ID TRMB_HUMAN Reviewed; 276 AA. AC Q9UBP6; B2RBX1; H7BXF2; Q14105; Q53FS9; DT 20-JUN-2003, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 27-MAR-2024, entry version 179. DE RecName: Full=tRNA (guanine-N(7)-)-methyltransferase {ECO:0000255|HAMAP-Rule:MF_03055}; DE EC=2.1.1.33 {ECO:0000255|HAMAP-Rule:MF_03055, ECO:0000269|PubMed:34352206, ECO:0000269|PubMed:34352207, ECO:0000269|PubMed:36599982, ECO:0000269|PubMed:36599985, ECO:0000269|PubMed:37369656}; DE AltName: Full=Methyltransferase-like protein 1 {ECO:0000255|HAMAP-Rule:MF_03055}; DE AltName: Full=mRNA (guanine-N(7)-)-methyltransferase {ECO:0000305}; DE EC=2.1.1.- {ECO:0000269|PubMed:31031084, ECO:0000269|PubMed:37379838}; DE AltName: Full=miRNA (guanine-N(7)-)-methyltransferase {ECO:0000305}; DE EC=2.1.1.- {ECO:0000269|PubMed:31031083}; DE AltName: Full=tRNA (guanine(46)-N(7))-methyltransferase {ECO:0000255|HAMAP-Rule:MF_03055}; DE AltName: Full=tRNA(m7G46)-methyltransferase {ECO:0000255|HAMAP-Rule:MF_03055}; GN Name=METTL1 {ECO:0000255|HAMAP-Rule:MF_03055, GN ECO:0000303|PubMed:10329009, ECO:0000312|HGNC:HGNC:7030}; GN Synonyms=C12orf1 {ECO:0000312|HGNC:HGNC:7030}; 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 [GENOMIC DNA / MRNA] (ISOFORM 1), AND TISSUE RP SPECIFICITY. RC TISSUE=Brain; RX PubMed=10329009; DOI=10.1006/geno.1999.5780; RA Bahr A., Hankeln T., Fiedler T., Hegemann J., Schmidt E.R.; RT "Molecular analysis of METTL1, a novel human methyltransferase-like gene RT with a high degree of phylogenetic conservation."; RL Genomics 57:424-428(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 MRNA] (ISOFORM 2). RC TISSUE=Kidney proximal tubule; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [6] RP FUNCTION, PATHWAY, AND INTERACTION WITH WDR4. RX PubMed=12403464; DOI=10.1017/s1355838202024019; RA Alexandrov A., Martzen M.R., Phizicky E.M.; RT "Two proteins that form a complex are required for 7-methylguanosine RT modification of yeast tRNA."; RL RNA 8:1253-1266(2002). RN [7] RP SUBCELLULAR LOCATION, INTERACTION WITH WDR4, PHOSPHORYLATION AT SER-27, AND RP MUTAGENESIS OF SER-27. RX PubMed=15861136; DOI=10.1038/sj.emboj.7600648; RA Cartlidge R.A., Knebel A., Peggie M., Alexandrov A., Phizicky E.M., RA Cohen P.; RT "The tRNA methylase METTL1 is phosphorylated and inactivated by PKB and RSK RT in vitro and in cells."; RL EMBO J. 24:1696-1705(2005). RN [8] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-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]. 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 [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=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 [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [12] RP SUBCELLULAR LOCATION. RX PubMed=26751069; DOI=10.1371/journal.pbio.1002349; RA Cheng I.C., Chen B.C., Shuai H.H., Chien F.C., Chen P., Hsieh T.S.; RT "Wuho is a new member in maintaining genome stability through its RT interaction with flap endonuclease 1."; RL PLoS Biol. 14:E1002349-E1002349(2016). RN [13] RP FUNCTION, PATHWAY, AND CATALYTIC ACTIVITY. RX PubMed=31031084; DOI=10.1016/j.molcel.2019.03.036; RA Zhang L.S., Liu C., Ma H., Dai Q., Sun H.L., Luo G., Zhang Z., Zhang L., RA Hu L., Dong X., He C.; RT "Transcriptome-wide mapping of internal N7-methylguanosine methylome in RT mammalian mRNA."; RL Mol. Cell 0:0-0(2019). RN [14] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF 107-GLU--ARG-109. RX PubMed=31031083; DOI=10.1016/j.molcel.2019.03.040; RA Pandolfini L., Barbieri I., Bannister A.J., Hendrick A., Andrews B., RA Webster N., Murat P., Mach P., Brandi R., Robson S.C., Migliori V., RA Alendar A., d'Onofrio M., Balasubramanian S., Kouzarides T.; RT "METTL1 promotes let-7 microRNA processing via m7G methylation."; RL Mol. Cell 0:0-0(2019). