ID METL5_HUMAN Reviewed; 209 AA. AC Q9NRN9; D3DPC9; Q9NVX1; DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 24-JAN-2024, entry version 154. DE RecName: Full=rRNA N6-adenosine-methyltransferase METTL5 {ECO:0000305}; DE EC=2.1.1.- {ECO:0000269|PubMed:31328227, ECO:0000269|PubMed:32217665, ECO:0000269|PubMed:33357433, ECO:0000269|PubMed:33428944, ECO:0000269|PubMed:35033535}; DE AltName: Full=Methyltransferase-like protein 5 {ECO:0000303|PubMed:31328227}; GN Name=METTL5 {ECO:0000303|PubMed:31328227, GN ECO:0000312|HGNC:HGNC:25006}; GN ORFNames=DC3 {ECO:0000303|Ref.1}, HSPC133; 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]. RC TISSUE=Dendritic cell; RA Peng Y., Li Y., Tu Y., Xu S., Han Z., Fu G., Chen Z.; RT "A novel gene from human dendritic cells."; RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Teratocarcinoma; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain, and Placenta; 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 [6] 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 [7] RP INVOLVEMENT IN MRT72, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=31564433; DOI=10.1016/j.ajhg.2019.09.007; RA Richard E.M., Polla D.L., Assir M.Z., Contreras M., Shahzad M., Khan A.A., RA Razzaq A., Akram J., Tarar M.N., Blanpied T.A., Ahmed Z.M., Abou Jamra R., RA Wieczorek D., van Bokhoven H., Riazuddin S., Riazuddin S.; RT "Bi-allelic variants in METTL5 cause autosomal-recessive intellectual RT disability and microcephaly."; RL Am. J. Hum. Genet. 105:869-878(2019). RN [8] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=33357433; DOI=10.1016/j.celrep.2020.108544; RA Rong B., Zhang Q., Wan J., Xing S., Dai R., Li Y., Cai J., Xie J., Song Y., RA Chen J., Zhang L., Yan G., Zhang W., Gao H., Han J.J., Qu Q., Ma H., RA Tian Y., Lan F.; RT "Ribosome 18S m6A methyltransferase METTL5 promotes translation initiation RT and breast cancer cell growth."; RL Cell Rep. 33:108544-108544(2020). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH TRMT112. RX PubMed=32217665; DOI=10.1101/gad.333369.119; RA Ignatova V.V., Stolz P., Kaiser S., Gustafsson T.H., Lastres P.R., RA Sanz-Moreno A., Cho Y.L., Amarie O.V., Aguilar-Pimentel A., RA Klein-Rodewald T., Calzada-Wack J., Becker L., Marschall S., Kraiger M., RA Garrett L., Seisenberger C., Hoelter S.M., Borland K., Van De Logt E., RA Jansen P.W.T.C., Baltissen M.P., Valenta M., Vermeulen M., Wurst W., RA Gailus-Durner V., Fuchs H., de Angelis M.H., Rando O.J., Kellner S.M., RA Bultmann S., Schneider R.; RT "The rRNA m6A methyltransferase METTL5 is involved in pluripotency and RT developmental programs."; RL Genes Dev. 34:715-729(2020). RN [10] RP INTERACTION WITH TRMT112. RX PubMed=34948388; DOI=10.3390/ijms222413593; RA Brumele B., Mutso M., Telanne L., Ounap K., Spunde K., Abroi A., Kurg R.; RT "Human TRMT112-Methyltransferase Network Consists of Seven Partners RT Interacting with a Common Co-Factor."; RL Int. J. Mol. Sci. 22:13593-13593(2021). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY RP REGULATION, AND INTERACTION WITH TRMT112. RX PubMed=33428944; DOI=10.1016/j.jbc.2021.100270; RA Yu D., Kaur G., Blumenthal R.M., Zhang X., Cheng X.; RT "Enzymatic characterization of three human RNA adenosine methyltransferases RT reveals diverse substrate affinities and reaction optima."; RL J. Biol. Chem. 296:100270-100270(2021). