YTHD1_MOUSE
ID YTHD1_MOUSE Reviewed; 559 AA.
AC P59326; Q3T9E2;
DT 12-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 12-FEB-2003, sequence version 1.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=YTH domain-containing family protein 1 {ECO:0000305};
DE AltName: Full=Dermatomyositis associated with cancer putative autoantigen 1 homolog {ECO:0000250|UniProtKB:Q9BYJ9};
DE Short=DACA-1 homolog {ECO:0000250|UniProtKB:Q9BYJ9};
GN Name=Ythdf1 {ECO:0000303|PubMed:30401835, ECO:0000312|MGI:MGI:1917431};
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 MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Medulla oblongata, and Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Embryo;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Pancreas, Spleen, and 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 [4]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=30401835; DOI=10.1038/s41586-018-0666-1;
RA Shi H., Zhang X., Weng Y.L., Lu Z., Liu Y., Lu Z., Li J., Hao P., Zhang Y.,
RA Zhang F., Wu Y., Delgado J.Y., Su Y., Patel M.J., Cao X., Shen B.,
RA Huang X., Ming G.L., Zhuang X., Song H., He C., Zhou T.;
RT "m6A facilitates hippocampus-dependent learning and memory through
RT YTHDF1.";
RL Nature 563:249-253(2018).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30728504; DOI=10.1038/s41586-019-0916-x;
RA Han D., Liu J., Chen C., Dong L., Liu Y., Chang R., Huang X., Liu Y.,
RA Wang J., Dougherty U., Bissonnette M.B., Shen B., Weichselbaum R.R.,
RA Xu M.M., He C.;
RT "Anti-tumour immunity controlled through mRNA m6A methylation and YTHDF1 in
RT dendritic cells.";
RL Nature 566:270-274(2019).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30843071; DOI=10.1093/nar/gkz157;
RA Zhuang M., Li X., Zhu J., Zhang J., Niu F., Liang F., Chen M., Li D.,
RA Han P., Ji S.J.;
RT "The m6A reader YTHDF1 regulates axon guidance through translational
RT control of Robo3.1 expression.";
RL Nucleic Acids Res. 47:4765-4777(2019).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=32943573; DOI=10.1101/gad.340695.120;
RA Lasman L., Krupalnik V., Viukov S., Mor N., Aguilera-Castrejon A.,
RA Schneir D., Bayerl J., Mizrahi O., Peles S., Tawil S., Sathe S.,
RA Nachshon A., Shani T., Zerbib M., Kilimnik I., Aigner S., Shankar A.,
RA Mueller J.R., Schwartz S., Stern-Ginossar N., Yeo G.W., Geula S.,
RA Novershtern N., Hanna J.H.;
RT "Context-dependent functional compensation between Ythdf m6A reader
RT proteins.";
RL Genes Dev. 34:1373-1391(2020).
CC -!- FUNCTION: Specifically recognizes and binds N6-methyladenosine (m6A)-
CC containing mRNAs, and regulates their stability (PubMed:30401835,
CC PubMed:32943573). M6A is a modification present at internal sites of
CC mRNAs and some non-coding RNAs and plays a role in mRNA stability and
CC processing (PubMed:30401835, PubMed:32943573). Acts as a regulator of
CC mRNA stability by promoting degradation of m6A-containing mRNAs via
CC interaction with the CCR4-NOT complex (By similarity). The YTHDF
CC paralogs (YTHDF1, YTHDF2 and YTHDF3) share m6A-containing mRNAs targets
CC and act redundantly to mediate mRNA degradation and cellular
CC differentiation (PubMed:32943573). Required to facilitate learning and
CC memory formation in the hippocampus by binding to m6A-containing
CC neuronal mRNAs (PubMed:30401835). Acts as a regulator of axon guidance
CC by binding to m6A-containing ROBO3 transcripts (PubMed:30843071). Acts
CC as a negative regulator of antigen cross-presentation in myeloid
CC dendritic cells (PubMed:30728504). In the context of tumorigenesis,
CC negative regulation of antigen cross-presentation limits the anti-tumor
CC response by reducing efficiency of tumor-antigen cross-presentation
CC (PubMed:30728504). 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 (By
CC similarity). The resulting mRNA-YTHDF complexes then partition into
CC different endogenous phase-separated membraneless compartments, such as
CC P-bodies, stress granules or neuronal RNA granules (By similarity).
CC {ECO:0000250|UniProtKB:Q9BYJ9, ECO:0000269|PubMed:30401835,
CC ECO:0000269|PubMed:30728504, ECO:0000269|PubMed:30843071,
CC ECO:0000269|PubMed:32943573}.
