ID TRMB_BOVIN Reviewed; 277 AA. AC Q2YDF1; DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot. DT 20-DEC-2005, sequence version 1. DT 24-JAN-2024, entry version 117. 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}; DE AltName: Full=Methyltransferase-like protein 1 {ECO:0000255|HAMAP-Rule:MF_03055}; DE AltName: Full=mRNA (guanine-N(7)-)-methyltransferase {ECO:0000255|HAMAP-Rule:MF_03055}; DE EC=2.1.1.- {ECO:0000255|HAMAP-Rule:MF_03055}; DE AltName: Full=miRNA (guanine-N(7)-)-methyltransferase {ECO:0000255|HAMAP-Rule:MF_03055}; DE EC=2.1.1.- {ECO:0000255|HAMAP-Rule:MF_03055}; 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}; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=16305752; DOI=10.1186/1471-2164-6-166; RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L., RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.; RT "Characterization of 954 bovine full-CDS cDNA sequences."; RL BMC Genomics 6:166-166(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Crossbred X Angus; TISSUE=Liver; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases. 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). Catalyzes the CC formation of N(7)-methylguanine at position 46 (m7G46) in a large CC subset of tRNAs that contain the 5'-RAGGU-3' motif within the variable CC loop. M7G46 interacts with C13-G22 in the D-loop to stabilize tRNA CC tertiary structure and protect tRNAs from decay. Also acts as a CC methyltransferase for a subset of internal N(7)-methylguanine in mRNAs. CC Internal N(7)-methylguanine methylation of mRNAs in response to stress CC promotes their relocalization to stress granules, thereby suppressing CC their translation. Also methylates a specific subset of miRNAs, such as CC let-7. N(7)-methylguanine methylation of let-7 miRNA promotes let-7 CC miRNA processing by disrupting an inhibitory secondary structure within CC the primary miRNA transcript (pri-miRNA). Acts as a regulator of CC embryonic stem cell self-renewal and differentiation. CC {ECO:0000255|HAMAP-Rule:MF_03055}. 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}; 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:0000255|HAMAP-Rule:MF_03055}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60509; CC Evidence={ECO:0000255|HAMAP-Rule:MF_03055}; 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:0000255|HAMAP-Rule:MF_03055}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60513; CC Evidence={ECO:0000255|HAMAP-Rule:MF_03055}; CC -!- PATHWAY: tRNA modification; N(7)-methylguanine-tRNA biosynthesis. CC {ECO:0000255|HAMAP-Rule:MF_03055}. CC -!- SUBUNIT: Catalytic component of the METTL1-WDR4 complex, composed of CC METTL1 and WDR4. {ECO:0000255|HAMAP-Rule:MF_03055}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03055}. 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. The N-terminal disordered region is part of the CC catalytic pocket and essential for methyltransferase activity: upon S- CC adenosyl-L-methionine- and tRNA-binding, the N-terminal disordered CC region becomes ordered, sandwiched between the bound cofactor and the CC tRNA, and the WDR4 C-terminus attaches to the METTL1 N-terminus to CC stabilize the bound tRNA together. Together with WDR4, which also binds CC tRNAs, tRNAs undergo bending to facilitate G46 flipping into the CC catalytic pocket to be modified. {ECO:0000255|HAMAP-Rule:MF_03055}. CC -!- PTM: Phosphorylation at Ser-28 by PKB/AKT1 inactivates its CC methyltransferase activity via a steric interference mechanism in the CC active site that locally disrupts the catalytic center. Phosphorylation CC at Ser-28 does not affect the interaction with WDR4. CC {ECO:0000255|HAMAP-Rule:MF_03055}. CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase CC superfamily. TrmB family. {ECO:0000255|HAMAP-Rule:MF_03055}. 