ID METL6_HUMAN Reviewed; 284 AA. AC Q8TCB7; Q96LU4; DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot. DT 24-NOV-2009, sequence version 2. DT 02-SEP-2026, entry version 168. DE RecName: Full=tRNA N(3)-cytidine methyltransferase METTL6 {ECO:0000305}; DE EC=2.1.1.- {ECO:0000269|PubMed:32923617, ECO:0000269|PubMed:34268557, ECO:0000269|PubMed:34862464, ECO:0000269|PubMed:34922197}; DE AltName: Full=Methyltransferase-like protein 6 {ECO:0000305}; DE Short=hMETTL6 {ECO:0000303|PubMed:34862464}; GN Name=METTL6 {ECO:0000303|PubMed:32923617, GN ECO:0000312|HGNC:HGNC:28343}; 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=Cerebellum; 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=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung; 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 INTERACTION WITH SARS1. RX PubMed=28655767; DOI=10.1074/jbc.m117.798298; RA Xu L., Liu X., Sheng N., Oo K.S., Liang J., Chionh Y.H., Xu J., Ye F., RA Gao Y.G., Dedon P.C., Fu X.Y.; RT "Three distinct 3-methylcytidine (m3C) methyltransferases modify tRNA and RT mRNA in mice and humans."; RL J. Biol. Chem. 292:14695-14703(2017). RN [5] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=32923617; DOI=10.1126/sciadv.aaz4551; RA Ignatova V.V., Kaiser S., Ho J.S.Y., Bing X., Stolz P., Tan Y.X., Lee C.L., RA Gay F.P.H., Lastres P.R., Gerlini R., Rathkolb B., Aguilar-Pimentel A., RA Sanz-Moreno A., Klein-Rodewald T., Calzada-Wack J., Ibragimov E., RA Valenta M., Lukauskas S., Pavesi A., Marschall S., Leuchtenberger S., RA Fuchs H., Gailus-Durner V., de Angelis M.H., Bultmann S., Rando O.J., RA Guccione E., Kellner S.M., Schneider R.; RT "METTL6 is a tRNA m3C methyltransferase that regulates pluripotency and RT tumor cell growth."; RL Sci. Adv. 6:eaaz4551-eaaz4551(2020). RN [6] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND INTERACTION WITH RP SARS1. RX PubMed=34268557; DOI=10.1093/nar/gkab603; RA Mao X.L., Li Z.H., Huang M.H., Wang J.T., Zhou J.B., Li Q.R., Xu H., RA Wang X.J., Zhou X.L.; RT "Mutually exclusive substrate selection strategy by human m3C RNA RT transferases METTL2A and METTL6."; RL Nucleic Acids Res. 49:8309-8323(2021). RN [7] RP X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) IN COMPLEX WITH RP S-ADENOSYL-L-METHIONINE, FUNCTION, CATALYTIC ACTIVITY, AND RP BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=34922197; DOI=10.1016/j.bbrc.2021.12.013; RA Li S., Zhou H., Liao S., Wang X., Zhu Z., Zhang J., Xu C.; RT "Structural basis for METTL6-mediated m3C RNA methylation."; RL Biochem. Biophys. Res. Commun. 589:159-164(2021). RN [8] RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH RP S-ADENOSYL-L-HOMOCYSTEINE, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND RP MUTAGENESIS OF TYR-49; HIS-61; GLU-85; CYS-93; ASP-110; PHE-111; SER-161 RP AND THR-217. RX PubMed=34862464; DOI=10.1038/s42003-021-02890-9; RA Chen R., Zhou J., Liu L., Mao X.L., Zhou X., Xie W.; RT "Crystal structure of human METTL6, the m3C methyltransferase."; RL Commun. Biol. 4:1361-1361(2021). CC -!