[1]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). DOI=10.1016/0888-7543(91)90409-8; PubMed=1903356 [NCBI, ExPASy, EBI, Israel, Japan] Giebel L.B., Strunk K.M., Spritz R.A.; "Organization and nucleotide sequences of the human tyrosinase gene and a truncated tyrosinase-related segment."; Genomics 9:435-445(1991).
[2]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). DOI=10.1073/pnas.84.21.7473; PubMed=2823263 [NCBI, ExPASy, EBI, Israel, Japan] Kwon B.S., Haq A.K., Pomerantz S.H., Halaban R.; "Isolation and sequence of a cDNA clone for human tyrosinase that maps at the mouse c-albino locus."; Proc. Natl. Acad. Sci. U.S.A. 84:7473-7477(1987).
[3]	ERRATUM, AND SEQUENCE REVISION TO 384-398. Kwon B.S., Haq A.K., Pomerantz S.H., Halaban R.; Proc. Natl. Acad. Sci. U.S.A. 85:6352-6352(1988).
[4]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). TISSUE=Melanoma; DOI=10.1084/jem.169.6.2029; PubMed=2499655 [NCBI, ExPASy, EBI, Israel, Japan] Bouchard B., Fuller B.B., Vijayasaradhi S., Houghton A.N.; "Induction of pigmentation in mouse fibroblasts by expression of human tyrosinase cDNA."; J. Exp. Med. 169:2029-2042(1989).
[5]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). DOI=10.1073/pnas.88.12.5272; PubMed=1711223 [NCBI, ExPASy, EBI, Israel, Japan] Chintamaneni C.D., Halaban R., Kobayashi Y., Witkop C.J., Kwon B.S.; "A single base insertion in the putative transmembrane domain of the tyrosinase gene as a cause for tyrosinase-negative oculocutaneous albinism."; Proc. Natl. Acad. Sci. U.S.A. 88:5272-5276(1991).
[6]	NUCLEOTIDE SEQUENCE (ISOFORM 1). TISSUE=Melanoma, and T-cell; DOI=10.1084/jem.178.2.489; PubMed=8340755 [NCBI, ExPASy, EBI, Israel, Japan] Brichard V., van Pel A., Woelfel T., Woelfel C., de Plaen E., Lethe B.G., Coulie P., Boon T.; "The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas."; J. Exp. Med. 178:489-495(1993).
[7]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANT TYR-192. DOI=10.1034/j.1600-0749.2000.130609.x; PubMed=11153699 [NCBI, ExPASy, EBI, Israel, Japan] Martinez-Arias R., Comas D., Andres A., Abello M.-T., Domingo-Roura X., Bertranpetit J.; "The tyrosinase gene in gorillas and the albinism of 'Snowflake'."; Pigment Cell Res. 13:467-470(2000).
[8]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). TISSUE=Skin; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[9]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-272. TISSUE=Liver; DOI=10.1016/0167-4781(89)90115-2; PubMed=2480811 [NCBI, ExPASy, EBI, Israel, Japan] Kikuchi H., Miura H., Yamamoto H., Takeuchi T., Dei T., Watanabe M.; "Characteristic sequences in the upstream region of the human tyrosinase gene."; Biochim. Biophys. Acta 1009:283-286(1989).
[10]	NUCLEOTIDE SEQUENCE [MRNA] OF 1-32. DOI=10.1016/0006-291X(89)90770-5; PubMed=2504160 [NCBI, ExPASy, EBI, Israel, Japan] Takeda A., Tomita Y., Okinaga S., Tagami H., Shibahara S.; "Functional analysis of the cDNA encoding human tyrosinase precursor."; Biochem. Biophys. Res. Commun. 162:984-990(1989).
[11]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 54-195, AND VARIANT TYR-192. DOI=10.1038/35054550; PubMed=11214319 [NCBI, ExPASy, EBI, Israel, Japan] Murphy W.J., Eizirik E., Johnson W.E., Zhang Y.-P., Ryder O.A., O'Brien S.J.; "Molecular phylogenetics and the origins of placental mammals."; Nature 409:614-618(2001).
