YTHD2_HUMAN
ID YTHD2_HUMAN Reviewed; 579 AA.
AC Q9Y5A9; A6NKG4; A8K966; B4E1G7; D3DPM8; Q5VSZ9; Q8TDH0; Q9BUJ5;
DT 12-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 16-JAN-2004, sequence version 2.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=YTH domain-containing family protein 2 {ECO:0000305};
DE Short=DF2 {ECO:0000303|PubMed:31292544, ECO:0000303|PubMed:32492408};
DE AltName: Full=CLL-associated antigen KW-14 {ECO:0000303|Ref.3};
DE AltName: Full=High-glucose-regulated protein 8 {ECO:0000303|Ref.2};
DE AltName: Full=Renal carcinoma antigen NY-REN-2 {ECO:0000303|PubMed:10508479};
GN Name=YTHDF2 {ECO:0000303|PubMed:24284625, ECO:0000312|HGNC:HGNC:31675};
GN Synonyms=HGRG8 {ECO:0000303|Ref.2};
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 IDENTIFICATION AS A RENAL
RP CANCER ANTIGEN.
RC TISSUE=Renal cell carcinoma;
RX PubMed=10508479;
RX DOI=10.1002/(sici)1097-0215(19991112)83:4<456::aid-ijc4>3.0.co;2-5;
RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H.,
RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T.,
RA Old L.J.;
RT "Antigens recognized by autologous antibody in patients with renal-cell
RT carcinoma.";
RL Int. J. Cancer 83:456-464(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Roberts T.P., Wright A., Wahab N.A., Weston B.S., Mason R.M.;
RT "Gene which is selectively expressed in hyperglycaemia.";
RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Krackhardt A.M., Witzens M., Harig S., Hodi F.S., Zauls A.J., Chessia M.,
RA Barrett P., Gribben J.G.;
RT "Identification of novel tumor antigens in CLL by SEREX: assessment of
RT their potential as targets for immunotherapeutic approaches.";
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Ovary, and Testis;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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 [8]
RP PROTEIN SEQUENCE OF 2-12; 179-205 AND 528-536, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lung carcinoma, and Ovarian carcinoma;
RA Bienvenut W.V., Vousden K.H., Lukashchuk N., Lilla S., von Kriegsheim A.,
RA Lempens A., Kolch W.;
RL Submitted (DEC-2008) to UniProtKB.
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-39, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [11]
RP IDENTIFICATION BY 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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP IDENTIFICATION BY MASS 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-39 AND SER-359, 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 [15]
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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394, 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 [17]
RP RNA-BINDING, AND FUNCTION.
RX PubMed=22575960; DOI=10.1038/nature11112;
RA Dominissini D., Moshitch-Moshkovitz S., Schwartz S., Salmon-Divon M.,
RA Ungar L., Osenberg S., Cesarkas K., Jacob-Hirsch J., Amariglio N.,
RA Kupiec M., Sorek R., Rechavi G.;
RT "Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq.";
RL Nature 485:201-206(2012).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; SER-4; SER-5 AND SER-196,
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 [20]
RP RNA-BINDING.
RX PubMed=24206186; DOI=10.1042/bj20130862;
RA Kang H.J., Jeong S.J., Kim K.N., Baek I.J., Chang M., Kang C.M., Park Y.S.,
RA Yun C.W.;
RT "A novel protein, Pho92, has a conserved YTH domain and regulates phosphate
RT metabolism by decreasing the mRNA stability of PHO4 in Saccharomyces
RT cerevisiae.";
RL Biochem. J. 457:391-400(2014).
RN [21]
RP RNA-BINDING, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=24284625; DOI=10.1038/nature12730;
RA Wang X., Lu Z., Gomez A., Hon G.C., Yue Y., Han D., Fu Y., Parisien M.,
RA Dai Q., Jia G., Ren B., Pan T., He C.;
RT "N-methyladenosine-dependent regulation of messenger RNA stability.";
RL Nature 505:117-120(2014).
RN [22]
RP FUNCTION.
RX PubMed=26046440; DOI=10.1016/j.cell.2015.05.014;
RA Wang X., Zhao B.S., Roundtree I.A., Lu Z., Han D., Ma H., Weng X., Chen K.,
RA Shi H., He C.;
RT "N(6)-methyladenosine modulates messenger RNA translation efficiency.";
RL Cell 161:1388-1399(2015).
RN [23]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=26318451; DOI=10.1074/jbc.m115.680389;
RA Xu C., Liu K., Ahmed H., Loppnau P., Schapira M., Min J.;
RT "structural basis for the discriminative recognition of N6-methyladenosine
RT RNA by the human YT521-B homology domain family of proteins.";
RL J. Biol. Chem. 290:24902-24913(2015).
RN [24]
RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
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 INTERACTION WITH CNOT1.
RX PubMed=27558897; DOI=10.1038/ncomms12626;
RA Du H., Zhao Y., He J., Zhang Y., Xi H., Liu M., Ma J., Wu L.;
RT "YTHDF2 destabilizes m(6)A-containing RNA through direct recruitment of the
RT CCR4-NOT deadenylase complex.";
RL Nat. Commun. 7:12626-12626(2016).
