TRRAP_HUMAN
ID TRRAP_HUMAN Reviewed; 3859 AA.
AC Q9Y4A5; A4D265; O75218; Q9Y631; Q9Y6H4;
DT 28-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 209.
DE RecName: Full=Transformation/transcription domain-associated protein;
DE AltName: Full=350/400 kDa PCAF-associated factor;
DE Short=PAF350/400;
DE AltName: Full=STAF40;
DE AltName: Full=Tra1 homolog;
GN Name=TRRAP; Synonyms=PAF400;
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), PARTIAL PROTEIN SEQUENCE, FUNCTION,
RP SUBCELLULAR LOCATION, AND INTERACTION WITH MYC AND E2F1.
RC TISSUE=Cervix carcinoma;
RX PubMed=9708738; DOI=10.1016/s0092-8674(00)81479-8;
RA McMahon S.B., Van Buskirk H.A., Dugan K.A., Copeland T.D., Cole M.D.;
RT "The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc
RT and E2F oncoproteins.";
RL Cell 94:363-374(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 41-90; 337-344;
RP 369-387; 879-892; 997-1005; 1171-1184; 1237-1247; 1545-1560; 1815-1820;
RP 1922-1934; 2211-2218; 2260-2275; 2534-2547; 2583-2594; 2706-2726;
RP 2830-2844; 3567-3573; 3583-3598; 3604-3614; 3712-3730 AND 3822-3834, AND
RP IDENTIFICATION IN THE PCAF COMPLEX WITH TADA2L; TADA3L; TAF5L; TAF6L;
RP TAF10; SUPT3H; TAF12 AND TAF9.
RC TISSUE=Fetal heart;
RX PubMed=9885574; DOI=10.1016/s1097-2765(00)80301-9;
RA Vassilev A., Yamauchi J., Kotani T., Prives C., Avantaggiati M.L., Qin J.,
RA Nakatani Y.;
RT "The 400 kDa subunit of the PCAF histone acetylase complex belongs to the
RT ATM superfamily.";
RL Mol. Cell 2:869-875(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [6]
RP SUBCELLULAR LOCATION, IDENTIFICATION IN THE STAGA COMPLEX WITH SUPT3H;
RP GCN5L2; KIAA0764; TAF5L; TAF6L; TADA3L; TAF10; TAF12 AND TAF9, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=11564863; DOI=10.1128/mcb.21.20.6782-6795.2001;
RA Martinez E., Palhan V.B., Tjernberg A., Lymar E.S., Gamper A.M.,
RA Kundu T.K., Chait B.T., Roeder R.G.;
RT "Human STAGA complex is a chromatin-acetylating transcription coactivator
RT that interacts with pre-mRNA splicing and DNA damage-binding factors in
RT vivo.";
RL Mol. Cell. Biol. 21:6782-6795(2001).
RN [7]
RP IDENTIFICATION IN THE TFTC-HAT COMPLEX WITH TAF5L; TAF6L; TADA3L; SUPT3H;
RP TAF2; TAF4; TAF5; GCN5L2 AND TAF10.
RX PubMed=10373431; DOI=10.1074/jbc.274.26.18285;
RA Brand M., Yamamoto K., Staub A., Tora L.;
RT "Identification of TATA-binding protein-free TAFII-containing complex
RT subunits suggests a role in nucleosome acetylation and signal
RT transduction.";
RL J. Biol. Chem. 274:18285-18289(1999).
RN [8]
RP IDENTIFICATION IN THE TIP60 HAT COMPLEX WITH KAT5; RUVBL1 AND RUVBL2.
RX PubMed=10966108; DOI=10.1016/s0092-8674(00)00051-9;
RA Ikura T., Ogryzko V.V., Grigoriev M., Groisman R., Wang J., Horikoshi M.,
RA Scully R., Qin J., Nakatani Y.;
RT "Involvement of the TIP60 histone acetylase complex in DNA repair and
RT apoptosis.";
RL Cell 102:463-473(2000).
RN [9]
RP INTERACTION WITH GCN5L2.
RX PubMed=10611234; DOI=10.1128/mcb.20.2.556-562.2000;
RA McMahon S.B., Wood M.A., Cole M.D.;
RT "The essential cofactor TRRAP recruits the histone acetyltransferase hGCN5
RT to c-Myc.";
RL Mol. Cell. Biol. 20:556-562(2000).
RN [10]
RP INTERACTION WITH E2F1 AND E2F4, AND FUNCTION.
RX PubMed=11418595; DOI=10.1074/jbc.m102067200;
RA Lang S.E., McMahon S.B., Cole M.D., Hearing P.;
RT "E2F transcriptional activation requires TRRAP and GCN5 cofactors.";
RL J. Biol. Chem. 276:32627-32634(2001).
RN [11]
RP DOMAIN.
RX PubMed=11445536; DOI=10.1101/gad.900101;
RA Park J., Kunjibettu S., McMahon S.B., Cole M.D.;
RT "The ATM-related domain of TRRAP is required for histone acetyltransferase
RT recruitment and Myc-dependent oncogenesis.";
RL Genes Dev. 15:1619-1624(2001).
RN [12]
RP FUNCTION, AND INTERACTION WITH TP53.
RX PubMed=12138177; DOI=10.1128/mcb.22.16.5650-5661.2002;
RA Ard P.G., Chatterjee C., Kunjibettu S., Adside L.R., Gralinski L.E.,
RA McMahon S.B.;
RT "Transcriptional regulation of the mdm2 oncogene by p53 requires TRRAP
RT acetyltransferase complexes.";
RL Mol. Cell. Biol. 22:5650-5661(2002).
