YTHD1_HUMAN
ID YTHD1_HUMAN Reviewed; 559 AA.
AC Q9BYJ9; Q8N3G5; Q8TBT1; Q96AN4; Q96S57; Q9BTI7; Q9NX79;
DT 12-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=YTH domain-containing family protein 1 {ECO:0000305};
DE Short=DF1 {ECO:0000303|PubMed:31292544, ECO:0000303|PubMed:32492408};
DE AltName: Full=Dermatomyositis associated with cancer putative autoantigen 1 {ECO:0000303|Ref.4};
DE Short=DACA-1 {ECO:0000303|Ref.4};
GN Name=YTHDF1 {ECO:0000303|Ref.4, ECO:0000312|HGNC:HGNC:15867};
GN Synonyms=C20orf21 {ECO:0000312|HGNC:HGNC:15867};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Ileal mucosa;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon, Lymph, Placenta, and Testis;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 123-559 (ISOFORM 1).
RC TISSUE=Cervix carcinoma;
RA Onouchi H., Muro Y., Tomita Y.;
RT "Dermatomyositis associated with cancer autoantigen.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 196-559 (ISOFORM 1).
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-182, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
RP RNA-BINDING, AND FUNCTION.
RX PubMed=24284625; DOI=10.1038/nature12730;
RA Wang X., Lu Z., Gomez A., Hon G.C., Yue Y., Han D., Fu Y., Parisien M.,
RA Dai Q., Jia G., Ren B., Pan T., He C.;
RT "N-methyladenosine-dependent regulation of messenger RNA stability.";
RL Nature 505:117-120(2014).
RN [15]
RP CAUTION, AND INTERACTION WITH RIBOSOMES; EIF3A AND EIF3B.
RX PubMed=26046440; DOI=10.1016/j.cell.2015.05.014;
RA Wang X., Zhao B.S., Roundtree I.A., Lu Z., Han D., Ma H., Weng X., Chen K.,
RA Shi H., He C.;
RT "N(6)-methyladenosine modulates messenger RNA translation efficiency.";
RL Cell 161:1388-1399(2015).
RN [16]
RP CAUTION.
RX PubMed=26593424; DOI=10.1016/j.cell.2015.10.012;
RA Meyer K.D., Patil D.P., Zhou J., Zinoviev A., Skabkin M.A., Elemento O.,
RA Pestova T.V., Qian S.B., Jaffrey S.R.;
RT "5' UTR m(6)A promotes cap-independent translation.";
RL Cell 163:999-1010(2015).
RN [17]
RP INTERACTION WITH YTHDF3.
RX PubMed=28106072; DOI=10.1038/cr.2017.15;
RA Shi H., Wang X., Lu Z., Zhao B.S., Ma H., Hsu P.J., Liu C., He C.;
RT "YTHDF3 facilitates translation and decay of N(6)-methyladenosine-modified
RT RNA.";
RL Cell Res. 27:315-328(2017).
RN [18]
RP FUNCTION.
RX PubMed=31388144; DOI=10.1038/s41422-019-0210-3;
RA Gao Y., Pei G., Li D., Li R., Shao Y., Zhang Q.C., Li P.;
RT "Multivalent m6A motifs promote phase separation of YTHDF proteins.";
RL Cell Res. 29:767-769(2019).
RN [19]
RP FUNCTION, AND DOMAIN.
RX PubMed=31292544; DOI=10.1038/s41586-019-1374-1;
RA Ries R.J., Zaccara S., Klein P., Olarerin-George A., Namkoong S.,
RA Pickering B.F., Patil D.P., Kwak H., Lee J.H., Jaffrey S.R.;
RT "m6A enhances the phase separation potential of mRNA.";
RL Nature 571:424-428(2019).
RN [20]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH THE CCR4-NOT COMPLEX.
RX PubMed=32492408; DOI=10.1016/j.cell.2020.05.012;
RA Zaccara S., Jaffrey S.R.;
RT "A unified model for the function of YTHDF proteins in regulating m6A-
RT modified mRNA.";
RL Cell 181:1582-1595(2020).
RN [21]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=32451507; DOI=10.1038/s41589-020-0524-y;
RA Fu Y., Zhuang X.;
RT "m6A-binding YTHDF proteins promote stress granule formation.";
RL Nat. Chem. Biol. 16:955-963(2020).
