Full text data of USP15
USP15
(KIAA0529)
[Confidence: high (present in two of the MS resources)]
Ubiquitin carboxyl-terminal hydrolase 15; 3.4.19.12 (Deubiquitinating enzyme 15; Ubiquitin thioesterase 15; Ubiquitin-specific-processing protease 15; Unph-2; Unph4)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Ubiquitin carboxyl-terminal hydrolase 15; 3.4.19.12 (Deubiquitinating enzyme 15; Ubiquitin thioesterase 15; Ubiquitin-specific-processing protease 15; Unph-2; Unph4)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00000728
IPI00000728 Splice Isoform 1 Of Ubiquitin carboxyl-terminal hydrolase 15 Ubiquitin C-terminal thiolester + H2O = ubiquitin + a thiol, cysteine-type endopeptidase activity, ubiquitin-specific protease activity soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a not mentioned Isoform 2 or 3 found at its expected molecular weight found at molecular weight
IPI00000728 Splice Isoform 1 Of Ubiquitin carboxyl-terminal hydrolase 15 Ubiquitin C-terminal thiolester + H2O = ubiquitin + a thiol, cysteine-type endopeptidase activity, ubiquitin-specific protease activity soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a not mentioned Isoform 2 or 3 found at its expected molecular weight found at molecular weight
UniProt
Q9Y4E8
ID UBP15_HUMAN Reviewed; 981 AA.
AC Q9Y4E8; Q08AL5; Q9H8G9; Q9HCA6; Q9UNP0; Q9Y5B5;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 12-FEB-2003, sequence version 3.
DT 22-JAN-2014, entry version 136.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 15;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 15;
DE AltName: Full=Ubiquitin thioesterase 15;
DE AltName: Full=Ubiquitin-specific-processing protease 15;
DE AltName: Full=Unph-2;
DE AltName: Full=Unph4;
GN Name=USP15; Synonyms=KIAA0529;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT enzyme 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.
RT The complete sequences of 100 new cDNA clones from brain which can
RT code for 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.,
RA Hwang S.Y., 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
RT by 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA 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.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA 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.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., 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
RT project: 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 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
RT localization of USP15, a novel human ubiquitin-specific protease
RT related to the UNP oncoprotein, and a systematic nomenclature for
RT human ubiquitin-specific 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
RT protease Usp15.";
RL Mamm. Genome 14:31-46(2003).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF CYS-812, IDENTIFICATION
RP IN A COMPLEX WITH THE COP9 SIGNALOSOME, PHOSPHORYLATION, AND
RP UBIQUITINATION.
RX PubMed=16005295; DOI=10.1016/j.cub.2005.05.059;
RA Hetfeld B.K., Helfrich A., Kapelari B., Scheel H., Hofmann K.,
RA Guterman A., Glickman M., Schade R., Kloetzel P.M., Dubiel W.;
RT "The zinc finger of the CSN-associated deubiquitinating enzyme USP15
RT is 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 MASS
RP SPECTROMETRY.
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
RT phosphorylation 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
RP SER-965, AND MASS SPECTROMETRY.
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, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a 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-
RT containing protein (VCP) and controls the ubiquitination status of
RT proteins bound to 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
RT deneddylation and blocks adenomatous polyposis coli destruction via
RT USP15.";
RL J. Mol. Biol. 391:691-702(2009).
RN [19]
RP FUNCTION, MUTAGENESIS OF CYS-298, AND INTERACTION WITH HUMAN
RP PAPILLOMAVIRUS TYPE 16 PROTEIN E6.
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
RT type 16 E6 protein stability.";
RL J. Virol. 83:8885-8892(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-229, AND MASS
RP SPECTROMETRY.
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
RP AND SER-965, AND MASS SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation 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.,
RA Buerckstuemmer T., 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
RP SMAD1; 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.,
RA Enzo E., 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-229, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [25]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH TGFBR1 AND SMAD7, AND
RP 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
RT the activation of TGF-beta signaling in glioblastoma.";
RL Nat. Med. 18:429-435(2012).
