FL2D_HUMAN
ID FL2D_HUMAN Reviewed; 396 AA.
AC Q15007; Q5TCL8; Q5TCL9; Q96T28; Q9BYJ7; Q9H4E2;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 2.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Pre-mRNA-splicing regulator WTAP {ECO:0000305};
DE AltName: Full=Female-lethal(2)D homolog {ECO:0000303|PubMed:12444081};
DE Short=hFL(2)D {ECO:0000303|PubMed:12444081};
DE AltName: Full=WT1-associated protein {ECO:0000303|PubMed:11001926};
DE AltName: Full=Wilms tumor 1-associating protein {ECO:0000303|PubMed:11001926};
GN Name=WTAP {ECO:0000303|PubMed:11001926, ECO:0000312|HGNC:HGNC:16846};
GN Synonyms=KIAA0105 {ECO:0000303|PubMed:7788527};
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 1), AND FUNCTION.
RX PubMed=12444081; DOI=10.1074/jbc.m210737200;
RA Ortega A., Niksic M., Bachi A., Wilm M., Sanchez L., Hastie N.,
RA Valcarcel J.;
RT "Biochemical function of female-lethal (2)D/Wilms' tumor suppressor-1-
RT associated proteins in alternative pre-mRNA splicing.";
RL J. Biol. Chem. 278:3040-3047(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Bone marrow;
RX PubMed=7788527; DOI=10.1093/dnares/2.1.37;
RA Nagase T., Miyajima N., Tanaka A., Sazuka T., Seki N., Sato S., Tabata S.,
RA Ishikawa K., Kawarabayasi Y., Kotani H., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. III. The
RT coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 2:37-43(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Lung, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 1-9; 44-56; 72-79; 99-123; 163-173; 180-192; 234-253
RP AND 380-396, ACETYLATION AT MET-1, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V., Lempens A., Norman J.C.;
RL Submitted (OCT-2009) to UniProtKB.
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-391 (ISOFORM 1), INTERACTION WITH WT1,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Fetal kidney;
RX PubMed=11001926; DOI=10.1093/oxfordjournals.hmg.a018914;
RA Little N.A., Hastie N.D., Davies R.C.;
RT "Identification of WTAP, a novel Wilms' tumour 1-associating protein.";
RL Hum. Mol. Genet. 9:2231-2239(2000).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 112-396 (ISOFORM 1).
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [10]
RP FUNCTION.
RX PubMed=17088532; DOI=10.1073/pnas.0608357103;
RA Horiuchi K., Umetani M., Minami T., Okayama H., Takada S., Yamamoto M.,
RA Aburatani H., Reid P.C., Housman D.E., Hamakubo T., Kodama T.;
RT "Wilms' tumor 1-associating protein regulates G2/M transition through
RT stabilization of cyclin A2 mRNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:17278-17283(2006).
RN [11]
RP FUNCTION, AND INTERACTION WITH WT1.
RX PubMed=17095724; DOI=10.1161/01.res.0000252289.79841.d3;
RA Small T.W., Bolender Z., Bueno C., O'Neil C., Nong Z., Rushlow W.,
RA Rajakumar N., Kandel C., Strong J., Madrenas J., Pickering J.G.;
RT "Wilms' tumor 1-associating protein regulates the proliferation of vascular
RT smooth muscle cells.";
RL Circ. Res. 99:1338-1346(2006).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306, AND IDENTIFICATION BY
RP 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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-305 AND SER-306, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306 AND SER-388, AND
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 [16]
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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [19]
RP IDENTIFICATION IN A MACOM-LIKE COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=24100041; DOI=10.1074/jbc.m113.500397;
RA Horiuchi K., Kawamura T., Iwanari H., Ohashi R., Naito M., Kodama T.,
RA Hamakubo T.;
RT "Identification of Wilms' tumor 1-associating protein complex and its role
RT in alternative splicing and the cell cycle.";
RL J. Biol. Chem. 288:33292-33302(2013).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14 AND SER-305, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [21]
RP FUNCTION, SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE WMM COMPLEX.
