ID TYRO_HUMAN Reviewed; 529 AA. AC P14679; Q15675; Q15676; Q15680; Q8TAK4; Q9BYY0; Q9BZX1; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1993, sequence version 3. DT 27-MAR-2024, entry version 237. DE RecName: Full=Tyrosinase {ECO:0000305}; DE EC=1.14.18.1 {ECO:0000269|PubMed:28661582}; DE AltName: Full=LB24-AB; DE AltName: Full=Monophenol monooxygenase; DE AltName: Full=SK29-AB; DE AltName: Full=Tumor rejection antigen AB; DE Flags: Precursor; GN Name=TYR {ECO:0000312|HGNC:HGNC:12442}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RX PubMed=1903356; DOI=10.1016/0888-7543(91)90409-8; RA Giebel L.B., Strunk K.M., Spritz R.A.; RT "Organization and nucleotide sequences of the human tyrosinase gene and a RT truncated tyrosinase-related segment."; RL Genomics 9:435-445(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=2823263; DOI=10.1073/pnas.84.21.7473; RA Kwon B.S., Haq A.K., Pomerantz S.H., Halaban R.; RT "Isolation and sequence of a cDNA clone for human tyrosinase that maps at RT the mouse c-albino locus."; RL Proc. Natl. Acad. Sci. U.S.A. 84:7473-7477(1987). RN [3] RP ERRATUM OF PUBMED:2823263, AND SEQUENCE REVISION TO 384-398. RA Kwon B.S., Haq A.K., Pomerantz S.H., Halaban R.; RL Proc. Natl. Acad. Sci. U.S.A. 85:6352-6352(1988). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Melanoma; RX PubMed=2499655; DOI=10.1084/jem.169.6.2029; RA Bouchard B., Fuller B.B., Vijayasaradhi S., Houghton A.N.; RT "Induction of pigmentation in mouse fibroblasts by expression of human RT tyrosinase cDNA."; RL J. Exp. Med. 169:2029-2042(1989). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1711223; DOI=10.1073/pnas.88.12.5272; RA Chintamaneni C.D., Halaban R., Kobayashi Y., Witkop C.J., Kwon B.S.; RT "A single base insertion in the putative transmembrane domain of the RT tyrosinase gene as a cause for tyrosinase-negative oculocutaneous RT albinism."; RL Proc. Natl. Acad. Sci. U.S.A. 88:5272-5276(1991). RN [6] RP NUCLEOTIDE SEQUENCE (ISOFORM 1). RC TISSUE=Melanoma, and T-cell; RX PubMed=8340755; DOI=10.1084/jem.178.2.489; RA Brichard V., van Pel A., Woelfel T., Woelfel C., de Plaen E., Lethe B.G., RA Coulie P., Boon T.; RT "The tyrosinase gene codes for an antigen recognized by autologous RT cytolytic T lymphocytes on HLA-A2 melanomas."; RL J. Exp. Med. 178:489-495(1993). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANT TYR-192. RX PubMed=11153699; DOI=10.1034/j.1600-0749.2000.130609.x; RA Martinez-Arias R., Comas D., Andres A., Abello M.-T., Domingo-Roura X., RA Bertranpetit J.; RT "The tyrosinase gene in gorillas and the albinism of 'Snowflake'."; RL Pigment Cell Res. 13:467-470(2000). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Skin; 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 [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-272. RC TISSUE=Liver; RX PubMed=2480811; DOI=10.1016/0167-4781(89)90115-2; RA Kikuchi H., Miura H., Yamamoto H., Takeuchi T., Dei T., Watanabe M.; RT "Characteristic sequences in the upstream region of the human tyrosinase RT gene."; RL Biochim. Biophys. Acta 1009:283-286(1989). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-32. RX PubMed=2504160; DOI=10.1016/0006-291x(89)90770-5; RA Takeda A., Tomita Y., Okinaga S., Tagami H., Shibahara S.; RT "Functional analysis of the cDNA encoding human tyrosinase precursor."; RL Biochem. Biophys. Res. Commun. 162:984-990(1989). RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 54-195, AND VARIANT TYR-192. RX PubMed=11214319; DOI=10.1038/35054550; RA Murphy W.J., Eizirik E., Johnson W.E., Zhang Y.-P., Ryder O.A., RA O'Brien S.J.; RT "Molecular phylogenetics and the origins of placental mammals."; RL Nature 409:614-618(2001). RN [12] RP REVIEW ON OCA VARIANTS. RX PubMed=8477259; DOI=10.1002/humu.1380020102; RA Oetting W.S., King R.A.; RT "Molecular basis of type I (tyrosinase-related) oculocutaneous albinism: RT mutations and polymorphisms of the human tyrosinase gene."; RL Hum. Mutat. 2:1-6(1993). RN [13] RP REVIEW ON OCA1 VARIANTS. RX PubMed=10094567; RX DOI=10.1002/(sici)1098-1004(1999)13:2<99::aid-humu2>3.0.co;2-c; RA Oetting W.S., King R.A.; RT "Molecular basis of albinism: mutations and polymorphisms of pigmentation RT genes associated with albinism."; RL Hum. Mutat. 13:99-115(1999). RN [14] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Melanoma; RX PubMed=12643545; DOI=10.1021/pr025562r; RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J., RA Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F., RA Appella E.; RT "Proteomic analysis of early melanosomes: identification of novel RT melanosomal proteins."; RL J. Proteome Res. 2:69-79(2003). RN [15] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Melanoma; RX PubMed=17081065; DOI=10.1021/pr060363j; RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.; RT "Proteomic and bioinformatic characterization of the biogenesis and RT function of melanosomes."; RL J. Proteome Res. 5:3135-3144(2006). RN [16] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=28661582; DOI=10.1002/anie.201704616; RA Lai X., Wichers H.J., Soler-Lopez M., Dijkstra B.W.; RT "Structure of Human Tyrosinase Related Protein1 Reveals a Binuclear Zinc RT Active Site Important for Melanogenesis."; RL Angew. Chem. Int. Ed. Engl. 56:9812-9815(2017). RN [17] RP INTERACTION WITH DCT. RX PubMed=28842328; DOI=10.1016/j.jid.2017.07.833; RA Regazzetti C., Sormani L., Debayle D., Bernerd F., Tulic M.K., RA De Donatis G.M., Chignon-Sicard B., Rocchi S., Passeron T.; RT "Melanocytes Sense Blue Light and Regulate Pigmentation through Opsin-3."; RL J. Invest. Dermatol. 