RN [26]
RP INTERACTION WITH YTHDF3.
RX PubMed=28106072; DOI=10.1038/cr.2017.15;
RA Shi H., Wang X., Lu Z., Zhao B.S., Ma H., Hsu P.J., Liu C., He C.;
RT "YTHDF3 facilitates translation and decay of N(6)-methyladenosine-modified
RT RNA.";
RL Cell Res. 27:315-328(2017).
RN [27]
RP FUNCTION.
RX PubMed=30428350; DOI=10.1016/j.celrep.2018.10.068;
RA Zhong X., Yu J., Frazier K., Weng X., Li Y., Cham C.M., Dolan K., Zhu X.,
RA Hubert N., Tao Y., Lin F., Martinez-Guryn K., Huang Y., Wang T., Liu J.,
RA He C., Chang E.B., Leone V.;
RT "Circadian clock regulation of hepatic lipid metabolism by modulation of
RT m6A mRNA methylation.";
RL Cell Rep. 25:1816-1828(2018).
RN [28]
RP FUNCTION.
RX PubMed=30065315; DOI=10.1038/s41422-018-0072-0;
RA Li Z., Qian P., Shao W., Shi H., He X.C., Gogol M., Yu Z., Wang Y., Qi M.,
RA Zhu Y., Perry J.M., Zhang K., Tao F., Zhou K., Hu D., Han Y., Zhao C.,
RA Alexander R., Xu H., Chen S., Peak A., Hall K., Peterson M., Perera A.,
RA Haug J.S., Parmely T., Li H., Shen B., Zeitlinger J., He C., Li L.;
RT "Suppression of m6A reader Ythdf2 promotes hematopoietic stem cell
RT expansion.";
RL Cell Res. 28:904-917(2018).
RN [29]
RP CAUTION.
RX PubMed=29109479; DOI=10.1038/s41564-017-0056-8;
RA Tan B., Liu H., Zhang S., da Silva S.R., Zhang L., Meng J., Cui X.,
RA Yuan H., Sorel O., Zhang S.W., Huang Y., Gao S.J.;
RT "Viral and cellular N6-methyladenosine and N6,2'-O-dimethyladenosine
RT epitranscriptomes in the KSHV life cycle.";
RL Nat. Microbiol. 3:108-120(2018).
RN [30]
RP FUNCTION (MICROBIAL INFECTION), AND CAUTION.
RX PubMed=29447282; DOI=10.1371/journal.ppat.1006919;
RA Tsai K., Courtney D.G., Cullen B.R.;
RT "Addition of m6A to SV40 late mRNAs enhances viral structural gene
RT expression and replication.";
RL PLoS Pathog. 14:E1006919-E1006919(2018).
RN [31]
RP FUNCTION (MICROBIAL INFECTION), AND CAUTION.
RX PubMed=29659627; DOI=10.1371/journal.ppat.1006995;
RA Hesser C.R., Karijolich J., Dominissini D., He C., Glaunsinger B.A.;
RT "N6-methyladenosine modification and the YTHDF2 reader protein play cell
RT type specific roles in lytic viral gene expression during Kaposi's sarcoma-
RT associated herpesvirus infection.";
RL PLoS Pathog. 14:E1006995-E1006995(2018).
RN [32]
RP FUNCTION, AND MUTAGENESIS OF TRP-432 AND TRP-486.
RX PubMed=31388144; DOI=10.1038/s41422-019-0210-3;
RA Gao Y., Pei G., Li D., Li R., Shao Y., Zhang Q.C., Li P.;
RT "Multivalent m6A motifs promote phase separation of YTHDF proteins.";
RL Cell Res. 29:767-769(2019).
RN [33]
RP FUNCTION, AND INTERACTION WITH RIDA.
RX PubMed=30930054; DOI=10.1016/j.molcel.2019.02.034;
RA Park O.H., Ha H., Lee Y., Boo S.H., Kwon D.H., Song H.K., Kim Y.K.;
RT "Endoribonucleolytic cleavage of m6A-containing RNAs by RNase P/MRP
RT complex.";
RL Mol. Cell 74:494-507(2019).
RN [34]
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF TRP-432.
RX PubMed=31292544; DOI=10.1038/s41586-019-1374-1;
RA Ries R.J., Zaccara S., Klein P., Olarerin-George A., Namkoong S.,
RA Pickering B.F., Patil D.P., Kwak H., Lee J.H., Jaffrey S.R.;
RT "m6A enhances the phase separation potential of mRNA.";
RL Nature 571:424-428(2019).
RN [35]
RP FUNCTION, AND CAUTION.
RX PubMed=30559377; DOI=10.1038/s41590-018-0275-z;
RA Winkler R., Gillis E., Lasman L., Safra M., Geula S., Soyris C.,
RA Nachshon A., Tai-Schmiedel J., Friedman N., Le-Trilling V.T.K.,
RA Trilling M., Mandelboim M., Hanna J.H., Schwartz S., Stern-Ginossar N.;
RT "m6A modification controls the innate immune response to infection by
RT targeting type I interferons.";
RL Nat. Immunol. 20:173-182(2019).