RN [22] {ECO:0007744|PDB:4RCI, ECO:0007744|PDB:4RCJ}
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 361-559 IN COMPLEX WITH
RP N6-METHYLADENOSINE (M6A)-CONTAINING RNA, FUNCTION, RNA-BINDING, AND
RP MUTAGENESIS OF TYR-397; ASP-401; TRP-411; TRP-465; TRP-470 AND ARG-506.
RX PubMed=26318451; DOI=10.1074/jbc.m115.680389;
RA Xu C., Liu K., Ahmed H., Loppnau P., Schapira M., Min J.;
RT "structural basis for the discriminative recognition of N6-methyladenosine
RT RNA by the human YT521-B homology domain family of proteins.";
RL J. Biol. Chem. 290:24902-24913(2015).
CC -!- FUNCTION: Specifically recognizes and binds N6-methyladenosine (m6A)-
CC containing mRNAs, and regulates their stability (PubMed:24284625,
CC PubMed:32492408, PubMed:26318451). M6A is a modification present at
CC internal sites of mRNAs and some non-coding RNAs and plays a role in
CC mRNA stability and processing (PubMed:24284625, PubMed:32492408). Acts
CC as a regulator of mRNA stability by promoting degradation of m6A-
CC containing mRNAs via interaction with the CCR4-NOT complex
CC (PubMed:32492408). The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3)
CC shares m6A-containing mRNAs targets and act redundantly to mediate mRNA
CC degradation and cellular differentiation (PubMed:28106072,
CC PubMed:32492408). Required to facilitate learning and memory formation
CC in the hippocampus by binding to m6A-containing neuronal mRNAs (By
CC similarity). Acts as a regulator of axon guidance by binding to m6A-
CC containing ROBO3 transcripts (By similarity). Acts as a negative
CC regulator of antigen cross-presentation in myeloid dendritic cells (By
CC similarity). In the context of tumorigenesis, negative regulation of
CC antigen cross-presentation limits the anti-tumor response by reducing
CC efficiency of tumor-antigen cross-presentation (By similarity).
CC Promotes formation of phase-separated membraneless compartments, such
CC as P-bodies or stress granules, by undergoing liquid-liquid phase
CC separation upon binding to mRNAs containing multiple m6A-modified
CC residues: polymethylated mRNAs act as a multivalent scaffold for the
CC binding of YTHDF proteins, juxtaposing their disordered regions and
CC thereby leading to phase separation (PubMed:31388144, PubMed:31292544,
CC PubMed:32451507). The resulting mRNA-YTHDF complexes then partition
CC into different endogenous phase-separated membraneless compartments,
CC such as P-bodies, stress granules or neuronal RNA granules
CC (PubMed:31292544). {ECO:0000250|UniProtKB:P59326,
CC ECO:0000269|PubMed:24284625, ECO:0000269|PubMed:26318451,
CC ECO:0000269|PubMed:28106072, ECO:0000269|PubMed:31292544,
CC ECO:0000269|PubMed:31388144, ECO:0000269|PubMed:32451507,
CC ECO:0000269|PubMed:32492408}.
CC -!- SUBUNIT: Interacts with CNOT1; promoting recruitment of the CCR4-NOT
CC complex (PubMed:32492408). Interacts with ribosomes (PubMed:26046440).
CC Interacts with eIF3 (EIF3A or EIF3B) (PubMed:26046440). Interacts with
CC YTHDF3 (PubMed:28106072). {ECO:0000269|PubMed:26046440,
CC ECO:0000269|PubMed:28106072, ECO:0000269|PubMed:32492408}.
CC -!- INTERACTION:
CC Q9BYJ9; Q8NFV4-4: ABHD11; NbExp=3; IntAct=EBI-1051237, EBI-12318443;
CC Q9BYJ9; Q8N1L9: BATF2; NbExp=3; IntAct=EBI-1051237, EBI-742695;
CC Q9BYJ9; Q6UXA7: C6orf15; NbExp=3; IntAct=EBI-1051237, EBI-11990870;
CC Q9BYJ9; Q92567-2: FAM168A; NbExp=3; IntAct=EBI-1051237, EBI-11978259;
CC Q9BYJ9; Q9Y5J3: HEY1; NbExp=3; IntAct=EBI-1051237, EBI-7231130;
CC Q9BYJ9; Q9ULV5-2: HSF4; NbExp=3; IntAct=EBI-1051237, EBI-12056251;
CC Q9BYJ9; Q6PEX3: KRTAP26-1; NbExp=3; IntAct=EBI-1051237, EBI-3957672;
CC Q9BYJ9; Q8IUC3: KRTAP7-1; NbExp=3; IntAct=EBI-1051237, EBI-18394498;
CC Q9BYJ9; Q8IUC2: KRTAP8-1; NbExp=3; IntAct=EBI-1051237, EBI-10261141;
CC Q9BYJ9; Q14847-2: LASP1; NbExp=3; IntAct=EBI-1051237, EBI-9088686;
CC Q9BYJ9; Q9Y5V3: MAGED1; NbExp=3; IntAct=EBI-1051237, EBI-716006;
CC Q9BYJ9; P35548: MSX2; NbExp=3; IntAct=EBI-1051237, EBI-6447480;
CC Q9BYJ9; O43482: OIP5; NbExp=3; IntAct=EBI-1051237, EBI-536879;
CC Q9BYJ9; B1ATL7: PRR32; NbExp=3; IntAct=EBI-1051237, EBI-18587059;
CC Q9BYJ9; Q08117-2: TLE5; NbExp=3; IntAct=EBI-1051237, EBI-11741437;
CC Q9BYJ9; A5D8V6: VPS37C; NbExp=3; IntAct=EBI-1051237, EBI-2559305;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:32492408}.