- FUNCTION: S-adenosyl-L-methionine-dependent methyltransferase that CC mediates N(3)-methylcytidine modification of residue 32 of the tRNA CC anticodon loop of tRNA(Ser), including tRNA(Ser)(UGA) and CC tRNA(Ser)(GCU) (PubMed:32923617, PubMed:34268557, PubMed:34862464, CC PubMed:34922197). Interaction with SARS1/SerRS is required for N(3)- CC methylcytidine methylation (PubMed:34268557). CC {ECO:0000269|PubMed:32923617, ECO:0000269|PubMed:34268557, CC ECO:0000269|PubMed:34862464, ECO:0000269|PubMed:34922197}. CC -!- CATALYTIC ACTIVITY: CC Reaction=cytidine(32) in tRNA(Ser) + S-adenosyl-L-methionine = N(3)- CC methylcytidine(32) in tRNA(Ser) + S-adenosyl-L-homocysteine + H(+); CC Xref=Rhea:RHEA:50956, Rhea:RHEA-COMP:12849, Rhea:RHEA-COMP:12851, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, CC ChEBI:CHEBI:74894, ChEBI:CHEBI:82748; CC Evidence={ECO:0000269|PubMed:32923617, ECO:0000269|PubMed:34268557, CC ECO:0000269|PubMed:34862464, ECO:0000269|PubMed:34922197}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50957; CC Evidence={ECO:0000269|PubMed:32923617, ECO:0000269|PubMed:34268557, CC ECO:0000269|PubMed:34862464, ECO:0000269|PubMed:34922197}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.24 uM for tRNA(Ser) {ECO:0000269|PubMed:34922197}; CC KM=0.68 uM for S-adenosyl-L-methionine {ECO:0000269|PubMed:34922197}; CC Note=kcat is 7200 min(-1) for tRNA(Ser) (PubMed:34922197). kcat is CC 7100 min(-1) for S-adenosyl-L-methionine (PubMed:34922197). CC {ECO:0000269|PubMed:34922197}; CC -!- SUBUNIT: Monomer (PubMed:34862464). Interacts with SARS1/SerRS; CC interaction is mediated via tRNA(Ser) and is required for N(3)- CC methylcytidine methylation (PubMed:28655767, PubMed:34268557). CC {ECO:0000269|PubMed:28655767, ECO:0000269|PubMed:34268557, CC ECO:0000269|PubMed:34862464}. CC -!- INTERACTION: CC Q8TCB7; O95872: GPANK1; NbExp=3; IntAct=EBI-17861723, EBI-751540; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:34268557}. Nucleus CC {ECO:0000269|PubMed:34268557}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q8TCB7-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8TCB7-2; Sequence=VSP_008480; CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. METL family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH22400.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK057791; BAB71574.1; -; mRNA. DR EMBL; AC027125; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC022400; AAH22400.1; ALT_SEQ; mRNA. DR CCDS; CCDS43056.1; -. [Q8TCB7-1] DR CCDS; CCDS87051.1; -. [Q8TCB7-2] DR RefSeq; NP_001288721.1; NM_001301792.2. DR RefSeq; NP_001317591.1; NM_001330662.2. [Q8TCB7-2] DR RefSeq; NP_689609.2; NM_152396.4. [Q8TCB7-1] DR RefSeq; XP_005264924.1; XM_005264867.5. [Q8TCB7-1] DR RefSeq; XP_006713033.1; XM_006712970.5. [Q8TCB7-1] DR RefSeq; XP_016861207.1; XM_017005718.3. [Q8TCB7-1] DR RefSeq; XP_047303406.1; XM_047447450.1. [Q8TCB7-1] DR RefSeq; XP_047303407.1; XM_047447451.1. [Q8TCB7-2] DR RefSeq; XP_054201222.1; XM_054345247.1. [Q8TCB7-1] DR RefSeq; XP_054201223.1; XM_054345248.1. [Q8TCB7-1] DR RefSeq; XP_054201224.1; XM_054345249.1. [Q8TCB7-1] DR RefSeq; XP_054201225.1; XM_054345250.1. [Q8TCB7-1] DR