RN [36]
RP FUNCTION, AND MUTAGENESIS OF TRP-342.
RX PubMed=31815440; DOI=10.1021/acs.analchem.9b04505;
RA Dai X., Gonzalez G., Li L., Li J., You C., Miao W., Hu J., Fu L., Zhao Y.,
RA Li R., Li L., Chen X., Xu Y., Gu W., Wang Y.;
RT "YTHDF2 binds to 5-methylcytosine in RNA and modulates the maturation of
RT ribosomal RNA.";
RL Anal. Chem. 92:1346-1354(2020).
RN [37]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH THE CCR4-NOT COMPLEX.
RX PubMed=32492408; DOI=10.1016/j.cell.2020.05.012;
RA Zaccara S., Jaffrey S.R.;
RT "A unified model for the function of YTHDF proteins in regulating m6A-
RT modified mRNA.";
RL Cell 181:1582-1595(2020).
RN [38]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=32451507; DOI=10.1038/s41589-020-0524-y;
RA Fu Y., Zhuang X.;
RT "m6A-binding YTHDF proteins promote stress granule formation.";
RL Nat. Chem. Biol. 16:955-963(2020).
RN [39]
RP FUNCTION, AND UBIQUITINATION.
RX PubMed=32267835; DOI=10.1371/journal.pbio.3000664;
RA Fei Q., Zou Z., Roundtree I.A., Sun H.L., He C.;
RT "YTHDF2 promotes mitotic entry and is regulated by cell cycle mediators.";
RL PLoS Biol. 18:e3000664-e3000664(2020).
RN [40]
RP FUNCTION.
RX PubMed=31642031; DOI=10.1007/s13238-019-00660-2;
RA Wang J., Wang L., Diao J., Shi Y.G., Shi Y., Ma H., Shen H.;
RT "Binding to m6A RNA promotes YTHDF2-mediated phase separation.";
RL Protein Cell 11:304-307(2020).
RN [41]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=32169943; DOI=10.1261/rna.073502.119;
RA Heck A.M., Russo J., Wilusz J., Nishimura E.O., Wilusz C.J.;
RT "YTHDF2 destabilizes m6A-modified neural-specific RNAs to restrain
RT differentiation in induced pluripotent stem cells.";
RL RNA 26:739-755(2020).
RN [42]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 408-552 IN COMPLEX WITH
RP N6-METHYLADENOSINE (M6A)-CONTAINING RNA, AND MUTAGENESIS OF TRP-432;
RP TRP-486 AND TRP-491.
RX PubMed=25412658; DOI=10.1038/cr.2014.153;
RA Li F., Zhao D., Wu J., Shi Y.;
RT "Structure of the YTH domain of human YTHDF2 in complex with an m(6)A
RT mononucleotide reveals an aromatic cage for m(6)A recognition.";
RL Cell Res. 24:1490-1492(2014).
RN [43]
RP X-RAY CRYSTALLOGRAPHY (2.12 ANGSTROMS) OF 383-553, FUNCTION, RNA-BINDING,
RP AND MUTAGENESIS OF ARG-411; LYS-416; TRP-432; ARG-441; TRP-486 AND ARG-527.
RX PubMed=25412661; DOI=10.1038/cr.2014.152;
RA Zhu T., Roundtree I.A., Wang P., Wang X., Wang L., Sun C., Tian Y., Li J.,
RA He C., Xu Y.;
RT "Crystal structure of the YTH domain of YTHDF2 reveals mechanism for
RT recognition of N6-methyladenosine.";
RL Cell Res. 24:1493-1496(2014).
CC -!- FUNCTION: Specifically recognizes and binds N6-methyladenosine (m6A)-
CC containing RNAs, and regulates their stability (PubMed:24284625,
CC PubMed:26046440, PubMed:26318451, PubMed:32492408). M6A is a
CC modification present at internal sites of mRNAs and some non-coding
CC RNAs and plays a role in mRNA stability and processing
CC (PubMed:22575960, PubMed:24284625, PubMed:32492408, PubMed:25412658,
CC PubMed:25412661). Acts as a regulator of mRNA stability by promoting
CC degradation of m6A-containing mRNAs via interaction with the CCR4-NOT
CC and ribonuclease P/MRP complexes, depending on the context
CC (PubMed:24284625, PubMed:26046440, PubMed:27558897, PubMed:30930054,
CC PubMed:32492408). The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) share
CC m6A-containing mRNAs targets and act redundantly to mediate mRNA
CC degradation and cellular differentiation (PubMed:28106072,
CC PubMed:32492408). M6A-containing mRNAs containing a binding site for
CC RIDA/HRSP12 (5'-GGUUC-3') are preferentially degraded by
CC endoribonucleolytic cleavage: cooperative binding of RIDA/HRSP12 and
CC YTHDF2 to transcripts leads to recruitment of the ribonuclease P/MRP
CC complex (PubMed:30930054). Other m6A-containing mRNAs undergo
CC deadenylation via direct interaction between YTHDF2 and CNOT1, leading
CC to recruitment of the CCR4-NOT and subsequent deadenylation of m6A-
CC containing mRNAs (PubMed:27558897). Required maternally to regulate
CC oocyte maturation: probably acts by binding to m6A-containing mRNAs,
CC thereby regulating maternal transcript dosage during oocyte maturation,
CC which is essential for the competence of oocytes to sustain early
CC zygotic development (By similarity). Also required during
CC spermatogenesis: regulates spermagonial adhesion by promoting
CC degradation of m6A-containing transcripts coding for matrix
CC metallopeptidases (By similarity). Also involved in hematopoietic stem
CC cells specification by binding to m6A-containing mRNAs, leading to
CC promote their degradation (PubMed:30065315). Also acts as a regulator
CC of neural development by promoting m6A-dependent degradation of neural
CC development-related mRNA targets (By similarity). Inhibits neural
CC specification of induced pluripotent stem cells by binding to
CC methylated neural-specific mRNAs and promoting their degradation,
CC thereby restraining neural differentiation (PubMed:32169943). Regulates
CC circadian regulation of hepatic lipid metabolism: acts by promoting
CC m6A-dependent degradation of PPARA transcripts (PubMed:30428350).