138:171-178(2018). RN [18] RP VARIANTS OCA1A LYS-373 AND ASN-383, AND VARIANTS TYR-192 AND GLN-402. RX PubMed=2342539; DOI=10.1056/nejm199006143222407; RA Spritz R.A., Strunk K.M., Giebel L.B., King R.A.; RT "Detection of mutations in the tyrosinase gene in a patient with type IA RT oculocutaneous albinism."; RL N. Engl. J. Med. 322:1724-1728(1990). RN [19] RP VARIANT OCA1A LEU-81. RX PubMed=1970634; DOI=10.1073/pnas.87.9.3255; RA Giebel L.B., Strunk K.M., King R.A., Hanifin J.M., Spritz R.A.; RT "A frequent tyrosinase gene mutation in classic, tyrosinase-negative (type RT IA) oculocutaneous albinism."; RL Proc. Natl. Acad. Sci. U.S.A. 87:3255-3258(1990). RN [20] RP VARIANTS OCA1B PHE-275 AND LEU-406. RX PubMed=1903591; RA Giebel L.B., Tripathi R.K., Strunk K.M., Hanifin J.M., Jackson C.E., RA King R.A., Spritz R.A.; RT "Tyrosinase gene mutations associated with type IB ('yellow') RT oculocutaneous albinism."; RL Am. J. Hum. Genet. 48:1159-1167(1991). RN [21] RP ERRATUM OF PUBMED:1903591. RA Giebel L.B., Tripathi R.K., Strunk K.M., Hanifin J.M., Jackson C.E., RA King R.A., Spritz R.A.; RL Am. J. Hum. Genet. 49:696-696(1991). RN [22] RP VARIANTS OCA1A SER-21; TRP-217; HIS-299; SER-403; SER-446 AND ASN-448. RX PubMed=1642278; DOI=10.1002/ajmg.1320430523; RA Tripathi R.K., Strunk K.M., Giebel L.B., Weleber R.G., Spritz R.A.; RT "Tyrosinase gene mutations in type I (tyrosinase-deficient) oculocutaneous RT albinism define two clusters of missense substitutions."; RL Am. J. Med. Genet. 43:865-871(1992). RN [23] RP VARIANT OCA1A ARG-89. RX PubMed=1899321; RA Spritz R.A., Strunk K.M., Hsieh C.-L., Sekhon G.S., Francke U.; RT "Homozygous tyrosinase gene mutation in an American black with tyrosinase- RT negative (type IA) oculocutaneous albinism."; RL Am. J. Hum. Genet. 48:318-324(1991). RN [24] RP VARIANT OCA1B GLN-422. RX PubMed=1900309; DOI=10.1172/jci115075; RA Giebel L.B., Tripathi R.K., King R.A., Spritz R.A.; RT "A tyrosinase gene missense mutation in temperature-sensitive type I RT oculocutaneous albinism. A human homologue to the Siamese cat and the RT Himalayan mouse."; RL J. Clin. Invest. 87:1119-1122(1991). RN [25] RP VARIANTS OCA1A GLY-42; TYR-55; THR-206 AND ARG-419. RX PubMed=1943686; RA King R.A., Mentink M.M., Oetting W.S.; RT "Non-random distribution of missense mutations within the human tyrosinase RT gene in type I (tyrosinase-related) oculocutaneous albinism."; RL Mol. Biol. Med. 8:19-29(1991). RN [26] RP VARIANTS OCA1A ILE-176 AND GLN-217. RX PubMed=1487241; DOI=10.1007/bf00220074; RA Oetting W.S., King R.A.; RT "Molecular analysis of type I-A (tyrosinase negative) oculocutaneous RT albinism."; RL Hum. Genet. 90:258-262(1992). RN [27] RP VARIANTS OCA1A GLN-328; ARG-419 AND LEU-431. RX PubMed=7902671; RA Tripathi R.K., Bundey S., Musarella M.A., Droetto S., Strunk K.M., RA Holmes S.A., Spritz R.A.; RT "Mutations of the tyrosinase gene in Indo-Pakistani patients with type I RT (tyrosinase-deficient) oculocutaneous albinism (OCA)."; RL Am. J. Hum. Genet. 53:1173-1179(1993). RN [28] RP VARIANTS OCA1A ASP-47; CYS-217 DEL; HIS-299 AND LYS-373, AND VARIANTS OCA1B RP SER-152 AND LYS-294. RX PubMed=8128955; RA Gershoni-Baruch R., Rosenmann A., Droetto S., Holmes S.A., Tripathi R.K., RA Spritz R.A.; RT "Mutations of the tyrosinase gene in patients with oculocutaneous albinism RT from various ethnic groups in Israel."; RL Am. J. Hum. Genet. 54:586-594(1994). RN [29] RP VARIANTS OCA1A TYR-367; THR-370 AND LYS-373, AND VARIANT GLN-402. RX PubMed=7955413; DOI=10.1016/0009-8981(94)90131-7; RA Breimer L.H., Winder A.F., Jay B., Jay M.; RT "Initiation codon mutation of the tyrosinase gene as a cause of human RT albinism."; RL Clin. Chim. Acta 227:17-22(1994). RN [30] RP VARIANTS OCA1A ARG-361 AND TYR-371. RX PubMed=8644824; DOI=10.1016/s0002-9394(14)70647-6; RA Summers C.G., Oetting W.S., King R.A.; RT "Diagnosis of oculocutaneous albinism with molecular analysis."; RL Am. J. Ophthalmol. 121:724-726(1996). RN [31] RP VARIANT GLN-402. RX PubMed=9158138; DOI=10.1093/hmg/6.5.659; RA Morell R., Spritz R.A., Ho L., Pierpont J., Guo W., Friedman T.B., RA Asher J.H. Jr.; RT "Apparent digenic inheritance of Waardenburg syndrome type 2 (WS2) and RT autosomal recessive ocular albinism (AROA)."; RL Hum. Mol. Genet. 6:659-664(1997). RN [32] RP VARIANTS OCA1A AND OCA1B. RX PubMed=9259202; RX DOI=10.1002/(sici)1098-1004(1997)10:2<171::aid-humu11>3.0.co;2-x; RA Spritz R.A., Oh J., Fukai K., Holmes S.A., Ho L., Chitayat D., France T.D., RA Musarella M.A., Orlow S.J., Schnur R.E., Weleber R.G., Levin A.V.; RT "Novel mutations of the tyrosinase (TYR) gene in type I oculocutaneous RT albinism (OCA1)."; RL Hum. Mutat. 10:171-174(1997). RN [33] RP VARIANTS OCA1A AND OCA1B. RX PubMed=10671066; RX DOI=10.1002/(sici)1098-1004(1998)12:6<433::aid-humu14>3.0.co;2-g; RA Oetting W.S., Fryer J.P., King R.A.; RT "Mutations of the human tyrosinase gene associated with tyrosinase related RT oculocutaneous albinism (OCA1)."; RL Hum. Mutat. 12:433-434(1998). RN [34] RP ERRATUM OF PUBMED:10671066. RA Oetting W.S., Fryer J.P., King R.A.; RL Hum. Mutat. 13:83-83(1999). RN [35] RP VARIANTS OCA1A TYR-36; GLN-77; TRP-77; LEU-81; ARG-97; GLN-217; TRP-217; RP SER-236; CYS-272; ARG-289; GLY-294; LYS-294; PRO-355; TYR-371; LYS-373; RP LEU-406; ARG-419; GLN-422; VAL-439; SER-446 AND ASN-448, VARIANT OCA1B RP SER-403, AND VARIANTS TYR-192 AND GLN-402. RX PubMed=10987646; DOI=10.1007/s004390051090; RA Passmore L.A., Kaesmann-Kellner B., Weber B.H.F.; RT "Novel and recurrent mutations in the tyrosinase gene and the P gene in the RT German albino population."; RL Hum. Genet. 105:200-210(1999). RN [36] RP ERRATUM OF PUBMED:10987646. RA Passmore L.A., Kaesmann-Kellner B., Weber B.H.F.; RL Hum. Genet. 