RN [13]
RP IDENTIFICATION IN THE BAF53 COMPLEX WITH BAF53A; RUVBL1 AND SMARCA4.
RX PubMed=11839798; DOI=10.1128/mcb.22.5.1307-1316.2002;
RA Park J., Wood M.A., Cole M.D.;
RT "BAF53 forms distinct nuclear complexes and functions as a critical c-Myc-
RT interacting nuclear cofactor for oncogenic transformation.";
RL Mol. Cell. Biol. 22:1307-1316(2002).
RN [14]
RP FUNCTION.
RX PubMed=12743606; DOI=10.1038/sj.onc.1206376;
RA Lang S.E., Hearing P.;
RT "The adenovirus E1A oncoprotein recruits the cellular TRRAP/GCN5 histone
RT acetyltransferase complex.";
RL Oncogene 22:2836-2841(2003).
RN [15]
RP FUNCTION.
RX PubMed=12660246; DOI=10.1074/jbc.m211795200;
RA Liu X., Tesfai J., Evrard Y.A., Dent S.Y.R., Martinez E.;
RT "c-Myc transformation domain recruits the human STAGA complex and requires
RT TRRAP and GCN5 acetylase activity for transcription activation.";
RL J. Biol. Chem. 278:20405-20412(2003).
RN [16]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE
RP NUA4 COMPLEX.
RX PubMed=14966270; DOI=10.1128/mcb.24.5.1884-1896.2004;
RA Doyon Y., Selleck W., Lane W.S., Tan S., Cote J.;
RT "Structural and functional conservation of the NuA4 histone
RT acetyltransferase complex from yeast to humans.";
RL Mol. Cell. Biol. 24:1884-1896(2004).
RN [17]
RP IDENTIFICATION IN STAGA COMPLEX.
RX PubMed=18206972; DOI=10.1016/j.molcel.2007.12.011;
RA Zhao Y., Lang G., Ito S., Bonnet J., Metzger E., Sawatsubashi S.,
RA Suzuki E., Le Guezennec X., Stunnenberg H.G., Krasnov A., Georgieva S.G.,
RA Schuele R., Takeyama K., Kato S., Tora L., Devys D.;
RT "A TFTC/STAGA module mediates histone H2A and H2B deubiquitination,
RT coactivates nuclear receptors, and counteracts heterochromatin silencing.";
RL Mol. Cell 29:92-101(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2051, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [19]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH NPAT.
RX PubMed=17967892; DOI=10.1128/mcb.00607-07;
RA DeRan M., Pulvino M., Greene E., Su C., Zhao J.;
RT "Transcriptional activation of histone genes requires NPAT-dependent
RT recruitment of TRRAP-Tip60 complex to histone promoters during the G1/S
RT phase transition.";
RL Mol. Cell. Biol. 28:435-447(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2051 AND SER-2077, 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 [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-3078, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [22]
RP INTERACTION WITH TELO2 AND TTI1.
RX PubMed=20427287; DOI=10.1074/jbc.m110.121699;
RA Kaizuka T., Hara T., Oshiro N., Kikkawa U., Yonezawa K., Takehana K.,
RA Iemura S., Natsume T., Mizushima N.;
RT "Tti1 and Tel2 are critical factors in mammalian target of rapamycin
RT complex assembly.";
RL J. Biol. Chem. 285:20109-20116(2010).
RN [23]
RP 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 [24]
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 [25]
RP PROBABLE INVOLVEMENT IN MELANOMA, VARIANT PHE-722, AND CHARACTERIZATION OF
RP VARIANT PHE-722.
RX PubMed=21499247; DOI=10.1038/ng.810;
RA Wei X., Walia V., Lin J.C., Teer J.K., Prickett T.D., Gartner J., Davis S.,
RA Stemke-Hale K., Davies M.A., Gershenwald J.E., Robinson W., Robinson S.,
RA Rosenberg S.A., Samuels Y.;
RT "Exome sequencing identifies GRIN2A as frequently mutated in melanoma.";
RL Nat. Genet. 43:442-446(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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1628; SER-2051 AND SER-2077,
RP AND 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 [28]
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 [29]
RP FUNCTION, AND IDENTIFICATION IN THE SWR1-LIKE COMPLEX.
RX PubMed=24463511; DOI=10.1038/nature12922;
RA Obri A., Ouararhni K., Papin C., Diebold M.L., Padmanabhan K., Marek M.,
RA Stoll I., Roy L., Reilly P.T., Mak T.W., Dimitrov S., Romier C.,
RA Hamiche A.;
RT "ANP32E is a histone chaperone that removes H2A.Z from chromatin.";
RL Nature 505:648-653(2014).
RN [30]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-2543, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [31]
RP VARIANTS [LARGE SCALE ANALYSIS] CYS-893; GLY-1070; HIS-1669; HIS-1724;
RP VAL-1925; LEU-1932; LEU-1947; GLY-2139; TRP-2302; GLY-2433; LEU-2690;
RP ASP-2750; GLU-2801 AND MET-2931.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [32]
RP INVOLVEMENT IN DEDDFA, AND VARIANT DEDDFA GLN-2004.
RX PubMed=30424743; DOI=10.1186/s12881-018-0711-9;
RA Mavros C.F., Brownstein C.A., Thyagrajan R., Genetti C.A., Tembulkar S.,
RA Graber K., Murphy Q., Cabral K., VanNoy G.E., Bainbridge M., Shi J.,
RA Agrawal P.B., Beggs A.H., D'Angelo E., Gonzalez-Heydrich J.;
RT "De novo variant of TRRAP in a patient with very early onset psychosis in
RT the context of non-verbal learning disability and obsessive-compulsive
RT disorder: a case report.";
RL BMC Med. Genet. 19:197-197(2018).
