TRMB_MOUSE
ID TRMB_MOUSE Reviewed; 268 AA.
AC Q9Z120; Q3TU83; Q921G5;
DT 20-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 152.
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:0000312|MGI:MGI:1339986};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Tamura M., Nashimoto M., Kaspar R.L.;
RT "Methyltransferase related protein.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Extraembryonic tissue, and Placenta;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-268.
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION, AND PATHWAY.
RX PubMed=29983320; DOI=10.1016/j.molcel.2018.06.001;
RA Lin S., Liu Q., Lelyveld V.S., Choe J., Szostak J.W., Gregory R.I.;
RT "Mettl1/Wdr4-mediated m7G tRNA methylome is required for normal mRNA
RT translation and embryonic stem cell self-renewal and differentiation.";
RL Mol. Cell 71:244-255(2018).
CC -!- FUNCTION: Methyltransferase that mediates the formation of N(7)-
CC methylguanine in a subset of RNA species, such as tRNAs, mRNAs and
CC microRNAs (miRNAs) (PubMed:29983320). Catalyzes the formation of N(7)-
CC methylguanine at position 46 (m7G46) in tRNA. Also acts as a
CC methyltransferase for a subset of internal N(7)-methylguanine in mRNAs
CC (PubMed:29983320). Internal N(7)-methylguanine methylation of mRNAs
CC regulates translation (PubMed:29983320). Also methylates a specific
CC subset of miRNAs, such as let-7. N(7)-methylguanine methylation of let-
CC 7 miRNA promotes let-7 miRNA processing by disrupting an inhibitory
CC secondary structure within the primary miRNA transcript (pri-miRNA) (By
CC similarity). Acts as a regulator of embryonic stem cell self-renewal
CC and differentiation (PubMed:29983320). {ECO:0000255|HAMAP-
CC Rule:MF_03055, ECO:0000269|PubMed:29983320}.
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:0000269|PubMed:29983320}.
CC -!- SUBUNIT: Forms a complex with WDR4. {ECO:0000255|HAMAP-Rule:MF_03055}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03055}.
CC -!- PTM: Phosphorylation at Ser-21 inactivates its catalytic activity but
CC does not affect the interaction with WDR4. {ECO:0000255|HAMAP-
CC Rule:MF_03055}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. TrmB family. {ECO:0000255|HAMAP-Rule:MF_03055}.
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DR EMBL; AB023619; BAA75230.1; -; mRNA.
DR EMBL; AK160914; BAE36088.1; -; mRNA.
DR EMBL; CH466578; EDL24462.1; -; Genomic_DNA.
DR EMBL; BC012649; AAH12649.1; -; mRNA.
DR EMBL; Y18644; CAA77240.1; -; mRNA.
DR CCDS; CCDS24223.1; -.
DR RefSeq; NP_034922.1; NM_010792.1.
DR AlphaFoldDB; Q9Z120; -.
DR SMR; Q9Z120; -.
DR BioGRID; 201404; 15.
DR STRING; 10090.ENSMUSP00000006915; -.
DR iPTMnet; Q9Z120; -.
DR PhosphoSitePlus; Q9Z120; -.
DR EPD; Q9Z120; -.
DR MaxQB; Q9Z120; -.
DR PaxDb; Q9Z120; -.
DR PeptideAtlas; Q9Z120; -.
DR PRIDE; Q9Z120; -.
DR ProteomicsDB; 258854; -.
DR Antibodypedia; 16399; 177 antibodies from 29 providers.
DR DNASU; 17299; -.
DR Ensembl; ENSMUST00000006915; ENSMUSP00000006915; ENSMUSG00000006732.
DR GeneID; 17299; -.
DR KEGG; mmu:17299; -.
DR UCSC; uc007hhq.1; mouse.
DR CTD; 4234; -.
DR MGI; MGI:1339986; Mettl1.
DR VEuPathDB; HostDB:ENSMUSG00000006732; -.
DR eggNOG; KOG3115; Eukaryota.
DR GeneTree; ENSGT00390000017840; -.
DR HOGENOM; CLU_050910_3_0_1; -.
DR InParanoid; Q9Z120; -.
DR OMA; DLHNWMV; -.
DR OrthoDB; 1417652at2759; -.
DR PhylomeDB; Q9Z120; -.
DR TreeFam; TF314083; -.
DR UniPathway; UPA00989; -.
DR BioGRID-ORCS; 17299; 17 hits in 74 CRISPR screens.
DR PRO; PR:Q9Z120; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q9Z120; protein.
DR Bgee; ENSMUSG00000006732; Expressed in lacrimal gland and 210 other tissues.
DR ExpressionAtlas; Q9Z120; baseline and differential.
DR Genevisible; Q9Z120; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0043527; C:tRNA methyltransferase complex; IBA:GO_Central.
DR GO; GO:0008176; F:tRNA (guanine-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:0030488; P:tRNA methylation; IBA:GO_Central.
DR GO; GO:0006400; P:tRNA modification; ISS:UniProtKB.
DR Gene3D; 3.40.50.150; -; 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 PANTHER; PTHR23417; PTHR23417; 1.
DR Pfam; PF02390; Methyltransf_4; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR TIGRFAMs; TIGR00091; TIGR00091; 1.
DR PROSITE; PS51625; SAM_MT_TRMB; 1.
PE 1: Evidence at protein level;
KW Methyltransferase; Nucleus; Phosphoprotein; Reference proteome;
KW RNA-binding; S-adenosyl-L-methionine; Transferase; tRNA processing;
KW tRNA-binding.
FT CHAIN 1..268
FT /note="tRNA (guanine-N(7)-)-methyltransferase"
FT /id="PRO_0000171432"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 157
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03055"
FT BINDING 78
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03055"
FT BINDING 101..102
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03055"
FT BINDING 134..135
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03055"
FT BINDING 154
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03055"
FT BINDING 232..234
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03055"
FT MOD_RES 21
FT /note="Phosphoserine; by PKB and RPS6KA3"
FT /evidence="ECO:0000250|UniProtKB:Q9UBP6, ECO:0000255|HAMAP-
FT Rule:MF_03055"
FT CONFLICT 52
FT /note="I -> N (in Ref. 4; AAH12649)"
FT /evidence="ECO:0000305"
FT CONFLICT 56
FT /note="S -> N (in Ref. 4; AAH12649)"
FT /evidence="ECO:0000305"
FT CONFLICT 213
FT /note="R -> C (in Ref. 4; AAH12649)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 268 AA; 30603 MW; 1DAE1EEAA4A07627 CRC64;
MMAGAEAPQP QKRYYRQRAH SNPMADHTLR YPVKPEEMDW SELYPEFFAP LIQNKSHDDP
KDEKEKHSGA QVEFADIGCG YGGLLVALSP LFPDTLILGL EIRVKVSDYV QDRIRALRAA
PGGGFQNIAC LRSNAMKHLP NFFRKGQLAK MFFLFPDPHF KRTKHKWRII SPTLLAEYAY
VLRVGGLVYT VTDVPELHEW MCTHFEEHPL FERVPLEELS EDPIVEHLGS STEEGKKVLR
NGGKNFPAVF RRIQDPLLQA VTPNPTLP