CC Regulates the innate immune response to infection by inhibiting the
CC type I interferon response: acts by binding to m6A-containing IFNB
CC transcripts and promoting their degradation (PubMed:30559377). May also
CC act as a promoter of cap-independent mRNA translation following heat
CC shock stress: upon stress, relocalizes to the nucleus and specifically
CC binds mRNAs with some m6A methylation mark at their 5'-UTR, protecting
CC demethylation of mRNAs by FTO, thereby promoting cap-independent mRNA
CC translation (PubMed:26458103). Regulates mitotic entry by promoting the
CC phase-specific m6A-dependent degradation of WEE1 transcripts
CC (PubMed:32267835). Promotes formation of phase-separated membraneless
CC compartments, such as P-bodies or stress granules, by undergoing
CC liquid-liquid phase separation upon binding to mRNAs containing
CC multiple m6A-modified residues: polymethylated mRNAs act as a
CC multivalent scaffold for the binding of YTHDF proteins, juxtaposing
CC their disordered regions and thereby leading to phase separation
CC (PubMed:31388144, PubMed:31292544, PubMed:32451507, PubMed:31642031).
CC The resulting mRNA-YTHDF complexes then partition into different
CC endogenous phase-separated membraneless compartments, such as P-bodies,
CC stress granules or neuronal RNA granules (PubMed:31292544). May also
CC recognize and bind RNAs modified by C5-methylcytosine (m5C) and act as
CC a regulator of rRNA processing (PubMed:31815440).
CC {ECO:0000250|UniProtKB:Q91YT7, ECO:0000269|PubMed:22575960,
CC ECO:0000269|PubMed:24284625, ECO:0000269|PubMed:25412658,
CC ECO:0000269|PubMed:25412661, ECO:0000269|PubMed:26046440,
CC ECO:0000269|PubMed:26318451, ECO:0000269|PubMed:26458103,
CC ECO:0000269|PubMed:27558897, ECO:0000269|PubMed:28106072,
CC ECO:0000269|PubMed:30065315, ECO:0000269|PubMed:30428350,
CC ECO:0000269|PubMed:30559377, ECO:0000269|PubMed:30930054,
CC ECO:0000269|PubMed:31292544, ECO:0000269|PubMed:31388144,
CC ECO:0000269|PubMed:31642031, ECO:0000269|PubMed:31815440,
CC ECO:0000269|PubMed:32169943, ECO:0000269|PubMed:32267835,
CC ECO:0000269|PubMed:32451507, ECO:0000269|PubMed:32492408}.
CC -!- FUNCTION: (Microbial infection) Promotes viral gene expression and
CC replication of polyomavirus SV40: acts by binding to N6-methyladenosine
CC (m6A)-containing viral RNAs (PubMed:29447282).
CC {ECO:0000269|PubMed:29447282}.
CC -!- FUNCTION: (Microbial infection) Promotes viral gene expression and
CC virion production of kaposis sarcoma-associated herpesvirus (KSHV) at
CC some stage of the KSHV life cycle (in iSLK.219 and iSLK.BAC16 cells)
CC (PubMed:29659627). Acts by binding to N6-methyladenosine (m6A)-
CC containing viral RNAs (PubMed:29659627). {ECO:0000269|PubMed:29659627}.
CC -!- SUBUNIT: Interacts with CNOT1; interaction is direct and promotes
CC recruitment of the CCR4-NOT complex (PubMed:27558897, PubMed:32492408).
CC Interacts with YTHDF3 (PubMed:28106072). Interacts with RIDA/HRSP12;
CC interaction leads to recruitment of the ribonuclease P/MRP complex
CC (PubMed:30930054). {ECO:0000269|PubMed:27558897,
CC ECO:0000269|PubMed:28106072, ECO:0000269|PubMed:30930054,
CC ECO:0000269|PubMed:32492408}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:26458103,
CC ECO:0000269|PubMed:31292544, ECO:0000269|PubMed:32492408}. Cytoplasm,
CC P-body {ECO:0000269|PubMed:24284625, ECO:0000269|PubMed:31292544,
CC ECO:0000269|PubMed:32492408}. Cytoplasm, Stress granule
CC {ECO:0000269|PubMed:31292544, ECO:0000269|PubMed:32451507}. Nucleus
CC {ECO:0000269|PubMed:26458103}. Note=Localizes to the cytosol and
CC relocates to the nucleus following heat shock stress (PubMed:26458103).