108:208-208(2001). RN [37] RP VARIANTS OCA1A TYR-55; ARG-77 INS; GLY-289; HIS-299; SER-299 AND LEU-400. RX PubMed=10571953; RX DOI=10.1002/(sici)1098-1004(199912)14:6<542::aid-humu14>3.0.co;2-3; RA Tsai C.-H., Tsai F.-J., Wu J.-Y., Lin S.-P., Chang J.-G., Yang C.-F., RA Lee C.-C.; RT "Insertion/deletion mutations of type I oculocutaneous albinism in Chinese RT patients from Taiwan."; RL Hum. Mutat. 14:542-542(1999). RN [38] RP VARIANTS OCA1A ASP-47; GLN-77; ARG-109; THR-205; TYR-256; PHE-275; LYS-294; RP GLY-339; PRO-355; LYS-373; ASN-383 AND SER-446. RX PubMed=11295837; DOI=10.1002/humu.38; RA Camand O., Marchant D., Boutboul S., Pequignot M., Odent S., Dollfus H., RA Sutherland J., Levin A., Menasche M., Marsac C., Dufier J.-L., Heon E., RA Abitbol M.; RT "Mutation analysis of the tyrosinase gene in oculocutaneous albinism."; RL Hum. Mutat. 17:352-352(2001). RN [39] RP VARIANT OCA1A TRP-239. RX PubMed=11858948; DOI=10.1016/s0923-1811(01)00141-4; RA Nakamura E., Miyamura Y., Matsunaga J., Kano Y., Dakeishi-Hara M., RA Tanita M., Kono M., Tomita Y.; RT "A novel mutation of the tyrosinase gene causing oculocutaneous albinism RT type 1 (OCA1)."; RL J. Dermatol. Sci. 28:102-105(2002). RN [40] RP VARIANTS OCA1A ARG-44; GLY-44; ASP-47; VAL-47; HIS-68; GLN-77; LEU-79; RP LEU-81; SER-155; PHE-177; LEU-179; ASN-180; ASN-199; SER-201; SER-217; RP LEU-236; VAL-240; THR-243; TYR-256; ARG-289; GLU-318; PRO-329; THR-332; RP GLY-345; PRO-355; LYS-373; LYS-378; ASN-383; PHE-393; ARG-395; VAL-398; RP ALA-398; LEU-402; SER-403; ASN-404; LEU-405; LEU-406; HIS-408; ASP-409; RP SER-416; HIS-417; ARG-419; GLN-422; PHE-424; LYS-426; GLY-427; ILE-434; RP ASP-435; GLY-444 AND ASN-448, AND VARIANTS TYR-192 AND GLN-402. RX PubMed=15146472; DOI=10.1002/humu.9248; RA Opitz S., Kaesmann-Kellner B., Kaufmann M., Schwinger E., Zuehlke C.; RT "Detection of 53 novel DNA variations within the tyrosinase gene and RT accumulation of mutations in 17 patients with albinism."; RL Hum. Mutat. 23:630-631(2004). RN [41] RP VARIANT TYR-192, AND ASSOCIATION WITH SHEP3. RX PubMed=17999355; DOI=10.1086/522235; RA Stokowski R.P., Pant P.V.K., Dadd T., Fereday A., Hinds D.A., Jarman C., RA Filsell W., Ginger R.S., Green M.R., van der Ouderaa F.J., Cox D.R.; RT "A genomewide association study of skin pigmentation in a South Asian RT population."; RL Am. J. Hum. Genet. 81:1119-1132(2007). RN [42] RP VARIANT TYR-192, AND ASSOCIATION WITH SHEP3. RX PubMed=17952075; DOI=10.1038/ng.2007.13; RA Sulem P., Gudbjartsson D.F., Stacey S.N., Helgason A., Rafnar T., RA Magnusson K.P., Manolescu A., Karason A., Palsson A., Thorleifsson G., RA Jakobsdottir M., Steinberg S., Palsson S., Jonasson F., Sigurgeirsson B., RA Thorisdottir K., Ragnarsson R., Benediktsdottir K.R., Aben K.K., RA Kiemeney L.A., Olafsson J.H., Gulcher J., Kong A., Thorsteinsdottir U., RA Stefansson K.; RT "Genetic determinants of hair, eye and skin pigmentation in Europeans."; RL Nat. Genet. 39:1443-1452(2007). RN [43] RP VARIANT OCA1A TYR-91. RX PubMed=22981120; DOI=10.1016/j.ajhg.2012.08.007; RA Chong J.X., Ouwenga R., Anderson R.L., Waggoner D.J., Ober C.; RT "A population-based study of autosomal-recessive disease-causing mutations RT in a founder population."; RL Am. J. Hum. Genet. 91:608-620(2012). RN [44] RP VARIANTS OCA1A LEU-50; TRP-77; PHE-275; TRP-298; VAL-355; HIS-364; LYS-373; RP ALA-384 AND ASP-490. RX PubMed=23504663; DOI=10.1002/humu.22315; RA Simeonov D.R., Wang X., Wang C., Sergeev Y., Dolinska M., Bower M., RA Fischer R., Winer D., Dubrovsky G., Balog J.Z., Huizing M., Hart R., RA Zein W.M., Gahl W.A., Brooks B.P., Adams D.R.; RT "DNA variations in oculocutaneous albinism: an updated mutation list and RT current outstanding issues in molecular diagnostics."; RL Hum. Mutat. 34:827-835(2013). RN [45] RP VARIANT OCA1A THR-198. RX PubMed=24934919; DOI=10.1111/ced.12382; RA Shah S.A., Din S.U., Raheem N., Daud S., Mubeen J., Nadeem A., Tayyab M., RA Baloch D.M., Babar M.E., Ahmad J.; RT "Identification of a novel mutation (p.Ile198Thr) in gene TYR in a RT Pakistani family with nonsyndromic oculocutaneous albinism."; RL Clin. Exp. Dermatol. 39:646-648(2014). CC -!- FUNCTION: This is a copper-containing oxidase that functions in the CC formation of pigments such as melanins and other polyphenolic CC compounds. Catalyzes the initial and rate limiting step in the cascade CC of reactions leading to melanin production from tyrosine (By CC similarity). In addition to hydroxylating tyrosine to DOPA (3,4- CC dihydroxyphenylalanine), also catalyzes the oxidation of DOPA to DOPA- CC quinone, and possibly the oxidation of DHI (5,6-dihydroxyindole) to CC indole-5,6 quinone (PubMed:28661582). {ECO:0000250|UniProtKB:P11344, CC ECO:0000269|PubMed:28661582}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2 L-dopa + O2 = 2 H2O + 2 L-dopaquinone; Xref=Rhea:RHEA:34287, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:57504, CC ChEBI:CHEBI:57924; EC=1.14.18.1; CC Evidence={ECO:0000269|PubMed:28661582}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34288; CC Evidence={ECO:0000305|PubMed:28661582}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-tyrosine + O2 = H2O + L-dopaquinone; Xref=Rhea:RHEA:18117, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:57924, CC ChEBI:CHEBI:58315; EC=1.14.18.1; CC Evidence={ECO:0000269|PubMed:28661582}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18118; CC Evidence={ECO:0000305|PubMed:28661582}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 5,6-dihydroxyindole-2-carboxylate + O2 = 2 H2O + 2 CC indole-5,6-quinone-2-carboxylate; Xref=Rhea:RHEA:68388, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16875, CC ChEBI:CHEBI:177869; Evidence={ECO:0000269|PubMed:28661582}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68389; CC Evidence={ECO:0000305|PubMed:28661582}; CC -!