UBP15_HUMAN
ID UBP15_HUMAN Reviewed; 981 AA.
AC Q9Y4E8; Q08AL5; Q9H8G9; Q9HCA6; Q9UNP0; Q9Y5B5;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 12-FEB-2003, sequence version 3.
DT 03-AUG-2022, entry version 210.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 15 {ECO:0000305};
DE EC=3.4.19.12 {ECO:0000269|PubMed:10444327, ECO:0000269|PubMed:16005295, ECO:0000269|PubMed:21947082, ECO:0000269|PubMed:22344298, ECO:0000269|PubMed:24852371, ECO:0000269|PubMed:27368102, ECO:0000269|PubMed:33093067};
DE AltName: Full=Deubiquitinating enzyme 15 {ECO:0000303|PubMed:10444327};
DE AltName: Full=Ubiquitin thioesterase 15 {ECO:0000303|PubMed:10444327};
DE AltName: Full=Ubiquitin-specific-processing protease 15 {ECO:0000303|PubMed:10444327};
DE AltName: Full=Unph-2 {ECO:0000303|Ref.9};
DE AltName: Full=Unph4 {ECO:0000303|Ref.1};
GN Name=USP15 {ECO:0000303|PubMed:10444327, ECO:0000312|HGNC:HGNC:12613};
GN Synonyms=KIAA0529 {ECO:0000303|PubMed:9628581};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RA Kim K.I., Nagase T., Chung C.H.;
RT "Identification and characterization of a new human deubiquitinating enzyme
RT Unph4.";
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Hair follicle dermal papilla;
RA Kim M.K., Kim Y.H., Seo J.M., Lee H.M., Chung H.J., Sohn M.Y., Hwang S.Y.,
RA Im S.U., Jung E.J., Lee J.H., Kim J.C.;
RT "A catalogue of genes in the human dermal papilla cells as identified by
RT expressed sequence tags.";
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4).
RC TISSUE=Brain, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 2-21; 475-482 AND 924-932, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Mammary carcinoma;
RA Bienvenut W.V., Matallanas D., Cooper W.N., Kolch W.;
RL Submitted (JUL-2007) to UniProtKB.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 19-981 (ISOFORM 3).
RC TISSUE=Fetal brain;
RA Kimura Y., Saya H., Nakao M.;
RT "Cloning and identification of human Unph-2.";
RL Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP IDENTIFICATION (ISOFORM 2), AND CATALYTIC ACTIVITY.
RX PubMed=10444327; DOI=10.1006/geno.1999.5879;
RA Baker R.T., Wang X.-W., Woollatt E., White J.A., Sutherland G.R.;
RT "Identification, functional characterization, and chromosomal localization
RT of USP15, a novel human ubiquitin-specific protease related to the UNP
RT oncoprotein, and a systematic nomenclature for human ubiquitin-specific
RT proteases.";
RL Genomics 59:264-274(1999).
RN [11]
RP ALTERNATIVE SPLICING (ISOFORMS 1 AND 2).
RX PubMed=12532266; DOI=10.1007/s00335-002-3035-0;
RA Angelats C., Wang X.-W., Jermiin L.S., Copeland N.G., Jenkins N.A.,
RA Baker R.T.;
RT "Isolation and characterization of the mouse ubiquitin-specific protease
RT Usp15.";
RL Mamm. Genome 14:31-46(2003).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF CYS-812, IDENTIFICATION IN A
RP COMPLEX WITH THE COP9 SIGNALOSOME, PHOSPHORYLATION, AND UBIQUITINATION.
RX PubMed=16005295; DOI=10.1016/j.cub.2005.05.059;
RA Hetfeld B.K., Helfrich A., Kapelari B., Scheel H., Hofmann K., Guterman A.,
RA Glickman M., Schade R., Kloetzel P.M., Dubiel W.;
RT "The zinc finger of the CSN-associated deubiquitinating enzyme USP15 is
RT essential to rescue the E3 ligase Rbx1.";
RL Curr. Biol. 15:1217-1221(2005).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-229, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [14]
RP FUNCTION.
RX PubMed=17318178; DOI=10.1038/sj.emboj.7601600;
RA Schweitzer K., Bozko P.M., Dubiel W., Naumann M.;
RT "CSN controls NF-kappaB by deubiquitinylation of IkappaBalpha.";
RL EMBO J. 26:1532-1541(2007).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-229; SER-961 AND SER-965, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [17]
RP FUNCTION.