[12]	REVIEW ON OCA VARIANTS. DOI=10.1002/humu.1380020102; PubMed=8477259 [NCBI, ExPASy, EBI, Israel, Japan] Oetting W.S., King R.A.; "Molecular basis of type I (tyrosinase-related) oculocutaneous albinism: mutations and polymorphisms of the human tyrosinase gene."; Hum. Mutat. 2:1-6(1993).
[13]	REVIEW ON OCA-I VARIANTS. DOI=10.1002/(SICI)1098-1004(1999)13:2<99::AID-HUMU2>3.3.CO;2-3; PubMed=10094567 [NCBI, ExPASy, EBI, Israel, Japan] Oetting W.S., King R.A.; "Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism."; Hum. Mutat. 13:99-115(1999).
[14]	SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY. DOI=10.1021/pr025562r; PubMed=12643545 [NCBI, ExPASy, EBI, Israel, Japan] Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F., Appella E.; "Proteomic analysis of early melanosomes: identification of novel melanosomal proteins."; J. Proteome Res. 2:69-79(2003).
[15]	SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY. DOI=10.1021/pr060363j; PubMed=17081065 [NCBI, ExPASy, EBI, Israel, Japan] Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.; "Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes."; J. Proteome Res. 5:3135-3144(2006).
[16]	VARIANTS OCA-IA LYS-373 AND ASN-383, AND VARIANTS TYR-192 AND GLN-402. PubMed=2342539 [NCBI, ExPASy, EBI, Israel, Japan] Spritz R.A., Strunk K.M., Giebel L.B., King R.A.; "Detection of mutations in the tyrosinase gene in a patient with type IA oculocutaneous albinism."; N. Engl. J. Med. 322:1724-1728(1990).
[17]	VARIANT OCA-IA LEU-81. DOI=10.1073/pnas.87.9.3255; PubMed=1970634 [NCBI, ExPASy, EBI, Israel, Japan] Giebel L.B., Strunk K.M., King R.A., Hanifin J.M., Spritz R.A.; "A frequent tyrosinase gene mutation in classic, tyrosinase-negative (type IA) oculocutaneous albinism."; Proc. Natl. Acad. Sci. U.S.A. 87:3255-3258(1990).
[18]	VARIANTS OCA-IB PHE-275 AND LEU-406. PubMed=1903591 [NCBI, ExPASy, EBI, Israel, Japan] Giebel L.B., Tripathi R.K., Strunk K.M., Hanifin J.M., Jackson C.E., King R.A., Spritz R.A.; "Tyrosinase gene mutations associated with type IB ('yellow') oculocutaneous albinism."; Am. J. Hum. Genet. 48:1159-1167(1991).
[19]	ERRATUM. Giebel L.B., Tripathi R.K., Strunk K.M., Hanifin J.M., Jackson C.E., King R.A., Spritz R.A.; Am. J. Hum. Genet. 49:696-696(1991).
[20]	VARIANTS OCA-IA SER-21; TRP-217; HIS-299; SER-403; SER-446 AND ASN-448. DOI=10.1002/ajmg.1320430523; PubMed=1642278 [NCBI, ExPASy, EBI, Israel, Japan] Tripathi R.K., Strunk K.M., Giebel L.B., Weleber R.G., Spritz R.A.; "Tyrosinase gene mutations in type I (tyrosinase-deficient) oculocutaneous albinism define two clusters of missense substitutions."; Am. J. Med. Genet. 43:865-871(1992).
[21]	VARIANT OCA-IA ARG-89. PubMed=1899321 [NCBI, ExPASy, EBI, Israel, Japan] Spritz R.A., Strunk K.M., Hsieh C.-L., Sekhon G.S., Francke U.; "Homozygous tyrosinase gene mutation in an American black with tyrosinase-negative (type IA) oculocutaneous albinism."; Am. J. Hum. Genet. 48:318-324(1991).
[22]	VARIANT OCA-ITS GLN-422. PubMed=1900309 [NCBI, ExPASy, EBI, Israel, Japan] Giebel L.B., Tripathi R.K., King R.A., Spritz R.A.; "A tyrosinase gene missense mutation in temperature-sensitive type I oculocutaneous albinism. A human homologue to the Siamese cat and the Himalayan mouse."; J. Clin. Invest. 87:1119-1122(1991).