RN [33]
RP VARIANTS DEDDFA PHE-805; LEU-860; LEU-893; MET-1031; GLN-1035; ARG-1037;
RP THR-1043; GLY-1104; LYS-1106; TRP-1111; ARG-1159; CYS-1859; CYS-1866;
RP ARG-1866; ARG-1883; LEU-1932 AND GLN-3757.
RX PubMed=30827496; DOI=10.1016/j.ajhg.2019.01.010;
RG CAUSES Study;
RG Deciphering Developmental Disorders study;
RA Cogne B., Ehresmann S., Beauregard-Lacroix E., Rousseau J., Besnard T.,
RA Garcia T., Petrovski S., Avni S., McWalter K., Blackburn P.R.,
RA Sanders S.J., Uguen K., Harris J., Cohen J.S., Blyth M., Lehman A.,
RA Berg J., Li M.H., Kini U., Joss S., von der Lippe C., Gordon C.T.,
RA Humberson J.B., Robak L., Scott D.A., Sutton V.R., Skraban C.M.,
RA Johnston J.J., Poduri A., Nordenskjoeld M., Shashi V., Gerkes E.H.,
RA Bongers E.M.H.F., Gilissen C., Zarate Y.A., Kvarnung M., Lally K.P.,
RA Kulch P.A., Daniels B., Hernandez-Garcia A., Stong N., McGaughran J.,
RA Retterer K., Tveten K., Sullivan J., Geisheker M.R., Stray-Pedersen A.,
RA Tarpinian J.M., Klee E.W., Sapp J.C., Zyskind J., Holla O.L., Bedoukian E.,
RA Filippini F., Guimier A., Picard A., Busk O.L., Punetha J., Pfundt R.,
RA Lindstrand A., Nordgren A., Kalb F., Desai M., Ebanks A.H., Jhangiani S.N.,
RA Dewan T., Coban Akdemir Z.H., Telegrafi A., Zackai E.H., Begtrup A.,
RA Song X., Toutain A., Wentzensen I.M., Odent S., Bonneau D., Latypova X.,
RA Deb W., Redon S., Bilan F., Legendre M., Troyer C., Whitlock K.,
RA Caluseriu O., Murphree M.I., Pichurin P.N., Agre K., Gavrilova R.,
RA Rinne T., Park M., Shain C., Heinzen E.L., Xiao R., Amiel J., Lyonnet S.,
RA Isidor B., Biesecker L.G., Lowenstein D., Posey J.E., Denomme-Pichon A.S.,
RA Ferec C., Yang X.J., Rosenfeld J.A., Gilbert-Dussardier B.,
RA Audebert-Bellanger S., Redon R., Stessman H.A.F., Nellaker C., Yang Y.,
RA Lupski J.R., Goldstein D.B., Eichler E.E., Bolduc F., Bezieau S., Kuery S.,
RA Campeau P.M.;
RT "Missense Variants in the Histone Acetyltransferase Complex Component Gene
RT TRRAP Cause Autism and Syndromic Intellectual Disability.";
RL Am. J. Hum. Genet. 104:530-541(2019).
RN [34]
RP VARIANTS DFNA75 CYS-171 AND ASN-394, VARIANT ASP-2750, AND INVOLVEMENT IN
RP DFNA75.
RX PubMed=31231791; DOI=10.1111/cge.13590;
RA Xia W., Hu J., Ma J., Huang J., Wang X., Jiang N., Zhang J., Ma Z., Ma D.;
RT "Novel TRRAP mutation causes autosomal dominant non-syndromic hearing
RT loss.";
RL Clin. Genet. 96:300-308(2019).
CC -!- FUNCTION: Adapter protein, which is found in various multiprotein
CC chromatin complexes with histone acetyltransferase activity (HAT),
CC which gives a specific tag for epigenetic transcription activation.
CC Component of the NuA4 histone acetyltransferase complex which is
CC responsible for acetylation of nucleosomal histones H4 and H2A. Plays a
CC central role in MYC transcription activation, and also participates in
CC cell transformation by MYC. Required for p53/TP53-, E2F1- and E2F4-
CC mediated transcription activation. Also involved in transcription
CC activation mediated by the adenovirus E1A, a viral oncoprotein that
CC deregulates transcription of key genes. Probably acts by linking
CC transcription factors such as E1A, MYC or E2F1 to HAT complexes such as
CC STAGA thereby allowing transcription activation. Probably not required
CC in the steps following histone acetylation in processes of
CC transcription activation. May be required for the mitotic checkpoint
CC and normal cell cycle progression. Component of a SWR1-like complex
CC that specifically mediates the removal of histone H2A.Z/H2AZ1 from the
CC nucleosome. May play a role in the formation and maintenance of the
CC auditory system (By similarity). {ECO:0000250|UniProtKB:A0A0R4ITC5,
CC ECO:0000269|PubMed:11418595, ECO:0000269|PubMed:12138177,
CC ECO:0000269|PubMed:12660246, ECO:0000269|PubMed:12743606,
CC ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:17967892,
CC ECO:0000269|PubMed:24463511, ECO:0000269|PubMed:9708738}.
CC -!- SUBUNIT: Interacts with MYC, E2F1 and E2F4 transcription factors.
