{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q9UI30","secondaryAccessions":["B2R539","J3KNG5","Q3MHC7","Q8N2Z4"],"uniProtkbId":"TR112_HUMAN","entryAudit":{"firstPublicDate":"2004-05-24","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2000-05-01","entryVersion":175,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Multifunctional methyltransferase subunit TRM112-like protein"}},"alternativeNames":[{"fullName":{"value":"tRNA methyltransferase 112 homolog"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"25851604"},{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:26940"}],"value":"TRMT112"},"orfNames":[{"value":"AD-001"},{"value":"HSPC152"},{"value":"HSPC170"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18539146"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20308323"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25851604"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31061526"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31328227"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31636962"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33428944"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34669960"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37283053"}],"value":"Acts as an activator of both rRNA/tRNA and protein methyltransferases (PubMed:18539146, PubMed:20308323, PubMed:25851604, PubMed:31061526, PubMed:31328227, PubMed:31636962, PubMed:37283053). Together with methyltransferase BUD23, methylates the N(7) position of a guanine in 18S rRNA (PubMed:25851604). The heterodimer with N6AMT1/HEMK2 catalyzes N5-methylation of ETF1 on 'Gln-185', using S-adenosyl L-methionine as methyl donor (PubMed:18539146, PubMed:31061526, PubMed:31636962). The heterodimer with N6AMT1/HEMK2 also monomethylates 'Lys-12' of histone H4 (H4K12me1) (PubMed:31061526). The heterodimer with ALKBH8 catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA species (PubMed:20308323). Together with methyltransferase THUMPD3, catalyzes the formation of N(2)-methylguanosine at position 6 in a broad range of tRNA substrates and at position 7 of tRNA(Trp) (PubMed:34669960, PubMed:37283053). Involved in the pre-rRNA processing steps leading to small-subunit rRNA production (PubMed:25851604). Together with methyltransferase METTL5, specifically methylates the 6th position of adenine in position 1832 of 18S rRNA (PubMed:31328227, PubMed:33428944, PubMed:35033535, PubMed:37283053)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20308323"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25851604"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31061526"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31328227"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31632689"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31636962"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32217665"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32969463"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33428944"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34669960"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34948388"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35033535"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37283053"}],"value":"Part of the heterodimeric BUD23-TRM112 methyltransferase complex; this heterodimerization is necessary for the metabolic stability and activity of the catalytic subunit BUD23 (PubMed:25851604, PubMed:34948388). Part of the heterodimeric N6AMT1-TRM112 methyltransferase complex; this heterodimerization is necessary for S-adenosyl-L-methionine-binding to N6AMT1/HEMK2 (PubMed:20308323, PubMed:25851604, PubMed:31061526, PubMed:31632689, PubMed:31636962, PubMed:32969463, PubMed:34948388). Part of the heterodimeric ALKBH8-TRM112 methyltransferase complex (PubMed:20308323, PubMed:34948388). Part of the heterodimeric METTL5-TRM112 methyltransferase complex; this heterodimerization is necessary for the stability of the catalytic subunit METTL5 (PubMed:31328227, PubMed:32217665, PubMed:33428944, PubMed:34948388, PubMed:35033535, PubMed:37283053). Part of the heterodimeric THUMPD3-TRM112 methyltransferase complex; this complex forms an active tRNA methyltransferase, where TRMT112 acts as an activator of the catalytic subunit THUMPD3 (PubMed:34669960, PubMed:34948388, PubMed:37283053). Part of the heterodimeric THUMPD2-TRM112 methyltransferase complex; this complex forms an active tRNA methyltransferase, where TRMT112 acts as an activator of the catalytic subunit THUMPD2 (PubMed:34948388, PubMed:37283053). Part of the heterodimeric TRMT11-TRM112 methyltransferase complex; this complex forms an active tRNA methyltransferase, where TRMT112 acts as an activator of the catalytic subunit TRMT11 (PubMed:34948388, PubMed:37283053)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q9UI30","intActId":"EBI-373326"},"interactantTwo":{"uniProtKBAccession":"Q96BT7","geneName":"ALKBH8","intActId":"EBI-10825637"},"numberOfExperiments":10,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UI30","intActId":"EBI-373326"},"interactantTwo":{"uniProtKBAccession":"O43709","geneName":"BUD23","intActId":"EBI-1044726"},"numberOfExperiments":13,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UI30","intActId":"EBI-373326"},"interactantTwo":{"uniProtKBAccession":"Q9Y5N5","geneName":"HEMK2","intActId":"EBI-7966667"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UI30","intActId":"EBI-373326"},"interactantTwo":{"uniProtKBAccession":"Q6FHY5","geneName":"MEOX2","intActId":"EBI-16439278"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UI30","intActId":"EBI-373326"},"interactantTwo":{"uniProtKBAccession":"Q9NRN9","geneName":"METTL5","intActId":"EBI-12360031"},"numberOfExperiments":8,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UI30","intActId":"EBI-373326"},"interactantTwo":{"uniProtKBAccession":"Q9BTF0","geneName":"THUMPD2","intActId":"EBI-15105991"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UI30","intActId":"EBI-373326"},"interactantTwo":{"uniProtKBAccession":"Q9BV44","geneName":"THUMPD3","intActId":"EBI-373253"},"numberOfExperiments":11,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UI30","intActId":"EBI-373326"},"interactantTwo":{"uniProtKBAccession":"Q7Z4G4","geneName":"TRMT11","intActId":"EBI-2515608"},"numberOfExperiments":6,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25851604"}],"value":"Localizes