNRIRK KPYIQLKDAD GRPDKVVAEE
     AWENHIKRND SIIVDIFHGL FKSTLVCPEC SKISVTFDPF CYLTLPLPMK KERALEVYLV
     RMDPLAKPMQ YKVIVPKIGN IMDLCTALSS LSGIAPEKMV VTDIYNHRFH RIFAMDENLS
     SIMERDDIYV FETSINRTED TEQVIIPVYL REKFRHTSYS HHHGSTLFGQ PFLITVPRNI
     TEDKLYNLLL LRMCRYVKAT NDTEENDGSL HCNKEHTVNG NGPNGIHEEG SPSEMETDEP
     DDESSQDQEL PSENENSQSE DSVGGDNDSE NGLCTEDTCK GQSVTGQKKR LFTFQFSNLG
     SSDITYIKDD TKYIRFDERQ LRLDERSYLA LDWDPKLKKK FFDENAAEDF EKHESVDFTP
     QKKAFMKLKD CIELFTTKEK LGAEDPWYCP NCKEHQQATK KLDLWSLPPV LVVHLKRFSY
     SRYMRDKLDT LVDFPISDLD MSTFLINPNA GPCCYNLIAV SNHYGGMGGG HYTAFAKNKD
     DGKWYYFDDS SVSTASEEQI VSKAAYVLFY QRQDTITGTG FFPLDKEVKQ GASAATGAPH
     ESDEESNEDE NDIENENCMH TN