CC Interacts directly with p53/TP53. Interacts with GCN5L2. Component of
CC various HAT complexes. Component of the PCAF complex, at least composed
CC of TADA2L/ADA2, SUPT3H, TADA3L/ADA3, TAF5L/PAF65-beta, TAF6L/PAF65-
CC alpha, TAF10/TAFII30, TAF12/TAFII20, TAF9/TAFII31 and TRRAP. Component
CC of the TFTC-HAT complex, at least composed of TAF5L, TAF6L, TADA3L,
CC SUPT3H/SPT3, TAF2/TAFII150, TAF4/TAFII135, TAF5/TAFII100, GCN5L2/GCN5,
CC TAF10 and TRRAP. Component of the NuA4 histone acetyltransferase
CC complex which contains the catalytic subunit KAT5/TIP60 and the
CC subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1,
CC RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15,
CC MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6. Component of
CC the STAGA complex, at least composed of SUPT3H, GCN5L2, SUPT7L, TAF5L,
CC TAF6L, TADA3L, TAD1L, TAF10, TAF12, TRRAP and TAF9. The STAGA core
CC complex is associated with a subcomplex required for histone
CC deubiquitination composed of ATXN7L3, ENY2 and USP22. Component of the
CC BAF53 complex, at least composed of BAF53A, RUVBL1, SMARCA4/BRG1, and
CC TRRAP, which preferentially acetylates histone H4 (and H2A) within
CC nucleosomes. Interacts with NPAT. Interaction with TELO2 AND TTI1.
CC Component of a SWR1-like complex. {ECO:0000269|PubMed:10373431,
CC ECO:0000269|PubMed:10611234, ECO:0000269|PubMed:10966108,
CC ECO:0000269|PubMed:11418595, ECO:0000269|PubMed:11564863,
CC ECO:0000269|PubMed:11839798, ECO:0000269|PubMed:12138177,
CC ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:17967892,
CC ECO:0000269|PubMed:18206972, ECO:0000269|PubMed:20427287,
CC ECO:0000269|PubMed:24463511, ECO:0000269|PubMed:9708738,
CC ECO:0000269|PubMed:9885574}.
CC -!- INTERACTION:
CC Q9Y4A5; O15265: ATXN7; NbExp=7; IntAct=EBI-399128, EBI-708350;
CC Q9Y4A5; P01106: MYC; NbExp=6; IntAct=EBI-399128, EBI-447544;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11564863,
CC ECO:0000269|PubMed:9708738}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y4A5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y4A5-2; Sequence=VSP_009102, VSP_009103;
CC -!- DOMAIN: The PI3K/PI4K domain is required for the recruitment of HAT
CC complexes, and the MYC-dependent transactivation. Although it is
CC strongly related to the PI3/PI4-kinase family, it lacks the typical
CC motifs that constitute the catalytic site of PI3/PI4-kinase proteins,
CC and lacks such activity. {ECO:0000269|PubMed:11445536}.
CC -!- DISEASE: Note=TRRAP mutation Phe-722 has been frequently found in
CC cutaneous malignant melanoma, suggesting that TRRAP may play a role in
CC the pathogenesis of melanoma. {ECO:0000269|PubMed:21499247}.
CC -!- DISEASE: Developmental delay with or without dysmorphic facies and
CC autism (DEDDFA) [MIM:618454]: An autosomal dominant neurodevelopmental
CC disorder apparent from infancy or early childhood. Some patients
CC present with intellectual disability and renal, cardiac, genitourinary
CC systems, as well as structural brain abnormalities. In some cases, the
CC phenotype is less severe, has no systemic involvement and is
CC characterized by autism spectrum disorder and/or intellectual
CC disability, sometimes associated with epilepsy. Affected individuals
CC manifest variable dysmorphic features. {ECO:0000269|PubMed:30424743,
CC ECO:0000269|PubMed:30827496}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Deafness, autosomal dominant, 75 (DFNA75) [MIM:618778]: A form
CC of non-syndromic deafness characterized by late-onset hearing loss that
CC involves mid and high frequencies, and progresses to encompass all
CC frequencies. {ECO:0000269|PubMed:31231791}. Note=The disease may be
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. TRA1 subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC62433.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; AF076974; AAD09420.1; -; mRNA.
DR EMBL; AF110377; AAD04629.1; -; mRNA.
DR EMBL; AC004893; AAC62433.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC004991; AAC27675.2; -; Genomic_DNA.
DR EMBL; CH471091; EAW76694.1; -; Genomic_DNA.
DR EMBL; CH236956; EAL23887.1; -; Genomic_DNA.
DR CCDS; CCDS5659.1; -. [Q9Y4A5-2]
DR CCDS; CCDS59066.1; -. [Q9Y4A5-1]
DR PIR; T02632; T02632.
DR RefSeq; NP_001231509.1; NM_001244580.1. [Q9Y4A5-1]
DR RefSeq; NP_003487.1; NM_003496.3. [Q9Y4A5-2]
DR SMR; Q9Y4A5; -.
DR BioGRID; 113900; 220.
DR ComplexPortal; CPX-6802; SAGA complex, KAT2B variant.
DR ComplexPortal; CPX-900; SAGA complex, KAT2A variant.
DR ComplexPortal; CPX-903; TFTC histone acetylation complex.
DR ComplexPortal; CPX-978; NuA4 histone acetyltransferase complex.
DR ComplexPortal; CPX-989; PCAF histone acetylase complex.
DR CORUM; Q9Y4A5; -.
DR DIP; DIP-28149N; -.
