ID   YTDC2_HUMAN             Reviewed;        1430 AA.
AC   Q9H6S0; B2RP66;
DT   05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT   16-JUN-2009, sequence version 2.
DT   27-MAR-2024, entry version 166.
DE   RecName: Full=3'-5' RNA helicase YTHDC2 {ECO:0000305};
DE            EC=3.6.4.13 {ECO:0000269|PubMed:29033321};
DE   AltName: Full=YTH domain-containing protein 2 {ECO:0000303|PubMed:29033321};
DE            Short=hYTHDC2 {ECO:0000303|PubMed:29033321};
GN   Name=YTHDC2 {ECO:0000303|PubMed:29033321,
GN   ECO:0000312|HGNC:HGNC:24721};
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 GENOMIC DNA].
RX   PubMed=15372022; DOI=10.1038/nature02919;
RA   Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA   Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA   She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA   Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA   Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA   Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA   Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA   Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA   Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA   Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA   Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA   Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT   "The DNA sequence and comparative analysis of human chromosome 5.";
RL   Nature 431:268-274(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 730-1430, AND VARIANT GLN-1409.
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   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1092 AND SER-1281, AND
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   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [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   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1089, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
RN   [7]
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   [8]
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   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1202, 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   [10]
RP   FUNCTION, AND RNA-BINDING.
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).
RN   [11]
RP   FUNCTION, CATALYTIC ACTIVITY, DOMAIN, RNA-BINDING, INTERACTION WITH XRN1,
RP   AND MUTAGENESIS OF GLU-317 AND TRP-1360.
RX   PubMed=29033321; DOI=10.1016/j.molcel.2017.09.021;
RA   Wojtas M.N., Pandey R.R., Mendel M., Homolka D., Sachidanandam R.,
RA   Pillai R.S.;
RT   "Regulation of m6A transcripts by the 3'-5' RNA helicase YTHDC2 is
RT   essential for a successful meiotic program in the mammalian germline.";
RL   Mol. Cell 68:374-387(2017).
RN   [12]
RP   TISSUE SPECIFICITY.
RX   PubMed=29087293; DOI=10.7554/elife.26116;
RA   Bailey A.S., Batista P.J., Gold R.S., Chen Y.G., de Rooij D.G., Chang H.Y.,
RA   Fuller M.T.;
RT   "The conserved RNA helicase YTHDC2 regulates the transition from
RT   proliferation to differentiation in the germline.";
RL   Elife 6:0-0(2017).
RN   [13]
RP   FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH XRN1.
RX   PubMed=29970596; DOI=10.1261/rna.064238.117;
RA   Kretschmer J., Rao H., Hackert P., Sloan K.E., Hoebartner C.,
RA   Bohnsack M.T.;
RT   "The m6A reader protein YTHDC2 interacts with the small ribosomal subunit
RT   and the 5'-3' exoribonuclease XRN1.";
RL   RNA 24:1339-1350(2018).
RN   [14]
RP   INTERACTION WITH ZCCHC4.
RX   PubMed=31799605; DOI=10.1093/nar/gkz1147;
RA   Pinto R., Vaagboe C.B., Jakobsson M.E., Kim Y., Baltissen M.P.,
RA   O'Donohue M.F., Guzman U.H., Malecki J.M., Wu J., Kirpekar F., Olsen J.V.,
RA   Gleizes P.E., Vermeulen M., Leidel S.A., Slupphaug G., Falnes P.O.;
RT   "The human methyltransferase ZCCHC4 catalyses N6-methyladenosine
RT   modification of 28S ribosomal RNA.";
RL   Nucleic Acids Res. 48:830-846(2020).
RN   [15]
RP   STRUCTURE BY NMR OF 1288-1421.
RG   RIKEN structural genomics initiative (RSGI);
RT   "Solution structure of the YTH domain in YTH domain-containing protein 2.";
RL   Submitted (OCT-2007) to the PDB data bank.
RN   [16] {ECO:0007744|PDB:6K6U}
RP   X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS) OF 1286-1426.
RX   PubMed=31472957; DOI=10.1016/j.bbrc.2019.08.107;
RA   Ma C., Liao S., Zhu Z.;
RT   "Crystal structure of human YTHDC2 YTH domain.";
RL   Biochem. Biophys. Res. Commun. 518:678-684(2019).
CC   -!- FUNCTION: 3'-5' RNA helicase that plays a key role in the male and
CC       female germline by promoting transition from mitotic to meiotic
CC       divisions in stem cells (PubMed:26318451, PubMed:29033321,
CC       PubMed:29970596). Specifically recognizes and binds N6-methyladenosine
CC       (m6A)-containing RNAs, a modification present at internal sites of
CC       mRNAs and some non-coding RNAs that plays a role in the efficiency of
CC       RNA processing and stability (PubMed:26318451, PubMed:29033321).