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH TRMT112, MUTAGENESIS OF RP 126-ASN--PRO-128, VARIANT ASP-61, AND CHARACTERIZATION OF VARIANT ASP-61. RX PubMed=35033535; DOI=10.1016/j.jbc.2022.101590; RA Sepich-Poore C., Zheng Z., Schmitt E., Wen K., Zhang Z.S., Cui X.L., RA Dai Q., Zhu A.C., Zhang L., Sanchez Castillo A., Tan H., Peng J., RA Zhuang X., He C., Nachtergaele S.; RT "The METTL5-TRMT112 N6-methyladenosine methyltransferase complex regulates RT mRNA translation via 18S rRNA methylation."; RL J. Biol. Chem. 298:101590-101590(2022). RN [13] {ECO:0007744|PDB:6H2U, ECO:0007744|PDB:6H2V} RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) IN COMPLEX WITH RP S-ADENOSYL-L-METHIONINE AND TRMT112, FUNCTION, CATALYTIC ACTIVITY, AND RP INTERACTION WITH TRMT112. RX PubMed=31328227; DOI=10.1093/nar/gkz619; RA van Tran N., Ernst F.G.M., Hawley B.R., Zorbas C., Ulryck N., Hackert P., RA Bohnsack K.E., Bohnsack M.T., Jaffrey S.R., Graille M., Lafontaine D.L.J.; RT "The human 18S rRNA m6A methyltransferase METTL5 is stabilized by RT TRMT112."; RL Nucleic Acids Res. 47:7719-7733(2019). CC -!- FUNCTION: Catalytic subunit of a heterodimer with TRMT112, which CC specifically methylates the 6th position of adenine in position 1832 of CC 18S rRNA (PubMed:31328227, PubMed:32217665, PubMed:33357433, CC PubMed:33428944, PubMed:35033535). N6-methylation of adenine(1832) in CC 18S rRNA resides in the decoding center of 18S rRNA and is required for CC translation and embryonic stem cells (ESCs) pluripotency and CC differentiation (PubMed:33357433). {ECO:0000269|PubMed:31328227, CC ECO:0000269|PubMed:32217665, ECO:0000269|PubMed:33357433, CC ECO:0000269|PubMed:33428944, ECO:0000269|PubMed:35033535}. CC -!- CATALYTIC ACTIVITY: CC Reaction=adenosine(1832) in 18S rRNA + S-adenosyl-L-methionine = H(+) + CC N(6)-methyladenosine(1832) in 18S rRNA + S-adenosyl-L-homocysteine; CC Xref=Rhea:RHEA:62612, Rhea:RHEA-COMP:16144, Rhea:RHEA-COMP:16145, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, CC ChEBI:CHEBI:74411, ChEBI:CHEBI:74449; CC Evidence={ECO:0000269|PubMed:31328227, ECO:0000269|PubMed:32217665, CC ECO:0000269|PubMed:33357433, ECO:0000269|PubMed:33428944, CC ECO:0000269|PubMed:35033535}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62613; CC Evidence={ECO:0000269|PubMed:31328227, ECO:0000269|PubMed:32217665, CC ECO:0000269|PubMed:33357433, ECO:0000269|PubMed:33428944, CC ECO:0000269|PubMed:35033535}; CC -!- ACTIVITY REGULATION: rRNA N6-adenosine-methyltransferase activity is CC inhibited by zinc. {ECO:0000269|PubMed:33428944}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.1 uM for 18S rRNA {ECO:0000269|PubMed:33428944}; CC KM=1 uM for S-adenosyl-L-methionine {ECO:0000269|PubMed:33428944}; CC Note=kcat is 13.1 h(-1) for 18S rRNA (PubMed:33428944). kcat is 17.6 CC h(-1) for S-adenosyl-L-methionine (PubMed:33428944). CC {ECO:0000269|PubMed:33428944}; CC -!- SUBUNIT: Heterodimer; heterodimerizes with TRMT112. CC {ECO:0000269|PubMed:31328227, ECO:0000269|PubMed:32217665, CC ECO:0000269|PubMed:33428944, ECO:0000269|PubMed:34948388, CC ECO:0000269|PubMed:35033535}. CC -!- INTERACTION: CC Q9NRN9; Q9UI30: TRMT112; NbExp=8; IntAct=EBI-12360031, EBI-373326; CC Q9NRN9; O15062: ZBTB5; NbExp=3; IntAct=EBI-12360031, EBI-722671; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:31564433}. Presynapse CC {ECO:0000269|PubMed:31564433}. Postsynapse CC {ECO:0000269|PubMed:31564433}. CC -!- TISSUE SPECIFICITY: Expressed from very early development (8 post- CC conceptual weeks) and expression persists through adulthood in multiple CC substructures of the brain, including the cerebellar cortex, CC hippocampus, and striatum. {ECO:0000269|PubMed:31564433}. CC -!