RX PubMed=19826004; DOI=10.1074/jbc.m109.037952;
RA Cayli S., Klug J., Chapiro J., Frohlich S., Krasteva G., Orel L.,
RA Meinhardt A.;
RT "COP9 signalosome interacts ATP-dependently with p97/valosin-containing
RT protein (VCP) and controls the ubiquitination status of proteins bound to
RT p97/VCP.";
RL J. Biol. Chem. 284:34944-34953(2009).
RN [18]
RP FUNCTION, AND MUTAGENESIS OF CYS-812.
RX PubMed=19576224; DOI=10.1016/j.jmb.2009.06.066;
RA Huang X., Langelotz C., Hetfeld-Pechoc B.K., Schwenk W., Dubiel W.;
RT "The COP9 signalosome mediates beta-catenin degradation by deneddylation
RT and blocks adenomatous polyposis coli destruction via USP15.";
RL J. Mol. Biol. 391:691-702(2009).
RN [19]
RP FUNCTION (MICROBIAL INFECTION), MUTAGENESIS OF CYS-298, AND INTERACTION
RP WITH HUMAN PAPILLOMAVIRUS TYPE 16 PROTEIN E6 (MICROBIAL INFECTION).
RX PubMed=19553310; DOI=10.1128/jvi.00605-09;
RA Vos R.M., Altreuter J., White E.A., Howley P.M.;
RT "The ubiquitin-specific peptidase USP15 regulates human papillomavirus type
RT 16 E6 protein stability.";
RL J. Virol. 83:8885-8892(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-229, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-229; SER-242; SER-961 AND
RP SER-965, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [23]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH SMAD1;
RP SMAD2 AND SMAD3, AND MUTAGENESIS OF CYS-298.
RX PubMed=21947082; DOI=10.1038/ncb2346;
RA Inui M., Manfrin A., Mamidi A., Martello G., Morsut L., Soligo S., Enzo E.,
RA Moro S., Polo S., Dupont S., Cordenonsi M., Piccolo S.;
RT "USP15 is a deubiquitylating enzyme for receptor-activated SMADs.";
RL Nat. Cell Biol. 13:1368-1375(2011).
RN [24]
RP INTERACTION WITH INCA1.
RX PubMed=21750715; DOI=10.1371/journal.pone.0021505;
RA Zhang F., Baeumer N., Rode M., Ji P., Zhang T., Berdel W.E.,
RA Mueller-Tidow C.;
RT "The inhibitor of growth protein 5 (ING5) depends on INCA1 as a co-factor
RT for its antiproliferative effects.";
RL PLoS ONE 6:E21505-E21505(2011).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-229, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [27]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH TGFBR1; SMAD7 AND SMURF2,
RP AND MUTAGENESIS OF CYS-298.
RX PubMed=22344298; DOI=10.1038/nm.2619;
RA Eichhorn P.J., Rodon L., Gonzalez-Junca A., Dirac A., Gili M.,
RA Martinez-Saez E., Aura C., Barba I., Peg V., Prat A., Cuartas I.,
RA Jimenez J., Garcia-Dorado D., Sahuquillo J., Bernards R., Baselga J.,
RA Seoane J.;
RT "USP15 stabilizes TGF-beta receptor I and promotes oncogenesis through the
RT activation of TGF-beta signaling in glioblastoma.";
RL Nat. Med. 18:429-435(2012).
RN [28]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-226; SER-229 AND SER-242, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [30]
RP FUNCTION, INTERACTION WITH RNF20; RNF40 AND SART3, REGION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=24526689; DOI=10.1074/jbc.m114.551754;
RA Long L., Thelen J.P., Furgason M., Haj-Yahya M., Brik A., Cheng D.,
RA Peng J., Yao T.;
RT "The U4/U6 recycling factor SART3 has histone chaperone activity and
RT associates with USP15 to regulate H2B deubiquitination.";
RL J. Biol. Chem. 289:8916-8930(2014).
RN [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [32]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-298.
RX PubMed=27368102; DOI=10.1016/j.cell.2016.05.078;
RA Jongsma M.L., Berlin I., Wijdeven R.H., Janssen L., Janssen G.M.,
RA Garstka M.A., Janssen H., Mensink M., van Veelen P.A., Spaapen R.M.,
RA Neefjes J.;
RT "An ER-associated pathway defines endosomal architecture for controlled
RT cargo transport.";
RL Cell 166:152-166(2016).
RN [33]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH PRKN, SUBCELLULAR LOCATION,
RP AND MUTAGENESIS OF CYS-298.
RX PubMed=24852371; DOI=10.1093/hmg/ddu244;
RA Cornelissen T., Haddad D., Wauters F., Van Humbeeck C., Mandemakers W.,
RA Koentjoro B., Sue C., Gevaert K., De Strooper B., Verstreken P.,
RA Vandenberghe W.;
RT "The deubiquitinase USP15 antagonizes Parkin-mediated mitochondrial
RT ubiquitination and mitophagy.";
RL Hum. Mol. Genet. 23:5227-5242(2014).
