{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P17643","secondaryAccessions":["P78468","P78469","Q13721","Q15679"],"uniProtkbId":"TYRP1_HUMAN","entryAudit":{"firstPublicDate":"1990-08-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2001-01-11","entryVersion":224,"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":{"value":"5,6-dihydroxyindole-2-carboxylic acid oxidase"},"shortNames":[{"value":"DHICA oxidase"}],"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28661582"}],"value":"1.14.18.-"}]},"alternativeNames":[{"fullName":{"value":"Catalase B"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"1693779"}],"value":"Glycoprotein 75"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"2324688"}],"value":"Melanoma antigen gp75"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"9434945"}],"value":"Tyrosinase-related protein 1"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"2111010"}],"value":"TRP"},{"value":"TRP-1"},{"value":"TRP1"}]}],"flag":"Precursor"},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:12450"}],"value":"TYRP1"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"1906272"}],"value":"CAS2"},{"value":"TYRP"},{"value":"TYRRP"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P07147"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16704458"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22556244"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23504663"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28661582"}],"value":"Plays a role in melanin biosynthesis (PubMed:16704458, PubMed:22556244, PubMed:23504663). Catalyzes the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into indole-5,6-quinone-2-carboxylic acid in the presence of bound Cu(2+) ions, but not in the presence of Zn(2+) (PubMed:28661582). May regulate or influence the type of melanin synthesized (PubMed:16704458, PubMed:22556244). Also to a lower extent, capable of hydroxylating tyrosine and producing melanin (By similarity)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"2 5,6-dihydroxyindole-2-carboxylate + O2 = 2 indole-5,6-quinone-2-carboxylate + 2 H2O","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:68388"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15379"},{"database":"ChEBI","id":"CHEBI:16875"},{"database":"ChEBI","id":"CHEBI:177869"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28661582"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:68389"},"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"28661582"}]}]},{"commentType":"COFACTOR","cofactors":[{"name":"Cu(2+)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28661582"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:29036"}},{"name":"Zn(2+)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28661582"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:29105"}}],"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28661582"}],"value":"Contains bound zinc ions after heterologous expression in insect cells, giving rise to a protein that lacks DHICA oxidase activity."}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28661582"}],"value":"The activity depends critically on the nature of the bound metal ion. Catalyzes the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) in the presence of bound Cu(2+) ions, but lacks activity in the presence of bound Zn(2+) ions"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16704458"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22556244"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23504663"}],"value":"Pigment biosynthesis; melanin biosynthesis"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P07147"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28661582"}],"value":"Monomer (PubMed:28661582). Interacts with ATP7A (By similarity) (PubMed:28661582). Interacts with SLC45A2 (By similarity)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P17643","intActId":"EBI-7900408"},"interactantTwo":{"uniProtKBAccession":"Q99767","geneName":"APBA2","intActId":"EBI-81711"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17643","intActId":"EBI-7900408"},"interactantTwo":{"uniProtKBAccession":"Q92796","geneName":"DLG3","intActId":"EBI-80440"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17643","intActId":"EBI-7900408"},"interactantTwo":{"uniProtKBAccession":"P78352","geneName":"DLG4","intActId":"EBI-80389"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17643","intActId":"EBI-7900408"},"interactantTwo":{"uniProtKBAccession":"Q68DX3","geneName":"FRMPD2","intActId":"EBI-53993476"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17643","intActId":"EBI-7900408"},"interactantTwo":{"uniProtKBAccession":"O14908","geneName":"GIPC1","intActId":"EBI-373132"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17643","intActId":"EBI-7900408"},"interactantTwo":{"uniProtKBAccession":"Q9Y3R0","geneName":"GRIP1","intActId":"EBI-5349621"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17643","intActId":"EBI-7900408"},"interactantTwo":{"uniProtKBAccession":"Q9C0E4","geneName":"GRIP2","intActId":"EBI-949557"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17643","intActId":"EBI-7900408"},"interactantTwo":{"uniProtKBAccession":"Q14005","geneName":"IL16","intActId":"EBI-2831580"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17643","intActId":"EBI-7900408"},"interactantTwo":{"uniProtKBAccession":"Q8TBB1","geneName":"LNX1","intActId":"EBI-739832"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17643","intActId":"EBI-7900408"},"interactantTwo":{"uniProtKBAccession":"Q8N448","geneName":"LNX2","intActId":"EBI-2340947"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17643","intActId":"EBI-7900408"},"interactantTwo":{"uniProtKBAccession":"Q96QZ7","geneName":"MAGI1","intActId":"EBI-924464"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17643","intActId":"EBI-7900408"},"interactantTwo":{"uniProtKBAccession":"Q86UL8","geneName":"MAGI2","intActId":"EBI-311035"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17643","intActId":"EBI-7900408"},"interactantTwo":{"uniProtKBAccession":"O75970","geneName":"MPDZ","intActId":"EBI-821405"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17643","intActId":"EBI-7900408"},"interactantTwo":{"uniProtKBAccession":"Q86UT5","geneName":"NHERF4","intActId":"EBI-8744528"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17643","intActId":"EBI-7900408"},"interactantTwo":{"uniProtKBAccession":"Q8NI35","geneName":"PATJ","intActId":"EBI-724390"},"numberOfExperiments":9,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17643","intActId":"EBI-7900408"},"interactantTwo":{"uniProtKBAccession":"Q5T2W1","geneName":"PDZK1","intActId":"EBI-349819"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17643","intActId":"EBI-7900408"},"interactantTwo":{"uniProtKBAccession":"Q14160","geneName":"SCRIB","intActId":"EBI-357345"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17643","intActId":"EBI-7900408"},"interactantTwo":{"uniProtKBAccession":"Q96IW7","geneName":"SEC22A","intActId":"EBI-8652744"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17643","intActId":"EBI-7900408"},"interactantTwo":{"uniProtKBAccession":"Q07157","geneName":"TJP1","intActId":"EBI-79553"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17643","intActId":"EBI-7900408"},"interactantTwo":{"uniProtKBAccession":"Q9P202","geneName":"WHRN","intActId":"EBI-310886"},"numberOfExperiments":2,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P07147"}],"value":"Located to mature stage III and IV melanosomes and apposed endosomal tubular membranes. Transported to pigmented melanosomes by the BLOC-1 complex. Proper trafficking to melanosome is regulated by SGSM2, ANKRD27, RAB9A, RAB32 and RAB38"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P07147"}],"value":"Melanosome membrane","id":"SL-0160"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P07147"}],"value":"Single-pass type I membrane protein","id":"SL-9905"}}]},{"texts":[{"value":"Pigment cells"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P07147"}],"value":"Glycosylated"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22556244"}],"value":"Genetic variants in TYRP1 define the skin/hair/eye pigmentation variation locus 11 (SHEP11) [MIM:612271] and are responsible for variability in hair color linked to chromosome 9p23 in Melanesians. Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification"}],"commentType":"POLYMORPHISM"},{"commentType":"DISEASE","disease":{"diseaseId":"Albinism, oculocutaneous, 3","diseaseAccession":"DI-02090","acronym":"OCA3","description":"An autosomal recessive disorder in which the biosynthesis of melanin pigment is reduced in skin, hair, and eyes. Tyrosinase activity is normal and patients have only moderate reduction of pigment. The eyes present red reflex on transillumination of the iris, dilution of color of iris, nystagmus and strabismus. Darker-skinned individuals have bright copper-red coloration of the skin and hair.","diseaseCrossReference":{"database":"MIM","id":"203290"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16704458"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23504663"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the tyrosinase family"}],"commentType":"SIMILARITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28661582"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9758418"}],"value":"The precise function of this protein in melanin biosynthesis is still under debate. DHICA oxidase activity is controversial (PubMed:28661582, PubMed:9758418). Lacks DHICA oxidase activity (PubMed:9758418). Has DHICA oxidase activity in the presence of Cu(2+), but lacks DHICA oxidase activity with Zn(2+) (PubMed:28661582)"}],"commentType":"CAUTION"},{"commentType":"WEB RESOURCE","resourceName":"Albinism database (ADB)","resourceUrl":"http://www.ifpcs.org/albinism/oca3mut.html","ftp":false,"note":"TYRP1 mutations"}],"features":[{"type":"Signal","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":24,"modifier":"EXACT"}},"description":""},{"type":"Chain","location":{"start":{"value":25,"modifier":"EXACT"},"end":{"value":537,"modifier":"EXACT"}},"description":"5,6-dihydroxyindole-2-carboxylic acid oxidase","featureId":"PRO_0000035889"},{"type":"Topological domain","location":{"start":{"value":25,"modifier":"EXACT"},"end":{"value":477,"modifier":"EXACT"}},"description":"Lumenal, 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