- COFACTOR: CC Name=Cu(2+); Xref=ChEBI:CHEBI:29036; CC Evidence={ECO:0000250|UniProtKB:Q9ZP19}; CC Note=Binds 2 copper ions per subunit. {ECO:0000250|UniProtKB:Q9ZP19}; CC -!- SUBUNIT: Forms an OPN3-dependent complex with DCT in response to blue CC light in melanocytes. {ECO:0000269|PubMed:28842328}. CC -!- INTERACTION: CC P14679; P51810: GPR143; NbExp=4; IntAct=EBI-25397340, EBI-2509708; CC P14679-2; Q14457: BECN1; NbExp=3; IntAct=EBI-25894402, EBI-949378; CC P14679-2; P26641: EEF1G; NbExp=3; IntAct=EBI-25894402, EBI-351467; CC P14679-2; Q8WTV1: THAP3; NbExp=3; IntAct=EBI-25894402, EBI-17438286; CC P14679-2; Q6ZMY6-2: WDR88; NbExp=3; IntAct=EBI-25894402, EBI-25857007; CC -!- SUBCELLULAR LOCATION: Melanosome membrane {ECO:0000269|PubMed:12643545, CC ECO:0000269|PubMed:17081065}; Single-pass type I membrane protein CC {ECO:0000269|PubMed:12643545, ECO:0000269|PubMed:17081065}. Melanosome CC {ECO:0000250|UniProtKB:P11344}. Note=Proper trafficking to melanosome CC is regulated by SGSM2, ANKRD27, RAB9A, RAB32 and RAB38. CC {ECO:0000250|UniProtKB:P11344}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P14679-1; Sequence=Displayed; CC Name=2; CC IsoId=P14679-2; Sequence=VSP_006701, VSP_006702; CC -!- INDUCTION: Increased expression after UVB irradiation. CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:P11344}. CC -!- POLYMORPHISM: Genetic variants in TYR define the skin/hair/eye CC pigmentation variation locus 3 (SHEP3) [MIM:601800]. Hair, eye and skin CC pigmentation are among the most visible examples of human phenotypic CC variation, with a broad normal range that is subject to substantial CC geographic stratification. In the case of skin, individuals tend to CC have lighter pigmentation with increasing distance from the equator. By CC contrast, the majority of variation in human eye and hair color is CC found among individuals of European ancestry, with most other human CC populations fixed for brown eyes and black hair. CC {ECO:0000269|PubMed:17952075, ECO:0000269|PubMed:17999355}. CC -!- POLYMORPHISM: Compound heterozygosity for the R402Q polymorphism and a CC mutant allele of TYR is a common cause of autosomal recessive ocular CC albinism. The R402Q polymorphism is also found in Waardenburg syndrome CC type II with ocular albinism in association with a deletion in the MITF CC gene. {ECO:0000269|PubMed:2342539, ECO:0000269|PubMed:7955413, CC ECO:0000269|PubMed:9158138}. CC -!- DISEASE: Albinism, oculocutaneous, 1A (OCA1A) [MIM:203100]: An CC autosomal recessive disorder in which the biosynthesis of melanin CC pigment is absent in skin, hair, and eyes. It is characterized by CC complete lack of tyrosinase activity due to production of an inactive CC enzyme. Patients present with a life-long absence of melanin pigment CC after birth, and manifest increased sensitivity to ultraviolet CC radiation with predisposition to skin cancer. Visual anomalies include CC decreased acuity, nystagmus, strabismus and photophobia. CC {ECO:0000269|PubMed:10571953, ECO:0000269|PubMed:10671066, CC ECO:0000269|PubMed:10987646, ECO:0000269|PubMed:11295837, CC ECO:0000269|PubMed:11858948, ECO:0000269|PubMed:1487241, CC ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:1642278, CC ECO:0000269|PubMed:1899321, ECO:0000269|PubMed:1943686, CC ECO:0000269|PubMed:1970634, ECO:0000269|PubMed:22981120, CC ECO:0000269|PubMed:2342539, ECO:0000269|PubMed:23504663, CC ECO:0000269|PubMed:24934919, ECO:0000269|PubMed:7902671, CC ECO:0000269|PubMed:7955413, ECO:0000269|PubMed:8128955, CC ECO:0000269|PubMed:8644824, ECO:0000269|PubMed:9259202}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Albinism, oculocutaneous, 1B (OCA1B) [MIM:606952]: An CC autosomal recessive disorder in which the biosynthesis of melanin CC pigment is reduced in skin, hair, and eyes. It is characterized by CC partial lack of tyrosinase activity. Patients have white hair at birth CC that rapidly turns yellow or blond. They manifest the development of CC minimal-to-moderate amounts of cutaneous and ocular pigment. Some CC patients may have with white hair in the warmer areas (scalp and CC axilla) and progressively darker hair in the cooler areas CC (extremities). This variant phenotype is due to a loss of tyrosinase CC activity above 35-37 degrees C. {ECO:0000269|PubMed:10987646, CC ECO:0000269|PubMed:1900309, ECO:0000269|PubMed:1903591, CC ECO:0000269|PubMed:8128955}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the tyrosinase family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA61241.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAA68756.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Mutations of the TYR gene; Note=Retina CC International's Scientific Newsletter; CC URL="https://www.retina-international.org/files/sci-news/tyrmut.htm"; CC -!