RN [34]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF CYS-298.
RX PubMed=33093067; DOI=10.4049/immunohorizons.2000036;
RA Xu W., Rush J.S., Graham D.B., Cao Z., Xavier R.J.;
RT "USP15 deubiquitinates CARD9 to downregulate C-type lectin receptor-
RT mediated signaling.";
RL Immunohorizons 4:670-678(2020).
RN [35]
RP STRUCTURE BY NMR OF 1-120.
RX PubMed=16298993; DOI=10.1074/jbc.m510993200;
RA de Jong R.N., Ab E., Diercks T., Truffault V., Danieels M., Kaptein R.,
RA Folkers G.E.;
RT "Solution structure of the human ubiquitin-specific protease 15 DUSP
RT domain.";
RL J. Biol. Chem. 281:5026-5031(2006).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 1-222.
RX PubMed=21848306; DOI=10.1021/bi200726e;
RA Harper S., Besong T.M., Emsley J., Scott D.J., Dreveny I.;
RT "Structure of the USP15 N-terminal domains: a beta-hairpin mediates close
RT association between the DUSP and UBL domains.";
RL Biochemistry 50:7995-8004(2011).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-223.
RX PubMed=22001210; DOI=10.1016/j.febslet.2011.09.040;
RA Elliott P.R., Liu H., Pastok M.W., Grossmann G.J., Rigden D.J.,
RA Clague M.J., Urbe S., Barsukov I.L.;
RT "Structural variability of the ubiquitin specific protease DUSP-UBL double
RT domains.";
RL FEBS Lett. 585:3385-3390(2011).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 1-133.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the human ubiquitin-specific protease 15 DUSP
RT domain.";
RL Submitted (APR-2010) to the PDB data bank.
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 (PubMed:21947082,
CC PubMed:22344298, PubMed:24852371, PubMed:16005295, PubMed:17318178,
CC PubMed:19826004, PubMed:19576224). 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 (SMAD1, SMAD2 and/or SMAD3), thereby
CC alleviating inhibition of R-SMADs and promoting activation of TGF-beta
CC target genes (PubMed:21947082). According to another reports, regulates
CC the TGF-beta receptor signaling pathway by mediating deubiquitination
CC and stabilization of TGFBR1, leading to an enhanced TGF-beta signal
CC (PubMed:22344298). Able to mediate deubiquitination of
CC monoubiquitinated substrates, 'Lys-27'-, 'Lys-48'- and 'Lys-63'-linked
CC polyubiquitin chains (PubMed:33093067). May also regulate gene
CC expression and/or DNA repair through the deubiquitination of histone
CC H2B (PubMed:24526689). 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 (PubMed:24852371). Acts as an associated component of
CC COP9 signalosome complex (CSN) and regulates different pathways via
CC this association: regulates NF-kappa-B by mediating deubiquitination of
CC NFKBIA and deubiquitinates substrates bound to VCP (PubMed:16005295,
CC PubMed:17318178, PubMed:19826004, PubMed:19576224). Involved in
CC endosome organization by mediating deubiquitination of SQSTM1:
CC ubiquitinated SQSTM1 forms a molecular bridge that restrains cognate
CC vesicles in the perinuclear region and its deubiquitination releases
CC target vesicles for fast transport into the cell periphery
CC (PubMed:27368102). Acts as a negative regulator of antifungal immunity
CC by mediating 'Lys-27'-linked deubiquitination of CARD9, thereby
CC inactivating CARD9 (PubMed:33093067). {ECO:0000269|PubMed:16005295,
CC ECO:0000269|PubMed:17318178, ECO:0000269|PubMed:19576224,
CC ECO:0000269|PubMed:19826004, ECO:0000269|PubMed:21947082,
CC ECO:0000269|PubMed:22344298, ECO:0000269|PubMed:24526689,
CC ECO:0000269|PubMed:24852371, ECO:0000269|PubMed:27368102,
CC ECO:0000269|PubMed:33093067}.
CC -!- FUNCTION: (Microbial infection) Protects APC and human papillomavirus
CC type 16 protein E6 against degradation via the ubiquitin proteasome
CC pathway. {ECO:0000269|PubMed:19553310}.
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:10444327,
CC ECO:0000269|PubMed:16005295, ECO:0000269|PubMed:21947082,
CC ECO:0000269|PubMed:22344298, ECO:0000269|PubMed:27368102,
CC ECO:0000269|PubMed:33093067};
CC -!- SUBUNIT: A homodimer structure has been reported; however it is unclear
CC whether the protein form a homodimer in vivo (PubMed:22001210).