RN [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [27]
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.,
RA Kaptein R., 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 [28]
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
RT close association between the DUSP and UBL domains.";
RL Biochemistry 50:7995-8004(2011).
RN [29]
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
RT double domains.";
RL FEBS Lett. 585:3385-3390(2011).
RN [30]
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
CC receptor signaling and NF-kappa-B pathways. Acts as a key
CC regulator of TGF-beta receptor signaling pathway, but the precise
CC mechanism is still unclear: according to a report, acts by
CC promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1,
CC SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and
CC promoting activation of TGF-beta target genes (PubMed:21947082).
CC According to another reports, regulates the TGF-beta receptor
CC signaling pathway by mediating deubiquitination and stabilization
CC of TGFBR1, leading to an enhanced TGF-beta signal
CC (PubMed:22344298). Able to mediate deubiquitination of
CC monoubiquitinated substrates as well as 'Lys-48'-linked
CC polyubiquitin chains, protecting them against proteasomal
CC degradation. Acts as an associated component of COP9 signalosome
CC complex (CSN) and regulates different pathways via this
CC association: regulates NF-kappa-B by mediating deubiquitination of
CC NFKBIA and deubiquitinates substrates bound to VCP. Protects APC
CC and human papillomavirus type 16 protein E6 against degradation
CC via the ubiquitin proteasome pathway.
CC -!- CATALYTIC ACTIVITY: Thiol-dependent hydrolysis of ester,
CC thioester, amide, peptide and isopeptide bonds formed by the C-
CC terminal Gly of ubiquitin (a 76-residue protein attached to
CC proteins as an intracellular targeting signal).
CC -!- SUBUNIT: A homodimer structure has been reported; however it is
CC unclear whether the protein form a homodimer in vivo
CC (PubMed:22001210). Identified in a complex with the COP9
CC signalosome complex (CSN). Interacts with SMAD1, SMAD2 and SMAD3;
CC the interaction is direct. Forms a complex with SMURF2 and SMAD7.
CC Interacts with TGFBR1. Interacts with human papillomavirus type 16
CC protein E6.
CC -!- INTERACTION:
CC Self; NbExp=5; IntAct=EBI-1043104, EBI-1043104;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
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
CC expression in other tissues.
CC -!- PTM: Phosphorylated. Phosphorylation protects against
CC ubiquitination and subsequent degradation by the proteasome.
CC -!- PTM: Ubiquitinated, leading to degradation by the proteasome.
CC -!- SIMILARITY: Belongs to the peptidase C19 family.
CC -!- SIMILARITY: Contains 1 DUSP domain.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and 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 RefSeq; NP_001239007.1; NM_001252078.1.
DR RefSeq; NP_001239008.1; NM_001252079.1.
DR RefSeq; NP_006304.1; NM_006313.2.
DR UniGene; Hs.434951; -.
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=6-223.
DR PDB; 4A3P; X-ray; 1.40 A; A=6-223.
DR PDBsum; 1W6V; -.
DR PDBsum; 3LMN; -.
DR PDBsum; 3PPA; -.
DR PDBsum; 3PV1; -.
DR PDBsum; 3T9L; -.
DR PDBsum; 4A3O; -.
DR PDBsum; 4A3P; -.
DR ProteinModelPortal; Q9Y4E8; -.
DR SMR; Q9Y4E8; 6-222, 285-470, 786-934.
DR DIP; DIP-50239N; -.
DR IntAct; Q9Y4E8; 35.
DR MINT; MINT-4542165; -.
DR STRING; 9606.ENSP00000258123; -.
DR MEROPS; C19.022; -.
DR PhosphoSite; Q9Y4E8; -.
DR DMDM; 28381406; -.
DR PaxDb; Q9Y4E8; -.
DR PRIDE; Q9Y4E8; -.
DR DNASU; 9958; -.
DR Ensembl; ENST00000280377; ENSP00000280377; ENSG00000135655.
