FL2D_MOUSE
ID FL2D_MOUSE Reviewed; 396 AA.
AC Q9ER69; Q3U120; Q566J5;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 3.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Pre-mRNA-splicing regulator WTAP {ECO:0000305};
DE AltName: Full=Female-lethal(2)D homolog {ECO:0000250|UniProtKB:Q15007};
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|MGI:MGI:1926395};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 18-396 (ISOFORM 1).
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=Czech II; TISSUE=Eye, and Mammary tumor;
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 [4]
RP INTERACTION WITH CPNE4.
RX PubMed=12522145; DOI=10.1074/jbc.m212632200;
RA Tomsig J.L., Snyder S.L., Creutz C.E.;
RT "Identification of targets for calcium signaling through the copine family
RT of proteins. Characterization of a coiled-coil copine-binding motif.";
RL J. Biol. Chem. 278:10048-10054(2003).
RN [5]
RP DISRUPTION PHENOTYPE.
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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-297; SER-341 AND THR-350, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION, AND IDENTIFICATION IN THE WMM COMPLEX.
RX PubMed=29535189; DOI=10.1101/gad.309146.117;
RA Knuckles P., Lence T., Haussmann I.U., Jacob D., Kreim N., Carl S.H.,
RA Masiello I., Hares T., Villasenor R., Hess D., Andrade-Navarro M.A.,
RA Biggiogera M., Helm M., Soller M., Buehler M., Roignant J.Y.;
RT "Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-
RT binding factor Rbm15/Spenito to the m6A machinery component Wtap/Fl(2)d.";
RL Genes Dev. 32:415-429(2018).
RN [8]
RP FUNCTION, IDENTIFICATION IN THE WMM COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=29547716; DOI=10.1016/j.molcel.2018.02.015;
RA Wen J., Lv R., Ma H., Shen H., He C., Wang J., Jiao F., Liu H., Yang P.,
RA Tan L., Lan F., Shi Y.G., He C., Shi Y., Diao J.;
RT "Zc3h13 regulates nuclear RNA m6A methylation and mouse embryonic stem cell
RT self-renewal.";
RL Mol. Cell 69:1028-1038(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:29535189, PubMed:29547716). Acts as a key regulator of m6A
CC methylation by promoting m6A methylation of mRNAs at the 3'-UTR
CC (PubMed:29547716). Required for accumulation of METTL3 and METTL14 to
CC nuclear speckle (By similarity). Acts as a mRNA splicing regulator (By
CC similarity). Regulates G2/M cell-cycle transition by binding to the 3'
CC UTR of CCNA2, which enhances its stability (By similarity). Impairs WT1
CC DNA-binding ability and inhibits expression of WT1 target genes (By
CC similarity). {ECO:0000250|UniProtKB:Q15007,
CC ECO:0000269|PubMed:29535189, ECO:0000269|PubMed:29547716}.
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:29535189, PubMed:29547716). The MAC
CC subcomplex is composed of METTL3 and METTL14 (PubMed:29535189,
CC PubMed:29547716). The MACOM subcomplex is composed of WTAP, ZC3H13,
CC CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B)
CC (PubMed:29535189, PubMed:29547716). Interacts with WT1 (By similarity).
CC Also a component of a MACOM-like complex, named WTAP complex, composed
CC of WTAP, ZC3H13, CBLL1, VIRMA, RBM15, BCLAF1 and THRAP3 (By
CC similarity). Interacts with CPNE4 (via VWFA domain) (PubMed:12522145).
CC {ECO:0000250|UniProtKB:Q15007, ECO:0000269|PubMed:12522145,
CC ECO:0000269|PubMed:29535189, ECO:0000269|PubMed:29547716}.
CC -!- SUBCELLULAR LOCATION: Nucleus speckle {ECO:0000250|UniProtKB:Q15007}.
CC Nucleus, nucleoplasm {ECO:0000269|PubMed:29547716}. Cytoplasm
CC {ECO:0000269|PubMed:29547716}. Note=Mainly nuclear with some fraction
CC located in the cytoplasm (PubMed:29547716). ZC3H13 is required to
CC anchor component of the MACOM subcomplex, such as VIRMA, in the nucleus
CC (PubMed:29547716). {ECO:0000269|PubMed:29547716}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9ER69-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9ER69-2; Sequence=VSP_010280, VSP_010281;
CC -!- DISRUPTION PHENOTYPE: Death at E6.5 due to defecs in cell
CC proliferation. {ECO:0000269|PubMed:17088532}.