[23]	VARIANTS OCA-IA GLY-42; TYR-55; THR-206 AND ARG-419. PubMed=1943686 [NCBI, ExPASy, EBI, Israel, Japan] King R.A., Mentink M.M., Oetting W.S.; "Non-random distribution of missense mutations within the human tyrosinase gene in type I (tyrosinase-related) oculocutaneous albinism."; Mol. Biol. Med. 8:19-29(1991).
[24]	VARIANTS OCA-IA ILE-176 AND GLN-217. DOI=10.1007/BF00220074; PubMed=1487241 [NCBI, ExPASy, EBI, Israel, Japan] Oetting W.S., King R.A.; "Molecular analysis of type I-A (tyrosinase negative) oculocutaneous albinism."; Hum. Genet. 90:258-262(1992).
[25]	VARIANTS OCA-IA GLN-328; ARG-419 AND LEU-431. PubMed=7902671 [NCBI, ExPASy, EBI, Israel, Japan] Tripathi R.K., Bundey S., Musarella M.A., Droetto S., Strunk K.M., Holmes S.A., Spritz R.A.; "Mutations of the tyrosinase gene in Indo-Pakistani patients with type I (tyrosinase-deficient) oculocutaneous albinism (OCA)."; Am. J. Hum. Genet. 53:1173-1179(1993).
[26]	VARIANTS OCA-IA ASP-47; CYS-217 DEL; HIS-299 AND LYS-373, AND VARIANTS OCA-IB SER-152 AND LYS-294. PubMed=8128955 [NCBI, ExPASy, EBI, Israel, Japan] Gershoni-Baruch R., Rosenmann A., Droetto S., Holmes S.A., Tripathi R.K., Spritz R.A.; "Mutations of the tyrosinase gene in patients with oculocutaneous albinism from various ethnic groups in Israel."; Am. J. Hum. Genet. 54:586-594(1994).
[27]	VARIANTS OCA TYR-367; THR-370 AND LYS-373, AND VARIANT GLN-402. DOI=10.1016/0009-8981(94)90131-7; PubMed=7955413 [NCBI, ExPASy, EBI, Israel, Japan] Breimer L.H., Winder A.F., Jay B., Jay M.; "Initiation codon mutation of the tyrosinase gene as a cause of human albinism."; Clin. Chim. Acta 227:17-22(1994).
[28]	VARIANTS OCA-IA ARG-361 AND TYR-371. PubMed=8644824 [NCBI, ExPASy, EBI, Israel, Japan] Summers C.G., Oetting W.S., King R.A.; "Diagnosis of oculocutaneous albinism with molecular analysis."; Am. J. Ophthalmol. 121:724-726(1996).
[29]	VARIANT GLN-402. DOI=10.1093/hmg/6.5.659; PubMed=9158138 [NCBI, ExPASy, EBI, Israel, Japan] Morell R., Spritz R.A., Ho L., Pierpont J., Guo W., Friedman T.B., Asher J.H. Jr.; "Apparent digenic inheritance of Waardenburg syndrome type 2 (WS2) and autosomal recessive ocular albinism (AROA)."; Hum. Mol. Genet. 6:659-664(1997).
[30]	VARIANTS OCA-IA AND OCA-IB. DOI=10.1002/(SICI)1098-1004(1997)10:2<171::AID-HUMU11>3.3.CO;2-9; PubMed=9259202 [NCBI, ExPASy, EBI, Israel, Japan] Spritz R.A., Oh J., Fukai K., Holmes S.A., Ho L., Chitayat D., France T.D., Musarella M.A., Orlow S.J., Schnur R.E., Weleber R.G., Levin A.V.; "Novel mutations of the tyrosinase (TYR) gene in type I oculocutaneous albinism (OCA1)."; Hum. Mutat. 10:171-174(1997).
[31]	VARIANTS OCA-IA AND OCA-IB. DOI=10.1002/(SICI)1098-1004(1998)12:6<433::AID-HUMU14>3.3.CO;2-7; PubMed=10671066 [NCBI, ExPASy, EBI, Israel, Japan] Oetting W.S., Fryer J.P., King R.A.; "Mutations of the human tyrosinase gene associated with tyrosinase related oculocutaneous albinism (OCA1)."; Hum. Mutat. 12:433-434(1998).
[32]	ERRATUM. Oetting W.S., Fryer J.P., King R.A.; Hum. Mutat. 13:83-83(1999).
[33]	VARIANTS OCA-IA TYR-36; GLN-77; TRP-77; LEU-81; ARG-97; GLN-217; TRP-217; SER-236; CYS-272; ARG-289; GLY-294; LYS-294; PRO-355; TYR-371; LYS-373; LEU-406; ARG-419; GLN-422; VAL-439; SER-446 AND ASN-448, VARIANT OCA-IB SER-403, AND VARIANTS TYR-192 AND GLN-402. DOI=10.1007/s004390051090; PubMed=10987646 [NCBI, ExPASy, EBI, Israel, Japan] Passmore L.A., Kaesmann-Kellner B., Weber B.H.F.; "Novel and recurrent mutations in the tyrosinase gene and the P gene in the German albino population."; Hum. Genet. 105:200-210(1999).
