YTDC1_MOUSE
ID YTDC1_MOUSE Reviewed; 736 AA.
AC E9Q5K9; E9PW44; E9Q7Z8; Q69Z54; Q80V25; Q8R5E6;
DT 19-FEB-2014, integrated into UniProtKB/Swiss-Prot.
DT 19-FEB-2014, sequence version 2.
DT 03-AUG-2022, entry version 70.
DE RecName: Full=YTH domain-containing protein 1 {ECO:0000305};
GN Name=Ythdc1 {ECO:0000312|MGI:MGI:2443713};
GN Synonyms=Kiaa1966 {ECO:0000303|PubMed:15368895};
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 222-736 (ISOFORM 2).
RC TISSUE=Pancreas islet cell;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 379-736 (ISOFORM 2).
RC STRAIN=FVB/N; TISSUE=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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-309 AND SER-425, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC Testis;
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 [5]
RP FUNCTION.
RX PubMed=29262316; DOI=10.1016/j.celrep.2017.11.092;
RA Shima H., Matsumoto M., Ishigami Y., Ebina M., Muto A., Sato Y.,
RA Kumagai S., Ochiai K., Suzuki T., Igarashi K.;
RT "S-Adenosylmethionine synthesis is regulated by selective N6-adenosine
RT methylation and mRNA degradation involving METTL16 and YTHDC1.";
RL Cell Rep. 21:3354-3363(2017).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, INTERACTION WITH
RP CPSF6; SRSF3 AND SRSF7, AND MUTAGENESIS OF TRP-378 AND TRP-429.
RX PubMed=29799838; DOI=10.1371/journal.pgen.1007412;
RA Kasowitz S.D., Ma J., Anderson S.J., Leu N.A., Xu Y., Gregory B.D.,
RA Schultz R.M., Wang P.J.;
RT "Nuclear m6A reader YTHDC1 regulates alternative polyadenylation and
RT splicing during mouse oocyte development.";
RL PLoS Genet. 14:e1007412-e1007412(2018).
CC -!- FUNCTION: Regulator of alternative splicing that specifically
CC recognizes and binds N6-methyladenosine (m6A)-containing RNAs
CC (PubMed:29262316, PubMed:29799838). M6A is a modification present at
CC internal sites of mRNAs and some non-coding RNAs and plays a role in
CC the efficiency of mRNA splicing, processing and stability
CC (PubMed:29799838). Acts as a key regulator of exon-inclusion or exon-
CC skipping during alternative splicing via interaction with mRNA splicing
CC factors SRSF3 and SRSF10 (By similarity). Specifically binds m6A-
CC containing mRNAs and promotes recruitment of SRSF3 to its mRNA-binding
CC elements adjacent to m6A sites, leading to exon-inclusion during
CC alternative splicing (By similarity). In contrast, interaction with
CC SRSF3 prevents interaction with SRSF10, a splicing factor that promotes
CC exon skipping: this prevents SRSF10 from binding to its mRNA-binding
CC sites close to m6A-containing regions, leading to inhibit exon skipping
CC during alternative splicing (By similarity). May also regulate
CC alternative splice site selection (By similarity). Also involved in
CC nuclear export of m6A-containing mRNAs via interaction with SRSF3:
CC interaction with SRSF3 facilitates m6A-containing mRNA-binding to both
CC SRSF3 and NXF1, promoting mRNA nuclear export (By similarity). Involved
CC in S-adenosyl-L-methionine homeostasis by regulating expression of
CC MAT2A transcripts, probably by binding m6A-containing MAT2A mRNAs
CC (PubMed:29262316). Also recognizes and binds m6A on other RNA molecules
CC (By similarity). Involved in random X inactivation mediated by Xist
CC RNA: recognizes and binds m6A-containing Xist and promotes
CC transcription repression activity of Xist (By similarity). Also
CC recognizes and binds m6A-containing single-stranded DNA (By
CC similarity). Involved in germline development: required for
CC spermatogonial development in males and oocyte growth and maturation in
CC females, probably via its role in alternative splicing
CC (PubMed:29799838). {ECO:0000250|UniProtKB:Q96MU7,
CC ECO:0000269|PubMed:29262316, ECO:0000269|PubMed:29799838}.
CC -!- SUBUNIT: Interacts with SRSF1. Interacts with SRSF2 (By similarity).
CC Interacts with SRSF3 (PubMed:29799838). Interacts with SRSF7
CC (PubMed:29799838). Interacts with SRSF10 (By similarity). Interacts
CC with CPSF6 (PubMed:29799838). Interacts with KHDRBS1/SAM68.: Interacts
CC with TRA2B. Interacts with KHDRBS3 (By similarity). Interacts with EMD
CC (By similarity). Interacts with RBMX (By similarity). Interacts with
CC ZCCHC8 (By similarity). {ECO:0000250|UniProtKB:Q96MU7,
CC ECO:0000250|UniProtKB:Q9QY02, ECO:0000269|PubMed:29799838}.