DR Ensembl; ENST00000312635; ENSP00000309240; ENSG00000135655.
DR Ensembl; ENST00000353364; ENSP00000258123; ENSG00000135655.
DR GeneID; 9958; -.
DR KEGG; hsa:9958; -.
DR UCSC; uc001sra.3; human.
DR CTD; 9958; -.
DR GeneCards; GC12P062706; -.
DR H-InvDB; HIX0010773; -.
DR HGNC; HGNC:12613; USP15.
DR HPA; HPA006237; -.
DR MIM; 604731; gene.
DR neXtProt; NX_Q9Y4E8; -.
DR PharmGKB; PA37239; -.
DR eggNOG; COG5560; -.
DR HOGENOM; HOG000264375; -.
DR HOVERGEN; HBG000864; -.
DR InParanoid; Q9Y4E8; -.
DR KO; K11835; -.
DR OMA; QMWSGKY; -.
DR OrthoDB; EOG77Q4VW; -.
DR PhylomeDB; Q9Y4E8; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR ChiTaRS; USP15; human.
DR EvolutionaryTrace; Q9Y4E8; -.
DR GeneWiki; USP15; -.
DR GenomeRNAi; 9958; -.
DR NextBio; 37576; -.
DR PRO; PR:Q9Y4E8; -.
DR ArrayExpress; Q9Y4E8; -.
DR Bgee; Q9Y4E8; -.
DR CleanEx; HS_USP15; -.
DR Genevestigator; Q9Y4E8; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IMP:UniProtKB.
DR GO; GO:0004843; F:deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0004221; F:ubiquitin thiolesterase activity; 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:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; TAS:Reactome.
DR GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; IMP: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 InterPro; IPR006615; Pept_C19_DUSP.
DR InterPro; IPR018200; Pept_C19ubi-hydrolase_C_CS.
DR InterPro; IPR001394; Peptidase_C19/C67.
DR InterPro; IPR013792; RNA3'P_cycl/enolpyr_Trfase_a/b.
DR InterPro; IPR028135; Ub_USP-typ.
DR Pfam; PF06337; DUSP; 1.
DR Pfam; PF14836; Ubiquitin_3; 1.
DR Pfam; PF00443; UCH; 1.
DR SMART; SM00695; DUSP; 1.
DR SUPFAM; SSF55205; SSF55205; 1.
DR PROSITE; PS51283; DUSP; 1.
DR PROSITE; PS00972; UCH_2_1; 1.
DR PROSITE; PS00973; UCH_2_2; 1.
DR PROSITE; PS50235; UCH_2_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Hydrolase; Nucleus;
KW Phosphoprotein; Protease; Reference proteome; Thiol protease;
KW Ubl conjugation; Ubl conjugation pathway.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 981 Ubiquitin carboxyl-terminal hydrolase 15.
FT /FTId=PRO_0000080641.
FT DOMAIN 7 118 DUSP.
FT ACT_SITE 298 298 Nucleophile.
FT ACT_SITE 891 891 Proton acceptor (By similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 229 229 Phosphoserine.
FT MOD_RES 242 242 Phosphoserine.
FT MOD_RES 961 961 Phosphoserine.
FT MOD_RES 965 965 Phosphoserine.
FT VAR_SEQ 217 256 DGTWPRGPSTPKSPGASNFSTLPKISPSSLSNNYNNMNNR
FT -> QKNEDGTWPRGPSTP (in isoform 3).
FT /FTId=VSP_005260.
FT VAR_SEQ 228 256 Missing (in isoform 2).
FT /FTId=VSP_005261.
FT VAR_SEQ 229 235 SPGASNF -> KPLEQSC (in isoform 4).
FT /FTId=VSP_045165.
FT VAR_SEQ 236 981 Missing (in isoform 4).
FT /FTId=VSP_045166.
FT MUTAGEN 298 298 C->A: Loss of enzyme activity.
FT MUTAGEN 812 812 C->A: Loss of activity towards
FT polyubiquitin.