RX PubMed=24407421; DOI=10.1038/cr.2014.3;
RA Ping X.L., Sun B.F., Wang L., Xiao W., Yang X., Wang W.J., Adhikari S.,
RA Shi Y., Lv Y., Chen Y.S., Zhao X., Li A., Yang Y., Dahal U., Lou X.M.,
RA Liu X., Huang J., Yuan W.P., Zhu X.F., Cheng T., Zhao Y.L., Wang X.,
RA Danielsen J.M., Liu F., Yang Y.G.;
RT "Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine
RT methyltransferase.";
RL Cell Res. 24:177-189(2014).
RN [22]
RP FUNCTION, AND IDENTIFICATION IN THE WMM COMPLEX.
RX PubMed=24981863; DOI=10.1016/j.celrep.2014.05.048;
RA Schwartz S., Mumbach M.R., Jovanovic M., Wang T., Maciag K., Bushkin G.G.,
RA Mertins P., Ter-Ovanesyan D., Habib N., Cacchiarelli D., Sanjana N.E.,
RA Freinkman E., Pacold M.E., Satija R., Mikkelsen T.S., Hacohen N., Zhang F.,
RA Carr S.A., Lander E.S., Regev A.;
RT "Perturbation of m6A writers reveals two distinct classes of mRNA
RT methylation at internal and 5' sites.";
RL Cell Rep. 8:284-296(2014).
RN [23]
RP FUNCTION, SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE WMM COMPLEX.
RX PubMed=24316715; DOI=10.1038/nchembio.1432;
RA Liu J., Yue Y., Han D., Wang X., Fu Y., Zhang L., Jia G., Yu M., Lu Z.,
RA Deng X., Dai Q., Chen W., He C.;
RT "A METTL3-METTL14 complex mediates mammalian nuclear RNA N-adenosine
RT methylation.";
RL Nat. Chem. Biol. 10:93-95(2014).
RN [24]
RP SUBCELLULAR LOCATION.
RX PubMed=26458103; DOI=10.1038/nature15377;
RA Zhou J., Wan J., Gao X., Zhang X., Jaffrey S.R., Qian S.B.;
RT "Dynamic m(6)A mRNA methylation directs translational control of heat shock
RT response.";
RL Nature 526:591-594(2015).
RN [25]
RP FUNCTION, AND IDENTIFICATION IN THE WMM COMPLEX.
RX PubMed=29507755; DOI=10.1038/s41421-018-0019-0;
RA Yue Y., Liu J., Cui X., Cao J., Luo G., Zhang Z., Cheng T., Gao M., Shu X.,
RA Ma H., Wang F., Wang X., Shen B., Wang Y., Feng X., He C., Liu J.;
RT "VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop
RT codon and associates with alternative polyadenylation.";
RL Cell Discov. 4:10-10(2018).
RN [26]
RP IDENTIFICATION IN THE WMM COMPLEX.
RX PubMed=29506078; DOI=10.1093/nar/gky156;
RA Du Y., Hou G., Zhang H., Dou J., He J., Guo Y., Li L., Chen R., Wang Y.,
RA Deng R., Huang J., Jiang B., Xu M., Cheng J., Chen G.Q., Zhao X., Yu J.;
RT "SUMOylation of the m6A-RNA methyltransferase METTL3 modulates its
RT function.";
RL Nucleic Acids Res. 46:5195-5208(2018).
RN [27]
RP IDENTIFICATION IN THE WMM COMPLEX.
RX PubMed=29348140; DOI=10.1261/rna.064063.117;
RA Schoeller E., Weichmann F., Treiber T., Ringle S., Treiber N., Flatley A.,
RA Feederle R., Bruckmann A., Meister G.;
RT "Interactions, localization, and phosphorylation of the m6A generating
RT METTL3-METTL14-WTAP complex.";
RL RNA 24:499-512(2018).
CC -!- FUNCTION: Associated component of the WMM complex, a complex that
CC mediates N6-methyladenosine (m6A) methylation of RNAs, a modification
CC that plays a role in the efficiency of mRNA splicing and RNA processing
CC (PubMed:29507755). Required for accumulation of METTL3 and METTL14 to
CC nuclear speckle (PubMed:24316715, PubMed:24407421, PubMed:24981863).