DR IntAct; Q9Y4A5; 81.
DR MINT; Q9Y4A5; -.
DR STRING; 9606.ENSP00000352925; -.
DR iPTMnet; Q9Y4A5; -.
DR MetOSite; Q9Y4A5; -.
DR PhosphoSitePlus; Q9Y4A5; -.
DR BioMuta; TRRAP; -.
DR DMDM; 116242829; -.
DR EPD; Q9Y4A5; -.
DR jPOST; Q9Y4A5; -.
DR MassIVE; Q9Y4A5; -.
DR MaxQB; Q9Y4A5; -.
DR PaxDb; Q9Y4A5; -.
DR PeptideAtlas; Q9Y4A5; -.
DR PRIDE; Q9Y4A5; -.
DR ProteomicsDB; 86142; -. [Q9Y4A5-1]
DR ProteomicsDB; 86143; -. [Q9Y4A5-2]
DR Antibodypedia; 16027; 188 antibodies from 23 providers.
DR DNASU; 8295; -.
DR Ensembl; ENST00000355540.7; ENSP00000347733.3; ENSG00000196367.14. [Q9Y4A5-2]
DR Ensembl; ENST00000359863.8; ENSP00000352925.4; ENSG00000196367.14. [Q9Y4A5-1]
DR GeneID; 8295; -.
DR KEGG; hsa:8295; -.
DR UCSC; uc003upp.3; human. [Q9Y4A5-1]
DR CTD; 8295; -.
DR DisGeNET; 8295; -.
DR GeneCards; TRRAP; -.
DR HGNC; HGNC:12347; TRRAP.
DR HPA; ENSG00000196367; Low tissue specificity.
DR MalaCards; TRRAP; -.
DR MIM; 603015; gene.
DR MIM; 618454; phenotype.
DR MIM; 618778; phenotype.
DR neXtProt; NX_Q9Y4A5; -.
DR OpenTargets; ENSG00000196367; -.
DR Orphanet; 90635; Autosomal dominant non-syndromic sensorineural deafness type DFNA.
DR PharmGKB; PA37020; -.
DR VEuPathDB; HostDB:ENSG00000196367; -.
DR eggNOG; KOG0889; Eukaryota.
DR GeneTree; ENSGT00390000017961; -.
DR InParanoid; Q9Y4A5; -.
DR OrthoDB; 7189at2759; -.
DR PhylomeDB; Q9Y4A5; -.
DR TreeFam; TF106414; -.
DR PathwayCommons; Q9Y4A5; -.
DR Reactome; R-HSA-201722; Formation of the beta-catenin:TCF transactivating complex.
DR Reactome; R-HSA-3214847; HATs acetylate histones.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR SignaLink; Q9Y4A5; -.
DR SIGNOR; Q9Y4A5; -.
DR BioGRID-ORCS; 8295; 742 hits in 1119 CRISPR screens.
DR ChiTaRS; TRRAP; human.
DR GenomeRNAi; 8295; -.
DR Pharos; Q9Y4A5; Tbio.
DR PRO; PR:Q9Y4A5; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9Y4A5; protein.
DR Bgee; ENSG00000196367; Expressed in ventricular zone and 154 other tissues.
DR ExpressionAtlas; Q9Y4A5; baseline and differential.
DR Genevisible; Q9Y4A5; HS.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0035267; C:NuA4 histone acetyltransferase complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0000786; C:nucleosome; IDA:ComplexPortal.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000124; C:SAGA complex; IDA:UniProtKB.
DR GO; GO:0000812; C:Swr1 complex; IDA:UniProtKB.
DR GO; GO:0033276; C:transcription factor TFTC complex; IDA:UniProtKB.
DR GO; GO:0003712; F:transcription coregulator activity; IDA:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IBA:GO_Central.
DR GO; GO:0016573; P:histone acetylation; NAS:UniProtKB.
DR GO; GO:0016578; P:histone deubiquitination; IDA:UniProtKB.
DR GO; GO:0043968; P:histone H2A acetylation; IDA:UniProtKB.
DR GO; GO:0043966; P:histone H3 acetylation; IDA:ComplexPortal.
DR GO; GO:0043967; P:histone H4 acetylation; IDA:UniProtKB.
DR GO; GO:0035521; P:monoubiquitinated histone deubiquitination; IDA:ComplexPortal.
DR GO; GO:0035522; P:monoubiquitinated histone H2A deubiquitination; IDA:ComplexPortal.
DR GO; GO:1905168; P:positive regulation of double-strand break repair via homologous recombination; IDA:ComplexPortal.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IC:ComplexPortal.
DR GO; GO:0042981; P:regulation of apoptotic process; IC:ComplexPortal.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:ComplexPortal.
DR GO; GO:0006282; P:regulation of DNA repair; IC:ComplexPortal.
DR GO; GO:2000779; P:regulation of double-strand break repair; IC:ComplexPortal.
DR GO; GO:0043484; P:regulation of RNA splicing; IC:ComplexPortal.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:ComplexPortal.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR003152; FATC_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR InterPro; IPR003151; PIK-rel_kinase_FAT.
DR InterPro; IPR014009; PIK_FAT.
DR InterPro; IPR033317; TRA1/TRRAP.
DR PANTHER; PTHR11139:SF1; PTHR11139:SF1; 2.
DR Pfam; PF02259; FAT; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR SMART; SM01343; FATC; 1.
DR SMART; SM00146; PI3Kc; 1.
DR SUPFAM; SSF48371; SSF48371; 3.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51189; FAT; 1.