to a polarized perinuclear structure, overlapping partially with the Golgi and lysosomes (PubMed:25851604)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25851604"}],"value":"Nucleus, nucleoplasm","id":"SL-0190"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25851604"}],"value":"Cytoplasm, perinuclear region","id":"SL-0198"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["Q9UI30-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["Q9UI30-2"],"sequenceIds":["VSP_054748"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the TRM112 family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":125,"modifier":"EXACT"}},"description":"Multifunctional methyltransferase subunit TRM112-like protein","featureId":"PRO_0000215797"},{"type":"Domain","location":{"start":{"value":2,"modifier":"EXACT"},"end":{"value":119,"modifier":"EXACT"}},"description":"TRM112"},{"type":"Modified residue","location":{"start":{"value":119,"modifier":"EXACT"},"end":{"value":119,"modifier":"EXACT"}},"description":"Phosphoserine","evidences":[{"evidenceCode":"ECO:0007744","source":"PubMed","id":"18669648"},{"evidenceCode":"ECO:0007744","source":"PubMed","id":"19690332"},{"evidenceCode":"ECO:0007744","source":"PubMed","id":"20068231"}]},{"type":"Modified residue","location":{"start":{"value":125,"modifier":"EXACT"},"end":{"value":125,"modifier":"EXACT"}},"description":"Phosphoserine","evidences":[{"evidenceCode":"ECO:0007744","source":"PubMed","id":"20068231"}]},{"type":"Alternative sequence","location":{"start":{"value":61,"modifier":"EXACT"},"end":{"value":65,"modifier":"EXACT"}},"description":"in isoform 2","evidences":[{"evidenceCode":"ECO:0000305"}],"featureId":"VSP_054748","alternativeSequence":{}},{"type":"Mutagenesis","location":{"start":{"value":5,"modifier":"EXACT"},"end":{"value":5,"modifier":"EXACT"}},"description":"Abolishes interaction with N6AMT1, METTL5, TRMT11, THUMPD3 and THUMPD2. Reduces interaction with BUD23 and ALKBH8. Reduces expression of exogenous TRMT112.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34948388"}],"alternativeSequence":{"originalSequence":"T","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":5,"modifier":"EXACT"},"end":{"value":5,"modifier":"EXACT"}},"description":"Loss of interaction with METTL5, THUMPD3, THUMPD2 and TRMT11.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37283053"}],"alternativeSequence":{"originalSequence":"T","alternativeSequences":["R"]}},{"type":"Mutagenesis","location":{"start":{"value":8,"modifier":"EXACT"},"end":{"value":8,"modifier":"EXACT"}},"description":"Strongly reduced ability to promote N5-methylation of ETF1 together with HEMK2/N6AMT1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31636962"}],"alternativeSequence":{"originalSequence":"L","alternativeSequences":["D"]}},{"type":"Mutagenesis","location":{"start":{"value":8,"modifier":"EXACT"},"end":{"value":8,"modifier":"EXACT"}},"description":"Abolishes interaction with METTL5 and THUMPD3. Reduces interaction with ALKBH8, THUMPD2 and TRMT11. No effect on interaction with N6AMT1 and BUD23. No effect on expression of exogenous TRMT112.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34948388"}],"alternativeSequence":{"originalSequence":"L","alternativeSequences":["W"]}},{"type":"Mutagenesis","location":{"start":{"value":9,"modifier":"EXACT"},"end":{"value":9,"modifier":"EXACT"}},"description":"Strongly reduced ability to promote N5-methylation of ETF1 together with HEMK2/N6AMT1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31636962"}],"alternativeSequence":{"originalSequence":"L","alternativeSequences":["D"]}},{"type":"Mutagenesis","location":{"start":{"value":10,"modifier":"EXACT"},"end":{"value":10,"modifier":"EXACT"}},"description":"Abolishes interaction with THUMPD2. Increases expression of exogenous TRMT112. No effect on interaction with N6AMT1, BUD23, METTL5, TRMT11, ALKBH8 and THUMPD3.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34948388"}],"alternativeSequence":{"originalSequence":"S","alternativeSequences":["F"]}},{"type":"Mutagenesis","location":{"start":{"value":45,"modifier":"EXACT"},"end":{"value":45,"modifier":"EXACT"}},"description":"Abolishes interaction with METTL5 and THUMPD3. Reduces interaction with ALKBH8 and THUMPD2. No effect on interaction with N6AMT1, BUD23 and TRMT11. Reduces expression of exogenous TRMT112.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34948388"}],"alternativeSequence":{"originalSequence":"M","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":48,"modifier":"EXACT"},"end":{"value":48,"modifier":"EXACT"}},"description":"Abolishes interaction with THUMPD2 and THUMPD3. Reduces interaction with TRMT11, ALKBH8 and N6AMT1. No effect on interaction with BUD23 and METTL5. No effect on expression of exogenous TRMT112.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34948388"}],"alternativeSequence":{"originalSequence":"K","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":50,"modifier":"EXACT"},"end":{"value":50,"modifier":"EXACT"}},"description":"Increases interaction with METTL5. No effect on interaction with TRMT11, THUMPD2, THUMPD3, N6AMT1, BUD23 and ALKBH8. No effect on expression of exogenous TRMT112.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34948388"}],"alternativeSequence":{"originalSequence":"E","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":92,"modifier":"EXACT"},"end":{"value":92,"modifier":"EXACT"}},"description":"Reduces interaction with THUMPD2, THUMPD3, ALKBH8, TRMT11, N6AMT1 and BUD23. Increases interaction with METTL5. Reduces expression of exogenous TRMT112.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34948388"}],"alternativeSequence":{"originalSequence":"E","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":107,"modifier":"EXACT"},"end":{"value":107,"modifier":"EXACT"}},"description":"Abolishes interaction with BUD23, THUMPD2 and THUMPD3. Reduces interaction with TRMT11, N6AMT1, METTL5 and ALKBH8. 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