CC -!- INTERACTION:
CC E9Q5K9; O88974: Setdb1; NbExp=2; IntAct=EBI-647644, EBI-79658;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:29799838}. Nucleus
CC speckle {ECO:0000250|UniProtKB:Q96MU7}. Note=Localizes to a novel
CC subnuclear structure, the YT bodies. {ECO:0000250|UniProtKB:Q9QY02}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=E9Q5K9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=E9Q5K9-2; Sequence=VSP_053720;
CC Name=3;
CC IsoId=E9Q5K9-3; Sequence=VSP_053719, VSP_053720;
CC -!- DOMAIN: The YTH domain mediates RNA-binding.
CC {ECO:0000250|UniProtKB:Q96MU7}.
CC -!- PTM: Tyrosine phosphorylated. {ECO:0000250|UniProtKB:Q9QY02}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality (PubMed:29799838).
CC Conditional deletion in germ cells leads to infertility in both males
CC and females: mice are viable and grossly normal but male mice lack any
CC germ cells including mitotic spermatogonia, while female oocyte
CC maturation is arrested at the primary follicle stage (PubMed:29799838).
CC Ythdc1-deficient oocytes contain large cytoplasmic RNA granules, show
CC extensive alternative polyadenylation, thereby altering 3'-UTR length,
CC and massive alternative splicing defects (PubMed:29799838).
CC {ECO:0000269|PubMed:29799838}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH48817.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AC102016; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK173312; BAD32590.1; -; Transcribed_RNA.
DR EMBL; BC022697; AAH22697.1; -; mRNA.
DR EMBL; BC048817; AAH48817.1; ALT_INIT; mRNA.
DR CCDS; CCDS39127.1; -. [E9Q5K9-1]
DR CCDS; CCDS84898.1; -. [E9Q5K9-2]
DR CCDS; CCDS84899.1; -. [E9Q5K9-3]
DR RefSeq; NP_001334304.1; NM_001347375.1. [E9Q5K9-2]
DR RefSeq; NP_001334305.1; NM_001347376.1. [E9Q5K9-3]
DR RefSeq; NP_808348.2; NM_177680.3. [E9Q5K9-1]
DR AlphaFoldDB; E9Q5K9; -.
DR BMRB; E9Q5K9; -.
DR SMR; E9Q5K9; -.
DR BioGRID; 231116; 1.
DR IntAct; E9Q5K9; 4.
DR MINT; E9Q5K9; -.
DR STRING; 10090.ENSMUSP00000039133; -.
DR iPTMnet; E9Q5K9; -.
DR PhosphoSitePlus; E9Q5K9; -.
DR EPD; E9Q5K9; -.
DR jPOST; E9Q5K9; -.
DR MaxQB; E9Q5K9; -.
DR PaxDb; E9Q5K9; -.
DR PeptideAtlas; E9Q5K9; -.
DR PRIDE; E9Q5K9; -.
DR ProteomicsDB; 275231; -. [E9Q5K9-1]
DR ProteomicsDB; 275232; -. [E9Q5K9-2]
DR ProteomicsDB; 275233; -. [E9Q5K9-3]
DR Antibodypedia; 52214; 101 antibodies from 23 providers.
DR Ensembl; ENSMUST00000038384; ENSMUSP00000039133; ENSMUSG00000035851. [E9Q5K9-1]
DR Ensembl; ENSMUST00000119339; ENSMUSP00000113000; ENSMUSG00000035851. [E9Q5K9-3]
DR Ensembl; ENSMUST00000120498; ENSMUSP00000113951; ENSMUSG00000035851. [E9Q5K9-2]
DR GeneID; 231386; -.
DR KEGG; mmu:231386; -.
DR UCSC; uc008xxw.1; mouse. [E9Q5K9-1]
DR CTD; 91746; -.
DR MGI; MGI:2443713; Ythdc1.
DR VEuPathDB; HostDB:ENSMUSG00000035851; -.
DR eggNOG; KOG1902; Eukaryota.
DR GeneTree; ENSGT00940000155803; -.
DR HOGENOM; CLU_029591_0_0_1; -.
DR OMA; CHTSTVY; -.
DR OrthoDB; 1523119at2759; -.
DR TreeFam; TF325590; -.
DR BioGRID-ORCS; 231386; 27 hits in 76 CRISPR screens.
DR ChiTaRS; Ythdc1; mouse.
DR PRO; PR:E9Q5K9; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; E9Q5K9; protein.
DR Bgee; ENSMUSG00000035851; Expressed in metanephric cortical collecting duct and 259 other tissues.
DR ExpressionAtlas; E9Q5K9; baseline and differential.