DR PROSITE; PS51190; FATC; 1.
DR PROSITE; PS50290; PI3_4_KINASE_3; 1.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Alternative splicing; Autism spectrum disorder;
KW Chromatin regulator; Deafness; Direct protein sequencing; Disease variant;
KW Intellectual disability; Isopeptide bond; Non-syndromic deafness; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895"
FT CHAIN 2..3859
FT /note="Transformation/transcription domain-associated
FT protein"
FT /id="PRO_0000088851"
FT DOMAIN 2692..3275
FT /note="FAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534"
FT DOMAIN 3500..3823
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT DOMAIN 3827..3859
FT /note="FATC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534,
FT ECO:0000255|PROSITE-ProRule:PRU00535"
FT REGION 491..541
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2010..2388
FT /note="Interaction with TP53"
FT /evidence="ECO:0000269|PubMed:12138177"
FT REGION 2023..2044
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2543..2578
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3506..3512
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 3687..3695
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 3707..3732
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT MOTIF 2047..2062
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 491..525
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2028..2044
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22223895"
FT MOD_RES 1628
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2051
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:23186163"
FT MOD_RES 2077
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 3078
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT CROSSLNK 2543
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1492..1509
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9708738"
FT /id="VSP_009102"
FT VAR_SEQ 3001..3012
FT /note="GKPTWSGMHSSS -> A (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9708738"
FT /id="VSP_009103"
FT VARIANT 171
FT /note="R -> C (in DFNA75; unknown pathological
FT significance; dbSNP:rs200157211)"
FT /evidence="ECO:0000269|PubMed:31231791"
FT /id="VAR_083794"
FT VARIANT 394
FT /note="D -> N (in DFNA75; unknown pathological
FT significance; dbSNP:rs1554407965)"
FT /evidence="ECO:0000269|PubMed:31231791"
FT /id="VAR_083795"
FT VARIANT 722
FT /note="S -> F (found in a cutaneous malignant melanoma
FT sample; somatic mutation; induces cell transformation and
FT confers resistance to apoptosis; dbSNP:rs147405090)"
FT /evidence="ECO:0000269|PubMed:21499247"
FT /id="VAR_067754"
FT VARIANT 805
FT /note="L -> F (in DEDDFA; unknown pathological
FT significance; dbSNP:rs1562940289)"
FT /evidence="ECO:0000269|PubMed:30827496"
FT /id="VAR_082969"
FT VARIANT 860
FT /note="F -> L (in DEDDFA; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:30827496"
FT /id="VAR_082970"
FT VARIANT 878
FT /note="R -> L (in dbSNP:rs17161510)"
FT /id="VAR_028359"
FT VARIANT 893
FT /note="R -> C (in an ovarian serous carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041658"
FT VARIANT 893
FT /note="R -> L (in DEDDFA; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:30827496"
FT /id="VAR_082971"
FT VARIANT 1031
FT /note="I -> M (in DEDDFA)"
FT /evidence="ECO:0000269|PubMed:30827496"
FT /id="VAR_082972"
FT VARIANT 1035
FT /note="R -> Q (in DEDDFA; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:30827496"
FT /id="VAR_082973"
FT VARIANT 1037
FT /note="S -> R (in DEDDFA; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:30827496"
FT /id="VAR_082974"
FT VARIANT 1043
FT /note="A -> T (in DEDDFA; dbSNP:rs1562945106)"
FT /evidence="ECO:0000269|PubMed:30827496"
FT /id="VAR_082975"
FT VARIANT 1070