CC -!- SIMILARITY: Belongs to the fl(2)d family. {ECO:0000305}.
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DR EMBL; AJ276707; CAC16790.1; -; mRNA.
DR EMBL; AK076111; BAC36191.1; -; mRNA.
DR EMBL; AK156334; BAE33680.1; -; mRNA.
DR EMBL; BC046416; AAH46416.1; -; mRNA.
DR EMBL; BC093504; AAH93504.1; -; mRNA.
DR CCDS; CCDS49949.1; -. [Q9ER69-2]
DR CCDS; CCDS49950.1; -. [Q9ER69-1]
DR RefSeq; NP_001107004.1; NM_001113532.1. [Q9ER69-2]
DR RefSeq; NP_780603.1; NM_175394.2. [Q9ER69-2]
DR AlphaFoldDB; Q9ER69; -.
DR SMR; Q9ER69; -.
DR BioGRID; 208601; 4.
DR ComplexPortal; CPX-1609; WMM N6-adenosine-methyltransferase complex.
DR DIP; DIP-58948N; -.
DR IntAct; Q9ER69; 2.
DR STRING; 10090.ENSMUSP00000007007; -.
DR iPTMnet; Q9ER69; -.
DR PhosphoSitePlus; Q9ER69; -.
DR EPD; Q9ER69; -.
DR MaxQB; Q9ER69; -.
DR PaxDb; Q9ER69; -.
DR PeptideAtlas; Q9ER69; -.
DR PRIDE; Q9ER69; -.
DR ProteomicsDB; 267480; -. [Q9ER69-1]
DR ProteomicsDB; 267481; -. [Q9ER69-2]
DR Antibodypedia; 2136; 360 antibodies from 31 providers.
DR DNASU; 60532; -.
DR Ensembl; ENSMUST00000159986; ENSMUSP00000123961; ENSMUSG00000060475. [Q9ER69-2]
DR Ensembl; ENSMUST00000160781; ENSMUSP00000124138; ENSMUSG00000060475. [Q9ER69-2]
DR GeneID; 60532; -.
DR KEGG; mmu:60532; -.
DR UCSC; uc008alt.2; mouse. [Q9ER69-2]
DR CTD; 9589; -.
DR MGI; MGI:1926395; Wtap.
DR VEuPathDB; HostDB:ENSMUSG00000060475; -.
DR eggNOG; KOG2991; Eukaryota.
DR GeneTree; ENSGT00390000013931; -.
DR HOGENOM; CLU_044551_3_0_1; -.
DR InParanoid; Q9ER69; -.
DR Reactome; R-MMU-72203; Processing of Capped Intron-Containing Pre-mRNA.
DR BioGRID-ORCS; 60532; 25 hits in 71 CRISPR screens.
DR ChiTaRS; Wtap; mouse.
DR PRO; PR:Q9ER69; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q9ER69; protein.
DR Bgee; ENSMUSG00000060475; Expressed in ureter smooth muscle and 244 other tissues.
DR ExpressionAtlas; Q9ER69; baseline and differential.
DR Genevisible; Q9ER69; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:MGI.
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; ISO:MGI.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0080009; P:mRNA methylation; ISS:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; ISS: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; mRNA processing; mRNA splicing; Nucleus;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..396
FT /note="Pre-mRNA-splicing regulator WTAP"
FT /id="PRO_0000065984"
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..352
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 353..368
FT /note="Basic and acidic 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:0000250|UniProtKB:Q15007"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15007"
FT MOD_RES 297
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 305
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15007"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15007"
FT MOD_RES 341
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 350
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 388
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15007"
FT VAR_SEQ 151
FT /note="S -> R (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_010280"
FT VAR_SEQ 152..396
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_010281"
SQ SEQUENCE 396 AA; 44177 MW; 0B190F535C97F5D2 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 TSRTTSSEPV DQAEVTSKDC SRLANGPSNG SSSRQRTSGS GFHREGSTPE
DDFPSSSGNG NKASNSSEER TGRGGSSYIN PLSAGYESVD SPTGSENSLT HHSNDTDSSH
DPQEEKAVSG KGNRTVGSRH VQNGLDSSVN VQGAVL