- DISEASE: Intellectual developmental disorder, autosomal recessive 72 CC (MRT72) [MIM:618665]: A form of intellectual disability, a disorder CC characterized by significantly below average general intellectual CC functioning associated with impairments in adaptive behavior and CC manifested during the developmental period. MRT72 patients manifest CC moderate to severe intellectual disability, microcephaly, and CC dysmorphic facial features. {ECO:0000269|PubMed:31564433}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. PrmA family. CC {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; AF201938; AAF86874.1; -; mRNA. DR EMBL; AK001321; BAA91622.1; -; mRNA. DR EMBL; AC009967; AAY14869.1; -; Genomic_DNA. DR EMBL; CH471058; EAX11254.1; -; Genomic_DNA. DR EMBL; CH471058; EAX11255.1; -; Genomic_DNA. DR EMBL; BC093014; AAH93014.1; -; mRNA. DR EMBL; BC000921; AAH00921.1; -; mRNA. DR CCDS; CCDS33320.1; -. DR RefSeq; NP_001280115.1; NM_001293186.1. DR RefSeq; NP_001280116.1; NM_001293187.1. DR RefSeq; NP_054887.2; NM_014168.3. DR PDB; 6H2U; X-ray; 1.60 A; A=1-209. DR PDB; 6H2V; X-ray; 2.49 A; A/C=1-209. DR PDBsum; 6H2U; -. DR PDBsum; 6H2V; -. DR AlphaFoldDB; Q9NRN9; -. DR SMR; Q9NRN9; -. DR BioGRID; 118851; 5. DR ComplexPortal; CPX-2850; METTL5-TRM112 methyltransferase complex. DR IntAct; Q9NRN9; 2. DR STRING; 9606.ENSP00000260953; -. DR iPTMnet; Q9NRN9; -. DR PhosphoSitePlus; Q9NRN9; -. DR BioMuta; METTL5; -. DR DMDM; 74761664; -. DR EPD; Q9NRN9; -. DR jPOST; Q9NRN9; -. DR MassIVE; Q9NRN9; -. DR MaxQB; Q9NRN9; -. DR PaxDb; 9606-ENSP00000260953; -. DR PeptideAtlas; Q9NRN9; -. DR ProteomicsDB; 82397; -. DR Pumba; Q9NRN9; -. DR Antibodypedia; 35324; 93 antibodies from 20 providers. DR DNASU; 29081; -. DR Ensembl; ENST00000260953.10; ENSP00000260953.5; ENSG00000138382.15. DR Ensembl; ENST00000392640.6; ENSP00000376415.2; ENSG00000138382.15. DR Ensembl; ENST00000409965.5; ENSP00000386582.1; ENSG00000138382.15. DR GeneID; 29081; -. DR KEGG; hsa:29081; -. DR MANE-Select; ENST00000260953.10; ENSP00000260953.5; NM_014168.4; NP_054887.2. DR UCSC; uc002ufn.4; human. DR AGR; HGNC:25006; -. DR CTD; 29081; -. DR DisGeNET; 29081; -. DR GeneCards; METTL5; -. DR HGNC; HGNC:25006; METTL5. DR HPA; ENSG00000138382; Low tissue specificity. DR MalaCards; METTL5; -. DR MIM; 618628; gene. DR MIM; 618665; phenotype. DR neXtProt; NX_Q9NRN9; -. DR OpenTargets; ENSG00000138382; -. DR Orphanet; 2512; Autosomal recessive primary microcephaly. DR PharmGKB; PA142671461; -. DR VEuPathDB; HostDB:ENSG00000138382; -. DR eggNOG; KOG3420; Eukaryota. DR GeneTree; ENSGT00390000000227; -. DR HOGENOM; CLU_074702_1_1_1; -. DR InParanoid; Q9NRN9; -. DR OMA; DVVYSIH; -. DR OrthoDB; 178393at2759; -. DR PhylomeDB; Q9NRN9; -. DR TreeFam; TF314953; -. DR PathwayCommons; Q9NRN9; -. DR SignaLink; Q9NRN9; -. DR BioGRID-ORCS; 29081; 69 hits in 1134 CRISPR screens. DR ChiTaRS; METTL5; human. DR GenomeRNAi; 29081; -. DR Pharos; Q9NRN9; Tbio. DR PRO; PR:Q9NRN9; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q9NRN9; Protein. DR Bgee; ENSG00000138382; Expressed in skeletal muscle tissue of biceps brachii and 205 other cell types or tissues. DR ExpressionAtlas; Q9NRN9; baseline and differential. DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0001650; C:fibrillar center; IDA:HPA. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0098794; C:postsynapse; IDA:UniProtKB. DR GO; GO:0098793; C:presynapse; IDA:UniProtKB. DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro. DR GO; GO:0008988; F:rRNA (adenine-N6-)-methyltransferase activity; IDA:UniProtKB. DR GO; GO:1904047; F:S-adenosyl-L-methionine binding; IDA:UniProtKB. DR GO; GO:0045727; P:positive regulation of translation; IMP:UniProtKB. DR GO; GO:0031167; P:rRNA methylation; IDA:UniProtKB. DR GO; GO:0048863; P:stem cell differentiation; ISS:UniProtKB. DR CDD; cd02440; AdoMet_MTases; 1. DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1. DR InterPro; IPR002052; DNA_methylase_N6_adenine_CS. DR InterPro; IPR029063; SAM-dependent_MTases_sf. DR InterPro; IPR007848; Small_mtfrase_dom. DR PANTHER; PTHR23290:SF0; RRNA N6-ADENOSINE-METHYLTRANSFERASE METTL5; 1. DR PANTHER; PTHR23290; UNCHARACTERIZED; 1. DR Pfam; PF05175; MTS; 1. DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1. DR PROSITE; PS00092; N6_MTASE; 1. DR Genevisible; Q9NRN9; HS. PE 1: Evidence at protein level; KW 3D-structure; Cell projection; Intellectual disability; Methyltransferase; KW Nucleus; Reference proteome; S-adenosyl-L-methionine; Synapse; Transferase. FT CHAIN 1..209 FT /note="rRNA N6-adenosine-methyltransferase METTL5" FT /id="PRO_0000251919" FT BINDING 28 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:31328227, FT ECO:0007744|PDB:6H2U, ECO:0007744|PDB:6H2V" FT BINDING 31 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:31328227, FT ECO:0007744|PDB:6H2U, ECO:0007744|PDB:6H2V" FT BINDING 59 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:31328227, FT ECO:0007744|PDB:6H2U, ECO:0007744|PDB:6H2V" FT BINDING 62 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:31328227, FT ECO:0007744|PDB:6H2U" FT BINDING 64 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:31328227, FT ECO:0007744|PDB:6H2V" FT BINDING 81 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:31328227, FT ECO:0007744|PDB:6H2U, ECO:0007744|PDB:6H2V" FT BINDING 108..109 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:31328227, FT ECO:0007744|PDB:6H2U, ECO:0007744|PDB:6H2V" FT VARIANT 61 FT /note="G -> D (found in patients with intellectual FT disability and microcephaly; uncertain significance; FT impaired interaction with TRMT112)" FT /evidence="ECO:0000269|PubMed:35033535" FT /id="VAR_086154" FT VARIANT 202 FT /note="V -> G (in dbSNP:rs1051387)" FT /id="VAR_051507" FT MUTAGEN 126..128 FT /note="NPP->AAA: In METTL5-3A; abolished methyltransferase FT activity." FT /evidence="ECO:0000269|PubMed:35033535" FT CONFLICT 27 FT /note="E -> G (in Ref. 2; BAA91622)" FT /evidence="ECO:0000305" FT HELIX 6..13 FT /evidence="ECO:0007829|PDB:6H2V" FT TURN 24..27 FT /evidence="ECO:0007829|PDB:6H2V" FT HELIX 33..45 FT /evidence="ECO:0007829|PDB:6H2V" FT STRAND 54..59 FT /evidence="ECO:0007829|PDB:6H2V" FT HELIX 64..71 FT /evidence="ECO:0007829|PDB:6H2V" FT STRAND 75..82 FT /evidence="ECO:0007829|PDB:6H2V" FT HELIX 84..97 FT /evidence="ECO:0007829|PDB:6H2V" FT STRAND 101..106 FT /evidence="ECO:0007829|PDB:6H2V" FT HELIX 109..111 FT /evidence="ECO:0007829|PDB:6H2V" FT HELIX 114..116 FT /evidence="ECO:0007829|PDB:6H2V" FT STRAND 120..125 FT /evidence="ECO:0007829|PDB:6H2V" FT HELIX 137..148 FT /evidence="ECO:0007829|PDB:6H2V" FT STRAND 149..159 FT /evidence="ECO:0007829|PDB:6H2V" FT HELIX 162..172 FT /evidence="ECO:0007829|PDB:6H2V" FT STRAND 175..184 FT /evidence="ECO:0007829|PDB:6H2V" FT STRAND 195..197 FT /evidence="ECO:0007829|PDB:6H2V" FT STRAND 199..208 FT /evidence="ECO:0007829|PDB:6H2V" SQ SEQUENCE 209 AA; 23719 MW; 060B1C2C0D2BA169 CRC64; MKKVRLKELE SRLQQVDGFE KPKLLLEQYP TRPHIAACML YTIHNTYDDI ENKVVADLGC GCGVLSIGTA MLGAGLCVGF DIDEDALEIF NRNAEEFELT NIDMVQCDVC LLSNRMSKSF DTVIMNPPFG TKNNKGTDMA FLKTALEMAR TAVYSLHKSS TREHVQKKAA EWKIKIDIIA ELRYDLPASY KFHKKKSVDI EVDLIRFSF //