CC Cytoplasm, P-body {ECO:0000269|PubMed:32492408}. Cytoplasm, Stress
CC granule {ECO:0000269|PubMed:32451507}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BYJ9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BYJ9-2; Sequence=VSP_006815, VSP_006816, VSP_006817;
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 (PubMed:31292544). This leads to the partition of m6A-containing mRNAs
CC into membraneless compartments, where mRNAs may be stored, degraded or
CC used to transport mRNAs to dendritic arbors in neurons
CC (PubMed:31292544). {ECO:0000269|PubMed:31292544}.
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:26046440, PubMed:26593424). These studies suggested that the 3
CC different paralogs (YTHDF1, YTHDF2 and YTHDF3) have unique functions
CC with limited redundancy (PubMed:26046440, PubMed:26593424). However,
CC later studies showed that YTHDF1, YTHDF2 and YTHDF3 paralogs have
CC redundant functions to a profound extent and directly promote
CC degradation of m6A-containing mRNAs (PubMed:32492408). The effect on
CC translation efficiency observed earlier is probably indirect
CC (PubMed:32492408). {ECO:0000269|PubMed:26046440,
CC ECO:0000269|PubMed:26593424, ECO:0000269|PubMed:32492408}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=On the benefits of disorder
CC - Issue 238 of August 2021;
CC URL="https://web.expasy.org/spotlight/back_issues/238/";
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DR EMBL; AK000398; BAA91138.1; -; mRNA.
DR EMBL; AL096828; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC003681; AAH03681.1; -; mRNA.
DR EMBL; BC016920; AAH16920.2; -; mRNA.
DR EMBL; BC025264; AAH25264.1; -; mRNA.
DR EMBL; BC050284; AAH50284.1; -; mRNA.
DR EMBL; AB055518; BAB62751.1; -; mRNA.
DR EMBL; AL834366; CAD39029.1; -; mRNA.
DR CCDS; CCDS13511.1; -. [Q9BYJ9-1]
DR RefSeq; NP_060268.2; NM_017798.3. [Q9BYJ9-1]
DR PDB; 4RCI; X-ray; 1.97 A; A/B/C/D=361-559.
DR PDB; 4RCJ; X-ray; 1.60 A; A=365-554.
DR PDBsum; 4RCI; -.
DR PDBsum; 4RCJ; -.
DR AlphaFoldDB; Q9BYJ9; -.
DR SMR; Q9BYJ9; -.
DR BioGRID; 120257; 326.
DR IntAct; Q9BYJ9; 65.
DR MINT; Q9BYJ9; -.
DR STRING; 9606.ENSP00000359364; -.
DR GlyConnect; 2853; 1 O-Linked glycan (1 site).
DR GlyGen; Q9BYJ9; 15 sites, 2 O-linked glycans (15 sites).
DR iPTMnet; Q9BYJ9; -.
DR MetOSite; Q9BYJ9; -.
DR PhosphoSitePlus; Q9BYJ9; -.
DR BioMuta; YTHDF1; -.
DR DMDM; 28380041; -.
DR EPD; Q9BYJ9; -.
DR jPOST; Q9BYJ9; -.
DR MassIVE; Q9BYJ9; -.
DR MaxQB; Q9BYJ9; -.
DR PaxDb; Q9BYJ9; -.
DR PeptideAtlas; Q9BYJ9; -.
DR PRIDE; Q9BYJ9; -.