[34]	ERRATUM. Passmore L.A., Kaesmann-Kellner B., Weber B.H.F.; Hum. Genet. 108:208-208(2001).
[35]	VARIANTS OCA-IA TYR-55; ARG-77 INS; GLY-289; HIS-299; SER-299 AND LEU-400. DOI=10.1002/(SICI)1098-1004(199912)14:6<542::AID-HUMU14>3.0.CO;2-3; PubMed=10571953 [NCBI, ExPASy, EBI, Israel, Japan] Tsai C.-H., Tsai F.-J., Wu J.-Y., Lin S.-P., Chang J.-G., Yang C.-F., Lee C.-C.; "Insertion/deletion mutations of type I oculocutaneous albinism in Chinese patients from Taiwan."; Hum. Mutat. 14:542-542(1999).
[36]	VARIANTS OCA-IA ASP-47; GLN-77; ARG-109; THR-205; TYR-256; PHE-275; LYS-294; GLY-339; PRO-355; LYS-373; ASN-383 AND SER-446. DOI=10.1002/humu.38; PubMed=11295837 [NCBI, ExPASy, EBI, Israel, Japan] Camand O., Marchant D., Boutboul S., Pequignot M., Odent S., Dollfus H., Sutherland J., Levin A., Menasche M., Marsac C., Dufier J.-L., Heon E., Abitbol M.; "Mutation analysis of the tyrosinase gene in oculocutaneous albinism."; Hum. Mutat. 17:352-352(2001).
[37]	VARIANT OCA-IA TRP-239. DOI=10.1016/S0923-1811(01)00141-4; PubMed=11858948 [NCBI, ExPASy, EBI, Israel, Japan] Nakamura E., Miyamura Y., Matsunaga J., Kano Y., Dakeishi-Hara M., Tanita M., Kono M., Tomita Y.; "A novel mutation of the tyrosinase gene causing oculocutaneous albinism type 1 (OCA1)."; J. Dermatol. Sci. 28:102-105(2002).
[38]	VARIANTS OCA-IA ARG-44; GLY-44; ASP-47; VAL-47; HIS-68; GLN-77; LEU-79; LEU-81; SER-155; PHE-177; LEU-179; ASN-180; ASN-199; SER-201; SER-217; LEU-236; VAL-240; THR-243; TYR-256; ARG-289; GLU-318; PRO-329; THR-332; GLY-345; PRO-355; LYS-373; LYS-378; ASN-383; PHE-393; ARG-395; VAL-398; ALA-398; LEU-402; SER-403; ASN-404; LEU-405; LEU-406; HIS-408; ASP-409; SER-416; HIS-417; ARG-419; GLN-422; PHE-424; LYS-426; GLY-427; ILE-434; ASP-435; GLY-444 AND ASN-448, AND VARIANTS TYR-192 AND GLN-402. DOI=10.1002/humu.9248; PubMed=15146472 [NCBI, ExPASy, EBI, Israel, Japan] Opitz S., Kaesmann-Kellner B., Kaufmann M., Schwinger E., Zuehlke C.; "Detection of 53 novel DNA variations within the tyrosinase gene and accumulation of mutations in 17 patients with albinism."; Hum. Mutat. 23:630-631(2004).
[39]	VARIANT TYR-192, AND ASSOCIATION WITH SHEP3. DOI=10.1086/522235; PubMed=17999355 [NCBI, ExPASy, EBI, Israel, Japan] Stokowski R.P., Pant P.V.K., Dadd T., Fereday A., Hinds D.A., Jarman C., Filsell W., Ginger R.S., Green M.R., van der Ouderaa F.J., Cox D.R.; "A genomewide association study of skin pigmentation in a South Asian population."; Am. J. Hum. Genet. 81:1119-1132(2007).
[40]	VARIANT TYR-192, AND ASSOCIATION WITH SHEP3. DOI=10.1038/ng.2007.13; PubMed=17952075 [NCBI, ExPASy, EBI, Israel, Japan] Sulem P., Gudbjartsson D.F., Stacey S.N., Helgason A., Rafnar T., Magnusson K.P., Manolescu A., Karason A., Palsson A., Thorleifsson G., Jakobsdottir M., Steinberg S., Palsson S., Jonasson F., Sigurgeirsson B., Thorisdottir K., Ragnarsson R., Benediktsdottir K.R., Aben K.K., Kiemeney L.A., Olafsson J.H., Gulcher J., Kong A., Thorsteinsdottir U., Stefansson K.; "Genetic determinants of hair, eye and skin pigmentation in Europeans."; Nat. Genet. 39:1443-1452(2007).