FT /note="S -> G (in dbSNP:rs55920979)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041659"
FT VARIANT 1104
FT /note="E -> G (in DEDDFA)"
FT /evidence="ECO:0000269|PubMed:30827496"
FT /id="VAR_082976"
FT VARIANT 1106
FT /note="E -> K (in DEDDFA; dbSNP:rs1584324956)"
FT /evidence="ECO:0000269|PubMed:30827496"
FT /id="VAR_082977"
FT VARIANT 1111
FT /note="G -> W (in DEDDFA; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:30827496"
FT /id="VAR_082978"
FT VARIANT 1159
FT /note="G -> R (in DEDDFA)"
FT /evidence="ECO:0000269|PubMed:30827496"
FT /id="VAR_082979"
FT VARIANT 1669
FT /note="R -> H (in a colorectal adenocarcinoma sample;
FT somatic mutation; dbSNP:rs373632999)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041660"
FT VARIANT 1724
FT /note="R -> H (in a gastric adenocarcinoma sample; somatic
FT mutation; dbSNP:rs782203759)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041661"
FT VARIANT 1859
FT /note="R -> C (in DEDDFA)"
FT /evidence="ECO:0000269|PubMed:30827496"
FT /id="VAR_082980"
FT VARIANT 1866
FT /note="W -> C (in DEDDFA; unknown pathological
FT significance; dbSNP:rs1562957576)"
FT /evidence="ECO:0000269|PubMed:30827496"
FT /id="VAR_082981"
FT VARIANT 1866
FT /note="W -> R (in DEDDFA; dbSNP:rs1562957569)"
FT /evidence="ECO:0000269|PubMed:30827496"
FT /id="VAR_082982"
FT VARIANT 1883
FT /note="G -> R (in DEDDFA)"
FT /evidence="ECO:0000269|PubMed:30827496"
FT /id="VAR_082983"
FT VARIANT 1925
FT /note="A -> V (in dbSNP:rs56197298)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041662"
FT VARIANT 1932
FT /note="P -> L (in DEDDFA; unknown pathological
FT significance; also found in a colorectal adenocarcinoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:30827496"
FT /id="VAR_041663"
FT VARIANT 1947
FT /note="R -> L (in an ovarian mucinous carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041664"
FT VARIANT 2004
FT /note="R -> Q (in DEDDFA; unknown pathological
FT significance; dbSNP:rs1562959030)"
FT /evidence="ECO:0000269|PubMed:30424743"
FT /id="VAR_082984"
FT VARIANT 2139
FT /note="W -> G (in dbSNP:rs34185633)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041665"
FT VARIANT 2302
FT /note="R -> W (in a colorectal adenocarcinoma sample;
FT somatic mutation; dbSNP:rs528967912)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041666"
FT VARIANT 2433
FT /note="S -> G (in dbSNP:rs35634065)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041667"
FT VARIANT 2690
FT /note="P -> L (in a lung large cell carcinoma sample;
FT somatic mutation; dbSNP:rs753661271)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041668"
FT VARIANT 2750
FT /note="E -> D (in dbSNP:rs55755466)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:31231791"
FT /id="VAR_041669"
FT VARIANT 2801
FT /note="K -> E (in dbSNP:rs56341061)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041670"
FT VARIANT 2931
FT /note="T -> M (in a colorectal adenocarcinoma sample;
FT somatic mutation; dbSNP:rs1294404368)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041671"
FT VARIANT 3757
FT /note="R -> Q (in DEDDFA; unknown pathological
FT significance; dbSNP:rs987263983)"
FT /evidence="ECO:0000269|PubMed:30827496"
FT /id="VAR_082985"
FT CONFLICT 660
FT /note="E -> D (in Ref. 2; AAD04629)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 3859 AA; 437600 MW; 391E467C0047B00B CRC64;
MAFVATQGAT VVDQTTLMKK YLQFVAALTD VNTPDETKLK MMQEVSENFE NVTSSPQYST
FLEHIIPRFL TFLQDGEVQF LQEKPAQQLR KLVLEIIHRI PTNEHLRPHT KNVLSVMFRF
LETENEENVL ICLRIIIELH KQFRPPITQE IHHFLDFVKQ IYKELPKVVN RYFENPQVIP
ENTVPPPEMV GMITTIAVKV NPEREDSETR THSIIPRGSL SLKVLAELPI IVVLMYQLYK
LNIHNVVAEF VPLIMNTIAI QVSAQARQHK LYNKELYADF IAAQIKTLSF LAYIIRIYQE
LVTKYSQQMV KGMLQLLSNC PAETAHLRKE LLIAAKHILT TELRNQFIPC MDKLFDESIL
IGSGYTARET LRPLAYSTLA DLVHHVRQHL PLSDLSLAVQ LFAKNIDDES LPSSIQTMSC