DR ProteomicsDB; 79659; -. [Q9BYJ9-1]
DR ProteomicsDB; 79660; -. [Q9BYJ9-2]
DR Antibodypedia; 44459; 149 antibodies from 26 providers.
DR DNASU; 54915; -.
DR Ensembl; ENST00000370339.8; ENSP00000359364.3; ENSG00000149658.18. [Q9BYJ9-1]
DR GeneID; 54915; -.
DR KEGG; hsa:54915; -.
DR MANE-Select; ENST00000370339.8; ENSP00000359364.3; NM_017798.4; NP_060268.2.
DR UCSC; uc002yeh.4; human. [Q9BYJ9-1]
DR CTD; 54915; -.
DR DisGeNET; 54915; -.
DR GeneCards; YTHDF1; -.
DR HGNC; HGNC:15867; YTHDF1.
DR HPA; ENSG00000149658; Low tissue specificity.
DR MIM; 616529; gene.
DR neXtProt; NX_Q9BYJ9; -.
DR OpenTargets; ENSG00000149658; -.
DR PharmGKB; PA25737; -.
DR VEuPathDB; HostDB:ENSG00000149658; -.
DR eggNOG; KOG1901; Eukaryota.
DR GeneTree; ENSGT00940000156911; -.
DR HOGENOM; CLU_022715_0_0_1; -.
DR InParanoid; Q9BYJ9; -.
DR OMA; DIGTWDH; -.
DR OrthoDB; 1523251at2759; -.
DR PhylomeDB; Q9BYJ9; -.
DR TreeFam; TF323736; -.
DR PathwayCommons; Q9BYJ9; -.
DR SignaLink; Q9BYJ9; -.
DR BioGRID-ORCS; 54915; 11 hits in 1073 CRISPR screens.
DR ChiTaRS; YTHDF1; human.
DR GenomeRNAi; 54915; -.
DR Pharos; Q9BYJ9; Tbio.
DR PRO; PR:Q9BYJ9; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9BYJ9; protein.
DR Bgee; ENSG00000149658; Expressed in secondary oocyte and 213 other tissues.
DR ExpressionAtlas; Q9BYJ9; baseline and differential.
DR Genevisible; Q9BYJ9; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
DR GO; GO:0000932; C:P-body; IDA: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; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR GO; GO:0007612; P:learning; ISS:UniProtKB.
DR GO; GO:0007613; P:memory; ISS:UniProtKB.
DR GO; GO:0061157; P:mRNA destabilization; IDA:UniProtKB.
DR GO; GO:0070925; P:organelle assembly; IDA:UniProtKB.
DR GO; GO:0045727; P:positive regulation of translation; IMP:UniProtKB.
DR GO; GO:0045948; P:positive regulation of translational initiation; IDA:UniProtKB.
DR GO; GO:0002577; P:regulation of antigen processing and presentation; ISS:UniProtKB.
DR GO; GO:1902667; P:regulation of axon guidance; ISS:UniProtKB.
DR GO; GO:1900271; P:regulation of long-term synaptic potentiation; ISS:UniProtKB.
DR GO; GO:0043488; P:regulation of mRNA stability; IDA:UniProtKB.
DR GO; GO:0034063; P:stress granule assembly; IDA: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 3D-structure; Acetylation; Alternative splicing; Cytoplasm; Immunity;
KW Phosphoprotein; Reference proteome; RNA-binding.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..559
FT /note="YTH domain-containing family protein 1"
FT /id="PRO_0000223073"
FT DOMAIN 389..523
FT /note="YTH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00225"
FT REGION 1..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 238..363
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 35..50
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 283..317
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 339..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:0000269|PubMed:26318451,
FT ECO:0007744|PDB:4RCJ"
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:0000269|PubMed:26318451,
FT ECO:0007744|PDB:4RCJ"
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:0000269|PubMed:26318451,
FT ECO:0007744|PDB:4RCJ"
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:0000269|PubMed:26318451,
FT ECO:0007744|PDB:4RCJ"
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:0000269|PubMed:26318451,
FT ECO:0007744|PDB:4RCJ"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 182
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..190
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_006815"
FT VAR_SEQ 191..260
FT /note="KIGDVSSSAVKTVGSVVSSVALTGVLSGNGGTNVNMPVSKPTSWAAIASKPA
FT KPQPKMKTKSGPVMGGGL -> MLFLGSLGAWGTTSISTGSIFSLKTLRSQHGGQVGLK
FT VSRPRAPRMGAATPTPRAPWVARWLMGSQAFTATPSAR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_006816"
FT VAR_SEQ 383..559
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_006817"
FT MUTAGEN 397
FT /note="Y->A: Strongly reduced binding to N6-methyladenosine
FT (m6A)-containing RNAs."