CC -!- SUBUNIT: Interacts with CNOT1; promoting recruitment of the CCR4-NOT
CC complex (By similarity). Interacts with ribosomes (By similarity).
CC Interacts with eIF3 (EIF3A or EIF3B). Interacts with YTHDF3 (By
CC similarity). {ECO:0000250|UniProtKB:Q9BYJ9}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:32943573}.
CC Cytoplasm, P-body {ECO:0000250|UniProtKB:Q9BYJ9}. Cytoplasm, Stress
CC granule {ECO:0000250|UniProtKB:Q9BYJ9}.
CC -!- TISSUE SPECIFICITY: In brain, preferentially expressed in the
CC hippocampus. {ECO:0000269|PubMed:30401835}.
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 This leads to the partition of m6A-containing mRNAs into membraneless
CC compartments, where mRNAs may be stored, degraded or used to transport
CC mRNAs to dendritic arbors in neurons. {ECO:0000250|UniProtKB:Q9BYJ9}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and were born at the expected
CC Mendelian ratio (PubMed:32943573). They however display learning and
CC memory defects (PubMed:30401835). Mice develop normally up to four
CC months of age and have normal gross hippocampal histology
CC (PubMed:30401835). They however show learning and memory defects as
CC well as impaired hippocampal synaptic transmission and long-term
CC potentiation (PubMed:30401835). Hippocampal CA1 neurons show reduced
CC dendritic spine density but unaltered spine size (PubMed:30401835).
CC Conditional deletion in spinal commissural neurons results in pre-
CC crossing axon guidance defects (PubMed:30843071). Knockout mice show an
CC improved tumor control associated with increased infiltration of the
CC tumor by T-cells, due to elevated antigen-specific CD8(+) T-cell anti-
CC tumor response (PubMed:30728504). Conditional deletion in myeloid
CC dendritic cells causes increased cross-presentation of tumor antigens
CC and the cross-priming of CD8(+) T-cells (PubMed:30728504). Mice lacking
CC Ythdf1, Ythdf2 and Ythdf3 display early embryonic lethality and show
CC defects in embryonic stem cell differentiation (PubMed:32943573).
CC {ECO:0000269|PubMed:30401835, ECO:0000269|PubMed:30728504,
CC ECO:0000269|PubMed:30843071, ECO:0000269|PubMed:32943573}.
CC -!- SIMILARITY: Belongs to the YTHDF family. YTHDF1 subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: Was initially reported to act as a regulator of mRNA
CC translation efficiency by promoting ribosome loading to m6A-containing
CC mRNAs and by interacting with translation initiation factors eIF3
CC (EIF3A or EIF3B), thereby facilitating translation initiation
CC (PubMed:30401835, PubMed:30728504, PubMed:30843071). These studies
CC suggested that the 3 different paralogs (YTHDF1, YTHDF2 and YTHDF3)
CC have unique functions with limited redundancy (PubMed:30401835,
CC PubMed:30728504, PubMed:30843071). However, later studies showed that
CC YTHDF1, YTHDF2 and YTHDF3 paralogs have redundant functions to a
CC profound extent and directly promote degradation of m6A-containing
CC mRNAs (PubMed:32943573). The effect on translation efficiency observed
CC earlier is probably indirect (PubMed:32943573).
CC {ECO:0000269|PubMed:30401835, ECO:0000269|PubMed:30728504,
CC ECO:0000269|PubMed:30843071, ECO:0000269|PubMed:32943573}.
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DR EMBL; AK046768; BAC32861.1; -; mRNA.
DR EMBL; AK172582; BAE43080.1; -; mRNA.
DR EMBL; BC061479; AAH61479.1; -; mRNA.
DR EMBL; BC065050; AAH65050.1; -; mRNA.
DR CCDS; CCDS17188.1; -.
DR RefSeq; NP_776122.1; NM_173761.3.
DR AlphaFoldDB; P59326; -.
DR SMR; P59326; -.
DR BioGRID; 230804; 8.
DR STRING; 10090.ENSMUSP00000037808; -.
DR iPTMnet; P59326; -.
DR PhosphoSitePlus; P59326; -.
DR EPD; P59326; -.
DR MaxQB; P59326; -.
DR PaxDb; P59326; -.
DR PRIDE; P59326; -.
DR ProteomicsDB; 275120; -.
DR Antibodypedia; 44459; 149 antibodies from 26 providers.