CC       Essential for ensuring a successful progression of the meiotic program
CC       in the germline by regulating the level of m6A-containing RNAs (By
CC       similarity). Acts by binding and promoting degradation of m6A-
CC       containing mRNAs: the 3'-5' RNA helicase activity is required for this
CC       process and RNA degradation may be mediated by XRN1 exoribonuclease
CC       (PubMed:29033321). Required for both spermatogenesis and oogenesis (By
CC       similarity). {ECO:0000250|UniProtKB:B2RR83,
CC       ECO:0000269|PubMed:26318451, ECO:0000269|PubMed:29033321,
CC       ECO:0000269|PubMed:29970596}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
CC         Evidence={ECO:0000269|PubMed:29033321};
CC   -!- SUBUNIT: Interacts with MEIOC; binds transcripts that regulate the
CC       mitotic cell cycle inhibiting progression into metaphase, thereby
CC       allowing meiotic prophase to proceed normally (By similarity).
CC       Interacts (via ANK repeats) with XRN1 (PubMed:29033321,
CC       PubMed:29970596). Interacts with ZCCHC4 (PubMed:31799605). Associates
CC       with the small ribosomal subunit (PubMed:29970596). Interacts with
CC       RBM46 (By similarity). {ECO:0000250|UniProtKB:B2RR83,
CC       ECO:0000269|PubMed:29033321, ECO:0000269|PubMed:29970596,
CC       ECO:0000269|PubMed:31799605}.
CC   -!- INTERACTION:
CC       Q9H6S0; Q15306: IRF4; NbExp=2; IntAct=EBI-1057466, EBI-751345;
CC       Q9H6S0; Q99J34: Irak1; Xeno; NbExp=2; IntAct=EBI-1057466, EBI-6117042;
CC       Q9H6S0; A2AG06: Meioc; Xeno; NbExp=2; IntAct=EBI-1057466, EBI-11664020;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:B2RR83}.
CC       Cytoplasm, perinuclear region {ECO:0000269|PubMed:29970596}.
CC   -!- TISSUE SPECIFICITY: Expressed in testis (PubMed:29087293). Not detected
CC       in spermatogonia next to the tubule wall but is strongly expressed in
CC       spermatocytes, suggesting that it is up-regulated in germ cells upon
CC       entry into meiosis (PubMed:29087293). {ECO:0000269|PubMed:29087293}.
CC   -!- DOMAIN: The YTH domain mediates RNA-binding. It recognizes and binds
CC       N6-methyladenosine (m6A)-containing RNAs.
CC       {ECO:0000269|PubMed:29033321}.
CC   -!- SIMILARITY: Belongs to the DEAD box helicase family. DEAH subfamily.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAB15183.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AC093208; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC010389; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC137285; AAI37286.1; -; mRNA.
DR   EMBL; AK025593; BAB15183.1; ALT_INIT; mRNA.
DR   CCDS; CCDS4113.1; -.
DR   RefSeq; NP_073739.3; NM_022828.4.
DR   RefSeq; XP_016865219.1; XM_017009730.1.
DR   PDB; 2YU6; NMR; -; A=1288-1421.
DR   PDB; 6K6U; X-ray; 2.27 A; A/B=1286-1426.
DR   PDB; 6LR2; NMR; -; A=1288-1421.
DR   PDBsum; 2YU6; -.
DR   PDBsum; 6K6U; -.
DR   PDBsum; 6LR2; -.
DR   AlphaFoldDB; Q9H6S0; -.
DR   SMR; Q9H6S0; -.
DR   BioGRID; 122321; 217.
DR   IntAct; Q9H6S0; 65.
DR   MINT; Q9H6S0; -.
DR   STRING; 9606.ENSP00000161863; -.
DR   GlyGen; Q9H6S0; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9H6S0; -.
DR   PhosphoSitePlus; Q9H6S0; -.
DR   BioMuta; YTHDC2; -.
DR   DMDM; 239938805; -.
DR   EPD; Q9H6S0; -.
DR   jPOST; Q9H6S0; -.
DR   MassIVE; Q9H6S0; -.
DR   MaxQB; Q9H6S0; -.
DR   PaxDb; 9606-ENSP00000161863; -.
DR   PeptideAtlas; Q9H6S0; -.
DR   ProteomicsDB; 81025; -.