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, AND INDUCTION. RX PubMed=34352207; DOI=10.1016/j.molcel.2021.06.031; RA Orellana E.A., Liu Q., Yankova E., Pirouz M., De Braekeleer E., Zhang W., RA Lim J., Aspris D., Sendinc E., Garyfallos D.A., Gu M., Ali R., RA Gutierrez A., Mikutis S., Bernardes G.J.L., Fischer E.S., Bradley A., RA Vassiliou G.S., Slack F.J., Tzelepis K., Gregory R.I.; RT "METTL1-mediated m7G modification of Arg-TCT tRNA drives oncogenic RT transformation."; RL Mol. Cell 81:3323-3338(2021). RN [16] RP FUNCTION, CATALYTIC ACTIVITY, INDUCTION, AND MUTAGENESIS OF RP 160-LEU--ASP-163. RX PubMed=34352206; DOI=10.1016/j.molcel.2021.07.003; RA Dai Z., Liu H., Liao J., Huang C., Ren X., Zhu W., Zhu S., Peng B., Li S., RA Lai J., Liang L., Xu L., Peng S., Lin S., Kuang M.; RT "N7-Methylguanosine tRNA modification enhances oncogenic mRNA translation RT and promotes intrahepatic cholangiocarcinoma progression."; RL Mol. Cell 81:3339-3355(2021). RN [17] RP INDUCTION. RX PubMed=34371184; DOI=10.1016/j.ymthe.2021.08.005; RA Ma J., Han H., Huang Y., Yang C., Zheng S., Cai T., Bi J., Huang X., RA Liu R., Huang L., Luo Y., Li W., Lin S.; RT "METTL1/WDR4-mediated m7G tRNA modifications and m7G codon usage promote RT mRNA translation and lung cancer progression."; RL Mol. Ther. 29:3422-3435(2021). RN [18] RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH WDR4, AND MUTAGENESIS OF RP 107-GLU--ARG-109. RX PubMed=37379838; DOI=10.1016/j.cell.2023.05.047; RA Zhao Z., Qing Y., Dong L., Han L., Wu D., Li Y., Li W., Xue J., Zhou K., RA Sun M., Tan B., Chen Z., Shen C., Gao L., Small A., Wang K., Leung K., RA Zhang Z., Qin X., Deng X., Xia Q., Su R., Chen J.; RT "QKI shuttles internal m7G-modified transcripts into stress granules and RT modulates mRNA metabolism."; RL Cell 0:0-0(2023). RN [19] RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 32-265 IN COMPLEX WITH RP S-ADENOSYL-L-METHIONINE. RG Structural genomics consortium (SGC); RT "Crystal structure of human methyltransferase-like protein 1."; RL Submitted (APR-2008) to the PDB data bank. RN [20] RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 30-265 IN COMPLEX WITH WDR4, RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH WDR4, AND RP MUTAGENESIS OF LYS-40; LYS-143; LYS-151 AND LYS-172. RX PubMed=37369656; DOI=10.1038/s41421-023-00562-y; RA Jin X., Guan Z., Hu N., He C., Yin P., Gong Z., Zhang D.; RT "Structural insight into how WDR4 promotes the tRNA N7-methylguanosine RT methyltransferase activity of METTL1."; RL Cell Discov. 9:65-65(2023). RN [21] RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 20-265 IN COMPLEX WITH RP S-ADENOSYL-L-HOMOCYSTEINE AND WDR4, STRUCTURE BY ELECTRON MICROSCOPY (3.53 RP ANGSTROMS) IN COMPLEX WITH S-ADENOSYL-L-METHIONINE; RP S-ADENOSYL-L-HOMOCYSTEINE; WDR4 AND TRNA, FUNCTION, CATALYTIC ACTIVITY, RP PATHWAY, ACTIVE SITE, DOMAIN, INTERACTION WITH WDR4, AND MUTAGENESIS OF RP ARG-24; SER-27; PRO-29; ASP-163; LYS-167; ARG-168; TRP-173; ASP-199; RP GLU-240; LYS-243 AND ARG-246. RX PubMed=36599982; DOI=10.1038/s41586-022-05565-5; RA Ruiz-Arroyo V.M., Raj R., Babu K., Onolbaatar O., Roberts P.H., Nam Y.; RT "Structures and mechanisms of tRNA methylation by METTL1-WDR4."; RL Nature 613:383-390(2023). RN [22] RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) IN COMPLEX WITH RP S-ADENOSYL-L-HOMOCYSTEINE; WDR4 AND TRNA, STRUCTURE BY ELECTRON MICROSCOPY RP (3.3 