DR DNASU; 228994; -.
DR Ensembl; ENSMUST00000037299; ENSMUSP00000037808; ENSMUSG00000038848.
DR GeneID; 228994; -.
DR KEGG; mmu:228994; -.
DR UCSC; uc008okd.1; mouse.
DR CTD; 54915; -.
DR MGI; MGI:1917431; Ythdf1.
DR VEuPathDB; HostDB:ENSMUSG00000038848; -.
DR eggNOG; KOG1901; Eukaryota.
DR GeneTree; ENSGT00940000156911; -.
DR HOGENOM; CLU_022715_0_0_1; -.
DR InParanoid; P59326; -.
DR OMA; DIGTWDH; -.
DR OrthoDB; 1523251at2759; -.
DR PhylomeDB; P59326; -.
DR TreeFam; TF323736; -.
DR BioGRID-ORCS; 228994; 6 hits in 74 CRISPR screens.
DR PRO; PR:P59326; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P59326; protein.
DR Bgee; ENSMUSG00000038848; Expressed in paneth cell and 264 other tissues.
DR ExpressionAtlas; P59326; baseline and differential.
DR Genevisible; P59326; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISS:UniProtKB.
DR GO; GO:0000932; C:P-body; ISS: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:0043022; F:ribosome binding; ISS:UniProtKB.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR GO; GO:0007612; P:learning; IMP:UniProtKB.
DR GO; GO:0007613; P:memory; IMP:UniProtKB.
DR GO; GO:0061157; P:mRNA destabilization; IMP:UniProtKB.
DR GO; GO:0070925; P:organelle assembly; ISS:UniProtKB.
DR GO; GO:0045727; P:positive regulation of translation; IDA:UniProtKB.
DR GO; GO:0045948; P:positive regulation of translational initiation; ISS:UniProtKB.
DR GO; GO:0002577; P:regulation of antigen processing and presentation; IMP:UniProtKB.
DR GO; GO:1902667; P:regulation of axon guidance; IMP:UniProtKB.
DR GO; GO:1900271; P:regulation of long-term synaptic potentiation; IMP:UniProtKB.
DR GO; GO:0043488; P:regulation of mRNA stability; IMP:UniProtKB.
DR GO; GO:0034063; P:stress granule assembly; ISS: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 Acetylation; Cytoplasm; Immunity; Phosphoprotein; Reference proteome;
KW RNA-binding.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9BYJ9"
FT CHAIN 2..559
FT /note="YTH domain-containing family protein 1"
FT /id="PRO_0000223074"
FT DOMAIN 389..523
FT /note="YTH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00225"
FT REGION 1..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 239..365
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..23
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 291..317
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 338..362
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 395..397
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:Q9BYJ9"
FT BINDING 401
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:Q9BYJ9"
FT BINDING 411..412
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:Q9BYJ9"
FT BINDING 441
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 465
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:Q9BYJ9"
FT BINDING 470
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:Q9BYJ9"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BYJ9"
FT MOD_RES 182
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BYJ9"
SQ SEQUENCE 559 AA; 60879 MW; 2DFA0E2D8751FA24 CRC64;
MSATSVDPQR TKGQDNKVQN GSLHQKDAVH DNDFEPYLSG QSNPSNSYPS MSDPYLSSYY
PPSIGFPYSL SEAPWSTAGD PPIPYLTTYG QLSNGDHHFM HDAVFGQPGG LGNNIYQHRF
NFFPENPAFS AWGTSGSQGQ QTQSSAYGSS YTYPPSSLGG TVVDGQTGFH SDSLNKAPGM
NSLEQGMVGL KIGDVTTSAV KTVGSVVNSV ALTGVLSGNG GTNVNMPVSK PTSWAAIASK
PAKPQPKMKT KSGPIVGGAL PPPPIKHNMD IGTWDNKGPA PKASAPQQTP SPQAAPQPQQ
VAQPLPVQPP PLVQPQYQSP QQPLQPRWVA PRNRNAAFGQ SGGANSDSNS VGNAQPTSAP
SVESHPVLEK LKAAHSYNPK EFDWNLKSGR VFIIKSYSED DIHRSIKYSI WCSTEHGNKR
LDGAFRSMSS KGPVYLLFSV NGSGHFCGVA EMKSPVDYGT SAGVWSQDKW KGKFDVKWIF
VKDVPNNQLR HIRLENNDNK PVTNSRDTQE VPLEKAKQVL KIIASYKHTT SIFDDFSHYE
KRQEEEEVVR KERQNRNKQ