CC Identified in a complex with the COP9 signalosome complex (CSN)
CC (PubMed:16005295). Interacts with SMAD1, SMAD2 and SMAD3; the
CC interaction is direct (PubMed:21947082). Forms a complex with SMURF2
CC and SMAD7 (PubMed:22344298). Interacts with TGFBR1 (PubMed:22344298).
CC Interacts with SART3; the interaction is direct (PubMed:24526689). May
CC interact with RNF20 and RNF40 (PubMed:24526689). May interact with PRKN
CC (PubMed:24852371). Interacts with INCA1 (PubMed:21750715).
CC {ECO:0000269|PubMed:16005295, ECO:0000269|PubMed:21750715,
CC ECO:0000269|PubMed:21947082, ECO:0000269|PubMed:22001210,
CC ECO:0000269|PubMed:22344298, ECO:0000269|PubMed:24526689,
CC ECO:0000269|PubMed:24852371}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human papillomavirus type
CC 16 protein E6. {ECO:0000269|PubMed:19553310}.
CC -!- INTERACTION:
CC Q9Y4E8; Q9H257: CARD9; NbExp=4; IntAct=EBI-1043104, EBI-751319;
CC Q9Y4E8; Q2TAC2: CCDC57; NbExp=3; IntAct=EBI-1043104, EBI-2808286;
CC Q9Y4E8; Q0VD86: INCA1; NbExp=2; IntAct=EBI-1043104, EBI-6509505;
CC Q9Y4E8; Q9Y6D9: MAD1L1; NbExp=3; IntAct=EBI-1043104, EBI-742610;
CC Q9Y4E8; Q96EA4: SPDL1; NbExp=3; IntAct=EBI-1043104, EBI-715381;
CC Q9Y4E8; Q86TM6: SYVN1; NbExp=8; IntAct=EBI-1043104, EBI-947849;
CC Q9Y4E8; Q6ZNK6: TIFAB; NbExp=5; IntAct=EBI-1043104, EBI-26453465;
CC Q9Y4E8; P19474: TRIM21; NbExp=3; IntAct=EBI-1043104, EBI-81290;
CC Q9Y4E8; Q9BTM9: URM1; NbExp=2; IntAct=EBI-1043104, EBI-714589;
CC Q9Y4E8; Q9Y4E8: USP15; NbExp=5; IntAct=EBI-1043104, EBI-1043104;
CC Q9Y4E8-2; G5E9A7: DMWD; NbExp=3; IntAct=EBI-12041225, EBI-10976677;
CC Q9Y4E8-2; P57678: GEMIN4; NbExp=3; IntAct=EBI-12041225, EBI-356700;
CC Q9Y4E8-2; Q08379: GOLGA2; NbExp=3; IntAct=EBI-12041225, EBI-618309;
CC Q9Y4E8-2; Q9NYA3: GOLGA6A; NbExp=3; IntAct=EBI-12041225, EBI-11163335;
CC Q9Y4E8-2; P02545: LMNA; NbExp=3; IntAct=EBI-12041225, EBI-351935;
CC Q9Y4E8-2; Q9Y6D9: MAD1L1; NbExp=3; IntAct=EBI-12041225, EBI-742610;
CC Q9Y4E8-2; Q4G0R1: PIBF1; NbExp=3; IntAct=EBI-12041225, EBI-14066006;
CC Q9Y4E8-2; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-12041225, EBI-5235340;
CC Q9Y4E8-2; Q8IYF3-3: TEX11; NbExp=3; IntAct=EBI-12041225, EBI-11523345;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21947082,
CC ECO:0000269|PubMed:24526689}. Nucleus {ECO:0000269|PubMed:21947082,
CC ECO:0000269|PubMed:24526689}. Mitochondrion
CC {ECO:0000269|PubMed:24852371}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9Y4E8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y4E8-2; Sequence=VSP_005261;
CC Name=3;
CC IsoId=Q9Y4E8-3; Sequence=VSP_005260;
CC Name=4;
CC IsoId=Q9Y4E8-4; Sequence=VSP_045165, VSP_045166;
CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle, kidney, heart,
CC placenta, liver, thymus, lung, and ovary, with little or no expression
CC in other tissues.
CC -!- PTM: Phosphorylated. Phosphorylation protects against ubiquitination
CC and subsequent degradation by the proteasome.
CC {ECO:0000269|PubMed:16005295}.
CC -!- PTM: Ubiquitinated, leading to degradation by the proteasome.
CC {ECO:0000269|PubMed:16005295}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/USP15ID44585ch12q14.html";
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DR EMBL; AF106069; AAD52099.1; -; mRNA.