ANGSTROMS) IN COMPLEX WITH WDR4 AND TRNA, FUNCTION, CATALYTIC RP ACTIVITY, PATHWAY, ACTIVE SITE, DOMAIN, INTERACTION WITH WDR4, RP PHOSPHORYLATION AT SER-27, AND MUTAGENESIS OF LYS-18; SER-27; ARG-109; RP LYS-111; ASP-118; LYS-143; 160-LEU--ASP-163; HIS-165; LYS-167; LYS-170; RP LYS-243 AND ARG-246. RX PubMed=36599985; DOI=10.1038/s41586-022-05566-4; RA Li J., Wang L., Hahn Q., Nowak R.P., Viennet T., Orellana E.A., RA Roy Burman S.S., Yue H., Hunkeler M., Fontana P., Wu H., Arthanari H., RA Fischer E.S., Gregory R.I.; RT "Structural basis of regulated m7G tRNA modification by METTL1-WDR4."; RL Nature 613:391-397(2023). CC -!- FUNCTION: Catalytic component of METTL1-WDR4 methyltransferase complex CC that mediates the formation of N(7)-methylguanine in a subset of RNA CC species, such as tRNAs, mRNAs and microRNAs (miRNAs) (PubMed:12403464, CC PubMed:31031083, PubMed:31031084, PubMed:36599982, PubMed:36599985, CC PubMed:37379838, PubMed:37369656). Catalyzes the formation of N(7)- CC methylguanine at position 46 (m7G46) in a large subset of tRNAs that CC contain the 5'-RAGGU-3' motif within the variable loop CC (PubMed:12403464, PubMed:34352207, PubMed:34352206, PubMed:36599982, CC PubMed:36599985, PubMed:37369656). M7G46 interacts with C13-G22 in the CC D-loop to stabilize tRNA tertiary structure and protect tRNAs from CC decay (PubMed:36599982, PubMed:36599985). Also acts as a CC methyltransferase for a subset of internal N(7)-methylguanine in mRNAs CC (PubMed:31031084, PubMed:37379838). Internal N(7)-methylguanine CC methylation of mRNAs in response to stress promotes their CC relocalization to stress granules, thereby suppressing their CC translation (PubMed:31031084, PubMed:37379838). Also methylates a CC specific subset of miRNAs, such as let-7 (PubMed:31031083). N(7)- CC methylguanine methylation of let-7 miRNA promotes let-7 miRNA CC processing by disrupting an inhibitory secondary structure within the CC primary miRNA transcript (pri-miRNA) (PubMed:31031083). Acts as a CC regulator of embryonic stem cell self-renewal and differentiation (By CC similarity). {ECO:0000255|HAMAP-Rule:MF_03055, CC ECO:0000269|PubMed:12403464, ECO:0000269|PubMed:31031083, CC ECO:0000269|PubMed:31031084, ECO:0000269|PubMed:34352206, CC ECO:0000269|PubMed:34352207, ECO:0000269|PubMed:36599982, CC ECO:0000269|PubMed:36599985, ECO:0000269|PubMed:37369656, CC ECO:0000269|PubMed:37379838}. CC -!- CATALYTIC ACTIVITY: CC Reaction=guanosine(46) in tRNA + S-adenosyl-L-methionine = N(7)- CC methylguanosine(46) in tRNA + S-adenosyl-L-homocysteine; CC Xref=Rhea:RHEA:42708, Rhea:RHEA-COMP:10188, Rhea:RHEA-COMP:10189, CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:74269, CC ChEBI:CHEBI:74480; EC=2.1.1.33; Evidence={ECO:0000255|HAMAP- CC Rule:MF_03055, ECO:0000269|PubMed:34352206, CC ECO:0000269|PubMed:34352207, ECO:0000269|PubMed:36599982, CC ECO:0000269|PubMed:36599985, ECO:0000269|PubMed:37369656}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a guanosine in mRNA + S-adenosyl-L-methionine = an N(7)- CC methylguanosine in mRNA + S-adenosyl-L-homocysteine; CC Xref=Rhea:RHEA:60508, Rhea:RHEA-COMP:15584, Rhea:RHEA-COMP:15585, CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:74269, CC ChEBI:CHEBI:74480; Evidence={ECO:0000269|PubMed:31031084, CC ECO:0000269|PubMed:37379838}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60509; CC Evidence={ECO:0000269|PubMed:31031084, ECO:0000269|PubMed:37379838}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a guanosine in miRNA + S-adenosyl-L-methionine = an N(7)- CC methylguanosine in miRNA + S-adenosyl-L-homocysteine; CC Xref=Rhea:RHEA:60512, Rhea:RHEA-COMP:15587, Rhea:RHEA-COMP:15588, CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:74269, CC ChEBI:CHEBI:74480; Evidence={ECO:0000269|PubMed:31031083}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60513; CC Evidence={ECO:0000269|PubMed:31031083}; CC -!