KLLLNLVDCI RSKSEQESGN GRDVLMRMLE VFVLKFHTIA RYQLSAIFKK CKPQSELGAV
EAALPGVPTA PAAPGPAPSP APVPAPPPPP PPPPPATPVT PAPVPPFEKQ GEKDKEDKQT
FQVTDCRSLV KTLVCGVKTI TWGITSCKAP GEAQFIPNKQ LQPKETQIYI KLVKYAMQAL
DIYQVQIAGN GQTYIRVANC QTVRMKEEKE VLEHFAGVFT MMNPLTFKEI FQTTVPYMVE
RISKNYALQI VANSFLANPT TSALFATILV EYLLDRLPEM GSNVELSNLY LKLFKLVFGS
VSLFAAENEQ MLKPHLHKIV NSSMELAQTA KEPYNYFLLL RALFRSIGGG SHDLLYQEFL
PLLPNLLQGL NMLQSGLHKQ HMKDLFVELC LTVPVRLSSL LPYLPMLMDP LVSALNGSQT
LVSQGLRTLE LCVDNLQPDF LYDHIQPVRA ELMQALWRTL RNPADSISHV AYRVLGKFGG
SNRKMLKESQ KLHYVVTEVQ GPSITVEFSD CKASLQLPME KAIETALDCL KSANTEPYYR
RQAWEVIKCF LVAMMSLEDN KHALYQLLAH PNFTEKTIPN VIISHRYKAQ DTPARKTFEQ
ALTGAFMSAV IKDLRPSALP FVASLIRHYT MVAVAQQCGP FLLPCYQVGS QPSTAMFHSE
ENGSKGMDPL VLIDAIAICM AYEEKELCKI GEVALAVIFD VASIILGSKE RACQLPLFSY
IVERLCACCY EQAWYAKLGG VVSIKFLMER LPLTWVLQNQ QTFLKALLFV MMDLTGEVSN
GAVAMAKTTL EQLLMRCATP LKDEERAEEI VAAQEKSFHH VTHDLVREVT SPNSTVRKQA
MHSLQVLAQV TGKSVTVIME PHKEVLQDMV PPKKHLLRHQ PANAQIGLME GNTFCTTLQP
RLFTMDLNVV EHKVFYTELL NLCEAEDSAL TKLPCYKSLP SLVPLRIAAL NALAACNYLP
QSREKIIAAL FKALNSTNSE LQEAGEACMR KFLEGATIEV DQIHTHMRPL LMMLGDYRSL
TLNVVNRLTS VTRLFPNSFN DKFCDQMMQH LRKWMEVVVI THKGGQRSDG NESISECGRC
PLSPFCQFEE MKICSAIINL FHLIPAAPQT LVKPLLEVVM KTERAMLIEA GSPFREPLIK
FLTRHPSQTV ELFMMEATLN DPQWSRMFMS FLKHKDARPL RDVLAANPNR FITLLLPGGA
QTAVRPGSPS TSTMRLDLQF QAIKIISIIV KNDDSWLASQ HSLVSQLRRV WVSENFQERH
RKENMAATNW KEPKLLAYCL LNYCKRNYGD IELLFQLLRA FTGRFLCNMT FLKEYMEEEI
PKNYSIAQKR ALFFRFVDFN DPNFGDELKA KVLQHILNPA FLYSFEKGEG EQLLGPPNPE
GDNPESITSV FITKVLDPEK QADMLDSLRI YLLQYATLLV EHAPHHIHDN NKNRNSKLRR
LMTFAWPCLL SKACVDPACK YSGHLLLAHI IAKFAIHKKI VLQVFHSLLK AHAMEARAIV
RQAMAILTPA VPARMEDGHQ MLTHWTRKII VEEGHTVPQL VHILHLIVQH FKVYYPVRHH
LVQHMVSAMQ RLGFTPSVTI EQRRLAVDLS EVVIKWELQR IKDQQPDSDM DPNSSGEGVN
SVSSSIKRGL SVDSAQEVKR FRTATGAISA VFGRSQSLPG ADSLLAKPID KQHTDTVVNF
LIRVACQVND NTNTAGSPGE VLSRRCVNLL KTALRPDMWP KSELKLQWFD KLLMTVEQPN
QVNYGNICTG LEVLSFLLTV LQSPAILSSF KPLQRGIAAC MTCGNTKVLR AVHSLLSRLM
SIFPTEPSTS SVASKYEELE CLYAAVGKVI YEGLTNYEKA TNANPSQLFG TLMILKSACS
NNPSYIDRLI SVFMRSLQKM VREHLNPQAA SGSTEATSGT SELVMLSLEL VKTRLAVMSM
EMRKNFIQAI LTSLIEKSPD AKILRAVVKI VEEWVKNNSP MAANQTPTLR EKSILLVKMM
TYIEKRFPED LELNAQFLDL VNYVYRDETL SGSELTAKLE PAFLSGLRCA QPLIRAKFFE
VFDNSMKRRV YERLLYVTCS QNWEAMGNHF WIKQCIELLL AVCEKSTPIG TSCQGAMLPS
ITNVINLADS HDRAAFAMVT HVKQEPRERE NSESKEEDVE IDIELAPGDQ TSTPKTKELS
EKDIGNQLHM LTNRHDKFLD TLREVKTGAL LSAFVQLCHI STTLAEKTWV QLFPRLWKIL
SDRQQHALAG EISPFLCSGS HQVQRDCQPS ALNCFVEAMS QCVPPIPIRP CVLKYLGKTH
NLWFRSTLML EHQAFEKGLS LQIKPKQTTE FYEQESITPP QQEILDSLAE LYSLLQEEDM
WAGLWQKRCK YSETATAIAY EQHGFFEQAQ ESYEKAMDKA KKEHERSNAS PAIFPEYQLW
EDHWIRCSKE LNQWEALTEY GQSKGHINPY LVLECAWRVS NWTAMKEALV QVEVSCPKEM
AWKVNMYRGY LAICHPEEQQ LSFIERLVEM ASSLAIREWR RLPHVVSHVH TPLLQAAQQI
IELQEAAQIN AGLQPTNLGR NNSLHDMKTV VKTWRNRLPI VSDDLSHWSS IFMWRQHHYQ
GKPTWSGMHS SSIVTAYENS SQHDPSSNNA MLGVHASASA IIQYGKIARK QGLVNVALDI
LSRIHTIPTV PIVDCFQKIR QQVKCYLQLA GVMGKNECMQ GLEVIESTNL KYFTKEMTAE
FYALKGMFLA QINKSEEANK AFSAAVQMHD VLVKAWAMWG DYLENIFVKE RQLHLGVSAI
TCYLHACRHQ NESKSRKYLA KVLWLLSFDD DKNTLADAVD KYCIGVPPIQ WLAWIPQLLT
CLVGSEGKLL LNLISQVGRV YPQAVYFPIR TLYLTLKIEQ RERYKSDPGP IRATAPMWRC
SRIMHMQREL HPTLLSSLEG IVDQMVWFRE NWHEEVLRQL QQGLAKCYSV AFEKSGAVSD
AKITPHTLNF VKKLVSTFGV GLENVSNVST MFSSAASESL ARRAQATAQD PVFQKLKGQF
TTDFDFSVPG SMKLHNLISK LKKWIKILEA KTKQLPKFFL IEEKCRFLSN FSAQTAEVEI
PGEFLMPKPT HYYIKIARFM PRVEIVQKHN TAARRLYIRG HNGKIYPYLV MNDACLTESR
REERVLQLLR LLNPCLEKRK ETTKRHLFFT VPRVVAVSPQ MRLVEDNPSS LSLVEIYKQR
CAKKGIEHDN PISRYYDRLA TVQARGTQAS HQVLRDILKE VQSNMVPRSM LKEWALHTFP
NATDYWTFRK MFTIQLALIG FAEFVLHLNR LNPEMLQIAQ DTGKLNVAYF RFDINDATGD
LDANRPVPFR LTPNISEFLT TIGVSGPLTA SMIAVARCFA QPNFKVDGIL KTVLRDEIIA
WHKKTQEDTS SPLSAAGQPE NMDSQQLVSL VQKAVTAIMT RLHNLAQFEG GESKVNTLVA
AANSLDNLCR MDPAWHPWL