FT CONFLICT 559 559 T -> A (in Ref. 9; AAG28973).
FT CONFLICT 747 747 S -> F (in Ref. 7; AAI25124).
FT CONFLICT 968 968 N -> H (in Ref. 9; AAG28973).
FT STRAND 4 6
FT HELIX 9 19
FT STRAND 29 34
FT HELIX 35 45
FT TURN 46 48
FT TURN 53 56
FT HELIX 58 60
FT HELIX 68 70
FT STRAND 73 76
FT TURN 86 88
FT STRAND 89 93
FT HELIX 94 104
FT STRAND 114 120
FT STRAND 127 129
FT STRAND 134 140
FT STRAND 143 152
FT HELIX 158 168
FT STRAND 173 175
FT STRAND 177 184
FT STRAND 187 190
FT HELIX 198 201
FT STRAND 208 213
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
//
ID UBP15_HUMAN Reviewed; 981 AA.
AC Q9Y4E8; Q08AL5; Q9H8G9; Q9HCA6; Q9UNP0; Q9Y5B5;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 12-FEB-2003, sequence version 3.
DT 22-JAN-2014, entry version 136.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 15;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 15;
DE AltName: Full=Ubiquitin thioesterase 15;
DE AltName: Full=Ubiquitin-specific-processing protease 15;
DE AltName: Full=Unph-2;
DE AltName: Full=Unph4;
GN Name=USP15; Synonyms=KIAA0529;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT enzyme 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.
RT The complete sequences of 100 new cDNA clones from brain which can
RT code for 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.,
RA Hwang S.Y., 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
RT by 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA 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.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA 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.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., 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
RT project: 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 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
RT localization of USP15, a novel human ubiquitin-specific protease
RT related to the UNP oncoprotein, and a systematic nomenclature for
RT human ubiquitin-specific 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
RT protease Usp15.";
RL Mamm. Genome 14:31-46(2003).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF CYS-812, IDENTIFICATION
RP IN A COMPLEX WITH THE COP9 SIGNALOSOME, PHOSPHORYLATION, AND
RP UBIQUITINATION.
RX PubMed=16005295; DOI=10.1016/j.cub.2005.05.059;
RA Hetfeld B.K., Helfrich A., Kapelari B., Scheel H., Hofmann K.,
RA Guterman A., Glickman M., Schade R., Kloetzel P.M., Dubiel W.;
RT "The zinc finger of the CSN-associated deubiquitinating enzyme USP15
RT is 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 MASS
RP SPECTROMETRY.
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
RT phosphorylation 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
RP SER-965, AND MASS SPECTROMETRY.
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, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a 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-
RT containing protein (VCP) and controls the ubiquitination status of
RT proteins bound to 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
RT deneddylation and blocks adenomatous polyposis coli destruction via
RT USP15.";
RL J. Mol. Biol. 391:691-702(2009).
RN [19]
RP FUNCTION, MUTAGENESIS OF CYS-298, AND INTERACTION WITH HUMAN
RP PAPILLOMAVIRUS TYPE 16 PROTEIN E6.
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
RT type 16 E6 protein stability.";
RL J. Virol. 83:8885-8892(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-229, AND MASS
RP SPECTROMETRY.
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
RP AND SER-965, AND MASS SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation 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.,
RA Buerckstuemmer T., 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
RP SMAD1; 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.,
RA Enzo E., 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-229, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [25]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH TGFBR1 AND SMAD7, AND
RP 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
RT the activation of TGF-beta signaling in glioblastoma.";
RL Nat. Med. 18:429-435(2012).
RN [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [27]
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.,
RA Kaptein R., 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 [28]
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
RT close association between the DUSP and UBL domains.";
RL Biochemistry 50:7995-8004(2011).
RN [29]
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
RT double domains.";
RL FEBS Lett. 585:3385-3390(2011).
RN [30]
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
CC receptor signaling and NF-kappa-B pathways. Acts as a key
CC regulator of TGF-beta receptor signaling pathway, but the precise
CC mechanism is still unclear: according to a report, acts by
CC promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1,
CC SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and
CC promoting activation of TGF-beta target genes (PubMed:21947082).