- PATHWAY: tRNA modification; N(7)-methylguanine-tRNA biosynthesis. CC {ECO:0000269|PubMed:12403464, ECO:0000269|PubMed:36599982, CC ECO:0000269|PubMed:36599985, ECO:0000269|PubMed:37369656}. CC -!- SUBUNIT: Catalytic component of the METTL1-WDR4 complex, composed of CC METTL1 and WDR4. {ECO:0000269|PubMed:12403464, CC ECO:0000269|PubMed:15861136, ECO:0000269|PubMed:36599982, CC ECO:0000269|PubMed:36599985, ECO:0000269|PubMed:37369656, CC ECO:0000269|PubMed:37379838}. CC -!- INTERACTION: CC Q9UBP6; P57081: WDR4; NbExp=13; IntAct=EBI-750415, EBI-750427; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15861136, CC ECO:0000269|PubMed:26751069}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9UBP6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UBP6-2; Sequence=VSP_044671, VSP_044672; CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10329009}. CC -!- INDUCTION: Amplified and overexpressed in a number of cancers and is CC associated with poor prognosis (at protein level). CC {ECO:0000269|PubMed:34352206, ECO:0000269|PubMed:34352207, CC ECO:0000269|PubMed:34371184}. CC -!- DOMAIN: Upon tRNA-binding, the alphaC region transforms into a helix, CC which together with the alpha6 helix secures both ends of the tRNA CC variable loop (PubMed:36599985). The N-terminal disordered region is CC part of the catalytic pocket and essential for methyltransferase CC activity: upon S-adenosyl-L-methionine- and tRNA-binding, the N- CC terminal disordered region becomes ordered, sandwiched between the CC bound cofactor and the tRNA, and the WDR4 C-terminus attaches to the CC METTL1 N-terminus to stabilize the bound tRNA together CC (PubMed:36599982, PubMed:36599985). Together with WDR4, which also CC binds tRNAs, tRNAs undergo bending to facilitate G46 flipping into the CC catalytic pocket to be modified (PubMed:36599982, PubMed:36599985). CC {ECO:0000269|PubMed:36599982, ECO:0000269|PubMed:36599985}. CC -!- PTM: Phosphorylation at Ser-27 by PKB/AKT1 inactivates its CC methyltransferase activity via a steric interference mechanism in the CC active site that locally disrupts the catalytic center CC (PubMed:15861136, PubMed:36599985). Phosphorylation at Ser-27 does not CC affect the interaction with WDR4 (PubMed:15861136). CC {ECO:0000269|PubMed:15861136, ECO:0000269|PubMed:36599985}. CC -!- MISCELLANEOUS: In the context of cancer, overexpression of the METTL1- CC WDR4 methyltransferase complex promotes cancer progression by driving CC oncogenic transformation (PubMed:34352207, PubMed:34352206, CC PubMed:34371184). Drives oncogenesis by mediating the formation of CC N(7)-methylguanine at position 46 (m7G46) in some tRNAs, in particular CC Arg-TCT-4-1 (TRR-TCT4-1), leading to increased translation of mRNAs, CC including cell cycle regulators that are enriched in the corresponding CC AGA codon (PubMed:34352207, PubMed:34352206, PubMed:34371184). CC {ECO:0000269|PubMed:34352206, ECO:0000269|PubMed:34352207, CC ECO:0000269|PubMed:34371184}. CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase CC superfamily. TrmB family. {ECO:0000255|HAMAP-Rule:MF_03055}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA65470.1; Type=Erroneous initiation; 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; Y18643; CAA77239.1; -; mRNA. DR