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YTDC1_DROME
ID   YTDC1_DROME             Reviewed;         721 AA.
AC   Q9VZQ1; Q8IH35; Q8IRD2; Q9Y172;
DT   20-JUN-2018, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 2.
DT   03-AUG-2022, entry version 148.
DE   RecName: Full=YTH domain-containing protein 1 {ECO:0000305};
DE   AltName: Full=Splicing factor YT521 {ECO:0000303|PubMed:27919077, ECO:0000303|PubMed:28675155};
DE            Short=YT521-B {ECO:0000303|PubMed:27919077, ECO:0000303|PubMed:28675155};
GN   Name=Ythdc1 {ECO:0000312|FlyBase:FBgn0027616};
GN   ORFNames=CG12076 {ECO:0000312|FlyBase:FBgn0027616};
OS   Drosophila melanogaster (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila; Sophophora.
OX   NCBI_TaxID=7227;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley;
RX   PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA   Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA   Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA   George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA   Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA   Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA   Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA   An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA   Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA   Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA   Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA   Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA   Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA   Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA   Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA   Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA   Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA   Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA   Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA   Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA   Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA   Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA   McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA   Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA   Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA   Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA   Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA   Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA   Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA   Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA   Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA   Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA   Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA   Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA   Venter J.C.;
RT   "The genome sequence of Drosophila melanogaster.";
RL   Science 287:2185-2195(2000).
RN   [2]
RP   GENOME REANNOTATION.
RC   STRAIN=Berkeley;
RX   PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA   Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA   Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA   Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA   Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA   Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA   Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT   "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT   review.";
RL   Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC   STRAIN=Berkeley; TISSUE=Head;
RX   PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA   Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA   Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA   Celniker S.E.;
RT   "A Drosophila full-length cDNA resource.";
RL   Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC   STRAIN=Berkeley; TISSUE=Head;
RA   Celniker S., Carlson J., Wan K., Frise E., Hoskins R., Park S.,
RA   Svirskas R., Rubin G.;
RL   Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX   PubMed=27919077; DOI=10.1038/nature20568;
RA   Lence T., Akhtar J., Bayer M., Schmid K., Spindler L., Ho C.H., Kreim N.,
RA   Andrade-Navarro M.A., Poeck B., Helm M., Roignant J.Y.;
RT   "m(6)A modulates neuronal functions and sex determination in Drosophila.";
RL   Nature 540:242-247(2016).
RN   [6]
RP   FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX   PubMed=27919081; DOI=10.1038/nature20577;
RA   Haussmann I.U., Bodi Z., Sanchez-Moran E., Mongan N.P., Archer N.,
RA   Fray R.G., Soller M.;
RT   "m(6)A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila
RT   sex determination.";
RL   Nature 540:301-304(2016).
RN   [7]
RP   FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX   PubMed=28675155; DOI=10.1038/ncomms15737;
RA   Kan L., Grozhik A.V., Vedanayagam J., Patil D.P., Pang N., Lim K.S.,
RA   Huang Y.C., Joseph B., Lin C.J., Despic V., Guo J., Yan D., Kondo S.,
RA   Deng W.M., Dedon P.C., Jaffrey S.R., Lai E.C.;
RT   "The m6A pathway facilitates sex determination in Drosophila.";
RL   Nat. Commun. 8:15737-15737(2017).
CC   -!- FUNCTION: Regulator of alternative splicing that specifically
CC       recognizes and binds N6-methyladenosine (m6A)-containing RNAs
CC       (PubMed:27919077, PubMed:27919081, PubMed:28675155). Acts by acting as
CC       a reader of m6A methylation (PubMed:27919077, PubMed:27919081).
CC       Required for sex determination and dosage compensation via Sxl
CC       alternative splicing: m6A methylation acts as a key regulator of Sxl
CC       pre-mRNA and promotes female-specific alternative splicing of Sxl,
CC       which determines female physiognomy (PubMed:27919077, PubMed:27919081,
CC       PubMed:28675155). M6A methylation is also required for neuronal
CC       functions (PubMed:27919077). {ECO:0000269|PubMed:27919077,
CC       ECO:0000269|PubMed:27919081, ECO:0000269|PubMed:28675155}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:27919077,
CC       ECO:0000269|PubMed:27919081, ECO:0000269|PubMed:28675155}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=A;
CC         IsoId=Q9VZQ1-1; Sequence=Displayed;
CC       Name=B;
CC         IsoId=Q9VZQ1-2; Sequence=VSP_059632;
CC   -!- DISRUPTION PHENOTYPE: Mutant flies survive until adulthood but exhibit
CC       flight defects and poor locomotion (PubMed:27919077, PubMed:27919081,
CC       PubMed:28675155). Flies display sexual transformations dues to Sxl
CC       splicing defects (PubMed:27919081, PubMed:28675155).
CC       {ECO:0000269|PubMed:27919077, ECO:0000269|PubMed:27919081,
CC       ECO:0000269|PubMed:28675155}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAN71205.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence.; Evidence={ECO:0000305};
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DR   EMBL; AE014296; AAF47768.2; -; Genomic_DNA.
DR   EMBL; AE014296; AAN11564.1; -; Genomic_DNA.
DR   EMBL; AF145594; AAD38569.1; -; mRNA.
DR   EMBL; BT001450; AAN71205.1; ALT_SEQ; mRNA.
DR   EMBL; BT150336; AGW25618.1; -; mRNA.
DR   RefSeq; NP_647811.2; NM_139554.4. [Q9VZQ1-1]
DR   RefSeq; NP_728876.1; NM_168029.2. [Q9VZQ1-2]
DR   AlphaFoldDB; Q9VZQ1; -.
DR   SMR; Q9VZQ1; -.
