YTHDF_DROME
ID YTHDF_DROME Reviewed; 700 AA.
AC Q9VBZ5; A8JRA4; Q8IGP2; Q8IMU5;
DT 20-JUN-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=YTH domain-containing family protein {ECO:0000305};
GN Name=Ythdf {ECO:0000303|PubMed:33428246, ECO:0000312|FlyBase:FBgn0039261};
GN ORFNames=CG6422 {ECO:0000312|FlyBase:FBgn0039261};
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].
RC STRAIN=Berkeley; TISSUE=Embryo;
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 B).
RC STRAIN=Berkeley; TISSUE=Embryo;
RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.;
RL Submitted (JAN-2012) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
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 SUBCELLULAR LOCATION.
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, AND SUBCELLULAR LOCATION.
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).
RN [8]
RP FUNCTION, INTERACTION WITH FMR1, AND DISRUPTION PHENOTYPE.
RX PubMed=33428246; DOI=10.15252/embj.2020104975;
RA Worpenberg L., Paolantoni C., Longhi S., Mulorz M.M., Lence T.,
RA Wessels H.H., Dassi E., Aiello G., Sutandy F.X.R., Scheibe M.,
RA Edupuganti R.R., Busch A., Moeckel M.M., Vermeulen M., Butter F.,
RA Koenig J., Notarangelo M., Ohler U., Dieterich C., Quattrone A.,
RA Soldano A., Roignant J.Y.;
RT "Ythdf is a N6-methyladenosine reader that modulates Fmr1 target mRNA
RT selection and restricts axonal growth in Drosophila.";
RL EMBO J. 40:e104975-e104975(2021).
CC -!- FUNCTION: Specifically recognizes and binds N6-methyladenosine (m6A)-
CC containing RNAs (PubMed:28675155, PubMed:33428246). M6A is a
CC modification present at internal sites of mRNAs and some non-coding
CC RNAs and plays a role in the efficiency of mRNA processing and
CC stability (PubMed:28675155, PubMed:33428246). Together with Fmr1,
CC regulates axonal growth in the mushroom bodies and neuromuscular
CC junctions by repressing the translation of several mRNAs, such as those
CC of chic and futsch (PubMed:33428246). {ECO:0000269|PubMed:28675155,
CC ECO:0000269|PubMed:33428246}.
CC -!- SUBUNIT: Interacts with Fmr1; the interaction is RNA independent.
CC {ECO:0000269|PubMed:33428246}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27919077,
CC ECO:0000269|PubMed:27919081, ECO:0000269|PubMed:28675155}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=A;
CC IsoId=Q9VBZ5-1; Sequence=Displayed;
CC Name=B;
CC IsoId=Q9VBZ5-2; Sequence=VSP_059633;
CC Name=C;
CC IsoId=Q9VBZ5-3; Sequence=VSP_059634;
CC -!- DEVELOPMENTAL STAGE: Strongly enriched during the first 2 hours after
CC fertilization but then declines and remains at low levels during
CC development and adulthood. {ECO:0000269|PubMed:27919077}.
CC -!- DISRUPTION PHENOTYPE: Results in fusion of the adult Beta lobes in the
CC mushroom bodies. {ECO:0000269|PubMed:33428246}.
CC -!- SIMILARITY: Belongs to the YTHDF family. {ECO:0000305}.
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DR EMBL; AE014297; AAF56381.1; -; Genomic_DNA.
DR EMBL; AE014297; AAN14031.1; -; Genomic_DNA.
DR EMBL; AE014297; ABW08751.1; -; Genomic_DNA.
DR EMBL; AE014297; AGB96323.1; -; Genomic_DNA.
DR EMBL; AY069675; AAL39820.1; -; mRNA.
DR EMBL; BT001679; AAN71434.1; -; mRNA.
DR EMBL; BT133047; AEX93133.1; -; mRNA.
DR RefSeq; NP_001097905.1; NM_001104435.2. [Q9VBZ5-3]
DR RefSeq; NP_001262943.1; NM_001276014.1. [Q9VBZ5-1]
DR RefSeq; NP_651322.1; NM_143065.3. [Q9VBZ5-1]
DR RefSeq; NP_733067.1; NM_170188.2. [Q9VBZ5-2]
DR AlphaFoldDB; Q9VBZ5; -.
DR SMR; Q9VBZ5; -.
DR IntAct; Q9VBZ5; 1.
DR STRING; 7227.FBpp0084169; -.
DR PaxDb; Q9VBZ5; -.