EMBL; Y18642; CAA77238.1; -; Genomic_DNA. DR EMBL; X96698; CAA65470.1; ALT_INIT; mRNA. DR EMBL; AK314851; BAG37368.1; -; mRNA. DR EMBL; AK223202; BAD96922.1; -; mRNA. DR EMBL; AC025165; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000550; AAH00550.1; -; mRNA. DR CCDS; CCDS8955.3; -. [Q9UBP6-1] DR CCDS; CCDS8956.1; -. [Q9UBP6-2] DR RefSeq; NP_005362.3; NM_005371.5. [Q9UBP6-1] DR RefSeq; NP_075422.3; NM_023033.3. [Q9UBP6-2] DR PDB; 3CKK; X-ray; 1.55 A; A=32-265. DR PDB; 7OGJ; X-ray; 1.59 A; A/B=32-265. DR PDB; 7PL1; X-ray; 1.85 A; A=32-265. DR PDB; 7U20; X-ray; 3.10 A; A=1-276. DR PDB; 8CTH; EM; 3.30 A; A=1-276. DR PDB; 8CTI; EM; 3.60 A; A=1-276. DR PDB; 8D58; X-ray; 2.47 A; A=20-265. DR PDB; 8D59; X-ray; 2.26 A; A=20-265. DR PDB; 8D5B; X-ray; 1.93 A; A=20-265. DR PDB; 8D9K; EM; 3.72 A; A=1-276. DR PDB; 8D9L; EM; 4.04 A; A=1-276. DR PDB; 8EG0; EM; 3.53 A; A=1-276. DR PDB; 8H0N; X-ray; 1.80 A; B=30-265. DR PDBsum; 3CKK; -. DR PDBsum; 7OGJ; -. DR PDBsum; 7PL1; -. DR PDBsum; 7U20; -. DR PDBsum; 8CTH; -. DR PDBsum; 8CTI; -. DR PDBsum; 8D58; -. DR PDBsum; 8D59; -. DR PDBsum; 8D5B; -. DR PDBsum; 8D9K; -. DR PDBsum; 8D9L; -. DR PDBsum; 8EG0; -. DR PDBsum; 8H0N; -. DR AlphaFoldDB; Q9UBP6; -. DR SMR; Q9UBP6; -. DR BioGRID; 110392; 45. DR ComplexPortal; CPX-848; METTL1-WDR4 tRNA (guanine-N(7)-)-methyltransferase. DR DIP; DIP-61920N; -. DR IntAct; Q9UBP6; 3. DR MINT; Q9UBP6; -. DR STRING; 9606.ENSP00000314441; -. DR GlyGen; Q9UBP6; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9UBP6; -. DR PhosphoSitePlus; Q9UBP6; -. DR BioMuta; METTL1; -. DR DMDM; 32171926; -. DR EPD; Q9UBP6; -. DR jPOST; Q9UBP6; -. DR MassIVE; Q9UBP6; -. DR MaxQB; Q9UBP6; -. DR PaxDb; 9606-ENSP00000314441; -. DR PeptideAtlas; Q9UBP6; -. DR ProteomicsDB; 43260; -. DR ProteomicsDB; 84026; -. [Q9UBP6-1] DR Pumba; Q9UBP6; -. DR Antibodypedia; 16399; 206 antibodies from 29 providers. DR DNASU; 4234; -. DR Ensembl; ENST00000257848.7; ENSP00000257848.7; ENSG00000037897.17. [Q9UBP6-2] DR Ensembl; ENST00000324871.12; ENSP00000314441.7; ENSG00000037897.17. [Q9UBP6-1] DR GeneID; 4234; -. DR KEGG; hsa:4234; -. DR MANE-Select; ENST00000324871.12; ENSP00000314441.7; NM_005371.6; NP_005362.3. DR UCSC; uc009zqc.4; human. [Q9UBP6-1] DR AGR; HGNC:7030; -. DR CTD; 4234; -. DR DisGeNET; 4234; -. DR GeneCards; METTL1; -. DR HGNC; HGNC:7030; METTL1. DR HPA; ENSG00000037897; Low tissue specificity. DR MIM; 604466; gene. DR neXtProt; NX_Q9UBP6; -. DR OpenTargets; ENSG00000037897; -. DR PharmGKB; PA30766; -. DR VEuPathDB; HostDB:ENSG00000037897; -. DR eggNOG; KOG3115; Eukaryota. DR GeneTree; ENSGT00390000017840; -. DR HOGENOM; CLU_050910_3_0_1; -. DR InParanoid; Q9UBP6; -. DR OMA; LPNYFAK; -. DR OrthoDB; 116813at2759; -. DR PhylomeDB; Q9UBP6; -. DR TreeFam; TF314083; -. DR PathwayCommons; Q9UBP6; -. DR Reactome; R-HSA-6782315; tRNA modification in the nucleus and cytosol. DR SignaLink; Q9UBP6; -. DR SIGNOR; Q9UBP6; -. DR UniPathway; UPA00989; -. DR BioGRID-ORCS; 4234; 350 hits in 1176 CRISPR screens. DR ChiTaRS; METTL1; human. DR EvolutionaryTrace; Q9UBP6; -. DR GeneWiki; METTL1; -. DR GenomeRNAi; 4234; -. DR Pharos; Q9UBP6; Tbio. DR PRO; PR:Q9UBP6; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q9UBP6; Protein. DR Bgee; ENSG00000037897; Expressed in cervix squamous epithelium and 145 other cell types or tissues. DR ExpressionAtlas; Q9UBP6; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0106143; C:tRNA (m7G46) methyltransferase complex; IDA:UniProtKB. DR GO; GO:0043527; C:tRNA methyltransferase complex; IBA:GO_Central. DR GO; GO:0160090; F:internal mRNA (guanine-N7-)-methyltransferase activity; IDA:UniProt. DR