- WEB RESOURCE: Name=Albinism database (ADB); Note=TYR mutations; CC URL="http://www.ifpcs.org/albinism/oca1mut.html"; CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Snowy stardom - Issue 49 of CC August 2004; CC URL="https://web.expasy.org/spotlight/back_issues/049"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Tyrosinase entry; CC URL="https://en.wikipedia.org/wiki/Tyrosinase"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/42738/TYR"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M27160; AAB37227.1; -; mRNA. DR EMBL; M63239; AAA61242.1; -; Genomic_DNA. DR EMBL; M63235; AAA61242.1; JOINED; Genomic_DNA. DR EMBL; M63236; AAA61242.1; JOINED; Genomic_DNA. DR EMBL; M63237; AAA61242.1; JOINED; Genomic_DNA. DR EMBL; M63238; AAA61242.1; JOINED; Genomic_DNA. DR EMBL; J03581; AAA61241.1; ALT_INIT; mRNA. DR EMBL; Y00819; CAA68756.1; ALT_INIT; mRNA. DR EMBL; U01873; AAB60319.1; ALT_SEQ; mRNA. DR EMBL; M74314; AAA61244.1; -; mRNA. DR EMBL; X16073; CAA34205.1; -; Genomic_DNA. DR EMBL; AF237811; AAK00805.1; -; Genomic_DNA. DR EMBL; AF237807; AAK00805.1; JOINED; Genomic_DNA. DR EMBL; AF237808; AAK00805.1; JOINED; Genomic_DNA. DR EMBL; AF237809; AAK00805.1; JOINED; Genomic_DNA. DR EMBL; AF237810; AAK00805.1; JOINED; Genomic_DNA. DR EMBL; BC027179; AAH27179.1; -; mRNA. DR EMBL; AY012019; AAG38762.1; -; Genomic_DNA. DR CCDS; CCDS8284.1; -. [P14679-1] DR PIR; A38444; YRHU1. DR RefSeq; NP_000363.1; NM_000372.4. [P14679-1] DR PDB; 7RK7; X-ray; 2.54 A; C=369-377. DR PDBsum; 7RK7; -. DR AlphaFoldDB; P14679; -. DR SMR; P14679; -. DR BioGRID; 113150; 4. DR IntAct; P14679; 5. DR STRING; 9606.ENSP00000263321; -. DR BindingDB; P14679; -. DR ChEMBL; CHEMBL1973; -. DR DrugBank; DB11217; Arbutin. DR DrugBank; DB00548; Azelaic acid. DR DrugBank; DB09130; Copper. DR DrugBank; DB11254; Hexylresorcinol. DR DrugBank; DB09526; Hydroquinone. DR DrugBank; DB01055; Mimosine. DR DrugBank; DB00600; Monobenzone. DR DrugBank; DB00157; NADH. DR DrugCentral; P14679; -. DR TCDB; 9.B.423.1.1; the tysrosinase (tyr) family. DR GlyCosmos; P14679; 6 sites, No reported glycans. DR GlyGen; P14679; 7 sites. DR iPTMnet; P14679; -. DR PhosphoSitePlus; P14679; -. DR SwissPalm; P14679; -. DR BioMuta; TYR; -. DR DMDM; 401235; -. DR MassIVE; P14679; -. DR PaxDb; 9606-ENSP00000263321; -. DR PeptideAtlas; P14679; -. DR ProteomicsDB; 53077; -. [P14679-1] DR ProteomicsDB; 53078; -. [P14679-2] DR ABCD; P14679; 3 sequenced antibodies. DR Antibodypedia; 3663; 982 antibodies from 38 providers. DR DNASU; 7299; -. DR Ensembl; ENST00000263321.6; ENSP00000263321.4; ENSG00000077498.9. [P14679-1] DR GeneID; 7299; -. DR KEGG; hsa:7299; -. DR MANE-Select; ENST00000263321.6; ENSP00000263321.4; NM_000372.5; NP_000363.1. DR UCSC; uc001pcs.4; human. [P14679-1] DR AGR; HGNC:12442; -. DR CTD; 7299; -. DR DisGeNET; 7299; -. DR GeneCards; TYR; -. DR HGNC; HGNC:12442; TYR. DR HPA; ENSG00000077498; Tissue enriched (skin). DR MalaCards; TYR; -. DR MIM; 203100; phenotype. DR MIM; 601800; phenotype. DR MIM; 606933; gene. DR MIM; 606952; phenotype. DR neXtProt; NX_P14679; -. DR OpenTargets; ENSG00000077498; -. DR Orphanet; 352734; Minimal pigment oculocutaneous albinism type 1. DR Orphanet; 79431; Oculocutaneous albinism type 1A. DR Orphanet; 79434; Oculocutaneous albinism type 1B. DR Orphanet; 352737; Temperature-sensitive oculocutaneous albinism type 1. DR Orphanet; 895; Waardenburg syndrome type 2. DR PharmGKB; PA37095; -. DR VEuPathDB; HostDB:ENSG00000077498; -. DR eggNOG; ENOG502QRET; Eukaryota. DR GeneTree; ENSGT00940000155336; -. DR HOGENOM; CLU_038693_1_0_1; -. DR InParanoid; P14679; -. DR OMA; MEAEDYQ; -. DR OrthoDB; 70287at2759; -. DR PhylomeDB; P14679; -. DR TreeFam; TF315865; -. DR BioCyc; MetaCyc:HS01248-MONOMER; -. DR BRENDA; 1.14.18.1; 2681. DR PathwayCommons; P14679; -. DR Reactome; R-HSA-5662702; Melanin biosynthesis. DR SABIO-RK; P14679; -. DR SignaLink; P14679; -. DR SIGNOR; P14679; -. DR BioGRID-ORCS; 7299; 10 hits in 1155 CRISPR screens. DR ChiTaRS; TYR; human. DR GeneWiki; Tyrosinase; -. DR GenomeRNAi; 7299; -. DR Pharos; P14679; Tclin. DR PRO; PR:P14679; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P14679; Protein. DR Bgee; ENSG00000077498; Expressed in pigmented layer of retina and 43 other cell types or tissues. DR ExpressionAtlas; P14679; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005798; C:Golgi-associated vesicle; TAS:ProtInc. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005764; C:lysosome; TAS:UniProtKB. DR GO; GO:0042470; C:melanosome; ISS:UniProtKB. DR GO; GO:0033162; C:melanosome membrane; TAS:Reactome. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0005507; F:copper ion binding; IMP:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. DR GO; GO:0004503; F:tyrosinase activity; IDA:UniProtKB. DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl. DR GO; GO:0006726; P:eye pigment biosynthetic process; TAS:ProtInc. DR GO; GO:0042438; P:melanin biosynthetic process; IDA:CACAO. DR GO; GO:0006583; P:melanin biosynthetic process from tyrosine; TAS:ProtInc. DR GO; GO:0043473; P:pigmentation; IBA:GO_Central. DR GO; GO:0009637; P:response to blue light; IDA:UniProtKB. DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl. DR GO; GO:0009411; P:response to UV; IEA:Ensembl. DR GO; GO:0033280; P:response to vitamin D; IEA:Ensembl. DR GO; GO:0048538; P:thymus development; IEA:Ensembl. DR GO; GO:0007601; P:visual perception; TAS:ProtInc. DR Gene3D; 1.10.1280.10; Di-copper center containing domain from catechol oxidase; 1. DR InterPro; IPR008922; Di-copper_centre_dom_sf. DR InterPro; IPR002227; Tyrosinase_Cu-bd. DR PANTHER; PTHR11474:SF124; TYROSINASE; 1. DR PANTHER; PTHR11474; TYROSINASE FAMILY MEMBER; 1. DR Pfam; PF00264; Tyrosinase; 1. DR PRINTS; PR00092; TYROSINASE. DR SUPFAM; SSF48056; Di-copper centre-containing domain; 1. DR PROSITE; PS00497; TYROSINASE_1; 1. DR PROSITE; PS00498; TYROSINASE_2; 1. DR Genevisible; P14679; HS. PE 1: Evidence at protein level; KW 3D-structure; Albinism; Alternative splicing; Copper; Deafness; KW Disease variant; Glycoprotein; Melanin biosynthesis; Membrane; KW Metal-binding; Monooxygenase; Oxidoreductase; Reference proteome; Signal; KW Transmembrane; Transmembrane helix; Tumor antigen; Waardenburg syndrome. FT SIGNAL 1..18 FT /evidence="ECO:0000255" FT CHAIN 19..529 FT /note="Tyrosinase" FT /id="PRO_0000035879" FT TOPO_DOM 19..476 FT /note="Lumenal, melanosome" FT /evidence="ECO:0000255" FT TRANSMEM 477..497 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 498..529 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 