DR EMBL; AB011101; BAA25455.2; -; mRNA.
DR EMBL; AF153604; AAD41086.1; -; mRNA.
DR EMBL; AK023703; BAB14648.1; -; mRNA.
DR EMBL; AK292337; BAF85026.1; -; mRNA.
DR EMBL; AC048342; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC079035; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC117370; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC020688; AAH20688.1; -; mRNA.
DR EMBL; BC063454; AAH63454.1; -; mRNA.
DR EMBL; BC125123; AAI25124.1; -; mRNA.
DR EMBL; AF013990; AAG28973.1; -; mRNA.
DR CCDS; CCDS58250.1; -. [Q9Y4E8-4]
DR CCDS; CCDS58251.1; -. [Q9Y4E8-1]
DR CCDS; CCDS8963.1; -. [Q9Y4E8-2]
DR RefSeq; NP_001239007.1; NM_001252078.1. [Q9Y4E8-1]
DR RefSeq; NP_001239008.1; NM_001252079.1. [Q9Y4E8-4]
DR RefSeq; NP_006304.1; NM_006313.2. [Q9Y4E8-2]
DR PDB; 1W6V; NMR; -; A=1-120.
DR PDB; 3LMN; X-ray; 2.15 A; A/B=1-133.
DR PDB; 3PPA; X-ray; 2.35 A; A=6-223.
DR PDB; 3PV1; X-ray; 2.60 A; A/B=1-223.
DR PDB; 3T9L; X-ray; 1.50 A; A=1-222.
DR PDB; 4A3O; X-ray; 2.20 A; A/B=4-223.
DR PDB; 4A3P; X-ray; 1.40 A; A=6-223.
DR PDB; 5JJW; X-ray; 3.01 A; B=1-223.
DR PDB; 6CPM; X-ray; 2.01 A; C/D=275-862, C/D=873-934.
DR PDB; 6CRN; X-ray; 2.50 A; A/B/C/D=275-934.
DR PDB; 6DJ9; X-ray; 3.10 A; A/B/C/D/E/F=1-134.
DR PDB; 6GH9; X-ray; 2.09 A; A/B=284-468, A/B=786-951.
DR PDB; 6GHA; X-ray; 1.98 A; A=284-468, A=786-948.
DR PDB; 6ML1; X-ray; 1.90 A; A/B=275-862, A/B=873-934.
DR PDBsum; 1W6V; -.
DR PDBsum; 3LMN; -.
DR PDBsum; 3PPA; -.
DR PDBsum; 3PV1; -.
DR PDBsum; 3T9L; -.
DR PDBsum; 4A3O; -.
DR PDBsum; 4A3P; -.
DR PDBsum; 5JJW; -.
DR PDBsum; 6CPM; -.
DR PDBsum; 6CRN; -.
DR PDBsum; 6DJ9; -.
DR PDBsum; 6GH9; -.
DR PDBsum; 6GHA; -.
DR PDBsum; 6ML1; -.
DR AlphaFoldDB; Q9Y4E8; -.
DR BMRB; Q9Y4E8; -.
DR SMR; Q9Y4E8; -.
DR BioGRID; 115283; 377.
DR DIP; DIP-50239N; -.
DR IntAct; Q9Y4E8; 91.
DR MINT; Q9Y4E8; -.
DR STRING; 9606.ENSP00000280377; -.
DR BindingDB; Q9Y4E8; -.
DR ChEMBL; CHEMBL4523508; -.
DR MEROPS; C19.022; -.
DR GlyGen; Q9Y4E8; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y4E8; -.
DR MetOSite; Q9Y4E8; -.
DR PhosphoSitePlus; Q9Y4E8; -.
DR BioMuta; USP15; -.
DR DMDM; 28381406; -.
DR EPD; Q9Y4E8; -.
DR jPOST; Q9Y4E8; -.
DR MassIVE; Q9Y4E8; -.
DR MaxQB; Q9Y4E8; -.
DR PaxDb; Q9Y4E8; -.
DR PeptideAtlas; Q9Y4E8; -.
DR PRIDE; Q9Y4E8; -.
DR ProteomicsDB; 81207; -.
DR ProteomicsDB; 86183; -. [Q9Y4E8-1]
DR ProteomicsDB; 86184; -. [Q9Y4E8-2]
DR ProteomicsDB; 86185; -. [Q9Y4E8-3]
DR Antibodypedia; 1729; 344 antibodies from 38 providers.
DR DNASU; 9958; -.