DR Genevisible; E9Q5K9; MM.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:1990247; F:N6-methyladenosine-containing RNA binding; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; ISS:UniProtKB.
DR GO; GO:0009048; P:dosage compensation by inactivation of X chromosome; ISS:UniProtKB.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0110104; P:mRNA alternative polyadenylation; IMP:MGI.
DR GO; GO:0006406; P:mRNA export from nucleus; ISS:UniProtKB.
DR GO; GO:0006376; P:mRNA splice site selection; ISS:UniProtKB.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; ISO:MGI.
DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0048160; P:primary follicle stage; IMP:MGI.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IMP:MGI.
DR GO; GO:0048024; P:regulation of mRNA splicing, via spliceosome; ISS:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IMP:MGI.
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 1: Evidence at protein level;
KW Alternative splicing; Isopeptide bond; mRNA processing; mRNA splicing;
KW Nucleus; Phosphoprotein; Reference proteome; RNA-binding; Ubl conjugation.
FT CHAIN 1..736
FT /note="YTH domain-containing protein 1"
FT /id="PRO_0000425545"
FT DOMAIN 356..493
FT /note="YTH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00225"
FT REGION 1..339
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 510..564
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 616..652
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 678..736
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..16
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 33..63
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 64..91
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 92..120
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 129..180
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 181..197
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 198..257
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 272..291
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 292..309
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 325..339
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 521..564
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 616..646
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 682..736
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 362..364
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 378
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:0000305|PubMed:29799838"
FT BINDING 429
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:0000305|PubMed:29799838"
FT BINDING 477
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 MOD_RES 35
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QY02"
FT MOD_RES 118
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96MU7"
FT MOD_RES 120
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96MU7"
FT MOD_RES 146
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96MU7"
FT MOD_RES 148
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q96MU7"
FT MOD_RES 309
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 316
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96MU7"
FT MOD_RES 318
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96MU7"
FT MOD_RES 319
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96MU7"
FT MOD_RES 321
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96MU7"
FT MOD_RES 425
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 436
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96MU7"
FT MOD_RES 546
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96MU7"
FT CROSSLNK 96
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96MU7"
FT VAR_SEQ 326..343
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_053719"
FT VAR_SEQ 575..582
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15368895,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_053720"
FT MUTAGEN 378
FT /note="W->A: Abolished binding to N6-methyladenosine (m6A)-
FT containing RNAs; when associated with A-429."
FT /evidence="ECO:0000269|PubMed:29799838"
FT MUTAGEN 429
FT /note="W->A: Abolished binding to N6-methyladenosine (m6A)-
FT containing RNAs; when associated with A-378."
FT /evidence="ECO:0000269|PubMed:29799838"
FT CONFLICT 680
FT /note="V -> A (in Ref. 2; BAD32590)"
FT /evidence="ECO:0000305"
FT CONFLICT 733
FT /note="R -> C (in Ref. 3; AAH48817)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 736 AA; 85649 MW; DBB90CA82B28A9E0 CRC64;
MAADSREEKD GELNVLDDIL TEVPEQDDEL YNPESEQDKN EKKGSKRKSE RMESTDTKRQ
KPSIHSRQLI SKPLSSSVSN NKRIVSTKGK SVTEYKNEEY QRSERNKRLD ADRKIRLSSS
SSREPYKSQP EKTCLRKRDS ERRAKSPTPD GSERIGLEVD RRASRSSQSS KEEVNSEDYG
SDHETGSSGS SEQGNNTENE EEGGEEDVEE DEEVDEDAED DEEVDEDAEE EEEEDEEEEE
DEDEDEEEEE YEQDERDQKE EGNDYDTRSE ASDSGSESVS FTDGSVRSGS GTDGSDEKKK
ERKRARGISP IVFDRSGSSA SESYAGSEKK HEKLSSSVRA VRKDQTSKLK YVLQDARFFL
IKSNNHENVS LAKAKGVWST LPVNEKKLNL AFRSARSVIL IFSVRESGKF QGFARLSSES
HHGGSPIHWV LPAGMSAKML GGVFKIDWIC RRELPFTKSA HLTNPWNEHK PVKIGRDGQE
IELECGTQLC LLFPPDESID LYQLIHKMRH KRRMHSQPRS RGRPSRREPV RDVGRRRPED
YDIHNSRKKP RIDYPPEFHQ RPGYVKDPRY QEVDSFTNLI PNRRFSGVRR DVFLNGSYND
YVREFHNMGP PPPWQGMPPY PGIEQPPHHP YYQHHAPPPQ AHPPYSGHHP VPHEARYRDK
RVHDYDMRVD DFLRRTQAVV SGRRSRPRER DRERERDRPR DNRRDRERDR GRDRERERER
ICDRDRDRGE RGRYRR
