{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q08J23","secondaryAccessions":["A8K529","B2RNR4","B3KP09","B4DQW2","G3V1R4","Q9BVN4","Q9H858","Q9NXD9"],"uniProtkbId":"NSUN2_HUMAN","entryAudit":{"firstPublicDate":"2007-05-29","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2007-05-29","entryVersion":169,"sequenceVersion":2},"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":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"RNA cytosine C(5)-methyltransferase NSUN2"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17071714"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22395603"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31186410"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31276587"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31358969"}],"value":"2.1.1.-"}]},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"19596847"}],"value":"Myc-induced SUN domain-containing protein"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"19596847"}],"value":"Misu"}]},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"17215513"}],"value":"NOL1/NOP2/Sun domain family member 2"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"17215513"}],"value":"Substrate of AIM1/Aurora kinase B"}},{"fullName":{"value":"mRNA cytosine C(5)-methyltransferase"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22395603"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28418038"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31358969"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34556860"}],"value":"2.1.1.-"}]},{"fullName":{"value":"tRNA cytosine C(5)-methyltransferase"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31276587"}],"value":"2.1.1.-"},{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17071714"}],"value":"2.1.1.203"}]},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"17071714"}],"value":"tRNA methyltransferase 4 homolog"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"17071714"}],"value":"hTrm4"}]}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"17215513"},{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:25994"}],"value":"NSUN2"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"17215513"}],"value":"SAKI"},{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"17071714"}],"value":"TRM4"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q1HFZ0"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17071714"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19596847"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22395603"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22995836"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23871666"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28418038"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31186410"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31199786"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31276587"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31358969"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34556860"}],"value":"RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs) (PubMed:17071714, PubMed:22995836, PubMed:31199786, PubMed:31358969). Involved in various processes, such as epidermal stem cell differentiation, testis differentiation and maternal to zygotic transition during early development: acts by increasing protein synthesis; cytosine C(5)-methylation promoting tRNA stability and preventing mRNA decay (PubMed:31199786). Methylates cytosine to 5-methylcytosine (m5C) at positions 34 and 48 of intron-containing tRNA(Leu)(CAA) precursors, and at positions 48, 49 and 50 of tRNA(Gly)(GCC) precursors (PubMed:17071714, PubMed:22995836, PubMed:31199786). tRNA methylation is required generation of RNA fragments derived from tRNAs (tRFs) (PubMed:31199786). Also mediates C(5)-methylation of mitochondrial tRNAs (PubMed:31276587). Catalyzes cytosine C(5)-methylation of mRNAs, leading to stabilize them and prevent mRNA decay: mRNA stabilization involves YBX1 that specifically recognizes and binds m5C-modified transcripts (PubMed:22395603, PubMed:31358969, PubMed:34556860). Cytosine C(5)-methylation of mRNAs also regulates mRNA export: methylated transcripts are specifically recognized by THOC4/ALYREF, which mediates mRNA nucleo-cytoplasmic shuttling (PubMed:28418038). Also mediates cytosine C(5)-methylation of non-coding RNAs, such as vault RNAs (vtRNAs), promoting their processing into regulatory small RNAs (PubMed:23871666). Cytosine C(5)-methylation of vtRNA VTRNA1.1 promotes its processing into small-vault RNA4 (svRNA4) and regulates epidermal differentiation (PubMed:31186410). May act downstream of Myc to regulate epidermal cell growth and proliferation (By similarity). Required for proper spindle assembly and chromosome segregation, independently of its methyltransferase activity (PubMed:19596847)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"cytidine(48) in tRNA + S-adenosyl-L-methionine = 5-methylcytidine(48) in tRNA + S-adenosyl-L-homocysteine + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:42948"},{"database":"Rhea","id":"RHEA-COMP:10293"},{"database":"Rhea","id":"RHEA-COMP:10297"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:57856"},{"database":"ChEBI","id":"CHEBI:59789"},{"database":"ChEBI","id":"CHEBI:74483"},{"database":"ChEBI","id":"CHEBI:82748"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31276587"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:42949"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31276587"}]}]},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"cytidine(49) in tRNA + S-adenosyl-L-methionine = 5-methylcytidine(49) in tRNA + S-adenosyl-L-homocysteine + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:42952"},{"database":"Rhea","id":"RHEA-COMP:10294"},{"database":"Rhea","id":"RHEA-COMP:10385"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:57856"},{"database":"ChEBI","id":"CHEBI:59789"},{"database":"ChEBI","id":"CHEBI:74483"},{"database":"ChEBI","id":"CHEBI:82748"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31276587"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:42953"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31276587"}]}]},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"cytidine(50) in tRNA + S-adenosyl-L-methionine = 5-methylcytidine(50) in tRNA + S-adenosyl-L-homocysteine + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:61488"},{"database":"Rhea","id":"RHEA-COMP:15838"},{"database":"Rhea","id":"RHEA-COMP:15839"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:57856"},{"database":"ChEBI","id":"CHEBI:59789"},{"database":"ChEBI","id":"CHEBI:74483"},{"database":"ChEBI","id":"CHEBI:82748"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31276587"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:61489"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31276587"}]}]},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"cytidine(34) in tRNA precursor + S-adenosyl-L-methionine = 5-methylcytidine(34) in tRNA precursor + S-adenosyl-L-homocysteine + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:42940"},{"database":"Rhea","id":"RHEA-COMP:10291"},{"database":"Rhea","id":"RHEA-COMP:10295"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:57856"},{"database":"ChEBI","id":"CHEBI:59789"},{"database":"ChEBI","id":"CHEBI:74483"},{"database":"ChEBI","id":"CHEBI:82748"}],"ecNumber":"2.1.1.203","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17071714"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:42941"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17071714"}]}]},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"a cytidine in mRNA + S-adenosyl-L-methionine = a 5-methylcytidine in mRNA + S-adenosyl-L-homocysteine + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:61464"},{"database":"Rhea","id":"RHEA-COMP:15145"},{"database":"Rhea","id":"RHEA-COMP:15826"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:57856"},{"database":"ChEBI","id":"CHEBI:59789"},{"database":"ChEBI","id":"CHEBI:74483"},{"database":"ChEBI","id":"CHEBI:82748"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22395603"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28418038"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31358969"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34556860"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:61465"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22395603"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28418038"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31358969"}]}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22995836"}],"value":"Inhibited by magnesium ions"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17215513"}],"value":"Interacts with NPM1 and NCL during interphase; interaction is disrupted following phosphorylation at Ser-139"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q08J23","intActId":"EBI-1642839"},"interactantTwo":{"uniProtKBAccession":"Q05086","geneName":"UBE3A","intActId":"EBI-954357"},"numberOfExperiments":2,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q1HFZ0"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19596847"}],"value":"Concentrated in the nucleolus during interphase and translocates to the spindle during mitosis as an RNA-protein complex that includes 18S ribosomal RNA (PubMed:19596847). In testis, localizes to the chromatoid body (By similarity)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17071714"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17215513"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31276587"}],"value":"Nucleus, nucleolus","id":"SL-0188"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17071714"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31276587"}],"value":"Cytoplasm","id":"SL-0086"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31276587"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31287866"}],"value":"Mitochondrion","id":"SL-0173"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19596847"}],"value":"Cytoplasm, cytoskeleton, spindle","id":"SL-0251"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q1HFZ0"}],"value":"Secreted, extracellular exosome","id":"SL-0466"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["Q08J23-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["Q08J23-2"],"sequenceIds":["VSP_042621"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["Q08J23-3"],"sequenceIds":["VSP_053598"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22541559"}],"value":"Expressed in adult and fetal brain and in lymphoblastoid cells"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17215513"}],"value":"Phosphorylated at Ser-139 by AURKB during mitosis, leading to abolish methyltransferase activity and the interaction with NPM1"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Intellectual developmental disorder, autosomal recessive 5","diseaseAccession":"DI-03476","acronym":"MRT5","description":"A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.","diseaseCrossReference":{"database":"MIM","id":"611091"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22541559"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22541562"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU01023"}],"value":"Belongs to the class I-like SAM-binding methyltransferase superfamily. RsmB/NOP family. TRM4 subfamily"}],"commentType":"SIMILARITY"},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"BAA91075.1","note":"Truncated N-terminus.","evidences":[{"evidenceCode":"ECO:0000305"}]},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"BAB14762.1","note":"Truncated N-terminus.","evidences":[{"evidenceCode":"ECO:0000305"}]}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":767,"modifier":"EXACT"}},"description":"RNA cytosine C(5)-methyltransferase NSUN2","featureId":"PRO_0000289223"},{"type":"Region","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":36,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":436,"modifier":"EXACT"},"end":{"value":481,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":719,"modifier":"EXACT"},"end":{"value":767,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":461,"modifier":"EXACT"},"end":{"value":470,"modifier":"EXACT"}},"description":"Basic and acidic residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":719,"modifier":"EXACT"},"end":{"value":730,"modifier":"EXACT"}},"description":"Polar residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Active site","location":{"start":{"value":321,"modifier":"EXACT"},"end":{"value":321,"modifier":"EXACT"}},"description":"Nucleophile","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU01023"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"28418038"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"31358969"}]},{"type":"Binding site","location":{"start":{"value":184,"modifier":"EXACT"},"end":{"value":190,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:59789"}],"evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU01023"}],"ligand":{"name":"S-adenosyl-L-methionine","id":"ChEBI:CHEBI:59789"}},{"type":"Binding site","location":{"start":{"value":215,"modifier":"EXACT"},"end":{"value":215,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:59789"}],"evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU01023"}],"ligand":{"name":"S-adenosyl-L-methionine","id":"ChEBI:CHEBI:59789"}},{"type":"Binding site","location":{"start":{"value":242,"modifier":"EXACT"},"end":{"value":242,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:59789"}],"evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU01023"}],"ligand":{"name":"S-adenosyl-L-methionine","id":"ChEBI:CHEBI:59789"}},{"type":"Binding site","location":{"start":{"value":268,"modifier":"EXACT"},"end":{"value":268,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:59789"}],"evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU01023"}],"ligand":{"name":"S-adenosyl-L-methionine","id":"ChEBI:CHEBI:59789"}},{"type":"Modified residue","location":{"start":{"value":139,"modifier":"EXACT"},"end":{"value":139,"modifier":"EXACT"}},"description":"Phosphoserine; 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