DR   Pumba; Q9H6S0; -.
DR   Antibodypedia; 48855; 58 antibodies from 16 providers.
DR   DNASU; 64848; -.
DR   Ensembl; ENST00000161863.9; ENSP00000161863.4; ENSG00000047188.16.
DR   GeneID; 64848; -.
DR   KEGG; hsa:64848; -.
DR   MANE-Select; ENST00000161863.9; ENSP00000161863.4; NM_022828.5; NP_073739.3.
DR   UCSC; uc003kqn.4; human.
DR   AGR; HGNC:24721; -.
DR   CTD; 64848; -.
DR   DisGeNET; 64848; -.
DR   GeneCards; YTHDC2; -.
DR   HGNC; HGNC:24721; YTHDC2.
DR   HPA; ENSG00000047188; Low tissue specificity.
DR   MIM; 616530; gene.
DR   neXtProt; NX_Q9H6S0; -.
DR   OpenTargets; ENSG00000047188; -.
DR   PharmGKB; PA134912676; -.
DR   VEuPathDB; HostDB:ENSG00000047188; -.
DR   eggNOG; KOG0920; Eukaryota.
DR   eggNOG; KOG0922; Eukaryota.
DR   eggNOG; KOG1902; Eukaryota.
DR   GeneTree; ENSGT00940000155826; -.
DR   HOGENOM; CLU_001832_1_6_1; -.
DR   InParanoid; Q9H6S0; -.
DR   OMA; XDYRHSE; -.
DR   OrthoDB; 1095660at2759; -.
DR   PhylomeDB; Q9H6S0; -.
DR   TreeFam; TF318311; -.
DR   PathwayCommons; Q9H6S0; -.
DR   SignaLink; Q9H6S0; -.
DR   SIGNOR; Q9H6S0; -.
DR   BioGRID-ORCS; 64848; 11 hits in 1155 CRISPR screens.
DR   ChiTaRS; YTHDC2; human.
DR   EvolutionaryTrace; Q9H6S0; -.
DR   GenomeRNAi; 64848; -.
DR   Pharos; Q9H6S0; Tbio.
DR   PRO; PR:Q9H6S0; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; Q9H6S0; Protein.
DR   Bgee; ENSG00000047188; Expressed in endothelial cell and 204 other cell types or tissues.
DR   ExpressionAtlas; Q9H6S0; baseline and differential.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:WormBase.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0035770; C:ribonucleoprotein granule; ISS:UniProtKB.
DR   GO; GO:0034458; F:3'-5' RNA helicase activity; IDA:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR   GO; GO:0008186; F:ATP-dependent activity, acting on RNA; IDA:AgBase.
DR   GO; GO:0004386; F:helicase activity; IBA:GO_Central.
DR   GO; GO:1990247; F:N6-methyladenosine-containing RNA reader activity; IDA:UniProtKB.
DR   GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR   GO; GO:0070063; F:RNA polymerase binding; IPI:AgBase.
DR   GO; GO:0051729; P:germline cell cycle switching, mitotic to meiotic cell cycle; ISS:UniProtKB.
DR   GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0048599; P:oocyte development; ISS:UniProtKB.
DR   GO; GO:0044829; P:positive regulation by host of viral genome replication; IMP:AgBase.
DR   GO; GO:0070555; P:response to interleukin-1; IDA:AgBase.
DR   GO; GO:0034612; P:response to tumor necrosis factor; IDA:AgBase.
DR   GO; GO:0007286; P:spermatid development; ISS:UniProtKB.
DR   CDD; cd17987; DEXHc_YTHDC2; 1.
DR   CDD; cd06007; R3H_DEXH_helicase; 1.
DR   CDD; cd18791; SF2_C_RHA; 1.
DR   CDD; cd21134; YTH; 1.
DR   Gene3D; 1.20.120.1080; -; 1.
DR   Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2.
DR   Gene3D; 3.10.590.10; ph1033 like domains; 1.
DR   Gene3D; 3.30.1370.50; R3H-like domain; 1.
DR   InterPro; IPR002110; Ankyrin_rpt.
DR   InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR   InterPro; IPR011709; DEAD-box_helicase_OB_fold.
DR   InterPro; IPR011545; DEAD/DEAH_box_helicase_dom.
DR   InterPro; IPR048333; HA2_WH.
DR   InterPro; IPR007502; Helicase-assoc_dom.
DR   InterPro; IPR014001; Helicase_ATP-bd.
DR   InterPro; IPR001650; Helicase_C.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR034083; R3H_DEXH_helicase.