CC Can partition into different structures: into P-bodies in unstressed
CC cells, and into stress granules during stress (PubMed:31292544).
CC {ECO:0000269|PubMed:26458103, ECO:0000269|PubMed:31292544}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y5A9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y5A9-2; Sequence=VSP_009297;
CC -!- TISSUE SPECIFICITY: Highly expressed in induced pluripotent stem cells
CC (iPSCs) and down-regulated during neural differentiation.
CC {ECO:0000269|PubMed:32169943}.
CC -!- INDUCTION: Following heat shock stress. {ECO:0000269|PubMed:26458103}.
CC -!- DOMAIN: The disordered regions have the ability to interact with each
CC other and to 'phase separate' into liquid droplets within the cytosol
CC following binding to mRNAs containing multiple m6A-modified residues
CC (PubMed:31292544). This leads to the partition of m6A-containing mRNAs
CC into membraneless compartments, where mRNAs may be stored, degraded or
CC used to transport mRNAs to dendritic arbors in neurons
CC (PubMed:31292544). {ECO:0000269|PubMed:31292544}.
CC -!- PTM: Ubiquitinated by the SCF(SKP2) complex, leading to its
CC degradation. {ECO:0000269|PubMed:32267835}.
CC -!- SIMILARITY: Belongs to the YTHDF family. YTHDF2 subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: The role of YTHDF2 and N6-methyladenosine (m6A) in virus
CC expression and replication is unclear (PubMed:29109479,
CC PubMed:29447282, PubMed:29659627, PubMed:30559377). According to some
CC reports, YTHDF2 promotes viral gene expression and replication of
CC polyomavirus SV40 and herpesvirus (KSHV) by binding to N6-
CC methyladenosine (m6A)-containing viral RNAs (PubMed:29447282,
CC PubMed:29659627). Another report however suggests that YTHDF2 regulates
CC virus expression and replication indirectly, via its ability to inhibit
CC the type I interferon response, thereby promoting virus expression
CC (PubMed:30559377). Indirect regulation via inhibition of type I
CC interferon response might explain why contradictory results have been
CC reported for its role in KSHV virus replication (PubMed:29109479,
CC PubMed:29659627). {ECO:0000269|PubMed:29109479,
CC ECO:0000269|PubMed:29447282, ECO:0000269|PubMed:29659627,
CC ECO:0000269|PubMed:30559377}.
CC -!- CAUTION: Previous studies suggested the 3 different paralogs (YTHDF1,
CC YTHDF2 and YTHDF3) have unique functions with limited redundancy
CC (PubMed:26046440). However, later studies showed that YTHDF1, YTHDF2
CC and YTHDF3 paralogs have redundant functions to a profound extent and
CC directly promote degradation of m6A-containing mRNAs (PubMed:32492408).
CC {ECO:0000269|PubMed:26046440, ECO:0000269|PubMed:32492408}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD42861.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAF08813.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAL99921.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=On the benefits of disorder
CC - Issue 238 of August 2021;
CC URL="https://web.expasy.org/spotlight/back_issues/238/";
CC ---------------------------------------------------------------------------
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DR EMBL; AF155095; AAD42861.1; ALT_FRAME; mRNA.
DR EMBL; AF192968; AAF08813.1; ALT_FRAME; mRNA.
DR EMBL; AF432214; AAL99921.1; ALT_SEQ; mRNA.
DR EMBL; AK292581; BAF85270.1; -; mRNA.
DR EMBL; AK303833; BAG64779.1; -; mRNA.
DR EMBL; AL645729; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356786; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX07673.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07675.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07674.1; -; Genomic_DNA.
DR EMBL; BC002559; AAH02559.1; -; mRNA.
DR CCDS; CCDS41296.1; -. [Q9Y5A9-1]
DR CCDS; CCDS53287.1; -. [Q9Y5A9-2]
DR RefSeq; NP_001166299.1; NM_001172828.1. [Q9Y5A9-2]
DR RefSeq; NP_001166599.1; NM_001173128.1. [Q9Y5A9-1]
DR RefSeq; NP_057342.2; NM_016258.2. [Q9Y5A9-1]
DR PDB; 4RDN; X-ray; 2.10 A; A/B=408-552.
DR PDB; 4RDO; X-ray; 2.15 A; A/B/C/D/E/F=408-552.
DR PDB; 4WQN; X-ray; 2.12 A; A/B=383-553.
DR PDB; 7A1V; X-ray; 2.20 A; A/B=408-552.
DR PDB; 7BIK; X-ray; 2.10 A; A/B=408-552.
DR PDB; 7R5F; X-ray; 2.00 A; A/B=408-552.
DR PDB; 7R5L; X-ray; 1.70 A; A=408-552.
DR PDB; 7R5W; X-ray; 1.75 A; A/B=408-552.