Comments

FUNCTION: This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the rate-limiting conversions of tyrosine to DOPA, DOPA to DOPA-quinone and possibly 5,6-dihydroxyindole to indole-5,6 quinone.
CATALYTIC ACTIVITY: L-tyrosine + L-dopa + O₂ = L-dopa + dopaquinone + H₂O.
COFACTOR: Binds 2 copper ions per subunit.
SUBCELLULAR LOCATION: Melanosome membrane; Single-pass type I membrane protein.

ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing.

Name	1
Isoform ID	P14679-1
This is the isoform sequence displayed in this entry.

Name	2
Isoform ID	P14679-2
Note: No experimental confirmation available.
Features which should be applied to build the isoform sequence: VSP_006701, VSP_006702.

INDUCTION: Increased expression after UV-B radiation.
POLYMORPHISM: Genetic variations in TYR are associated with skin/hair/eye pigmentation type 3 (SHEP3) [MIM:601800]. 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. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair.
POLYMORPHISM: Compound heterozygosity for the R402Q polymorphism and a mutant allele of TYR is a common cause of autosomal recessive ocular albinism. The R402Q polymorphism is also found in Waardenburg syndrome type II with ocular albinism (WS2-OA) in association with a deletion in the MITF gene.
DISEASE: Defects in TYR are the cause of oculocutaneous albinism type IA (OCA-IA) [MIM:203100]. OCA-I, also known as tyrosinase negative oculocutaneous albinism, is an autosomal recessive disorder characterized by absence of pigment in hair, skin and eyes. OCA-I is divided into 2 types: type IA, characterized by complete lack of tyrosinase activity due to production of an inactive enzyme, and type IB characterized by reduced activity of tyrosinase. OCA-IA patients presents with the life-long absence of melanin pigment after birth and manifest increased sensitivity to ultraviolet radiation and to predisposition to skin cancer.
DISEASE: Defects in TYR are the cause of oculocutaneous albinism type IB (OCA-IB) [MIM:606952]; also known as albinism yellow mutant type. OCA-IB patients have white hair at birth that rapidly turns yellow or blond. They manifest the development of minimal-to-moderate amounts of cutaneous and ocular pigment.
DISEASE: Defects in TYR are the cause of oculocutaneous albinism type I temperature-sensitive (OCA-ITS) [MIM:606952]. OCA-ITS patients have white axillary and scalp hair and pigmented arm and leg hair.
SIMILARITY: Belongs to the tyrosinase family.
WEB RESOURCE: Name=Mutations of the TYR gene; Note=Retina International's Scientific Newsletter; URL="http://www.retina-international.com/sci-news/tyrmut.htm";.
WEB RESOURCE: Name=Albinism database (ADB); Note=TYR mutations; URL="http://albinismdb.med.umn.edu/oca1mut.html";.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=TYR";.
WEB RESOURCE: Name=Protein Spotlight; Note=Snowy stardom - Issue 49 of August 2004; URL="http://www.expasy.org/spotlight/back_issues/sptlt049.shtml";.
WEB RESOURCE: Name=Wikipedia; Note=Tyrosinase entry; URL="http://en.wikipedia.org/wiki/Tyrosinase";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

M27160; AAB37227.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M63239; AAA61242.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M63235; AAA61242.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M63236; AAA61242.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M63237; AAA61242.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M63238; AAA61242.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
J03581; AAA61241.1; ALT_INIT; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
Y00819; CAA68756.1; ALT_INIT; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U01873; AAB60319.1; ALT_SEQ; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M74314; AAA61244.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X16073; CAA34205.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF237811; AAK00805.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF237807; AAK00805.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF237808; AAK00805.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF237809; AAK00805.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF237810; AAK00805.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC027179; AAH27179.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY012019; AAG38762.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI

IPI00027286; -.
IPI00218270; -.