DR Ensembl; ENST00000280377.10; ENSP00000280377.5; ENSG00000135655.16. [Q9Y4E8-1]
DR Ensembl; ENST00000312635.10; ENSP00000309240.6; ENSG00000135655.16. [Q9Y4E8-4]
DR Ensembl; ENST00000353364.7; ENSP00000258123.4; ENSG00000135655.16. [Q9Y4E8-2]
DR GeneID; 9958; -.
DR KEGG; hsa:9958; -.
DR MANE-Select; ENST00000280377.10; ENSP00000280377.5; NM_001252078.2; NP_001239007.1.
DR UCSC; uc001sra.4; human. [Q9Y4E8-1]
DR CTD; 9958; -.
DR DisGeNET; 9958; -.
DR GeneCards; USP15; -.
DR HGNC; HGNC:12613; USP15.
DR HPA; ENSG00000135655; Tissue enhanced (bone).
DR MIM; 604731; gene.
DR neXtProt; NX_Q9Y4E8; -.
DR OpenTargets; ENSG00000135655; -.
DR PharmGKB; PA37239; -.
DR VEuPathDB; HostDB:ENSG00000135655; -.
DR eggNOG; KOG1870; Eukaryota.
DR GeneTree; ENSGT00940000154932; -.
DR HOGENOM; CLU_001060_7_1_1; -.
DR InParanoid; Q9Y4E8; -.
DR OMA; ELPCHAQ; -.
DR OrthoDB; 1283205at2759; -.
DR PhylomeDB; Q9Y4E8; -.
DR TreeFam; TF106276; -.
DR PathwayCommons; Q9Y4E8; -.
DR Reactome; R-HSA-2173788; Downregulation of TGF-beta receptor signaling.
DR Reactome; R-HSA-5689603; UCH proteinases.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR SignaLink; Q9Y4E8; -.
DR BioGRID-ORCS; 9958; 28 hits in 1080 CRISPR screens.
DR ChiTaRS; USP15; human.
DR EvolutionaryTrace; Q9Y4E8; -.
DR GeneWiki; USP15; -.
DR GenomeRNAi; 9958; -.
DR Pharos; Q9Y4E8; Tbio.
DR PRO; PR:Q9Y4E8; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9Y4E8; protein.
DR Bgee; ENSG00000135655; Expressed in monocyte and 197 other tissues.
DR ExpressionAtlas; Q9Y4E8; baseline and differential.
DR Genevisible; Q9Y4E8; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
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; IMP:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:1990380; F:Lys48-specific deubiquitinase activity; IDA:CACAO.
DR GO; GO:0046332; F:SMAD binding; IPI:UniProtKB.
DR GO; GO:0005160; F:transforming growth factor beta receptor binding; IPI:UniProtKB.
DR GO; GO:0061649; F:ubiquitin modification-dependent histone binding; IDA:UniProtKB.
DR GO; GO:0030509; P:BMP signaling pathway; IDA:UniProtKB.
DR GO; GO:0035616; P:histone H2B conserved C-terminal lysine deubiquitination; IDA:UniProtKB.
DR GO; GO:0035520; P:monoubiquitinated protein deubiquitination; IDA:UniProtKB.
DR GO; GO:1905035; P:negative regulation of antifungal innate immune response; IDA:UniProtKB.
DR GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; IMP:UniProtKB.
DR GO; GO:1900246; P:positive regulation of RIG-I signaling pathway; IDA:CACAO.
DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
DR GO; GO:1990167; P:protein K27-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA: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 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Direct protein sequencing; Host-virus interaction; Hydrolase;
KW Mitochondrion; Nucleus; Phosphoprotein; Protease; Reference proteome;
KW Thiol protease; Ubl conjugation; Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT CHAIN 2..981
FT /note="Ubiquitin carboxyl-terminal hydrolase 15"
FT /id="PRO_0000080641"
FT DOMAIN 7..118
FT /note="DUSP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00613"
FT DOMAIN 289..933
FT /note="USP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT REGION 2..223
FT /note="Mediates interaction with SART3"
FT /evidence="ECO:0000269|PubMed:24526689"
FT REGION 216..237
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 629..694
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 952..981
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 219..237
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 633..647
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 655..670
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 671..694
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 298
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035,
FT ECO:0000305|PubMed:19553310, ECO:0000305|PubMed:21947082,
FT ECO:0000305|PubMed:22344298, ECO:0000305|PubMed:24852371,
FT ECO:0000305|PubMed:27368102, ECO:0000305|PubMed:33093067"
FT ACT_SITE 891
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:0000269|Ref.8, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT MOD_RES 226
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 229
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 242
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 602
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8R5H1"
FT MOD_RES 961
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 965
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT VAR_SEQ 217..256
FT /note="DGTWPRGPSTPKSPGASNFSTLPKISPSSLSNNYNNMNNR -> QKNEDGTW
FT PRGPSTP (in isoform 3)"
FT /evidence="ECO:0000303|Ref.9"
FT /id="VSP_005260"
FT VAR_SEQ 228..256
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9628581, ECO:0000303|Ref.1"
FT /id="VSP_005261"
FT VAR_SEQ 229..235
FT /note="SPGASNF -> KPLEQSC (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_045165"
FT VAR_SEQ 236..981
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_045166"
FT MUTAGEN 298
FT /note="C->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:19553310,
FT ECO:0000269|PubMed:21947082, ECO:0000269|PubMed:22344298,
FT ECO:0000269|PubMed:24852371, ECO:0000269|PubMed:27368102,
FT ECO:0000269|PubMed:33093067"
FT MUTAGEN 812
FT /note="C->A: Loss of activity towards polyubiquitin."