DR PDB; 7YWB; X-ray; 1.92 A; A/B=408-552.
DR PDB; 7YX6; X-ray; 1.80 A; A/B=408-552.
DR PDB; 7YXE; X-ray; 1.85 A; A/B=408-552.
DR PDB; 7Z26; X-ray; 1.90 A; A/B=408-552.
DR PDB; 7Z4U; X-ray; 1.83 A; A/B=408-552.
DR PDB; 7Z7F; X-ray; 1.95 A; A/B=408-552.
DR PDB; 7Z8P; X-ray; 1.97 A; A/B=408-552.
DR PDB; 7Z8W; X-ray; 1.90 A; A/B=408-552.
DR PDB; 7Z8X; X-ray; 1.96 A; A/B=408-552.
DR PDB; 7Z92; X-ray; 1.91 A; A/B=408-552.
DR PDB; 7Z93; X-ray; 1.97 A; A/B=408-552.
DR PDBsum; 4RDN; -.
DR PDBsum; 4RDO; -.
DR PDBsum; 4WQN; -.
DR PDBsum; 7A1V; -.
DR PDBsum; 7BIK; -.
DR PDBsum; 7R5F; -.
DR PDBsum; 7R5L; -.
DR PDBsum; 7R5W; -.
DR PDBsum; 7YWB; -.
DR PDBsum; 7YX6; -.
DR PDBsum; 7YXE; -.
DR PDBsum; 7Z26; -.
DR PDBsum; 7Z4U; -.
DR PDBsum; 7Z7F; -.
DR PDBsum; 7Z8P; -.
DR PDBsum; 7Z8W; -.
DR PDBsum; 7Z8X; -.
DR PDBsum; 7Z92; -.
DR PDBsum; 7Z93; -.
DR AlphaFoldDB; Q9Y5A9; -.
DR SMR; Q9Y5A9; -.
DR BioGRID; 119543; 244.
DR IntAct; Q9Y5A9; 47.
DR MINT; Q9Y5A9; -.
DR STRING; 9606.ENSP00000362918; -.
DR ChEMBL; CHEMBL4295992; -.
DR GlyGen; Q9Y5A9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y5A9; -.
DR MetOSite; Q9Y5A9; -.
DR PhosphoSitePlus; Q9Y5A9; -.
DR SwissPalm; Q9Y5A9; -.
DR BioMuta; YTHDF2; -.
DR DMDM; 41019527; -.
DR EPD; Q9Y5A9; -.
DR jPOST; Q9Y5A9; -.
DR MassIVE; Q9Y5A9; -.
DR MaxQB; Q9Y5A9; -.
DR PaxDb; Q9Y5A9; -.
DR PeptideAtlas; Q9Y5A9; -.
DR PRIDE; Q9Y5A9; -.
DR ProteomicsDB; 86326; -. [Q9Y5A9-1]
DR ProteomicsDB; 86327; -. [Q9Y5A9-2]
DR Antibodypedia; 30989; 141 antibodies from 28 providers.
DR DNASU; 51441; -.
DR Ensembl; ENST00000373812.8; ENSP00000362918.3; ENSG00000198492.16. [Q9Y5A9-1]
DR Ensembl; ENST00000541996.5; ENSP00000439394.1; ENSG00000198492.16. [Q9Y5A9-2]
DR Ensembl; ENST00000542507.5; ENSP00000444660.1; ENSG00000198492.16. [Q9Y5A9-1]
DR GeneID; 51441; -.
DR KEGG; hsa:51441; -.
DR MANE-Select; ENST00000373812.8; ENSP00000362918.3; NM_016258.3; NP_057342.2.
DR UCSC; uc001brc.4; human. [Q9Y5A9-1]
DR CTD; 51441; -.
DR DisGeNET; 51441; -.
DR GeneCards; YTHDF2; -.
DR HGNC; HGNC:31675; YTHDF2.
DR HPA; ENSG00000198492; Low tissue specificity.
DR MIM; 610640; gene.
DR neXtProt; NX_Q9Y5A9; -.
DR PharmGKB; PA134964518; -.
DR VEuPathDB; HostDB:ENSG00000198492; -.
DR eggNOG; KOG1901; Eukaryota.
DR GeneTree; ENSGT00940000156761; -.
DR HOGENOM; CLU_022715_0_0_1; -.
DR InParanoid; Q9Y5A9; -.
DR OMA; RTNGFGD; -.
DR OrthoDB; 1523251at2759; -.
DR PhylomeDB; Q9Y5A9; -.
DR TreeFam; TF323736; -.
DR PathwayCommons; Q9Y5A9; -.
DR SignaLink; Q9Y5A9; -.
DR BioGRID-ORCS; 51441; 168 hits in 1084 CRISPR screens.
DR ChiTaRS; YTHDF2; human.
DR GenomeRNAi; 51441; -.
DR Pharos; Q9Y5A9; Tbio.
DR PRO; PR:Q9Y5A9; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9Y5A9; protein.
DR Bgee; ENSG00000198492; Expressed in cortical plate and 102 other tissues.
DR ExpressionAtlas; Q9Y5A9; baseline and differential.
DR Genevisible; Q9Y5A9; HS.