DR   InterPro; IPR001374; R3H_dom.
DR   InterPro; IPR036867; R3H_dom_sf.
DR   InterPro; IPR007275; YTH_domain.
DR   PANTHER; PTHR18934:SF213; 3'-5' RNA HELICASE YTHDC2; 1.
DR   PANTHER; PTHR18934; ATP-DEPENDENT RNA HELICASE; 1.
DR   Pfam; PF00270; DEAD; 1.
DR   Pfam; PF21010; HA2_C; 1.
DR   Pfam; PF04408; HA2_N; 1.
DR   Pfam; PF00271; Helicase_C; 1.
DR   Pfam; PF07717; OB_NTP_bind; 1.
DR   Pfam; PF01424; R3H; 1.
DR   Pfam; PF04146; YTH; 1.
DR   SMART; SM00487; DEXDc; 1.
DR   SMART; SM00847; HA2; 1.
DR   SMART; SM00490; HELICc; 1.
DR   SMART; SM00393; R3H; 1.
DR   SUPFAM; SSF48403; Ankyrin repeat; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2.
DR   SUPFAM; SSF82708; R3H domain; 1.
DR   PROSITE; PS50297; ANK_REP_REGION; 1.
DR   PROSITE; PS50088; ANK_REPEAT; 1.
DR   PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR   PROSITE; PS51194; HELICASE_CTER; 1.
DR   PROSITE; PS51061; R3H; 1.
DR   PROSITE; PS50882; YTH; 1.
DR   Genevisible; Q9H6S0; HS.
PE   1: Evidence at protein level;
KW   3D-structure; ANK repeat; ATP-binding; Cytoplasm; Differentiation;
KW   Helicase; Hydrolase; Meiosis; Nucleotide-binding; Oogenesis;
KW   Phosphoprotein; Reference proteome; Repeat; RNA-binding; Spermatogenesis.
FT   CHAIN           1..1430
FT                   /note="3'-5' RNA helicase YTHDC2"
FT                   /id="PRO_0000249340"
FT   DOMAIN          38..106
FT                   /note="R3H"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00382"
FT   DOMAIN          203..369
FT                   /note="Helicase ATP-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT   REPEAT          506..538
FT                   /note="ANK 1"
FT   REPEAT          539..571
FT                   /note="ANK 2"
FT   DOMAIN          612..784
FT                   /note="Helicase C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT   DOMAIN          1288..1418
FT                   /note="YTH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00225"
FT   REGION          1..37
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1164..1288
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           316..319
FT                   /note="DEAH box"
FT   COMPBIAS        1164..1178
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1188..1202
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1232..1252
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         216..223
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT   BINDING         1294..1296
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         1310
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         1360
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         1089
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19690332"
FT   MOD_RES         1090
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:B2RR83"
FT   MOD_RES         1092
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   MOD_RES         1202
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         1263
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:B2RR83"
FT   MOD_RES         1267
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:B2RR83"
FT   MOD_RES         1281
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   VARIANT         652
FT                   /note="S -> N (in dbSNP:rs10071816)"
FT                   /id="VAR_058002"
FT   VARIANT         1409
FT                   /note="L -> Q (in dbSNP:rs1132528)"
FT                   /evidence="ECO:0000269|PubMed:14702039"
FT                   /id="VAR_058003"
FT   MUTAGEN         317
FT                   /note="E->A: Abolished 3'-5' RNA helicase activity."
FT                   /evidence="ECO:0000269|PubMed:29033321"
FT   MUTAGEN         1360
FT                   /note="W->A: Abolished ability to bind N6-methyladenosine
FT                   (m6A)-containing RNAs."