GO; GO:0008176; F:tRNA (guanine(46)-N7)-methyltransferase activity; IDA:UniProtKB. DR GO; GO:0000049; F:tRNA binding; IEA:UniProtKB-UniRule. DR GO; GO:0036265; P:RNA (guanine-N7)-methylation; IDA:UniProt. DR GO; GO:0106004; P:tRNA (guanine-N7)-methylation; IDA:UniProtKB. DR GO; GO:0030488; P:tRNA methylation; IBA:GO_Central. DR GO; GO:0006400; P:tRNA modification; IDA:UniProtKB. DR GO; GO:0036416; P:tRNA stabilization; IDA:UniProt. DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1. DR HAMAP; MF_03055; tRNA_methyltr_TrmB_euk; 1. DR InterPro; IPR029063; SAM-dependent_MTases_sf. DR InterPro; IPR025763; Trm8_euk. DR InterPro; IPR003358; tRNA_(Gua-N-7)_MeTrfase_Trmb. DR NCBIfam; TIGR00091; tRNA (guanosine(46)-N7)-methyltransferase TrmB; 1. DR PANTHER; PTHR23417; 3-DEOXY-D-MANNO-OCTULOSONIC-ACID TRANSFERASE/TRNA GUANINE-N 7 - -METHYLTRANSFERASE; 1. DR PANTHER; PTHR23417:SF24; TRNA (GUANINE-N(7)-)-METHYLTRANSFERASE; 1. DR Pfam; PF02390; Methyltransf_4; 1. DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1. DR PROSITE; PS51625; SAM_MT_TRMB; 1. DR Genevisible; Q9UBP6; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Methyltransferase; KW Nucleus; Phosphoprotein; Reference proteome; RNA-binding; KW S-adenosyl-L-methionine; Transferase; tRNA processing; tRNA-binding. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330" FT CHAIN 2..276 FT /note="tRNA (guanine-N(7)-)-methyltransferase" FT /id="PRO_0000171431" FT REGION 1..36 FT /note="Disordered" FT /evidence="ECO:0000305|PubMed:36599985" FT REGION 164..172 FT /note="AlphaC helix" FT /evidence="ECO:0000269|PubMed:36599985" FT REGION 238..246 FT /note="Alpha6 helix" FT /evidence="ECO:0000269|PubMed:36599985" FT ACT_SITE 163 FT /evidence="ECO:0000305|PubMed:36599982, FT ECO:0000305|PubMed:36599985" FT BINDING 84 FT /ligand="S-adenosyl-L-homocysteine" FT /ligand_id="ChEBI:CHEBI:57856" FT /evidence="ECO:0000269|PubMed:36599982, FT ECO:0000269|PubMed:36599985, ECO:0007744|PDB:8CTH, FT ECO:0007744|PDB:8D5B, ECO:0007744|PDB:8EG0" FT BINDING 84 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:36599982, ECO:0000269|Ref.19, FT ECO:0007744|PDB:3CKK, ECO:0007744|PDB:8D9L" FT BINDING 107 FT /ligand="S-adenosyl-L-homocysteine" FT /ligand_id="ChEBI:CHEBI:57856" FT /evidence="ECO:0000269|PubMed:36599982, FT ECO:0000269|PubMed:36599985, ECO:0007744|PDB:8CTH, FT ECO:0007744|PDB:8D5B, ECO:0007744|PDB:8EG0" FT BINDING 107 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:36599982, ECO:0000269|Ref.19, FT ECO:0007744|PDB:3CKK, ECO:0007744|PDB:8D9L" FT BINDING 108 FT /ligand="S-adenosyl-L-homocysteine" FT /ligand_id="ChEBI:CHEBI:57856" FT /evidence="ECO:0000269|PubMed:36599985, FT ECO:0007744|PDB:8CTH" FT BINDING 109 FT /ligand="S-adenosyl-L-homocysteine" FT /ligand_id="ChEBI:CHEBI:57856" FT /evidence="ECO:0000269|PubMed:36599982, FT ECO:0007744|PDB:8EG0" FT BINDING 109 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|Ref.19, ECO:0007744|PDB:3CKK" FT BINDING 140 FT /ligand="S-adenosyl-L-homocysteine" FT /ligand_id="ChEBI:CHEBI:57856" FT /evidence="ECO:0000269|PubMed:36599982, FT ECO:0007744|PDB:8D5B, ECO:0007744|PDB:8EG0" FT BINDING 140 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:36599982, ECO:0000269|Ref.19, FT ECO:0007744|PDB:3CKK, ECO:0007744|PDB:8D9L" FT BINDING 141 FT /ligand="S-adenosyl-L-homocysteine" FT /ligand_id="ChEBI:CHEBI:57856" FT /evidence="ECO:0000269|PubMed:36599982, FT ECO:0000269|PubMed:36599985, ECO:0007744|PDB:8CTH, FT ECO:0007744|PDB:8D5B, ECO:0007744|PDB:8EG0" FT BINDING 141 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|Ref.19, ECO:0007744|PDB:3CKK" FT