FT /evidence="ECO:0000269|PubMed:16005295,
FT ECO:0000269|PubMed:19576224"
FT CONFLICT 559
FT /note="T -> A (in Ref. 9; AAG28973)"
FT /evidence="ECO:0000305"
FT CONFLICT 747
FT /note="S -> F (in Ref. 7; AAI25124)"
FT /evidence="ECO:0000305"
FT CONFLICT 968
FT /note="N -> H (in Ref. 9; AAG28973)"
FT /evidence="ECO:0000305"
FT STRAND 4..6
FT /evidence="ECO:0007829|PDB:1W6V"
FT HELIX 9..19
FT /evidence="ECO:0007829|PDB:4A3P"
FT STRAND 29..34
FT /evidence="ECO:0007829|PDB:4A3P"
FT HELIX 35..45
FT /evidence="ECO:0007829|PDB:4A3P"
FT TURN 46..48
FT /evidence="ECO:0007829|PDB:3T9L"
FT TURN 53..56
FT /evidence="ECO:0007829|PDB:4A3P"
FT HELIX 58..60
FT /evidence="ECO:0007829|PDB:4A3P"
FT HELIX 68..70
FT /evidence="ECO:0007829|PDB:4A3P"
FT STRAND 73..76
FT /evidence="ECO:0007829|PDB:3T9L"
FT TURN 86..88
FT /evidence="ECO:0007829|PDB:4A3P"
FT STRAND 89..93
FT /evidence="ECO:0007829|PDB:4A3P"
FT HELIX 94..104
FT /evidence="ECO:0007829|PDB:4A3P"
FT STRAND 114..120
FT /evidence="ECO:0007829|PDB:4A3P"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:5JJW"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:4A3P"
FT STRAND 134..140
FT /evidence="ECO:0007829|PDB:4A3P"
FT STRAND 143..152
FT /evidence="ECO:0007829|PDB:4A3P"
FT HELIX 158..168
FT /evidence="ECO:0007829|PDB:4A3P"
FT STRAND 173..175
FT /evidence="ECO:0007829|PDB:4A3O"
FT STRAND 177..184
FT /evidence="ECO:0007829|PDB:4A3P"
FT STRAND 187..190
FT /evidence="ECO:0007829|PDB:4A3P"
FT HELIX 198..201
FT /evidence="ECO:0007829|PDB:4A3P"
FT STRAND 208..213
FT /evidence="ECO:0007829|PDB:4A3P"
FT HELIX 300..308
FT /evidence="ECO:0007829|PDB:6ML1"
FT HELIX 311..318
FT /evidence="ECO:0007829|PDB:6ML1"
FT TURN 319..322
FT /evidence="ECO:0007829|PDB:6GHA"
FT HELIX 323..325
FT /evidence="ECO:0007829|PDB:6ML1"
FT HELIX 337..349
FT /evidence="ECO:0007829|PDB:6ML1"
FT STRAND 351..353
FT /evidence="ECO:0007829|PDB:6ML1"
FT STRAND 355..357
FT /evidence="ECO:0007829|PDB:6ML1"
FT HELIX 360..369
FT /evidence="ECO:0007829|PDB:6ML1"
FT HELIX 371..373
FT /evidence="ECO:0007829|PDB:6CRN"
FT STRAND 374..377
FT /evidence="ECO:0007829|PDB:6CRN"
FT HELIX 384..395
FT /evidence="ECO:0007829|PDB:6ML1"
FT HELIX 415..429
FT /evidence="ECO:0007829|PDB:6ML1"
FT HELIX 433..438
FT /evidence="ECO:0007829|PDB:6ML1"
FT STRAND 440..447
FT /evidence="ECO:0007829|PDB:6ML1"
FT TURN 449..451
FT /evidence="ECO:0007829|PDB:6ML1"
FT STRAND 454..466
