{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P57081","secondaryAccessions":["A8KA58","B2RCA3","B4DNQ7","D3DSK3","Q9BVM5","Q9HCR3"],"uniProtkbId":"WDR4_HUMAN","entryAudit":{"firstPublicDate":"2000-12-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2002-02-11","entryVersion":193,"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:0000255","source":"HAMAP-Rule","id":"MF_03056"}],"value":"tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4"}},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"26751069"}],"value":"Protein Wuho homolog"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"26751069"}],"value":"hWH"}]},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_03056"}],"value":"WD repeat-containing protein 4"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_03056"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"10950928"},{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:12756"}],"value":"WDR4"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12403464"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26751069"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31031083"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31031084"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34352206"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34352207"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36599982"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36599985"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37369656"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37379838"}],"value":"Non-catalytic component of the METTL1-WDR4 methyltransferase complex required for the formation of N(7)-methylguanine in a subset of RNA species, such as tRNAs, mRNAs and microRNAs (miRNAs) (PubMed:12403464, PubMed:31031083, PubMed:31031084, PubMed:36599982, PubMed:36599985, PubMed:37369656). In the METTL1-WDR4 methyltransferase complex, WDR4 acts as a scaffold for tRNA-binding (PubMed:36599982, PubMed:36599985, PubMed:37369656). Required for the formation of N(7)-methylguanine at position 46 (m7G46) in a large subset of tRNAs that contain the 5'-RAGGU-3' motif within the variable loop (PubMed:12403464, PubMed:34352206, PubMed:34352207, PubMed:36599982, PubMed:36599985, PubMed:37369656). M7G46 interacts with C13-G22 in the D-loop to stabilize tRNA tertiary structure and protect tRNAs from decay (PubMed:36599982, PubMed:36599985). Also required for the formation of N(7)-methylguanine at internal sites in a subset of mRNAs (PubMed:31031084, PubMed:37379838). Also required for methylation of a specific subset of miRNAs, such as let-7 (PubMed:31031083). Independently of METTL1, also plays a role in genome stability: localizes at the DNA replication site and regulates endonucleolytic activities of FEN1 (PubMed:26751069)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12403464"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36599982"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36599985"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37369656"}],"value":"tRNA modification; N(7)-methylguanine-tRNA biosynthesis"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12403464"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26751069"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36599982"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36599985"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37369656"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37379838"}],"value":"Non-catalytic component of the METTL1-WDR4 complex, composed of METTL1 and WDR4 (PubMed:12403464, PubMed:26751069, PubMed:36599982, PubMed:36599985, PubMed:37379838). Interacts with FEN1; the interaction is direct (PubMed:26751069)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P57081","intActId":"EBI-750427"},"interactantTwo":{"uniProtKBAccession":"Q9NWS6","geneName":"FAM118A","intActId":"EBI-8638992"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P57081","intActId":"EBI-750427"},"interactantTwo":{"uniProtKBAccession":"P39748","geneName":"FEN1","intActId":"EBI-707816"},"numberOfExperiments":8,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P57081","intActId":"EBI-750427"},"interactantTwo":{"uniProtKBAccession":"Q9UBP6","geneName":"METTL1","intActId":"EBI-750415"},"numberOfExperiments":15,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P57081","intActId":"EBI-750427"},"interactantTwo":{"uniProtKBAccession":"P53611","geneName":"RABGGTB","intActId":"EBI-536715"},"numberOfExperiments":6,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26751069"}],"value":"Localizes at the site of nascent DNA synthesis"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15861136"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26751069"}],"value":"Nucleus","id":"SL-0191"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26751069"}],"value":"Chromosome","id":"SL-0468"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["P57081-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["P57081-2"],"sequenceIds":["VSP_036936"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["P57081-3"],"sequenceIds":["VSP_036935"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34352206"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34352207"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34371184"}],"value":"Amplified and overexpressed in a number of cancers (at protein level)"}],"commentType":"INDUCTION"},{"commentType":"DISEASE","disease":{"diseaseId":"Galloway-Mowat syndrome 6","diseaseAccession":"DI-05498","acronym":"GAMOS6","description":"A form of Galloway-Mowat syndrome, a severe renal-neurological disease characterized by early-onset nephrotic syndrome associated with microcephaly, central nervous system abnormalities, developmental delays, and a propensity for seizures. 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Renal impairment may be age-dependent or may not be present.","diseaseCrossReference":{"database":"MIM","id":"618347"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28617965"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29597095"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30079490"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36599985"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37369656"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Microcephaly, growth deficiency, seizures, and brain malformations","diseaseAccession":"DI-05506","acronym":"MIGSB","description":"An autosomal recessive disorder characterized by intrauterine growth retardation, postnatal growth deficiency, microcephaly, facial dysmorphism, early-onset seizures, brain malformations such as partial agenesis of the corpus callosum and simplified gyration, and poor or absent psychomotor development.","diseaseCrossReference":{"database":"MIM","id":"618346"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26416026"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37369656"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34352206"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34352207"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34371184"}],"value":"In the context of cancer, overexpression of the METTL1-WDR4 methyltransferase complex promotes cancer progression by driving oncogenic transformation (PubMed:34352206, PubMed:34352207, PubMed:34371184). The METTL1-WDR4 methyltransferase complex drives oncogenesis by mediating the formation of N(7)-methylguanine at position 46 (m7G46) in some tRNAs, in particular Arg-TCT-4-1 (TRR-TCT4-1), leading to increased translation of mRNAs, including cell cycle regulators that are enriched in the corresponding AGA codon (PubMed:34352206, PubMed:34352207, PubMed:34371184)"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_03056"}],"value":"Belongs to the WD repeat TRM82 family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Initiator methionine","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":1,"modifier":"EXACT"}},"description":"Removed","evidences":[{"evidenceCode":"ECO:0000269","source":"Reference","id":"Ref.6"}]},{"type":"Chain","location":{"start":{"value":2,"modifier":"EXACT"},"end":{"value":412,"modifier":"EXACT"}},"description":"tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit 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