DR GO; GO:0034451; C:centriolar satellite; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA.
DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000932; C:P-body; IDA:UniProtKB.
DR GO; GO:0062153; F:C5-methylcytidine-containing RNA binding; IDA:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:1990247; F:N6-methyladenosine-containing RNA binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0048598; P:embryonic morphogenesis; ISS:UniProtKB.
DR GO; GO:0098508; P:endothelial to hematopoietic transition; ISS:UniProtKB.
DR GO; GO:0007276; P:gamete generation; ISS:UniProtKB.
DR GO; GO:0071425; P:hematopoietic stem cell proliferation; ISS:UniProtKB.
DR GO; GO:0006959; P:humoral immune response; TAS:ProtInc.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0006402; P:mRNA catabolic process; IDA:UniProtKB.
DR GO; GO:0061157; P:mRNA destabilization; IDA:UniProtKB.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; ISS:UniProtKB.
DR GO; GO:2000737; P:negative regulation of stem cell differentiation; IMP:UniProtKB.
DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0001556; P:oocyte maturation; ISS:UniProtKB.
DR GO; GO:0070925; P:organelle assembly; IDA:UniProtKB.
DR GO; GO:1903679; P:positive regulation of cap-independent translational initiation; IDA:UniProtKB.
DR GO; GO:0030155; P:regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:1902036; P:regulation of hematopoietic stem cell differentiation; ISS:UniProtKB.
DR GO; GO:1903538; P:regulation of meiotic cell cycle process involved in oocyte maturation; ISS:UniProtKB.
DR GO; GO:0043488; P:regulation of mRNA stability; IDA:UniProtKB.
DR GO; GO:0050767; P:regulation of neurogenesis; IMP:UniProtKB.
DR GO; GO:2000232; P:regulation of rRNA processing; IMP:UniProtKB.
DR GO; GO:0007284; P:spermatogonial cell division; ISS:UniProtKB.
DR GO; GO:0034063; P:stress granule assembly; IDA:UniProtKB.
DR InterPro; IPR007275; YTH_domain.
DR InterPro; IPR045168; YTH_prot.
DR PANTHER; PTHR12357; PTHR12357; 1.
DR Pfam; PF04146; YTH; 1.
DR PROSITE; PS50882; YTH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell cycle; Cell division;
KW Cytoplasm; Differentiation; Direct protein sequencing;
KW Host-virus interaction; Immunity; Innate immunity; Mitosis; Nucleus;
KW Oogenesis; Phosphoprotein; Reference proteome; RNA-binding;
KW Spermatogenesis; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..579
FT /note="YTH domain-containing family protein 2"
FT /id="PRO_0000223075"
FT DOMAIN 410..544
FT /note="YTH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00225"
FT REGION 1..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..384
FT /note="Localization to mRNA processing bodies (P-bodies)"
FT /evidence="ECO:0000269|PubMed:24284625"
FT REGION 247..387
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 385..579
FT /note="Interaction with m6A-containing mRNAs"
FT /evidence="ECO:0000269|PubMed:24284625"
FT COMPBIAS 1..25
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 291..325
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 368..382
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 416..418
FT /ligand="RNA"
FT /ligand_id="ChEBI:CHEBI:33697"
FT /ligand_part="N(6)-methyladenosine 5'-phosphate residue"
FT /ligand_part_id="ChEBI:CHEBI:74449"
FT /evidence="ECO:0000269|PubMed:25412658,
FT ECO:0007744|PDB:4RDN"
FT BINDING 422
FT /ligand="RNA"
FT /ligand_id="ChEBI:CHEBI:33697"
FT /ligand_part="N(6)-methyladenosine 5'-phosphate residue"
FT /ligand_part_id="ChEBI:CHEBI:74449"
FT /evidence="ECO:0000269|PubMed:25412658,
FT ECO:0007744|PDB:4RDN"
FT BINDING 432..433
FT /ligand="RNA"
FT /ligand_id="ChEBI:CHEBI:33697"
FT /ligand_part="N(6)-methyladenosine 5'-phosphate residue"
FT /ligand_part_id="ChEBI:CHEBI:74449"
FT /evidence="ECO:0000269|PubMed:25412658,
FT ECO:0007744|PDB:4RDN"
FT BINDING 462
FT /ligand="RNA"
FT /ligand_id="ChEBI:CHEBI:33697"
FT /ligand_part="N(6)-methyladenosine 5'-phosphate residue"
FT /ligand_part_id="ChEBI:CHEBI:74449"
FT /evidence="ECO:0000269|PubMed:25412658,
FT ECO:0007744|PDB:4RDN"
FT BINDING 486
FT /ligand="RNA"
FT /ligand_id="ChEBI:CHEBI:33697"
FT /ligand_part="N(6)-methyladenosine 5'-phosphate residue"
FT /ligand_part_id="ChEBI:CHEBI:74449"
FT /evidence="ECO:0000269|PubMed:25412658,
FT ECO:0007744|PDB:4RDN"
FT BINDING 491
FT /ligand="RNA"
FT /ligand_id="ChEBI:CHEBI:33697"
FT /ligand_part="N(6)-methyladenosine 5'-phosphate residue"
FT /ligand_part_id="ChEBI:CHEBI:74449"
FT /evidence="ECO:0000269|PubMed:25412658,
FT ECO:0007744|PDB:4RDN"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 4
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 5
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z739"
FT MOD_RES 39
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 196
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 359
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 394
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT VAR_SEQ 1..50
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.3"
FT /id="VSP_009297"
FT VARIANT 217
FT /note="T -> S (in dbSNP:rs16838382)"
FT /id="VAR_053744"
FT VARIANT 454
FT /note="P -> S (in dbSNP:rs35288745)"
FT /id="VAR_053745"
FT MUTAGEN 411
FT /note="R->A: Slightly decreased binding to RNAs."