FT /evidence="ECO:0007829|PDB:6ML1"
FT STRAND 784..787
FT /evidence="ECO:0007829|PDB:6ML1"
FT HELIX 788..795
FT /evidence="ECO:0007829|PDB:6ML1"
FT STRAND 803..805
FT /evidence="ECO:0007829|PDB:6GH9"
FT STRAND 807..809
FT /evidence="ECO:0007829|PDB:6ML1"
FT TURN 810..813
FT /evidence="ECO:0007829|PDB:6ML1"
FT STRAND 814..816
FT /evidence="ECO:0007829|PDB:6ML1"
FT STRAND 819..827
FT /evidence="ECO:0007829|PDB:6ML1"
FT STRAND 829..835
FT /evidence="ECO:0007829|PDB:6ML1"
FT STRAND 838..840
FT /evidence="ECO:0007829|PDB:6CRN"
FT HELIX 841..843
FT /evidence="ECO:0007829|PDB:6ML1"
FT STRAND 845..847
FT /evidence="ECO:0007829|PDB:6CRN"
FT STRAND 851..853
FT /evidence="ECO:0007829|PDB:6ML1"
FT STRAND 859..861
FT /evidence="ECO:0007829|PDB:6ML1"
FT HELIX 862..864
FT /evidence="ECO:0007829|PDB:6GHA"
FT STRAND 873..884
FT /evidence="ECO:0007829|PDB:6ML1"
FT STRAND 891..897
FT /evidence="ECO:0007829|PDB:6ML1"
FT TURN 899..901
FT /evidence="ECO:0007829|PDB:6ML1"
FT STRAND 904..908
FT /evidence="ECO:0007829|PDB:6ML1"
FT STRAND 911..914
FT /evidence="ECO:0007829|PDB:6ML1"
FT HELIX 917..919
FT /evidence="ECO:0007829|PDB:6ML1"
FT STRAND 925..932
FT /evidence="ECO:0007829|PDB:6ML1"
FT HELIX 933..935
FT /evidence="ECO:0007829|PDB:6GHA"
SQ SEQUENCE 981 AA; 112419 MW; E81FEB9DE57F7089 CRC64;
MAEGGAADLD TQRSDIATLL KTSLRKGDTW YLVDSRWFKQ WKKYVGFDSW DKYQMGDQNV
YPGPIDNSGL LKDGDAQSLK EHLIDELDYI LLPTEGWNKL VSWYTLMEGQ EPIARKVVEQ
GMFVKHCKVE VYLTELKLCE NGNMNNVVTR RFSKADTIDT IEKEIRKIFS IPDEKETRLW
NKYMSNTFEP LNKPDSTIQD AGLYQGQVLV IEQKNEDGTW PRGPSTPKSP GASNFSTLPK
ISPSSLSNNY NNMNNRNVKN SNYCLPSYTA YKNYDYSEPG RNNEQPGLCG LSNLGNTCFM
NSAIQCLSNT PPLTEYFLND KYQEELNFDN PLGMRGEIAK SYAELIKQMW SGKFSYVTPR
AFKTQVGRFA PQFSGYQQQD CQELLAFLLD GLHEDLNRIR KKPYIQLKDA DGRPDKVVAE
EAWENHLKRN DSIIVDIFHG LFKSTLVCPE CAKISVTFDP FCYLTLPLPM KKERTLEVYL
VRMDPLTKPM QYKVVVPKIG NILDLCTALS ALSGIPADKM IVTDIYNHRF HRIFAMDENL
SSIMERDDIY VFEININRTE DTEHVIIPVC LREKFRHSSY THHTGSSLFG QPFLMAVPRN
NTEDKLYNLL LLRMCRYVKI STETEETEGS LHCCKDQNIN GNGPNGIHEE GSPSEMETDE
PDDESSQDQE LPSENENSQS EDSVGGDNDS ENGLCTEDTC KGQLTGHKKR LFTFQFNNLG
NTDINYIKDD TRHIRFDDRQ LRLDERSFLA LDWDPDLKKR YFDENAAEDF EKHESVEYKP
PKKPFVKLKD CIELFTTKEK LGAEDPWYCP NCKEHQQATK KLDLWSLPPV LVVHLKRFSY
SRYMRDKLDT LVDFPINDLD MSEFLINPNA GPCRYNLIAV SNHYGGMGGG HYTAFAKNKD
DGKWYYFDDS SVSTASEDQI VSKAAYVLFY QRQDTFSGTG FFPLDRETKG ASAATGIPLE
SDEDSNDNDN DIENENCMHT N