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; BT029912; ABM06158.1; -; mRNA. DR EMBL; BC110252; AAI10253.1; -; mRNA. DR RefSeq; NP_001039542.1; NM_001046077.2. DR AlphaFoldDB; Q2YDF1; -. DR SMR; Q2YDF1; -. DR STRING; 9913.ENSBTAP00000022487; -. DR PaxDb; 9913-ENSBTAP00000022487; -. DR Ensembl; ENSBTAT00000022487.6; ENSBTAP00000022487.5; ENSBTAG00000016908.6. DR GeneID; 511197; -. DR KEGG; bta:511197; -. DR CTD; 4234; -. DR VEuPathDB; HostDB:ENSBTAG00000016908; -. DR VGNC; VGNC:31400; METTL1. DR eggNOG; KOG3115; Eukaryota. DR GeneTree; ENSGT00390000017840; -. DR HOGENOM; CLU_050910_3_0_1; -. DR InParanoid; Q2YDF1; -. DR OMA; LPNYFAK; -. DR TreeFam; TF314083; -. DR UniPathway; UPA00989; -. DR Proteomes; UP000009136; Chromosome 5. DR Bgee; ENSBTAG00000016908; Expressed in digestive system secreted substance and 104 other cell types or tissues. DR GO; GO:0005829; C:cytosol; IEA:Ensembl. DR GO; GO:0005730; C:nucleolus; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0106143; C:tRNA (m7G46) methyltransferase complex; ISS:UniProtKB. DR GO; GO:0043527; C:tRNA methyltransferase complex; IBA:GO_Central. DR GO; GO:0160090; F:internal mRNA (guanine-N7-)-methyltransferase activity; IEA:Ensembl. DR GO; GO:0008176; F:tRNA (guanine(46)-N7)-methyltransferase activity; ISS:UniProtKB. DR GO; GO:0000049; F:tRNA binding; IEA:UniProtKB-UniRule. DR GO; GO:0036265; P:RNA (guanine-N7)-methylation; IBA:GO_Central. DR GO; GO:0106004; P:tRNA (guanine-N7)-methylation; ISS:UniProtKB. DR GO; GO:0030488; P:tRNA methylation; IBA:GO_Central. DR GO; GO:0006400; P:tRNA modification; ISS:UniProtKB. DR GO; GO:0036416; P:tRNA stabilization; IEA:Ensembl. 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:SF16; 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. PE 2: Evidence at transcript level; KW Methyltransferase; Nucleus; Phosphoprotein; Reference proteome; KW RNA-binding; S-adenosyl-L-methionine; Transferase; tRNA processing; KW tRNA-binding. FT CHAIN 1..277 FT /note="tRNA (guanine-N(7)-)-methyltransferase" FT /id="PRO_0000284065" FT REGION 1..37 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 165..173 FT /note="AlphaC helix" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03055" FT REGION 239..247 FT /note="Alpha6 helix" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03055" FT ACT_SITE 164 FT /evidence="ECO:0000255|HAMAP-Rule:MF_03055" FT BINDING 85 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03055" FT BINDING 108 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03055" FT BINDING 110 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03055" FT BINDING 141 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03055" FT BINDING 142 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03055" FT BINDING 161 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03055" FT BINDING 239 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03055" FT BINDING 241 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03055" FT MOD_RES 28 FT /note="Phosphoserine" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03055" SQ SEQUENCE 277 AA; 31323 MW; 4860363A97727ADC CRC64; MAGTETGDAA GTEAPQPQKR YYRQRAHSNP MADHTLRYPV KPEDMDWSEL YPEFFAPLPQ NQSHDDPKDK KEKRAQAQVE FADIGCGYGG LLVELSPLFP DTLILGLEIR VKVSDYVQDR IRALRAAPGG GFQNIACLRS NAMKHLPNFF HKGQLTKMFF LFPDPHFKRT KHKWRIISPT LLAEYAYVLR VGGLVYTITD VLELHEWMCT HFEGHPLFER VPLEELSEDP IVGHLGTSTE EGKKVLRNGG KNFPAIFRRI QDPALPAVTP TPTPPGH //