CC Acts as a mRNA splicing regulator (PubMed:12444081). Regulates G2/M
CC cell-cycle transition by binding to the 3' UTR of CCNA2, which enhances
CC its stability (PubMed:17088532). Impairs WT1 DNA-binding ability and
CC inhibits expression of WT1 target genes (PubMed:17095724).
CC {ECO:0000269|PubMed:12444081, ECO:0000269|PubMed:17088532,
CC ECO:0000269|PubMed:17095724, ECO:0000269|PubMed:24316715,
CC ECO:0000269|PubMed:24407421, ECO:0000269|PubMed:24981863,
CC ECO:0000269|PubMed:29507755}.
CC -!- SUBUNIT: Component of the WMM complex, a N6-methyltransferase complex
CC composed of a catalytic subcomplex, named MAC, and of an associated
CC subcomplex, named MACOM (PubMed:24407421, PubMed:24981863,
CC PubMed:24316715, PubMed:29507755, PubMed:29506078, PubMed:29348140).
CC The MAC subcomplex is composed of METTL3 and METTL14 (PubMed:29507755).
CC The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA,
CC and, in some cases of RBM15 (RBM15 or RBM15B) (PubMed:29507755).
CC Interacts with WT1 (PubMed:11001926, PubMed:17095724). Also a component
CC of a MACOM-like complex, named WTAP complex, composed of WTAP, ZC3H13,
CC CBLL1, VIRMA, RBM15, BCLAF1 and THRAP3 (PubMed:24100041).
CC {ECO:0000269|PubMed:11001926, ECO:0000269|PubMed:17095724,
CC ECO:0000269|PubMed:24100041, ECO:0000269|PubMed:24316715,
CC ECO:0000269|PubMed:24407421, ECO:0000269|PubMed:24981863,
CC ECO:0000269|PubMed:29348140, ECO:0000269|PubMed:29506078,
CC ECO:0000269|PubMed:29507755}.
CC -!- INTERACTION:
CC Q15007; Q6UXT9: ABHD15; NbExp=3; IntAct=EBI-751647, EBI-2824666;
CC Q15007; Q13895: BYSL; NbExp=3; IntAct=EBI-751647, EBI-358049;
CC Q15007; Q13422: IKZF1; NbExp=3; IntAct=EBI-751647, EBI-745305;
CC Q15007; Q13422-7: IKZF1; NbExp=7; IntAct=EBI-751647, EBI-11522367;
CC Q15007; P43364: MAGEA11; NbExp=4; IntAct=EBI-751647, EBI-739552;
CC Q15007; P25786: PSMA1; NbExp=3; IntAct=EBI-751647, EBI-359352;
CC Q15007; Q9GZT3: SLIRP; NbExp=4; IntAct=EBI-751647, EBI-1050793;
CC Q15007; Q99081-3: TCF12; NbExp=3; IntAct=EBI-751647, EBI-11952764;
CC Q15007; Q15025: TNIP1; NbExp=3; IntAct=EBI-751647, EBI-357849;
CC Q15007; Q93009: USP7; NbExp=2; IntAct=EBI-751647, EBI-302474;
CC Q15007; Q8N1B4: VPS52; NbExp=6; IntAct=EBI-751647, EBI-2799833;
CC Q15007; P19544-6: WT1; NbExp=3; IntAct=EBI-751647, EBI-11745701;
CC Q15007; Q15007: WTAP; NbExp=3; IntAct=EBI-751647, EBI-751647;
CC Q15007; Q16600: ZNF239; NbExp=3; IntAct=EBI-751647, EBI-8787052;
CC Q15007; Q7Z3I7: ZNF572; NbExp=3; IntAct=EBI-751647, EBI-10172590;
CC Q15007-1; Q9HCE5: METTL14; NbExp=5; IntAct=EBI-16084961, EBI-6661081;
CC Q15007-2; P54252: ATXN3; NbExp=3; IntAct=EBI-25840023, EBI-946046;
CC Q15007-2; P07339: CTSD; NbExp=3; IntAct=EBI-25840023, EBI-2115097;
CC Q15007-2; O43464: HTRA2; NbExp=3; IntAct=EBI-25840023, EBI-517086;
CC Q15007-2; P42858: HTT; NbExp=3; IntAct=EBI-25840023, EBI-466029;
CC Q15007-2; O60333-2: KIF1B; NbExp=3; IntAct=EBI-25840023, EBI-10975473;
CC Q15007-2; P41219: PRPH; NbExp=3; IntAct=EBI-25840023, EBI-752074;
CC Q15007-2; P60891: PRPS1; NbExp=3; IntAct=EBI-25840023, EBI-749195;
CC Q15007-2; O76024: WFS1; NbExp=3; IntAct=EBI-25840023, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Nucleus speckle {ECO:0000269|PubMed:24407421}.