CC According to another reports, regulates the TGF-beta receptor
CC signaling pathway by mediating deubiquitination and stabilization
CC of TGFBR1, leading to an enhanced TGF-beta signal
CC (PubMed:22344298). Able to mediate deubiquitination of
CC monoubiquitinated substrates as well as 'Lys-48'-linked
CC polyubiquitin chains, protecting them against proteasomal
CC degradation. Acts as an associated component of COP9 signalosome
CC complex (CSN) and regulates different pathways via this
CC association: regulates NF-kappa-B by mediating deubiquitination of
CC NFKBIA and deubiquitinates substrates bound to VCP. Protects APC
CC and human papillomavirus type 16 protein E6 against degradation
CC via the ubiquitin proteasome pathway.
CC -!- CATALYTIC ACTIVITY: Thiol-dependent hydrolysis of ester,
CC thioester, amide, peptide and isopeptide bonds formed by the C-
CC terminal Gly of ubiquitin (a 76-residue protein attached to
CC proteins as an intracellular targeting signal).
CC -!- SUBUNIT: A homodimer structure has been reported; however it is
CC unclear whether the protein form a homodimer in vivo
CC (PubMed:22001210). Identified in a complex with the COP9
CC signalosome complex (CSN). Interacts with SMAD1, SMAD2 and SMAD3;
CC the interaction is direct. Forms a complex with SMURF2 and SMAD7.
CC Interacts with TGFBR1. Interacts with human papillomavirus type 16
CC protein E6.
CC -!- INTERACTION:
CC Self; NbExp=5; IntAct=EBI-1043104, EBI-1043104;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
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
CC expression in other tissues.
CC -!- PTM: Phosphorylated. Phosphorylation protects against
CC ubiquitination and subsequent degradation by the proteasome.
CC -!- PTM: Ubiquitinated, leading to degradation by the proteasome.
CC -!- SIMILARITY: Belongs to the peptidase C19 family.
CC -!- SIMILARITY: Contains 1 DUSP domain.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/USP15ID44585ch12q14.html";
CC -----------------------------------------------------------------------
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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 RefSeq; NP_001239007.1; NM_001252078.1.
DR RefSeq; NP_001239008.1; NM_001252079.1.
DR RefSeq; NP_006304.1; NM_006313.2.
DR UniGene; Hs.434951; -.
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=6-223.
DR PDB; 4A3P; X-ray; 1.40 A; A=6-223.
DR PDBsum; 1W6V; -.
DR PDBsum; 3LMN; -.
DR PDBsum; 3PPA; -.
DR PDBsum; 3PV1; -.
DR PDBsum; 3T9L; -.
DR PDBsum; 4A3O; -.
DR PDBsum; 4A3P; -.
DR ProteinModelPortal; Q9Y4E8; -.
DR SMR; Q9Y4E8; 6-222, 285-470, 786-934.
DR DIP; DIP-50239N; -.
DR IntAct; Q9Y4E8; 35.
DR MINT; MINT-4542165; -.
DR STRING; 9606.ENSP00000258123; -.
DR MEROPS; C19.022; -.
DR PhosphoSite; Q9Y4E8; -.
DR DMDM; 28381406; -.
DR PaxDb; Q9Y4E8; -.
DR PRIDE; Q9Y4E8; -.
DR DNASU; 9958; -.
DR Ensembl; ENST00000280377; ENSP00000280377; ENSG00000135655.
DR Ensembl; ENST00000312635; ENSP00000309240; ENSG00000135655.
DR Ensembl; ENST00000353364; ENSP00000258123; ENSG00000135655.
DR GeneID; 9958; -.
DR KEGG; hsa:9958; -.
DR UCSC; uc001sra.3; human.
DR CTD; 9958; -.
DR GeneCards; GC12P062706; -.
DR H-InvDB; HIX0010773; -.