FT /evidence="ECO:0000269|PubMed:26318451"
FT MUTAGEN 401
FT /note="D->N: Increased binding to N6-methyladenosine (m6A)-
FT containing RNAs."
FT /evidence="ECO:0000269|PubMed:26318451"
FT MUTAGEN 411
FT /note="W->A: Abolished binding to N6-methyladenosine (m6A)-
FT containing RNAs."
FT /evidence="ECO:0000269|PubMed:26318451"
FT MUTAGEN 465
FT /note="W->A: Abolished binding to N6-methyladenosine (m6A)-
FT containing RNAs."
FT /evidence="ECO:0000269|PubMed:26318451"
FT MUTAGEN 470
FT /note="W->A: Abolished binding to N6-methyladenosine (m6A)-
FT containing RNAs."
FT /evidence="ECO:0000269|PubMed:26318451"
FT MUTAGEN 506
FT /note="R->A: Reduced binding to N6-methyladenosine (m6A)-
FT containing RNAs."
FT /evidence="ECO:0000269|PubMed:26318451"
FT CONFLICT 123..124
FT /note="FP -> AR (in Ref. 4; BAB62751)"
FT /evidence="ECO:0000305"
FT CONFLICT 283..284
FT /note="AP -> PH (in Ref. 5; CAD39029)"
FT /evidence="ECO:0000305"
FT HELIX 366..374
FT /evidence="ECO:0007829|PDB:4RCJ"
FT STRAND 390..397
FT /evidence="ECO:0007829|PDB:4RCJ"
FT HELIX 399..408
FT /evidence="ECO:0007829|PDB:4RCJ"
FT HELIX 415..428
FT /evidence="ECO:0007829|PDB:4RCJ"
FT STRAND 434..440
FT /evidence="ECO:0007829|PDB:4RCJ"
FT STRAND 443..452
FT /evidence="ECO:0007829|PDB:4RCJ"
FT STRAND 457..459
FT /evidence="ECO:0007829|PDB:4RCJ"
FT STRAND 465..467
FT /evidence="ECO:0007829|PDB:4RCJ"
FT STRAND 473..485
FT /evidence="ECO:0007829|PDB:4RCJ"
FT HELIX 486..488
FT /evidence="ECO:0007829|PDB:4RCJ"
FT TURN 489..491
FT /evidence="ECO:0007829|PDB:4RCJ"
FT HELIX 495..497
FT /evidence="ECO:0007829|PDB:4RCJ"
FT HELIX 502..504
FT /evidence="ECO:0007829|PDB:4RCJ"
FT HELIX 513..525
FT /evidence="ECO:0007829|PDB:4RCJ"
FT HELIX 532..535
FT /evidence="ECO:0007829|PDB:4RCJ"
FT HELIX 536..550
FT /evidence="ECO:0007829|PDB:4RCJ"
SQ SEQUENCE 559 AA; 60874 MW; DB8AA15636130E18 CRC64;
MSATSVDTQR TKGQDNKVQN GSLHQKDTVH DNDFEPYLTG QSNQSNSYPS MSDPYLSSYY
PPSIGFPYSL NEAPWSTAGD PPIPYLTTYG QLSNGDHHFM HDAVFGQPGG LGNNIYQHRF
NFFPENPAFS AWGTSGSQGQ QTQSSAYGSS YTYPPSSLGG TVVDGQPGFH SDTLSKAPGM
NSLEQGMVGL KIGDVSSSAV KTVGSVVSSV ALTGVLSGNG GTNVNMPVSK PTSWAAIASK
PAKPQPKMKT KSGPVMGGGL PPPPIKHNMD IGTWDNKGPV PKAPVPQQAP SPQAAPQPQQ
VAQPLPAQPP ALAQPQYQSP QQPPQTRWVA PRNRNAAFGQ SGGAGSDSNS PGNVQPNSAP
SVESHPVLEK LKAAHSYNPK EFEWNLKSGR VFIIKSYSED DIHRSIKYSI WCSTEHGNKR
LDSAFRCMSS KGPVYLLFSV NGSGHFCGVA EMKSPVDYGT SAGVWSQDKW KGKFDVQWIF
VKDVPNNQLR HIRLENNDNK PVTNSRDTQE VPLEKAKQVL KIISSYKHTT SIFDDFAHYE
KRQEEEEVVR KERQSRNKQ