287..313 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 180 FT /ligand="Cu cation" FT /ligand_id="ChEBI:CHEBI:23378" FT /ligand_label="A" FT /evidence="ECO:0000250|UniProtKB:Q9ZP19" FT BINDING 202 FT /ligand="Cu cation" FT /ligand_id="ChEBI:CHEBI:23378" FT /ligand_label="A" FT /evidence="ECO:0000250|UniProtKB:Q9ZP19" FT BINDING 211 FT /ligand="Cu cation" FT /ligand_id="ChEBI:CHEBI:23378" FT /ligand_label="A" FT /evidence="ECO:0000250|UniProtKB:Q9ZP19" FT BINDING 363 FT /ligand="Cu cation" FT /ligand_id="ChEBI:CHEBI:23378" FT /ligand_label="B" FT /evidence="ECO:0000250|UniProtKB:Q9ZP19" FT BINDING 367 FT /ligand="Cu cation" FT /ligand_id="ChEBI:CHEBI:23378" FT /ligand_label="B" FT /evidence="ECO:0000250|UniProtKB:Q9ZP19" FT BINDING 390 FT /ligand="Cu cation" FT /ligand_id="ChEBI:CHEBI:23378" FT /ligand_label="B" FT /evidence="ECO:0000250|UniProtKB:Q9ZP19" FT CARBOHYD 86 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 111 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 161 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 230 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 337 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 371 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 346..377 FT /note="GFASPLTGIADASQSSMHNALHIYMNGTMSQV -> EMGFLHVGWAGLKLLT FT SRDPPPWPPKMLGLQA (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_006701" FT VAR_SEQ 378..529 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_006702" FT VARIANT 19 FT /note="H -> Q (in OCA1A; dbSNP:rs61753177)" FT /id="VAR_007649" FT VARIANT 21 FT /note="P -> S (in OCA1A; dbSNP:rs61753178)" FT /evidence="ECO:0000269|PubMed:1642278" FT /id="VAR_007650" FT VARIANT 36 FT /note="C -> Y (in OCA1A; dbSNP:rs61753179)" FT /evidence="ECO:0000269|PubMed:10987646" FT /id="VAR_021683" FT VARIANT 42 FT /note="D -> G (in OCA1A; dbSNP:rs28940878)" FT /evidence="ECO:0000269|PubMed:1943686" FT /id="VAR_007651" FT VARIANT 44 FT /note="S -> G (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021684" FT VARIANT 44 FT /note="S -> R (in OCA1A; dbSNP:rs755700581)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021685" FT VARIANT 47 FT /note="G -> D (in OCA1A; dbSNP:rs61753180)" FT /evidence="ECO:0000269|PubMed:11295837, FT ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:8128955" FT /id="VAR_007652" FT VARIANT 47 FT /note="G -> V (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021686" FT VARIANT 50 FT /note="S -> L (in OCA1A; dbSNP:rs61753181)" FT /evidence="ECO:0000269|PubMed:23504663" FT /id="VAR_072592" FT VARIANT 52 FT /note="R -> I (in OCA1; dbSNP:rs61753182)" FT /id="VAR_007653" FT VARIANT 55 FT /note="C -> Y (in OCA1A; dbSNP:rs28940879)" FT /evidence="ECO:0000269|PubMed:10571953, FT ECO:0000269|PubMed:1943686" FT /id="VAR_007654" FT VARIANT 68 FT /note="Q -> H (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021687" FT VARIANT 77 FT /note="R -> Q (in OCA1A; dbSNP:rs61753185)" FT /evidence="ECO:0000269|PubMed:10987646, FT ECO:0000269|PubMed:11295837, ECO:0000269|PubMed:15146472" FT /id="VAR_007655" FT VARIANT 77 FT /note="R -> RR (in OCA1A)" FT /evidence="ECO:0000269|PubMed:10571953" FT /id="VAR_009236" FT VARIANT 77 FT /note="R -> W (in OCA1A; dbSNP:rs61753184)" FT /evidence="ECO:0000269|PubMed:10987646, FT ECO:0000269|PubMed:23504663" FT /id="VAR_007656" FT VARIANT 79 FT /note="S -> L (in OCA1A; dbSNP:rs544053015)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021688" FT VARIANT 80 FT /note="W -> R (in OCA1A; dbSNP:rs61753188)" FT /id="VAR_007657" FT VARIANT 81 FT /note="P -> L (in OCA1A; dbSNP:rs28940876)" FT /evidence="ECO:0000269|PubMed:10987646, FT ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:1970634" FT /id="VAR_007658" FT VARIANT 89 FT /note="C -> R (in OCA1A; dbSNP:rs28940877)" FT /evidence="ECO:0000269|PubMed:1899321" FT /id="VAR_007659" FT VARIANT 91 FT /note="C -> Y (in OCA1A; dbSNP:rs137854890)" FT /evidence="ECO:0000269|PubMed:22981120" FT /id="VAR_072593" FT VARIANT 97 FT /note="G -> R (in OCA1A; dbSNP:rs61753252)" FT /evidence="ECO:0000269|PubMed:10987646" FT /id="VAR_007660" FT VARIANT 109 FT /note="G -> R (in OCA1A; dbSNP:rs61753253)" FT /evidence="ECO:0000269|PubMed:11295837" FT /id="VAR_021689" FT VARIANT 134 FT /note="F -> C (in dbSNP:rs33955261)" FT /id="VAR_034576" FT VARIANT 142 FT /note="K -> N (in dbSNP:rs11545463)" FT /id="VAR_042665" FT VARIANT 152 FT /note="P -> S (in OCA1B; dbSNP:rs145513733)" FT /evidence="ECO:0000269|PubMed:8128955" FT /id="VAR_007925" FT VARIANT 155 FT /note="T -> S (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021690" FT VARIANT 176 FT /note="F -> I (in OCA1A; dbSNP:rs61753259)" FT /evidence="ECO:0000269|PubMed:1487241" FT /id="VAR_007661" FT VARIANT 177 FT /note="V -> F (in OCA1A; dbSNP:rs138487695)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021691" FT VARIANT 179 FT /note="M -> L (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021692" FT VARIANT 180 FT /note="H -> N (in OCA1A; dbSNP:rs779878377)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021693" FT VARIANT 192 FT /note="S -> Y (associated with SHEP3; light/dark skin; FT dbSNP:rs1042602)" FT /evidence="ECO:0000269|PubMed:10987646, FT ECO:0000269|PubMed:11153699, ECO:0000269|PubMed:11214319, FT ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:17952075, FT ECO:0000269|PubMed:17999355, ECO:0000269|PubMed:2342539" FT /id="VAR_007662" FT VARIANT 198 FT /note="I -> T (in OCA1A; dbSNP:rs750553908)" FT /evidence="ECO:0000269|PubMed:24934919" FT /id="VAR_071756" FT VARIANT 199 FT /note="D -> N (in OCA1A; dbSNP:rs1338186937)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021694" FT VARIANT 201 FT /note="A -> S (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021695" FT