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 27-MAR-2024, entry version 219. 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="https://atlasgeneticsoncology.org/gene/44585/USP15"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7R2G; X-ray; 1.98 A; A/B=284-948. 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 PDBsum; 7R2G; -. DR AlphaFoldDB; Q9Y4E8; -. DR BMRB; Q9Y4E8; -. DR SMR; Q9Y4E8; -. DR BioGRID; 115283; 489. DR DIP; DIP-50239N; -. DR IntAct; Q9Y4E8; 93. 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; 9606-ENSP00000280377; -. DR PeptideAtlas; Q9Y4E8; -. DR ProteomicsDB; 81207; -. DR ProteomicsDB; 86183; -. [Q9Y4E8-1] DR ProteomicsDB; 86184; -. [Q9Y4E8-2] DR ProteomicsDB; 86185; -. [Q9Y4E8-3] DR Pumba; Q9Y4E8; -. DR Antibodypedia; 1729; 385 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 AGR; HGNC:12613; -. 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; PCHAQQS; -. DR OrthoDB; 5474185at2759; -. 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 SIGNOR; Q9Y4E8; -. DR BioGRID-ORCS; 9958; 34 hits in 1159 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 199 other cell types or tissues. DR ExpressionAtlas; Q9Y4E8; baseline and differential. 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:0101005; F:deubiquitinase activity; IDA:UniProt. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:1990380; F:K48-linked 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:0035520; P:monoubiquitinated protein deubiquitination; IDA:UniProtKB. DR GO; GO:1905035; P:negative regulation of antifungal innate immune response; IDA:UniProtKB. DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; 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:0006508; P:proteolysis; IEA:UniProtKB-KW. DR GO; GO:1902238; P:regulation of intrinsic apoptotic signaling pathway in response to osmotic stress by p53 class mediator; IEA:Ensembl. DR GO; GO:0140673; P:transcription elongation-coupled chromatin remodeling; IDA:UniProtKB. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA: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. DR Genevisible; Q9Y4E8; HS. 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:7R2G" 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:7R2G" 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" FT HELIX 943..948 FT /evidence="ECO:0007829|PDB:7R2G" 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 //