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