VARIANT 205 FT /note="P -> T (in OCA1A; dbSNP:rs61754362)" FT /evidence="ECO:0000269|PubMed:11295837" FT /id="VAR_021696" FT VARIANT 206 FT /note="A -> T (in OCA1A; dbSNP:rs28940880)" FT /evidence="ECO:0000269|PubMed:1943686" FT /id="VAR_007663" FT VARIANT 216 FT /note="L -> M (in OCA1A; dbSNP:rs61754363)" FT /id="VAR_007664" FT VARIANT 217 FT /note="R -> G (in OCA1A; dbSNP:rs63159160)" FT /id="VAR_007665" FT VARIANT 217 FT /note="R -> Q (in OCA1A; dbSNP:rs61754365)" FT /evidence="ECO:0000269|PubMed:10987646, FT ECO:0000269|PubMed:1487241" FT /id="VAR_007667" FT VARIANT 217 FT /note="R -> S (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021697" FT VARIANT 217 FT /note="R -> W (in OCA1A; dbSNP:rs63159160)" FT /evidence="ECO:0000269|PubMed:10987646, FT ECO:0000269|PubMed:1642278" FT /id="VAR_007666" FT VARIANT 217 FT /note="Missing (in OCA1A)" FT /id="VAR_007926" FT VARIANT 227 FT /note="Missing (in OCA1A)" FT /id="VAR_021698" FT VARIANT 236 FT /note="W -> L (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021699" FT VARIANT 236 FT /note="W -> S (in OCA1A; dbSNP:rs61754367)" FT /evidence="ECO:0000269|PubMed:10987646" FT /id="VAR_021700" FT VARIANT 239 FT /note="R -> W (in OCA1A; dbSNP:rs774670098)" FT /evidence="ECO:0000269|PubMed:11858948" FT /id="VAR_021701" FT VARIANT 240 FT /note="D -> V (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021702" FT VARIANT 243 FT /note="K -> T (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021703" FT VARIANT 253 FT /note="G -> R (in OCA1A; dbSNP:rs61754369)" FT /id="VAR_007668" FT VARIANT 256 FT /note="H -> Y (in OCA1A; dbSNP:rs61754370)" FT /evidence="ECO:0000269|PubMed:11295837, FT ECO:0000269|PubMed:15146472" FT /id="VAR_021704" FT VARIANT 272 FT /note="W -> C (in OCA1A; dbSNP:rs62645902)" FT /evidence="ECO:0000269|PubMed:10987646" FT /id="VAR_021705" FT VARIANT 275 FT /note="V -> F (in OCA1B and OCA1A; dbSNP:rs104894314)" FT /evidence="ECO:0000269|PubMed:11295837, FT ECO:0000269|PubMed:1903591, ECO:0000269|PubMed:23504663" FT /id="VAR_007669" FT VARIANT 288 FT /note="L -> S (in OCA1A; dbSNP:rs1463109821)" FT /id="VAR_007927" FT VARIANT 289 FT /note="C -> G (in OCA1A)" FT /evidence="ECO:0000269|PubMed:10571953" FT /id="VAR_009237" FT VARIANT 289 FT /note="C -> R (in OCA1A; dbSNP:rs1468041471)" FT /evidence="ECO:0000269|PubMed:10987646, FT ECO:0000269|PubMed:15146472" FT /id="VAR_007670" FT VARIANT 294 FT /note="E -> G (in OCA1A; dbSNP:rs1565391875)" FT /evidence="ECO:0000269|PubMed:10987646" FT /id="VAR_021706" FT VARIANT 294 FT /note="E -> K (in OCA1A and OCA1B; dbSNP:rs757754120)" FT /evidence="ECO:0000269|PubMed:10987646, FT ECO:0000269|PubMed:11295837, ECO:0000269|PubMed:8128955" FT /id="VAR_007928" FT VARIANT 298 FT /note="R -> W (in OCA1A; dbSNP:rs200854796)" FT /evidence="ECO:0000269|PubMed:23504663" FT /id="VAR_072594" FT VARIANT 299 FT /note="R -> H (in OCA1A; dbSNP:rs61754375)" FT /evidence="ECO:0000269|PubMed:10571953, FT ECO:0000269|PubMed:1642278, ECO:0000269|PubMed:8128955" FT /id="VAR_007671" FT VARIANT 299 FT /note="R -> S (in OCA1A; dbSNP:rs61754374)" FT /evidence="ECO:0000269|PubMed:10571953" FT /id="VAR_007672" FT VARIANT 308 FT /note="R -> T (in dbSNP:rs1042608)" FT /id="VAR_011825" FT VARIANT 312 FT /note="L -> V (in OCA1; dbSNP:rs61754377)" FT /id="VAR_007673" FT VARIANT 313 FT /note="P -> R (in OCA1; dbSNP:rs61754378)" FT /id="VAR_007674" FT VARIANT 318 FT /note="V -> E (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021707" FT VARIANT 325 FT /note="T -> A (in OCA1B; dbSNP:rs61754379)" FT /id="VAR_007675" FT VARIANT 328 FT /note="E -> Q (in OCA1A; dbSNP:rs61754380)" FT /evidence="ECO:0000269|PubMed:7902671" FT /id="VAR_007929" FT VARIANT 329 FT /note="S -> P (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021708" FT VARIANT 332 FT /note="M -> T (in OCA1A; dbSNP:rs372534292)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021709" FT VARIANT 339 FT /note="S -> G (in OCA1A; dbSNP:rs62645906)" FT /evidence="ECO:0000269|PubMed:11295837" FT /id="VAR_007676" FT VARIANT 340 FT /note="F -> L (in OCA1; dbSNP:rs62645907)" FT /id="VAR_007677" FT VARIANT 345 FT /note="E -> G (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021710" FT VARIANT 346 FT /note="G -> E (in OCA1A; dbSNP:rs773970123)" FT /id="VAR_007930" FT VARIANT 355 FT /note="A -> E (in OCA1A)" FT /id="VAR_007931" FT VARIANT 355 FT /note="A -> P (in OCA1A; dbSNP:rs62645908)" FT /evidence="ECO:0000269|PubMed:10987646, FT ECO:0000269|PubMed:11295837, ECO:0000269|PubMed:15146472" FT /id="VAR_007678" FT VARIANT 355 FT /note="A -> V (in OCA1A; dbSNP:rs151206295)" FT /evidence="ECO:0000269|PubMed:23504663" FT /id="VAR_072595" FT VARIANT 361 FT /note="S -> R (in OCA1A; dbSNP:rs61754383)" FT /evidence="ECO:0000269|PubMed:8644824" FT /id="VAR_007932" FT VARIANT 364 FT /note="N -> H (in OCA1A)" FT /evidence="ECO:0000269|PubMed:23504663" FT /id="VAR_072596" FT VARIANT 367 FT /note="H -> Y (in OCA1A; dbSNP:rs776054795)" FT /evidence="ECO:0000269|PubMed:7955413" FT /id="VAR_007933" FT VARIANT 370 FT /note="M -> T (in OCA1A; dbSNP:rs61754385)" FT /evidence="ECO:0000269|PubMed:7955413" FT /id="VAR_007934" FT VARIANT 371 FT /note="N -> T (in OCA1A; dbSNP:rs61754387)" FT /id="VAR_007679" FT VARIANT 371 FT /note="N -> Y (in OCA1A; dbSNP:rs61754386)" FT /evidence="ECO:0000269|PubMed:10987646, FT ECO:0000269|PubMed:8644824" FT /id="VAR_007935" FT VARIANT 373 FT /note="T -> K (in OCA1A; dbSNP:rs61754388)" FT /evidence="ECO:0000269|PubMed:10987646, FT ECO:0000269|PubMed:11295837, ECO:0000269|PubMed:15146472, FT ECO:0000269|PubMed:2342539, ECO:0000269|PubMed:23504663, FT ECO:0000269|PubMed:7955413, ECO:0000269|PubMed:8128955" FT /id="VAR_007680" FT VARIANT 378 