CC Nucleus, nucleoplasm {ECO:0000269|PubMed:11001926,
CC ECO:0000269|PubMed:24316715, ECO:0000269|PubMed:26458103}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9ER69}. Note=Mainly nuclear with some fraction
CC located in the cytoplasm. ZC3H13 is required to anchor component of the
CC MACOM subcomplex, such as VIRMA, in the nucleus.
CC {ECO:0000250|UniProtKB:Q9ER69}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q15007-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15007-2; Sequence=VSP_010278, VSP_010279;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:11001926}.
CC -!- INDUCTION: In smooth muscle cells, up-regulated after serum withdrawal,
CC when cells become mature and non proliferative.
CC -!- SIMILARITY: Belongs to the fl(2)d family. {ECO:0000305}.
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DR EMBL; AF374416; AAK54764.1; -; mRNA.
DR EMBL; D14661; BAA03495.1; -; mRNA.
DR EMBL; AK127822; BAG54579.1; -; mRNA.
DR EMBL; AL135914; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW47622.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW47624.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW47625.1; -; Genomic_DNA.
DR EMBL; BC000383; AAH00383.1; -; mRNA.
DR EMBL; BC004432; AAH04432.1; -; mRNA.
DR EMBL; BC069192; AAH69192.1; -; mRNA.
DR EMBL; AJ276706; CAC10188.1; -; mRNA.
DR EMBL; AL583911; CAC29495.1; -; mRNA.
DR CCDS; CCDS5266.1; -. [Q15007-1]
DR CCDS; CCDS5267.1; -. [Q15007-2]
DR RefSeq; NP_001257460.1; NM_001270531.1. [Q15007-1]
DR RefSeq; NP_001257461.1; NM_001270532.1.
DR RefSeq; NP_001257462.1; NM_001270533.1.
DR RefSeq; NP_004897.2; NM_004906.4. [Q15007-1]
DR RefSeq; NP_690596.1; NM_152857.2. [Q15007-2]
DR RefSeq; NP_690597.1; NM_152858.2. [Q15007-2]
DR AlphaFoldDB; Q15007; -.
DR SMR; Q15007; -.
DR BioGRID; 114957; 165.
DR ComplexPortal; CPX-1605; WMM N6-adenosine-methyltransferase complex.
DR CORUM; Q15007; -.
DR DIP; DIP-57185N; -.
DR IntAct; Q15007; 145.
DR MINT; Q15007; -.
DR STRING; 9606.ENSP00000351141; -.
DR ChEMBL; CHEMBL4523298; -.
DR GlyGen; Q15007; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q15007; -.
DR MetOSite; Q15007; -.
DR PhosphoSitePlus; Q15007; -.
DR SwissPalm; Q15007; -.
DR BioMuta; WTAP; -.
DR DMDM; 47117889; -.
DR EPD; Q15007; -.
DR jPOST; Q15007; -.
DR MassIVE; Q15007; -.
DR MaxQB; Q15007; -.
DR PaxDb; Q15007; -.
DR PeptideAtlas; Q15007; -.
DR PRIDE; Q15007; -.
DR ProteomicsDB; 60358; -. [Q15007-1]
DR ProteomicsDB; 60359; -. [Q15007-2]
DR Antibodypedia; 2136; 360 antibodies from 31 providers.
DR DNASU; 9589; -.
DR Ensembl; ENST00000337387.4; ENSP00000336911.4; ENSG00000146457.16. [Q15007-2]
DR Ensembl; ENST00000358372.8; ENSP00000351141.4; ENSG00000146457.16. [Q15007-1]
DR Ensembl; ENST00000621533.5; ENSP00000479438.1; ENSG00000146457.16. [Q15007-1]
DR Ensembl; ENST00000650096.1; ENSP00000497840.1; ENSG00000146457.16. [Q15007-2]
DR GeneID; 9589; -.