RefSeq; XP_054201226.1; XM_054345251.1. [Q8TCB7-2] DR PDB; 7EZG; X-ray; 1.90 A; A=1-284. DR PDB; 7F1E; X-ray; 2.59 A; A/B=1-284. DR PDB; 8OWX; X-ray; 2.60 A; A/B=1-271. DR PDB; 8OWY; X-ray; 3.20 A; A/B=40-269. DR PDB; 8P7B; EM; 2.42 A; A=1-284. DR PDB; 8P7C; EM; 3.70 A; A/C=1-284. DR PDB; 8P7D; EM; 4.20 A; A=1-284. DR AlphaFoldDB; Q8TCB7; -. DR EMDB; EMD-17528; -. DR EMDB; EMD-17529; -. DR EMDB; EMD-17530; -. DR SMR; Q8TCB7; -. DR BioGRID; 126301; 19. DR ComplexPortal; CPX-26600; tRNA (cytosine(32)-N(3))-methytransferase complex. DR FunCoup; Q8TCB7; 3347. DR IntAct; Q8TCB7; 77. DR STRING; 9606.ENSP00000407613; -. DR iPTMnet; Q8TCB7; -. DR PhosphoSitePlus; Q8TCB7; -. DR BioMuta; METTL6; -. DR DMDM; 269849620; -. DR jPOST; Q8TCB7; -. DR MassIVE; Q8TCB7; -. DR PaxDb; 9606-ENSP00000407613; -. DR PeptideAtlas; Q8TCB7; -. DR ProteomicsDB; 74111; -. [Q8TCB7-1] DR ProteomicsDB; 74112; -. [Q8TCB7-2] DR Pumba; Q8TCB7; -. DR Antibodypedia; 26744; 126 antibodies from 21 providers. DR DNASU; 131965; -. DR Ensembl; ENST00000383789.9; ENSP00000373299.5; ENSG00000206562.13. [Q8TCB7-2] DR Ensembl; ENST00000383790.8; ENSP00000373300.3; ENSG00000206562.13. [Q8TCB7-1] DR Ensembl; ENST00000443029.5; ENSP00000407613.1; ENSG00000206562.13. [Q8TCB7-1] DR Ensembl; ENST00000916130.1; ENSP00000586189.1; ENSG00000206562.13. [Q8TCB7-1] DR Ensembl; ENST00000962394.1; ENSP00000632453.1; ENSG00000206562.13. [Q8TCB7-1] DR GeneID; 131965; -. DR KEGG; hsa:131965; -. DR MANE-Select; ENST00000383790.8; ENSP00000373300.3; NM_152396.4; NP_689609.2. DR UCSC; uc003bzs.2; human. [Q8TCB7-1] DR AGR; HGNC:28343; -. DR ClinPGx; PA142671462; -. DR CTD; 131965; -. DR DisGeNET; 131965; -. DR GeneCards; METTL6; -. DR HGNC; HGNC:28343; METTL6. DR HPA; ENSG00000206562; Low tissue specificity. DR MIM; 618903; gene. DR OpenTargets; ENSG00000206562; -. DR VEuPathDB; HostDB:ENSG00000206562; -. DR eggNOG; KOG2361; Eukaryota. DR GeneTree; ENSGT00940000156679; -. DR HOGENOM; CLU_029724_2_2_1; -. DR InParanoid; Q8TCB7; -. DR OMA; DAQRNWD; -. DR OrthoDB; 417697at2759; -. DR PAN-GO; Q8TCB7; 0 GO annotations based on evolutionary models. DR PhylomeDB; Q8TCB7; -. DR BRENDA; 2.1.1.268; 2681. DR PathwayCommons; Q8TCB7; -. DR SignaLink; Q8TCB7; -. DR Agora; ENSG00000206562; -. DR BioGRID-ORCS; 131965; 7 hits in 1155 CRISPR screens. DR GenomeRNAi; 131965; -. DR Pharos; Q8TCB7; Tbio. DR PRO; PR:Q8TCB7; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q8TCB7; protein. DR Bgee; ENSG00000206562; Expressed in body of pancreas and 154 other cell types or tissues. DR ExpressionAtlas; Q8TCB7; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0043527; C:tRNA methyltransferase complex; IPI:ComplexPortal. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0052735; F:tRNA (cytidine-N3)-methyltransferase activity; IDA:UniProtKB. DR GO; GO:0106217; P:tRNA C3-cytosine methylation; IDA:ComplexPortal. DR GO; GO:0030488; P:tRNA methylation; IDA:UniProtKB. DR GO; GO:0006400; P:tRNA modification; IDA:UniProt. DR CDD; cd02440; AdoMet_MTases; 1. DR FunFam; 3.40.50.150:FF:000279; Methyltransferase-like protein; 1. DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1. DR InterPro; IPR013217; Methyltransf_12. DR InterPro; IPR026113; METTL2/6/8-like. DR InterPro; IPR029063; SAM-dependent_MTases_sf. DR PANTHER; PTHR22809; METHYLTRANSFERASE-RELATED; 1. DR PANTHER; PTHR22809:SF5; TRNA N(3)-METHYLCYTIDINE METHYLTRANSFERASE METTL6; 1. DR Pfam; PF08242; Methyltransf_12; 1. DR PIRSF; PIRSF037755; Mettl2_prd; 1. DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1. DR PDBsum; 7EZG; -. DR PDBsum; 7F1E; -. DR PDBsum; 8OWX; -. DR PDBsum; 8OWY; -. DR PDBsum; 8P7B; -. DR PDBsum; 8P7C; -. DR PDBsum; 8P7D; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Methyltransferase; Nucleus; KW Proteomics identification; Reference proteome; S-adenosyl-L-methionine; KW Transferase; tRNA processing. FT CHAIN 1..284 FT /note="tRNA N(3)-cytidine methyltransferase METTL6" FT /id="PRO_0000204454" FT BINDING 45 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:34922197, FT ECO:0007744|PDB:7F1E" FT BINDING 49 FT /ligand="S-adenosyl-L-homocysteine" FT /ligand_id="ChEBI:CHEBI:57856" FT /evidence="ECO:0000269|PubMed:34862464, FT ECO:0007744|PDB:7EZG" FT BINDING 49 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:34922197, FT ECO:0007744|PDB:7F1E" FT BINDING 61 FT /ligand="S-adenosyl-L-homocysteine" FT /ligand_id="ChEBI:CHEBI:57856" FT /evidence="ECO:0000269|PubMed:34862464, FT ECO:0007744|PDB:7EZG" FT BINDING 85 FT /ligand="S-adenosyl-L-homocysteine" FT /ligand_id="ChEBI:CHEBI:57856" FT /evidence="ECO:0000269|PubMed:34862464, FT ECO:0007744|PDB:7EZG" FT BINDING 87 FT /ligand="S-adenosyl-L-homocysteine" FT /ligand_id="ChEBI:CHEBI:57856" FT /evidence="ECO:0000269|PubMed:34862464, FT ECO:0007744|PDB:7EZG" FT BINDING 87 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:34922197, FT ECO:0007744|PDB:7F1E" FT BINDING 110 FT /ligand="S-adenosyl-L-homocysteine" FT /ligand_id="ChEBI:CHEBI:57856" FT /evidence="ECO:0000269|PubMed:34862464, FT ECO:0007744|PDB:7EZG" FT BINDING 110 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:34922197, FT ECO:0007744|PDB:7F1E" FT BINDING 136 FT /ligand="S-adenosyl-L-homocysteine" FT /ligand_id="ChEBI:CHEBI:57856" FT /evidence="ECO:0000269|PubMed:34862464, FT ECO:0007744|PDB:7EZG" FT BINDING 136 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:34922197, FT ECO:0007744|PDB:7F1E" FT BINDING 137 FT /ligand="S-adenosyl-L-homocysteine" FT /ligand_id="ChEBI:CHEBI:57856" FT /evidence="ECO:0000269|PubMed:34862464, FT ECO:0007744|PDB:7EZG" FT BINDING 137 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:34922197, FT ECO:0007744|PDB:7F1E" FT BINDING 157 FT /ligand="S-adenosyl-L-homocysteine" FT /ligand_id="ChEBI:CHEBI:57856" FT /evidence="ECO:0000269|PubMed:34862464, FT ECO:0007744|PDB:7EZG" FT BINDING 157 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:34922197, FT ECO:0007744|PDB:7F1E" FT VAR_SEQ 178..284 FT /note="VLKPGKSVLFRDYGLYDHAMLRFKASSKLGENFYVRQDGTRSYFFTDDFLAQ FT LFMDTGYEEVVNEYVFRETVNKKEGLCVPRVFLQSKFLKPPKNPSPVVLGLDPKS -> FT CHGCSSELRQPWDKDDFAVTWDPWSPAIRVLLCHSGWSAVAWTWLTAASTSWAQAVLPP FT QPLK (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_008480" FT