FT /note="Q -> K (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021711" FT VARIANT 380 FT /note="S -> P (in OCA1B; dbSNP:rs61754391)" FT /id="VAR_007681" FT VARIANT 382 FT /note="N -> K (in OCA1A; dbSNP:rs104894315)" FT /id="VAR_007682" FT VARIANT 383 FT /note="D -> N (in OCA1A; dbSNP:rs121908011)" FT /evidence="ECO:0000269|PubMed:11295837, FT ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:2342539" FT /id="VAR_007683" FT VARIANT 384 FT /note="P -> A (in OCA1A)" FT /evidence="ECO:0000269|PubMed:23504663" FT /id="VAR_072597" FT VARIANT 390 FT /note="H -> D (in OCA1B; dbSNP:rs62645914)" FT /id="VAR_007684" FT VARIANT 393 FT /note="V -> F (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_007936" FT VARIANT 395 FT /note="S -> N (in OCA1A; dbSNP:rs752344007)" FT /id="VAR_007685" FT VARIANT 395 FT /note="S -> R (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021712" FT VARIANT 398 FT /note="E -> A (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021713" FT VARIANT 398 FT /note="E -> V (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021714" FT VARIANT 400 FT /note="W -> L (in OCA1A; dbSNP:rs62645916)" FT /evidence="ECO:0000269|PubMed:10571953" FT /id="VAR_009238" FT VARIANT 402 FT /note="R -> G (in OCA1B)" FT /id="VAR_007937" FT VARIANT 402 FT /note="R -> L (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021715" FT VARIANT 402 FT /note="R -> Q (in dbSNP:rs1126809)" FT /evidence="ECO:0000269|PubMed:10987646, FT ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:2342539, FT ECO:0000269|PubMed:7955413, ECO:0000269|PubMed:9158138" FT /id="VAR_007686" FT VARIANT 403 FT /note="R -> S (in OCA1A and OCA1B; dbSNP:rs104894316)" FT /evidence="ECO:0000269|PubMed:10987646, FT ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:1642278" FT /id="VAR_007687" FT VARIANT 404 FT /note="H -> N (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021716" FT VARIANT 404 FT /note="H -> P (in OCA-I; dbSNP:rs62645920)" FT /id="VAR_007688" FT VARIANT 405 FT /note="R -> L (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021717" FT VARIANT 406 FT /note="P -> L (in OCA1A and OCA1B; dbSNP:rs104894313)" FT /evidence="ECO:0000269|PubMed:10987646, FT ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:1903591" FT /id="VAR_007689" FT VARIANT 408 FT /note="Q -> H (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021718" FT VARIANT 409 FT /note="E -> D (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021719" FT VARIANT 416 FT /note="A -> S (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021720" FT VARIANT 417 FT /note="P -> H (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021721" FT VARIANT 419 FT /note="G -> R (in OCA1A; dbSNP:rs61754392)" FT /evidence="ECO:0000269|PubMed:10987646, FT ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:1943686, FT ECO:0000269|PubMed:7902671" FT /id="VAR_007690" FT VARIANT 422 FT /note="R -> Q (in OCA1A and OCA1B; temperature sensitive FT variant; dbSNP:rs61754393)" FT /evidence="ECO:0000269|PubMed:10987646, FT ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:1900309" FT /id="VAR_007691" FT VARIANT 424 FT /note="S -> F (in OCA1A; dbSNP:rs758747581)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021722" FT VARIANT 426 FT /note="M -> K (in OCA1A; dbSNP:rs1362285246)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021723" FT VARIANT 427 FT /note="V -> G (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021724" FT VARIANT 431 FT /note="P -> L (in OCA1A; dbSNP:rs281865325)" FT /evidence="ECO:0000269|PubMed:7902671" FT /id="VAR_007938" FT VARIANT 434 FT /note="R -> I (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021725" FT VARIANT 435 FT /note="N -> D (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021726" FT VARIANT 439 FT /note="F -> V (in OCA1A; dbSNP:rs281865327)" FT /evidence="ECO:0000269|PubMed:10987646" FT /id="VAR_021727" FT VARIANT 444 FT /note="D -> G (in OCA1A)" FT /evidence="ECO:0000269|PubMed:15146472" FT /id="VAR_021728" FT VARIANT 446 FT /note="G -> S (in OCA1A; dbSNP:rs104894317)" FT /evidence="ECO:0000269|PubMed:10987646, FT ECO:0000269|PubMed:11295837, ECO:0000269|PubMed:1642278" FT /id="VAR_007692" FT VARIANT 448 FT /note="D -> N (in OCA1A; dbSNP:rs104894318)" FT /evidence="ECO:0000269|PubMed:10987646, FT ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:1642278" FT /id="VAR_007693" FT VARIANT 490 FT /note="A -> D (in OCA1A; dbSNP:rs1050708792)" FT /evidence="ECO:0000269|PubMed:23504663" FT /id="VAR_072598" FT CONFLICT 42..45 FT /note="DRSP -> TGV (in Ref. 2; AAA61241)" FT /evidence="ECO:0000305" FT CONFLICT 179 FT /note="M -> I (in Ref. 4; CAA68756)" FT /evidence="ECO:0000305" FT CONFLICT 373..378 FT /note="TMSQVQ -> HVPGT (in Ref. 2; AAA61241)" FT /evidence="ECO:0000305" FT CONFLICT 495 FT /note="L -> P (in Ref. 2; AAA61241/AAA61244)" FT /evidence="ECO:0000305" FT CONFLICT 520..523 FT /note="DYHS -> GLPQ (in Ref. 2)" FT /evidence="ECO:0000305" FT CONFLICT 525..528 FT /note="YQSH -> VSEPFIKGLGNRVGPKSPDLTLTQSNVQVPENICWYFL (in FT Ref. 2)" FT /evidence="ECO:0000305" SQ SEQUENCE 529 AA; 60393 MW; 67211A91608A59E1 CRC64; MLLAVLYCLL WSFQTSAGHF PRACVSSKNL MEKECCPPWS GDRSPCGQLS GRGSCQNILL SNAPLGPQFP FTGVDDRESW PSVFYNRTCQ CSGNFMGFNC GNCKFGFWGP NCTERRLLVR RNIFDLSAPE KDKFFAYLTL AKHTISSDYV IPIGTYGQMK NGSTPMFNDI NIYDLFVWMH YYVSMDALLG GSEIWRDIDF AHEAPAFLPW HRLFLLRWEQ EIQKLTGDEN FTIPYWDWRD AEKCDICTDE YMGGQHPTNP NLLSPASFFS SWQIVCSRLE EYNSHQSLCN GTPEGPLRRN PGNHDKSRTP RLPSSADVEF CLSLTQYESG SMDKAANFSF RNTLEGFASP LTGIADASQS SMHNALHIYM NGTMSQVQGS ANDPIFLLHH AFVDSIFEQW LRRHRPLQEV YPEANAPIGH NRESYMVPFI PLYRNGDFFI SSKDLGYDYS YLQDSDPDSF QDYIKSYLEQ ASRIWSWLLG AAMVGAVLTA LLAGLVSLLC RHKRKQLPEE KQPLLMEKED YHSLYQSHL //