DR HGNC; HGNC:12613; USP15.
DR HPA; HPA006237; -.
DR MIM; 604731; gene.
DR neXtProt; NX_Q9Y4E8; -.
DR PharmGKB; PA37239; -.
DR eggNOG; COG5560; -.
DR HOGENOM; HOG000264375; -.
DR HOVERGEN; HBG000864; -.
DR InParanoid; Q9Y4E8; -.
DR KO; K11835; -.
DR OMA; QMWSGKY; -.
DR OrthoDB; EOG77Q4VW; -.
DR PhylomeDB; Q9Y4E8; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR ChiTaRS; USP15; human.
DR EvolutionaryTrace; Q9Y4E8; -.
DR GeneWiki; USP15; -.
DR GenomeRNAi; 9958; -.
DR NextBio; 37576; -.
DR PRO; PR:Q9Y4E8; -.
DR ArrayExpress; Q9Y4E8; -.
DR Bgee; Q9Y4E8; -.
DR CleanEx; HS_USP15; -.
DR Genevestigator; Q9Y4E8; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IMP:UniProtKB.
DR GO; GO:0004843; F:deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0004221; F:ubiquitin thiolesterase activity; 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:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; TAS:Reactome.
DR GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; IMP: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 InterPro; IPR006615; Pept_C19_DUSP.
DR InterPro; IPR018200; Pept_C19ubi-hydrolase_C_CS.
DR InterPro; IPR001394; Peptidase_C19/C67.
DR InterPro; IPR013792; RNA3'P_cycl/enolpyr_Trfase_a/b.
DR InterPro; IPR028135; Ub_USP-typ.
DR Pfam; PF06337; DUSP; 1.
DR Pfam; PF14836; Ubiquitin_3; 1.
DR Pfam; PF00443; UCH; 1.
DR SMART; SM00695; DUSP; 1.
DR SUPFAM; SSF55205; SSF55205; 1.
DR PROSITE; PS51283; DUSP; 1.
DR PROSITE; PS00972; UCH_2_1; 1.
DR PROSITE; PS00973; UCH_2_2; 1.
DR PROSITE; PS50235; UCH_2_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Hydrolase; Nucleus;
KW Phosphoprotein; Protease; Reference proteome; Thiol protease;
KW Ubl conjugation; Ubl conjugation pathway.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 981 Ubiquitin carboxyl-terminal hydrolase 15.
FT /FTId=PRO_0000080641.
FT DOMAIN 7 118 DUSP.
FT ACT_SITE 298 298 Nucleophile.
FT ACT_SITE 891 891 Proton acceptor (By similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 229 229 Phosphoserine.
FT MOD_RES 242 242 Phosphoserine.
FT MOD_RES 961 961 Phosphoserine.
FT MOD_RES 965 965 Phosphoserine.
FT VAR_SEQ 217 256 DGTWPRGPSTPKSPGASNFSTLPKISPSSLSNNYNNMNNR
FT -> QKNEDGTWPRGPSTP (in isoform 3).
FT /FTId=VSP_005260.
FT VAR_SEQ 228 256 Missing (in isoform 2).
FT /FTId=VSP_005261.
FT VAR_SEQ 229 235 SPGASNF -> KPLEQSC (in isoform 4).
FT /FTId=VSP_045165.
FT VAR_SEQ 236 981 Missing (in isoform 4).
FT /FTId=VSP_045166.
FT MUTAGEN 298 298 C->A: Loss of enzyme activity.
FT MUTAGEN 812 812 C->A: Loss of activity towards
FT polyubiquitin.
FT CONFLICT 559 559 T -> A (in Ref. 9; AAG28973).
FT CONFLICT 747 747 S -> F (in Ref. 7; AAI25124).
FT CONFLICT 968 968 N -> H (in Ref. 9; AAG28973).