MUTAGEN 49 FT /note="Y->F: Decreased affinity for FT S-adenosyl-L-methionine." FT /evidence="ECO:0000269|PubMed:34862464" FT MUTAGEN 61 FT /note="H->N: Decreased affinity for FT S-adenosyl-L-methionine." FT /evidence="ECO:0000269|PubMed:34862464" FT MUTAGEN 85 FT /note="E->Q: Strongly decreased affinity for FT S-adenosyl-L-methionine." FT /evidence="ECO:0000269|PubMed:34862464" FT MUTAGEN 93 FT /note="C->S: Does not affect affinity for FT S-adenosyl-L-methionine." FT /evidence="ECO:0000269|PubMed:34862464" FT MUTAGEN 110 FT /note="D->A: Nearly abolished affinity for FT S-adenosyl-L-methionine." FT /evidence="ECO:0000269|PubMed:34862464" FT MUTAGEN 111 FT /note="F->L: Decreased affinity for FT S-adenosyl-L-methionine." FT /evidence="ECO:0000269|PubMed:34862464" FT MUTAGEN 161 FT /note="S->A: Strongly reduced RNA FT (cytosine-3-)-methyltransferase activity." FT /evidence="ECO:0000269|PubMed:34862464" FT MUTAGEN 217 FT /note="T->A: Strongly reduced RNA FT (cytosine-3-)-methyltransferase activity." FT /evidence="ECO:0000269|PubMed:34862464" FT CONFLICT 67 FT /note="F -> L (in Ref. 1; BAB71574)" FT /evidence="ECO:0000305" FT HELIX 1..13 FT /evidence="ECO:0007829|PDB:7EZG" FT HELIX 16..25 FT /evidence="ECO:0007829|PDB:7EZG" FT HELIX 28..30 FT /evidence="ECO:0007829|PDB:8P7B" FT HELIX 31..39 FT /evidence="ECO:0007829|PDB:7EZG" FT HELIX 41..50 FT /evidence="ECO:0007829|PDB:7EZG" FT HELIX 64..71 FT /evidence="ECO:0007829|PDB:7EZG" FT STRAND 75..78 FT /evidence="ECO:0007829|PDB:7F1E" FT STRAND 81..86 FT /evidence="ECO:0007829|PDB:7EZG" FT HELIX 94..98 FT /evidence="ECO:0007829|PDB:7EZG" FT STRAND 104..111 FT /evidence="ECO:0007829|PDB:7EZG" FT HELIX 113..120 FT /evidence="ECO:0007829|PDB:7EZG" FT TURN 127..129 FT /evidence="ECO:0007829|PDB:7EZG" FT STRAND 130..134 FT /evidence="ECO:0007829|PDB:7EZG" FT TURN 137..139 FT /evidence="ECO:0007829|PDB:7EZG" FT HELIX 142..144 FT /evidence="ECO:0007829|PDB:7EZG" FT STRAND 151..158 FT /evidence="ECO:0007829|PDB:7EZG" FT HELIX 160..162 FT /evidence="ECO:0007829|PDB:7EZG" FT HELIX 165..167 FT /evidence="ECO:0007829|PDB:7EZG" FT HELIX 168..176 FT /evidence="ECO:0007829|PDB:7EZG" FT STRAND 179..191 FT /evidence="ECO:0007829|PDB:7EZG" FT HELIX 195..199 FT /evidence="ECO:0007829|PDB:7EZG" FT HELIX 202..204 FT /evidence="ECO:0007829|PDB:8P7B" FT STRAND 205..207 FT /evidence="ECO:0007829|PDB:7EZG" FT STRAND 210..212 FT /evidence="ECO:0007829|PDB:7EZG" FT STRAND 218..220 FT /evidence="ECO:0007829|PDB:7EZG" FT HELIX 224..233 FT /evidence="ECO:0007829|PDB:7EZG" FT STRAND 237..246 FT /evidence="ECO:0007829|PDB:7EZG" FT TURN 251..254 FT /evidence="ECO:0007829|PDB:8P7B" FT STRAND 259..267 FT /evidence="ECO:0007829|PDB:7EZG" FT HELIX 268..271 FT /evidence="ECO:0007829|PDB:7EZG" SQ SEQUENCE 284 AA; 33251 MW; 445CAAE4D669B07F CRC64; MASLQRKGLQ ARILTSEEEE KLKRDQTLVS DFKQQKLEQE AQKNWDLFYK RNSTNFFKDR HWTTREFEEL RSCREFEDQK LTMLEAGCGV GNCLFPLLEE DPNIFAYACD FSPRAIEYVK QNPLYDTERC KVFQCDLTKD DLLDHVPPES VDVVMLIFVL SAVHPDKMHL VLQNIYKVLK PGKSVLFRDY GLYDHAMLRF KASSKLGENF YVRQDGTRSY FFTDDFLAQL FMDTGYEEVV NEYVFRETVN KKEGLCVPRV FLQSKFLKPP KNPSPVVLGL DPKS //