A38444; YRHU1.

NP_000363.1; -.

3D structure databases

ModBase

P14679.

PTM databases

PhosphoSite

P14679; -.

Enzyme and pathway databases

BRENDA

1.14.18.1; 247.

Organism-specific databases

GC11P088550; -.

HIX0010011; -.

HGNC:12442; TYR.

TYR.

CAB000079; -.

103470; phenotype. [NCBI / EBI]
203100; phenotype. [NCBI / EBI]
601800; phenotype. [NCBI / EBI]
606933; gene. [NCBI / EBI]
606952; phenotype. [NCBI / EBI]

Orphanet

1000; Albinism ocular - late onset sensorineural deafness.
55; Oculocutaneous albinism.
895; Waardenburg syndrome type 2.

PharmGKB

PA37095; -.

Gene expression databases

P14679; -.

P14679; -.

HS_TYR; -.

ENSG00000077498; Homo sapiens.

Ontologies

GO:0005798;	Cellular component: Golgi-associated vesicle (traceable author statement from ProtInc).
GO:0016021;	Cellular component: integral to membrane (inferred from electronic annotation from UniProtKB-KW).
GO:0005764;	Cellular component: lysosome (traceable author statement from UniProtKB).
GO:0033162;	Cellular component: melanosome membrane (inferred from electronic annotation from UniProtKB-SubCell).
GO:0048471;	Cellular component: perinuclear region of cytoplasm (inferred from direct assay from UniProtKB).
GO:0005507;	Molecular function: copper ion binding (inferred from mutant phenotype from UniProtKB).
GO:0004503;	Molecular function: monophenol monooxygenase activity (inferred from direct assay from UniProtKB).
GO:0046982;	Molecular function: protein heterodimerization activity (inferred from sequence or structural similarity from UniProtKB).
GO:0042803;	Molecular function: protein homodimerization activity (inferred from sequence or structural similarity from UniProtKB).
GO:0006726;	Biological process: eye pigment biosynthetic process (traceable author statement from ProtInc).
GO:0006583;	Biological process: melanin biosynthetic process from tyrosine (traceable author statement from ProtInc).
GO:0055114;	Biological process: oxidation reduction (inferred from electronic annotation from UniProtKB-KW).
GO:0007605;	Biological process: sensory perception of sound (inferred from electronic annotation from UniProtKB-KW).
GO:0007601;	Biological process: visual perception (traceable author statement from ProtInc).
QuickGo view.

Family and domain databases

InterPro

IPR008922; Di-copper_centre.
IPR002227; Tyrosinase.
Graphical view of domain structure.

Gene3D

G3DSA:1.10.1280.10; Di-copper_centre; 1.

Pfam

PF00264; Tyrosinase; 1.
Pfam graphical view of domain structure.

PRINTS

PR00092; TYROSINASE.

PROSITE

PS00497; TYROSINASE_1; 1.
PS00498; TYROSINASE_2; 1.

Proteomic databases

PRIDE

P14679; -.

Genome annotation databases

Ensembl

ENSG00000077498; Homo sapiens. [Contig view]

GeneID

7299; -.

KEGG

hsa:7299; -.

Phylogenomic databases

HOVERGEN

P14679; -.

OMA

P14679; FSFRNTL.

Other

DrugBank

DB00548; Azelaic Acid.
DB01055; Mimosine.
DB00157; NADH.

28547; -.