FT STRAND 4 6
FT HELIX 9 19
FT STRAND 29 34
FT HELIX 35 45
FT TURN 46 48
FT TURN 53 56
FT HELIX 58 60
FT HELIX 68 70
FT STRAND 73 76
FT TURN 86 88
FT STRAND 89 93
FT HELIX 94 104
FT STRAND 114 120
FT STRAND 127 129
FT STRAND 134 140
FT STRAND 143 152
FT HELIX 158 168
FT STRAND 173 175
FT STRAND 177 184
FT STRAND 187 190
FT HELIX 198 201
FT STRAND 208 213
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
//
MIM
604731
*RECORD*
*FIELD* NO
604731
*FIELD* TI
*604731 UBIQUITIN-SPECIFIC PROTEASE 15; USP15
*FIELD* TX
DESCRIPTION
Ubiquitin (191339), a highly conserved protein involved in the
read moreregulation of intracellular protein breakdown, cell cycle regulation,
and stress response, is released from degraded proteins by disassembly
of the polyubiquitin chains. The disassembly process is mediated by
ubiquitin-specific proteases (USPs). Also see USP1 (603478).
CLONING
By screening human brain cDNAs for those encoding proteins larger than
50 kD, Nagase et al. (1998) identified a partial cDNA encoding USP15,
which they called KIAA0529. RT-PCR analysis detected USP15 expression in
skeletal muscle, kidney, heart, placenta, liver, thymus, lung, and
ovary, with little or no expression in other tissues.
By searching an EST database for sequences related to USP4 (603486),
Baker et al. (1999) identified a full-length cDNA encoding USP15. The
952-amino acid USP15 protein contains the conserved cysteine and
histidine boxes present in all USPs.
GENE FUNCTION
Baker et al. (1999) found that, like USP4, USP15 could cleave the
ubiquitin-proline bond.
TGFB (190180) and bone morphogenetic proteins (BMPs; see 112264)
phosphorylate receptor-activated SMADs (e.g., SMAD1; 601595), which then
associate with SMAD4 (600993) to regulate gene expression. Using a small
interfering RNA screen to identify deubiquitylating enzymes (DUB)
required for TGFB and BMP activity, Inui et al. (2011) identified human
USP15 as a DUB for receptor-activated SMADs. USP15 was required for TGFB
and BMP responses in both mammalian cells and frog embryos. Biochemical
analysis showed that USP15 primarily opposed receptor-activated SMAD
monoubiquitylation by targeting the DNA-binding domains of
receptor-activated SMADs, thus preventing promoter recognition. Inui et
al. (2011) concluded that USP15 is critical for the occupancy of
endogenous target promoters by the SMAD complex and adds a layer of
control by which the ubiquitin system regulates TGFB biology.
MAPPING
Nagase et al. (1998) mapped the USP15 gene to chromosome 12 by radiation
hybrid analysis. Using FISH, Baker et al. (1999) mapped the USP15 gene
to 12q14.
*FIELD* RF
1. Baker, R. T.; Wang, X.-W.; Woollatt, E.; White, J. A.; Sutherland,
G. R.: Identification, functional characterization, and chromosomal
localization of USP15, a novel human ubiquitin-specific protease related
to the UNP oncoprotein, and a systemic nomenclature for human ubiquitin-specific
proteases. Genomics 59: 264-274, 1999.
2. Inui, M.; Manfrin, A.; Mamidi, A.; Martello, G.; Morsut, L.; Soligo,
S.; Enzo, E.; Moro, S.; Polo, S.; Dupont, S.; Cordenonsi, M.; Piccolo,
S.: USP15 is a deubiquitylating enzyme for receptor-activated SMADs. Nature
Cell Biol. 13: 1368-1375, 2011.
3. Nagase, T.; Isikawa, K.; Miyajima, N.; Tanaka, A.; Kotani, H.;
Nomura, N.; Ohara, O.: Prediction of the coding sequences of unidentified
human genes. IX. The complete sequences of 100 new cDNA clones from
brain which can code for large proteins in vitro. DNA Res. 5: 31-39,
1998.