BINDING 160 FT /ligand="S-adenosyl-L-homocysteine" FT /ligand_id="ChEBI:CHEBI:57856" FT /evidence="ECO:0000269|PubMed:36599982, FT ECO:0007744|PDB:8D5B" FT BINDING 160 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|Ref.19, ECO:0007744|PDB:3CKK" FT BINDING 238 FT /ligand="S-adenosyl-L-homocysteine" FT /ligand_id="ChEBI:CHEBI:57856" FT /evidence="ECO:0000269|PubMed:36599982, FT ECO:0007744|PDB:8D5B" FT BINDING 238 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:36599982, ECO:0000269|Ref.19, FT ECO:0007744|PDB:3CKK, ECO:0007744|PDB:8D9L" FT BINDING 240 FT /ligand="S-adenosyl-L-homocysteine" FT /ligand_id="ChEBI:CHEBI:57856" FT /evidence="ECO:0000269|PubMed:36599982, FT ECO:0007744|PDB:8D5B, ECO:0007744|PDB:8EG0" FT BINDING 240 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|Ref.19, ECO:0007744|PDB:3CKK" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330" FT MOD_RES 27 FT /note="Phosphoserine; by PKB/AKT1 and RPS6KA3" FT /evidence="ECO:0000269|PubMed:15861136, FT ECO:0000269|PubMed:36599985, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT VAR_SEQ 92..155 FT /note="VELSPLFPDTLILGLEIRVKVSDYVQDRIRALRAAPAGGFQNIACLRSNAMK FT HLPNFFYKGQLT -> ADKDVLPLPRPTFQADKAQVANHQSHPASRICLRAKSWGAGVY FT HNRCAGATRLDVHSFRRAPTV (in isoform 2)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_044671" FT VAR_SEQ 156..276 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_044672" FT MUTAGEN 18 FT /note="K->A: Strongly reduced methyltransferase activity." FT /evidence="ECO:0000269|PubMed:36599985" FT MUTAGEN 24 FT /note="R->A: Abolished methyltransferase activity." FT /evidence="ECO:0000269|PubMed:36599982" FT MUTAGEN 27 FT /note="S->A,S,C,I: Abolished phosphorylation; does not FT affect methyltransferase activity." FT /evidence="ECO:0000269|PubMed:15861136, FT ECO:0000269|PubMed:36599985" FT MUTAGEN 27 FT /note="S->D,E: Mimics phosphorylation; abolished affect FT methyltransferase activity." FT /evidence="ECO:0000269|PubMed:15861136, FT ECO:0000269|PubMed:36599982, ECO:0000269|PubMed:36599985" FT MUTAGEN 27 FT /note="S->K,W: Abolished methyltransferase activity." FT /evidence="ECO:0000269|PubMed:36599985" FT MUTAGEN 29 FT /note="P->A: Strongly reduced methyltransferase activity." FT /evidence="ECO:0000269|PubMed:36599982" FT MUTAGEN 40 FT /note="K->D: Abolished interaction with WDR4; when FT associated with D-143, D-151 and D-172." FT /evidence="ECO:0000269|PubMed:37369656" FT MUTAGEN 107..109 FT /note="EIR->AAA: Abolished RNA methyltransferase activity." FT /evidence="ECO:0000269|PubMed:31031083, FT ECO:0000269|PubMed:37379838" FT MUTAGEN 109 FT /note="R->A: Abolished methyltransferase activity." FT /evidence="ECO:0000269|PubMed:36599985" FT MUTAGEN 111 FT /note="K->A: Slightly reduced methyltransferase activity." FT /evidence="ECO:0000269|PubMed:36599985" FT MUTAGEN 118 FT /note="D->A: Slightly reduced methyltransferase activity." FT /evidence="ECO:0000269|PubMed:36599985" FT MUTAGEN 143 FT /note="K->A: Abolished methyltransferase activity." FT /evidence="ECO:0000269|PubMed:36599985" FT MUTAGEN 143 FT /note="K->D: Abolished interaction with WDR4; when FT associated with D-40, D-151 and D-172." FT /evidence="ECO:0000269|PubMed:37369656" FT MUTAGEN 151 FT /note="K->D: Abolished interaction with WDR4; when FT associated with D-40, D-143 and D-172." FT /evidence="ECO:0000269|PubMed:37369656" FT MUTAGEN 160..163 FT /note="LFPD->AFPA: Abolished methyltransferase activity." FT /evidence="ECO:0000269|PubMed:34352206, FT ECO:0000269|PubMed:36599985" FT MUTAGEN 163 FT /note="D->A: Abolished methyltransferase activity." FT /evidence="ECO:0000269|PubMed:36599982" FT MUTAGEN 165 FT /note="H->A: Abolished tRNA-binding; when associated with FT A-167, A-170, A-243 and A-246." FT /evidence="ECO:0000269|PubMed:36599985" FT MUTAGEN 167 FT /note="K->A: Abolished methyltransferase activity. FT Abolished tRNA-binding; when associated with A-165, A-170, FT A-243 and A-246." FT /evidence="ECO:0000269|PubMed:36599982, FT ECO:0000269|PubMed:36599985" FT MUTAGEN 168 FT /note="R->A: Does not affect methyltransferase activity." FT /evidence="ECO:0000269|PubMed:36599982" FT MUTAGEN 170 FT /note="K->A: Abolished tRNA-binding; when associated with FT A-165, A-167, A-243 and A-246." FT /evidence="ECO:0000269|PubMed:36599985" FT MUTAGEN 172 FT /note="K->D: Abolished interaction with WDR4; when FT associated with D-40, D-143 and D-151." FT /evidence="ECO:0000269|PubMed:37369656" FT MUTAGEN 173 FT /note="W->A: Strongly reduced methyltransferase activity." FT /evidence="ECO:0000269|PubMed:36599982" FT MUTAGEN 199 FT /note="D->A: Abolished methyltransferase activity." FT /evidence="ECO:0000269|PubMed:36599982" FT MUTAGEN 240 FT /note="E->A: Abolished methyltransferase activity." FT /evidence="ECO:0000269|PubMed:36599982" FT MUTAGEN 243 FT /note="K->A: Slightly reduced tRNA-binding. Abolished FT tRNA-binding; when associated with A-165, A-167, A-170 and FT A-246. Strongly reduced methyltransferase activity." FT /evidence="ECO:0000269|PubMed:36599982, FT ECO:0000269|PubMed:36599985" FT MUTAGEN 246 FT /note="R->A: Slightly reduced tRNA-binding. Abolished FT tRNA-binding; when associated with A-165, A-167, A-170 and FT A-243. Does not affect methyltransferase activity." FT /evidence="ECO:0000269|PubMed:36599982, FT ECO:0000269|PubMed:36599985" FT CONFLICT 18 FT /note="K -> R (in Ref. 3; BAD96922)" FT /evidence="ECO:0000305" FT HELIX 41..43 FT /evidence="ECO:0007829|PDB:3CKK" FT TURN 47..49 FT /evidence="ECO:0007829|PDB:3CKK" FT TURN 51..53 FT /evidence="ECO:0007829|PDB:8H0N" FT STRAND 78..83 FT /evidence="ECO:0007829|PDB:3CKK" FT TURN 86..88 FT /evidence="ECO:0007829|PDB:8D58" FT HELIX 89..94 FT /evidence="ECO:0007829|PDB:3CKK" FT HELIX 95..97 FT /evidence="ECO:0007829|PDB:3CKK" FT STRAND 101..108 FT /evidence="ECO:0007829|PDB:3CKK" FT HELIX 110..125 FT /evidence="ECO:0007829|PDB:3CKK" FT STRAND 126..128 FT /evidence="ECO:0007829|PDB:7U20" FT STRAND 134..138 FT /evidence="ECO:0007829|PDB:3CKK" FT TURN 141..143 FT /evidence="ECO:0007829|PDB:3CKK" FT HELIX 145..148 FT /evidence="ECO:0007829|PDB:3CKK" FT STRAND 154..161 FT /evidence="ECO:0007829|PDB:3CKK" FT HELIX 166..168 FT /evidence="ECO:0007829|PDB:8H0N" FT HELIX 171..173 FT /evidence="ECO:0007829|PDB:8H0N" FT STRAND 174..176 FT /evidence="ECO:0007829|PDB:8H0N" FT HELIX 178..187 FT /evidence="ECO:0007829|PDB:3CKK" FT STRAND 188..199 FT /evidence="ECO:0007829|PDB:3CKK" FT HELIX 201..212 FT /evidence="ECO:0007829|PDB:3CKK" FT STRAND 217..220 FT /evidence="ECO:0007829|PDB:3CKK" FT HELIX 222..225 FT /evidence="ECO:0007829|PDB:3CKK" FT HELIX 231..233 FT /evidence="ECO:0007829|PDB:3CKK" FT TURN 234..236 FT /evidence="ECO:0007829|PDB:3CKK" FT HELIX 239..246 FT /evidence="ECO:0007829|PDB:3CKK" FT STRAND 252..258 FT /evidence="ECO:0007829|PDB:3CKK" FT TURN 262..264 FT /evidence="ECO:0007829|PDB:3CKK" SQ SEQUENCE 276 AA; 31471 MW; 715AE85A18632892 CRC64; MAAETRNVAG AEAPPPQKRY YRQRAHSNPM ADHTLRYPVK PEEMDWSELY PEFFAPLTQN QSHDDPKDKK EKRAQAQVEF ADIGCGYGGL LVELSPLFPD TLILGLEIRV KVSDYVQDRI RALRAAPAGG FQNIACLRSN AMKHLPNFFY KGQLTKMFFL FPDPHFKRTK HKWRIISPTL LAEYAYVLRV GGLVYTITDV LELHDWMCTH FEEHPLFERV PLEDLSEDPV VGHLGTSTEE GKKVLRNGGK NFPAIFRRIQ DPVLQAVTSQ TSLPGH //