FT                   /evidence="ECO:0000269|PubMed:29033321"
FT   CONFLICT        860
FT                   /note="I -> V (in Ref. 3; BAB15183)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        993
FT                   /note="L -> S (in Ref. 3; BAB15183)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1230
FT                   /note="Q -> R (in Ref. 3; BAB15183)"
FT                   /evidence="ECO:0000305"
FT   STRAND          1287..1296
FT                   /evidence="ECO:0007829|PDB:6K6U"
FT   HELIX           1298..1307
FT                   /evidence="ECO:0007829|PDB:6K6U"
FT   STRAND          1309..1311
FT                   /evidence="ECO:0007829|PDB:2YU6"
FT   HELIX           1314..1326
FT                   /evidence="ECO:0007829|PDB:6K6U"
FT   STRAND          1327..1336
FT                   /evidence="ECO:0007829|PDB:6K6U"
FT   STRAND          1339..1342
FT                   /evidence="ECO:0007829|PDB:6K6U"
FT   STRAND          1345..1348
FT                   /evidence="ECO:0007829|PDB:6K6U"
FT   STRAND          1352..1354
FT                   /evidence="ECO:0007829|PDB:2YU6"
FT   STRAND          1369..1375
FT                   /evidence="ECO:0007829|PDB:6K6U"
FT   HELIX           1381..1384
FT                   /evidence="ECO:0007829|PDB:6K6U"
FT   HELIX           1390..1392
FT                   /evidence="ECO:0007829|PDB:6K6U"
FT   STRAND          1404..1406
FT                   /evidence="ECO:0007829|PDB:2YU6"
FT   HELIX           1408..1416
FT                   /evidence="ECO:0007829|PDB:6K6U"
FT   HELIX           1417..1420
FT                   /evidence="ECO:0007829|PDB:6K6U"
SQ   SEQUENCE   1430 AA;  160248 MW;  A0C3B45771A3DE16 CRC64;
     MSRPSSVSPR QPAPGGGGGG GPSPCGPGGG GRAKGLKDIR IDEEVKIAVN IALERFRYGD
     QREMEFPSSL TSTERAFIHR LSQSLGLVSK SKGKGANRYL TVKKKDGSET AHAMMTCNLT
     HNTKHAVRSL IQRFPVTNKE RTELLPKTER GNVFAVEAEN REMSKTSGRL NNGIPQIPVK
     RGESEFDSFR QSLPVFEKQE EIVKIIKENK VVLIVGETGS GKTTQIPQFL LDDCFKNGIP
     CRIFCTQPRR LAAIAVAERV AAERRERIGQ TIGYQIRLES RVSPKTLLTF CTNGVLLRTL
     MAGDSTLSTV THVIVDEVHE RDRFSDFLLT KLRDLLQKHP TLKLILSSAA LDVNLFIRYF
     GSCPVIYIQG RPFEVKEMFL EDILRTTGYT NKEMLKYKKE KQQEEKQQTT LTEWYSAQEN
     SFKPESQRQR TVLNVTDEYD LLDDGGDAVF SQLTEKDVNC LEPWLIKEMD ACLSDIWLHK
     DIDAFAQVFH LILTENVSVD YRHSETSATA LMVAAGRGFA SQVEQLISMG ANVHSKASNG
     WMALDWAKHF GQTEIVDLLE SYSATLEFGN LDESSLVQTN GSDLSAEDRE LLKAYHHSFD
     DEKVDLDLIM HLLYNICHSC DAGAVLIFLP GYDEIVGLRD RILFDDKRFA DSTHRYQVFM
     LHSNMQTSDQ KKVLKNPPAG VRKIILSTNI AETSITVNDV VFVIDSGKVK EKSFDALNFV
     TMLKMVWISK ASAIQRKGRA GRCRPGICFR LFSRLRFQNM LEFQTPELLR MPLQELCLHT
     KLLAPVNCPI ADFLMKAPEP PPALIVRNAV QMLKTIDAMD TWEDLTELGY HLADLPVEPH
     LGKMVLCAVV LKCLDPILTI ACTLAYRDPF VLPTQASQKR AAMLCRKRFT AGAFSDHMAL
     LRAFQAWQKA RSDGWERAFC EKNFLSQATM EIIIGMRTQL LGQLRASGFV RARGGGDIRD
     VNTNSENWAV VKAALVAGMY PNLVHVDREN LVLTGPKEKK VRFHPASVLS QPQYKKIPPA
     NGQAAAIKAL PTDWLIYDEM TRAHRIANIR CCSAVTPVTI LVFCGPARLA SNALQEPSSF
     RVDGIPNDSS DSEMEDKTTA NLAALKLDEW LHFTLEPEAA SLLLQLRQKW HSLFLRRMRA
     PSKPWSQVDE ATIRAIIAVL STEEQSAGLQ QPSGIGQRPR PMSSEELPLA SSWRSNNSRK
     SSADTEFSDE CTTAERVLMK SPSPALHPPQ KYKDRGILHP KRGTEDRSDQ SSLKSTDSSS
     YPSPCASPSP PSSGKGSKSP SPRPNMPVRY FIMKSSNLRN LEISQQKGIW STTPSNERKL
     NRAFWESSIV YLVFSVQGSG HFQGFSRMSS EIGREKSQDW GSAGLGGVFK VEWIRKESLP
     FQFAHHLLNP WNDNKKVQIS RDGQELEPLV GEQLLQLWER LPLGEKNTTD
//