DR   IntAct; Q9VZQ1; 1.
DR   STRING; 7227.FBpp0072940; -.
DR   PaxDb; Q9VZQ1; -.
DR   EnsemblMetazoa; FBtr0073078; FBpp0072940; FBgn0027616. [Q9VZQ1-1]
DR   EnsemblMetazoa; FBtr0073079; FBpp0072941; FBgn0027616. [Q9VZQ1-2]
DR   GeneID; 38420; -.
DR   KEGG; dme:Dmel_CG12076; -.
DR   UCSC; CG12076-RA; d. melanogaster. [Q9VZQ1-1]
DR   CTD; 91746; -.
DR   FlyBase; FBgn0027616; Ythdc1.
DR   VEuPathDB; VectorBase:FBgn0027616; -.
DR   eggNOG; KOG1902; Eukaryota.
DR   GeneTree; ENSGT00940000155803; -.
DR   HOGENOM; CLU_388961_0_0_1; -.
DR   InParanoid; Q9VZQ1; -.
DR   OMA; KRSYHGP; -.
DR   OrthoDB; 806977at2759; -.
DR   PhylomeDB; Q9VZQ1; -.
DR   BioGRID-ORCS; 38420; 1 hit in 1 CRISPR screen.
DR   GenomeRNAi; 38420; -.
DR   PRO; PR:Q9VZQ1; -.
DR   Proteomes; UP000000803; Chromosome 3L.
DR   Bgee; FBgn0027616; Expressed in brain and 24 other tissues.
DR   ExpressionAtlas; Q9VZQ1; baseline and differential.
DR   Genevisible; Q8IRD2; DM.
DR   GO; GO:0005654; C:nucleoplasm; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR   GO; GO:0003729; F:mRNA binding; IDA:FlyBase.
DR   GO; GO:1990247; F:N6-methyladenosine-containing RNA binding; IDA:FlyBase.
DR   GO; GO:0036002; F:pre-mRNA binding; IDA:FlyBase.
DR   GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR   GO; GO:0000398; P:mRNA splicing, via spliceosome; IBA:GO_Central.
DR   GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IDA:FlyBase.
DR   GO; GO:0048024; P:regulation of mRNA splicing, via spliceosome; IBA:GO_Central.
DR   GO; GO:0007530; P:sex determination; IGI:FlyBase.
DR   GO; GO:0007548; P:sex differentiation; IEA:UniProtKB-KW.
DR   InterPro; IPR007275; YTH_domain.
DR   InterPro; IPR045168; YTH_prot.
DR   PANTHER; PTHR12357; PTHR12357; 1.
DR   Pfam; PF04146; YTH; 2.
DR   PROSITE; PS50882; YTH; 1.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Differentiation; mRNA processing; mRNA splicing;
KW   Nucleus; Reference proteome; Sexual differentiation.
FT   CHAIN           1..721
FT                   /note="YTH domain-containing protein 1"
FT                   /id="PRO_0000444615"
FT   DOMAIN          254..391
FT                   /note="YTH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00225"
FT   REGION          29..239
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          424..471
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          580..605
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          651..721
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        43..77
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        99..155
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        156..170
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        171..186
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        187..239
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        452..471
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        580..603
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        700..721
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         260..262
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:0000250|UniProtKB:Q9Y5A9"
FT   BINDING         276
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:0000250|UniProtKB:Q96MU7"
FT   BINDING         327
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:0000250|UniProtKB:Q96MU7"
FT   VAR_SEQ         1..11
FT                   /note="Missing (in isoform B)"
FT                   /id="VSP_059632"
FT   CONFLICT        637
FT                   /note="S -> G (in Ref. 3; AAD38569 and 4; AAN71205)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        647
FT                   /note="Q -> R (in Ref. 3; AAD38569)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   721 AA;  76259 MW;  35EB89185FF417B9 CRC64;
     MPRAARKQTL PMREMADLDA VHLGLDENEA DIAEELQDFE FNTRSEASES NGGDSSDSEP
     SISSVSTATS SLAGSSKRKT KKPAKQSPQP AVETKSSKSS AKNKAKREPT PEELNGGKKK
     KRTDSGTKKT TSSEASDKVK SKSPDTEDRQ PSAKKSRTKI PSNANDSAGH KSDLSEAEDE
     KPSLPTLESD SESSDSDSGT QHKRNGGNGG GNGRGKPSSK SSTPEKDSVG GGTHSHSQKG
     YDYMTKLNYL FRDTRFFLIK SNNSDNVQLS KNKSVWATLP QNDANLNQAF KEARNVLLIF
     SVNESGKFAG FARMAAPSRR DIPQVAWVLP PSISPKALGG VIELDWICRK ELSFNATLHL
     HNTWNEGKPV KIGRDGQEIE PKIGGELCRL FPEDEQIELT PILKKSKETA RVMREKGIHV
     IYKPPRSLSS RGHGGGGRGG GRGSNHDHLG PMRHKRSYHG APHHRPYRHH HGMGLPPGGG
     FKRSGSPYRQ MGGAAGAPPG GPGDMAMPSW ERYMSSAAAA EAYVADYMRN MHGQLPPLPF
     VPPFAQLPIP GAGAGAAGAL PPGAAAAMYE QLPPPVRYYD GPGAPPLPDY PPPQRPPPPG
     FDKAPSYEEF AAWKNAGLPT VPPPGFPVYG GAANGGSNGA GGLAAAQAAA AGGGMGAGGG
     SGGGMGGPGG YRNRDGNNGS AGGRRREYGN RSGGGGSSRD SRPFRERGGG GGQRSYRDNR
     R
 
 
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