DR KEGG; hsa:9589; -.
DR MANE-Select; ENST00000621533.5; ENSP00000479438.1; NM_001270531.2; NP_001257460.1.
DR UCSC; uc003qsl.6; human. [Q15007-1]
DR CTD; 9589; -.
DR DisGeNET; 9589; -.
DR GeneCards; WTAP; -.
DR HGNC; HGNC:16846; WTAP.
DR HPA; ENSG00000146457; Low tissue specificity.
DR MIM; 605442; gene.
DR neXtProt; NX_Q15007; -.
DR OpenTargets; ENSG00000146457; -.
DR PharmGKB; PA134864847; -.
DR VEuPathDB; HostDB:ENSG00000146457; -.
DR eggNOG; KOG2991; Eukaryota.
DR GeneTree; ENSGT00390000013931; -.
DR HOGENOM; CLU_044551_1_0_1; -.
DR InParanoid; Q15007; -.
DR OMA; FPMSPVV; -.
DR OrthoDB; 907345at2759; -.
DR PhylomeDB; Q15007; -.
DR TreeFam; TF325869; -.
DR PathwayCommons; Q15007; -.
DR Reactome; R-HSA-72203; Processing of Capped Intron-Containing Pre-mRNA.
DR SignaLink; Q15007; -.
DR BioGRID-ORCS; 9589; 480 hits in 1083 CRISPR screens.
DR ChiTaRS; WTAP; human.
DR GeneWiki; WTAP_(gene); -.
DR GenomeRNAi; 9589; -.
DR Pharos; Q15007; Tbio.
DR PRO; PR:Q15007; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q15007; protein.
DR Bgee; ENSG00000146457; Expressed in secondary oocyte and 202 other tissues.
DR ExpressionAtlas; Q15007; baseline and differential.
DR Genevisible; Q15007; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0036396; C:RNA N6-methyladenosine methyltransferase complex; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0080009; P:mRNA methylation; IMP:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IMP:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR InterPro; IPR033757; WTAP.
DR PANTHER; PTHR15217; PTHR15217; 1.
DR Pfam; PF17098; Wtap; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cell cycle; Cytoplasm;
KW Developmental protein; Direct protein sequencing; mRNA processing;
KW mRNA splicing; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..396
FT /note="Pre-mRNA-splicing regulator WTAP"
FT /id="PRO_0000065983"
FT REGION 240..396
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 240..294
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 301..356
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 375..396
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|Ref.7, ECO:0007744|PubMed:22814378"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 305
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 341
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ER69"
FT MOD_RES 350
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9ER69"
FT MOD_RES 388
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT VAR_SEQ 151
FT /note="S -> R (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:7788527"
FT /id="VSP_010278"
FT VAR_SEQ 152..396
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:7788527"
FT /id="VSP_010279"
FT VARIANT 84
FT /note="E -> D (in dbSNP:rs35059844)"
FT /id="VAR_036854"
SQ SEQUENCE 396 AA; 44244 MW; B4F81B3000F77A37 CRC64;
MTNEEPLPKK VRLSETDFKV MARDELILRW KQYEAYVQAL EGKYTDLNSN DVTGLRESEE
KLKQQQQESA RRENILVMRL ATKEQEMQEC TTQIQYLKQV QQPSVAQLRS TMVDPAINLF
FLKMKGELEQ TKDKLEQAQN ELSAWKFTPD SQTGKKLMAK CRMLIQENQE LGRQLSQGRI
AQLEAELALQ KKYSEELKSS QDELNDFIIQ LDEEVEGMQS TILVLQQQLK ETRQQLAQYQ
QQQSQASAPS TSRTTASEPV EQSEATSKDC SRLTNGPSNG SSSRQRTSGS GFHREGNTTE
DDFPSSPGNG NKSSNSSEER TGRGGSGYVN QLSAGYESVD SPTGSENSLT HQSNDTDSSH
DPQEEKAVSG KGNRTVGSRH VQNGLDSSVN VQGSVL