*FIELD* CN
Paul J. Converse - updated: 11/30/2012
*FIELD* CD
Paul J. Converse: 3/23/2000
*FIELD* ED
mgross: 12/03/2012
terry: 11/30/2012
carol: 5/12/2004
carol: 1/31/2003
mgross: 3/23/2000
*RECORD*
*FIELD* NO
604731
*FIELD* TI
*604731 UBIQUITIN-SPECIFIC PROTEASE 15; USP15
*FIELD* TX
DESCRIPTION
Ubiquitin (191339), a highly conserved protein involved in the
read moreregulation of intracellular protein breakdown, cell cycle regulation,
and stress response, is released from degraded proteins by disassembly
of the polyubiquitin chains. The disassembly process is mediated by
ubiquitin-specific proteases (USPs). Also see USP1 (603478).
CLONING
By screening human brain cDNAs for those encoding proteins larger than
50 kD, Nagase et al. (1998) identified a partial cDNA encoding USP15,
which they called KIAA0529. RT-PCR analysis detected USP15 expression in
skeletal muscle, kidney, heart, placenta, liver, thymus, lung, and
ovary, with little or no expression in other tissues.
By searching an EST database for sequences related to USP4 (603486),
Baker et al. (1999) identified a full-length cDNA encoding USP15. The
952-amino acid USP15 protein contains the conserved cysteine and
histidine boxes present in all USPs.
GENE FUNCTION
Baker et al. (1999) found that, like USP4, USP15 could cleave the
ubiquitin-proline bond.
TGFB (190180) and bone morphogenetic proteins (BMPs; see 112264)
phosphorylate receptor-activated SMADs (e.g., SMAD1; 601595), which then
associate with SMAD4 (600993) to regulate gene expression. Using a small
interfering RNA screen to identify deubiquitylating enzymes (DUB)
required for TGFB and BMP activity, Inui et al. (2011) identified human
USP15 as a DUB for receptor-activated SMADs. USP15 was required for TGFB
and BMP responses in both mammalian cells and frog embryos. Biochemical
analysis showed that USP15 primarily opposed receptor-activated SMAD
monoubiquitylation by targeting the DNA-binding domains of
receptor-activated SMADs, thus preventing promoter recognition. Inui et
al. (2011) concluded that USP15 is critical for the occupancy of
endogenous target promoters by the SMAD complex and adds a layer of
control by which the ubiquitin system regulates TGFB biology.
MAPPING
Nagase et al. (1998) mapped the USP15 gene to chromosome 12 by radiation
hybrid analysis. Using FISH, Baker et al. (1999) mapped the USP15 gene
to 12q14.
*FIELD* RF
1. Baker, R. T.; Wang, X.-W.; Woollatt, E.; White, J. A.; Sutherland,
G. R.: Identification, functional characterization, and chromosomal
localization of USP15, a novel human ubiquitin-specific protease related
to the UNP oncoprotein, and a systemic nomenclature for human ubiquitin-specific
proteases. Genomics 59: 264-274, 1999.
2. Inui, M.; Manfrin, A.; Mamidi, A.; Martello, G.; Morsut, L.; Soligo,
S.; Enzo, E.; Moro, S.; Polo, S.; Dupont, S.; Cordenonsi, M.; Piccolo,
S.: USP15 is a deubiquitylating enzyme for receptor-activated SMADs. Nature
Cell Biol. 13: 1368-1375, 2011.
3. Nagase, T.; Isikawa, K.; Miyajima, N.; Tanaka, A.; Kotani, H.;
Nomura, N.; Ohara, O.: Prediction of the coding sequences of unidentified
human genes. IX. The complete sequences of 100 new cDNA clones from
brain which can code for large proteins in vitro. DNA Res. 5: 31-39,
1998.
*FIELD* CN
Paul J. Converse - updated: 11/30/2012
*FIELD* CD
Paul J. Converse: 3/23/2000
*FIELD* ED
mgross: 12/03/2012
terry: 11/30/2012
carol: 5/12/2004
carol: 1/31/2003
mgross: 3/23/2000