FT /evidence="ECO:0000269|PubMed:25412661"
FT MUTAGEN 416
FT /note="K->A: Decreased binding to RNAs."
FT /evidence="ECO:0000269|PubMed:25412661"
FT MUTAGEN 432
FT /note="W->A: Reduced binding to N6-methyladenosine (m6A)-
FT containing RNAs. Reduced ability to undergo liquid-liquid
FT phase separation. Reduced binding to C5-methylcytosine
FT (m5C)-containing RNAs."
FT /evidence="ECO:0000269|PubMed:25412658,
FT ECO:0000269|PubMed:25412661, ECO:0000269|PubMed:31292544,
FT ECO:0000269|PubMed:31388144, ECO:0000269|PubMed:31815440"
FT MUTAGEN 441
FT /note="R->A: Slightly decreased binding to RNAs."
FT /evidence="ECO:0000269|PubMed:25412661"
FT MUTAGEN 486
FT /note="W->A: Reduced binding to N6-methyladenosine (m6A)-
FT containing RNAs. Reduced ability to undergo liquid-liquid
FT phase separation; when associated with A-432."
FT /evidence="ECO:0000269|PubMed:25412658,
FT ECO:0000269|PubMed:25412661, ECO:0000269|PubMed:31388144"
FT MUTAGEN 491
FT /note="W->A: Reduced binding to N6-methyladenosine (m6A)-
FT containing RNAs."
FT /evidence="ECO:0000269|PubMed:25412658"
FT MUTAGEN 527
FT /note="R->A: Decreased binding to RNAs."
FT /evidence="ECO:0000269|PubMed:25412661"
FT STRAND 411..418
FT /evidence="ECO:0007829|PDB:4RDN"
FT HELIX 420..429
FT /evidence="ECO:0007829|PDB:4RDN"
FT STRAND 430..432
FT /evidence="ECO:0007829|PDB:4WQN"
FT HELIX 436..449
FT /evidence="ECO:0007829|PDB:4RDN"
FT STRAND 455..461
FT /evidence="ECO:0007829|PDB:4RDN"
FT STRAND 464..473
FT /evidence="ECO:0007829|PDB:4RDN"
FT STRAND 478..481
FT /evidence="ECO:0007829|PDB:4RDO"
FT STRAND 486..488
FT /evidence="ECO:0007829|PDB:4RDN"
FT STRAND 494..506
FT /evidence="ECO:0007829|PDB:4RDN"
FT HELIX 507..509
FT /evidence="ECO:0007829|PDB:4RDN"
FT TURN 510..512
FT /evidence="ECO:0007829|PDB:4RDN"
FT TURN 516..520
FT /evidence="ECO:0007829|PDB:4RDN"
FT HELIX 523..525
FT /evidence="ECO:0007829|PDB:4RDN"
FT HELIX 534..546
FT /evidence="ECO:0007829|PDB:4RDN"
SQ SEQUENCE 579 AA; 62334 MW; BF3959B5561A464E CRC64;
MSASSLLEQR PKGQGNKVQN GSVHQKDGLN DDDFEPYLSP QARPNNAYTA MSDSYLPSYY
SPSIGFSYSL GEAAWSTGGD TAMPYLTSYG QLSNGEPHFL PDAMFGQPGA LGSTPFLGQH
GFNFFPSGID FSAWGNNSSQ GQSTQSSGYS SNYAYAPSSL GGAMIDGQSA FANETLNKAP
GMNTIDQGMA ALKLGSTEVA SNVPKVVGSA VGSGSITSNI VASNSLPPAT IAPPKPASWA
DIASKPAKQQ PKLKTKNGIA GSSLPPPPIK HNMDIGTWDN KGPVAKAPSQ ALVQNIGQPT
QGSPQPVGQQ ANNSPPVAQA SVGQQTQPLP PPPPQPAQLS VQQQAAQPTR WVAPRNRGSG
FGHNGVDGNG VGQSQAGSGS TPSEPHPVLE KLRSINNYNP KDFDWNLKHG RVFIIKSYSE
DDIHRSIKYN IWCSTEHGNK RLDAAYRSMN GKGPVYLLFS VNGSGHFCGV AEMKSAVDYN
TCAGVWSQDK WKGRFDVRWI FVKDVPNSQL RHIRLENNEN KPVTNSRDTQ EVPLEKAKQV
LKIIASYKHT TSIFDDFSHY EKRQEEEESV KKERQGRGK