DR EnsemblMetazoa; FBtr0084794; FBpp0084169; FBgn0039261. [Q9VBZ5-1]
DR EnsemblMetazoa; FBtr0084795; FBpp0084170; FBgn0039261. [Q9VBZ5-2]
DR EnsemblMetazoa; FBtr0113281; FBpp0112193; FBgn0039261. [Q9VBZ5-3]
DR EnsemblMetazoa; FBtr0334507; FBpp0306574; FBgn0039261. [Q9VBZ5-1]
DR GeneID; 42995; -.
DR KEGG; dme:Dmel_CG6422; -.
DR UCSC; CG6422-RA; d. melanogaster. [Q9VBZ5-1]
DR UCSC; CG6422-RB; d. melanogaster.
DR CTD; 42995; -.
DR FlyBase; FBgn0039261; Ythdf.
DR VEuPathDB; VectorBase:FBgn0039261; -.
DR eggNOG; KOG1901; Eukaryota.
DR GeneTree; ENSGT00940000170935; -.
DR HOGENOM; CLU_393932_0_0_1; -.
DR InParanoid; Q9VBZ5; -.
DR OMA; MAQMMTA; -.
DR OrthoDB; 806977at2759; -.
DR PhylomeDB; Q9VBZ5; -.
DR SignaLink; Q9VBZ5; -.
DR BioGRID-ORCS; 42995; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 42995; -.
DR PRO; PR:Q9VBZ5; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0039261; Expressed in cleaving embryo and 27 other tissues.
DR ExpressionAtlas; Q9VBZ5; baseline and differential.
DR Genevisible; A8JRA4; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
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:0036002; F:pre-mRNA binding; IDA:FlyBase.
DR GO; GO:0061157; P:mRNA destabilization; IBA:GO_Central.
DR GO; GO:0030517; P:negative regulation of axon extension; IGI: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 Alternative splicing; Cytoplasm; Reference proteome; RNA-binding.
FT CHAIN 1..700
FT /note="YTH domain-containing family protein"
FT /id="PRO_0000444616"
FT DOMAIN 382..517
FT /note="YTH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00225"
FT REGION 1..191
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 250..352
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 537..612
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 624..665
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 18..77
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 78..104
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 106..121
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 128..172
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 310..326
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 566..582
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 388..390
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:Q7Z739"
FT BINDING 394
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 404..405
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:Q7Z739"
FT BINDING 435
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 459
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:Q7Z739"
FT BINDING 464
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:Q7Z739"
FT VAR_SEQ 1..13
FT /note="MSGVDQMKIPGNT -> MRFSLFTMPHNA (in isoform B)"
FT /id="VSP_059633"
FT VAR_SEQ 1..6
FT /note="Missing (in isoform C)"
FT /id="VSP_059634"
FT CONFLICT 675
FT /note="F -> L (in Ref. 4; AAN71434)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 700 AA; 78916 MW; FD1D6C53F769C363 CRC64;
MSGVDQMKIP GNTAKSVEER NIPWSQQVDE ASYENLSSPT HDEVSGNDNS MQFQYPPFNF
KENCNTPWNN MNKGRKANAN HDSYRRHGHS IPNNTRRDEH QVNPWNSRKP AAQSFRNEND
QPSTKLDNRT SDEAQNQEVV AAPKKTTWAS IASQPAKLTS RAASTTSNSK KKGPGMPPPP
MVPGKHNLDV NVWDLPNNKP PPVPSPPSPI DLGYSDLSSD FSISSNTAPP LGARAEKVHK
DTENFLKYEH KGLGNNNNFS RAKVSPTGPV RRNLGPQQPV HHAAPRPATN AGPFGPPNAR
RHDGGPHPSR NSERSGNYSS FRGSEFESAS KFEYRDENQS RPVEATSATE ELPVDSQLVL
DELKDKNNYN PKVLDLKKAG SARFFVIKSY SEDDIHRSIK YEIWCSTDHG NKRLDDAFKE
RHEEGGNIML FFSVNGSGHF CGMAQMMTPV DYNSTSSVWS QDKWRGKFKV KWIYVKDVPN
GTLRHIRLEN NENKSVTNSR DTQEVPNDKG IEVLQILHSY NHSTSIFDDF FHYEKKQEEE
VSSKRPPMHG PDGNNHAPAP LARSFNRQAD DKDRDRDGRG GMSQKHFNSG GGAGFRNPGH
RGGAGSGGSH NNYSEYRRGF DIHKSSSDYQ FKDRDGPDFD RENDFGSHYG SNNRKNEYKH
NNTNKARLKT RDRDFSTEQI KIGVRFKDTD KDKMRSNEYS