TYR; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Albinism; Alternative splicing; Copper; Deafness; Disease mutation; Glycoprotein; Melanin biosynthesis; Membrane; Metal-binding; Monooxygenase; Oxidoreductase; Polymorphism; Signal; Transmembrane; Tumor antigen; Waardenburg syndrome.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`SIGNAL`	`1 18`	`18`	`Potential.`
`CHAIN`	`19 529`	`511`	`Tyrosinase.`	`PRO_0000035879`
`TOPO_DOM`	`19 476`	`458`	`Lumenal, melanosome (Potential).`
`TRANSMEM`	`477 497`	`21`	`Potential.`
`TOPO_DOM`	`498 529`	`32`	`Cytoplasmic (Potential).`
`METAL`	`180 180`		`Copper A (By similarity).`
`METAL`	`202 202`		`Copper A (By similarity).`
`METAL`	`211 211`		`Copper A (By similarity).`
`METAL`	`363 363`		`Copper B (By similarity).`
`METAL`	`367 367`		`Copper B (By similarity).`
`METAL`	`390 390`		`Copper B (By similarity).`
`CARBOHYD`	`86 86`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`111 111`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`161 161`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`230 230`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`337 337`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`371 371`		`N-linked (GlcNAc...) (Potential).`
`VAR_SEQ`	`346 377`		`GFASPLTGIADASQSSMHNALHIYMNGTMSQV -> EMGFLHVGWAGLKLLTSRDPPPWPPKMLGLQA (in isoform 2).`	`VSP_006701`
`VAR_SEQ`	`378 529`		`Missing (in isoform 2).`	`VSP_006702`
`VARIANT`	`19 19`	`1`	`H -> Q (in OCA-IA).`	`VAR_007649`
`VARIANT`	`21 21`	`1`	`P -> S (in OCA-IA).`	`VAR_007650`
`VARIANT`	`36 36`	`1`	`C -> Y (in OCA-IA).`	`VAR_021683`
`VARIANT`	`42 42`	`1`	`D -> G (in OCA-IA; dbSNP:rs28940878 [NCBI]).`	`VAR_007651`
`VARIANT`	`44 44`	`1`	`S -> G (in OCA-IA).`	`VAR_021684`
`VARIANT`	`44 44`	`1`	`S -> R (in OCA-IA).`	`VAR_021685`
`VARIANT`	`47 47`	`1`	`G -> D (in OCA-IA).`	`VAR_007652`
`VARIANT`	`47 47`	`1`	`G -> V (in OCA-IA).`	`VAR_021686`
`VARIANT`	`52 52`	`1`	`R -> I (in OCA-I).`	`VAR_007653`
`VARIANT`	`55 55`	`1`	`C -> Y (in OCA-IA; dbSNP:rs28940879 [NCBI]).`	`VAR_007654`
`VARIANT`	`68 68`	`1`	`Q -> H (in OCA-IA).`	`VAR_021687`
`VARIANT`	`77 77`	`1`	`R -> Q (in OCA-IA).`	`VAR_007655`
`VARIANT`	`77 77`	`1`	`R -> RR (in OCA-IA).`	`VAR_009236`
`VARIANT`	`77 77`	`1`	`R -> W (in OCA-IA and OCA-IB).`	`VAR_007656`
`VARIANT`	`79 79`	`1`	`S -> L (in OCA-IA).`	`VAR_021688`
`VARIANT`	`80 80`	`1`	`W -> R (in OCA-IA).`	`VAR_007657`
`VARIANT`	`81 81`	`1`	`P -> L (in OCA-IA; dbSNP:rs28940876 [NCBI]).`	`VAR_007658`
`VARIANT`	`89 89`	`1`	`C -> R (in OCA-IA; dbSNP:rs28940877 [NCBI]).`	`VAR_007659`
`VARIANT`	`97 97`	`1`	`G -> R (in OCA-IA).`	`VAR_007660`
`VARIANT`	`109 109`	`1`	`G -> R (in OCA-IA).`	`VAR_021689`
`VARIANT`	`134 134`	`1`	`F -> C (in dbSNP:rs33955261 [NCBI]).`	`VAR_034576`
`VARIANT`	`142 142`	`1`	`K -> N (in dbSNP:rs11545463 [NCBI]).`	`VAR_042665`
`VARIANT`	`152 152`	`1`	`P -> S (in OCA-IB).`	`VAR_007925`
`VARIANT`	`155 155`	`1`	`T -> S (in OCA-IA).`	`VAR_021690`
`VARIANT`	`176 176`	`1`	`F -> I (in OCA-IA).`	`VAR_007661`
`VARIANT`	`177 177`	`1`	`V -> F (in OCA-IA).`	`VAR_021691`
`VARIANT`	`179 179`	`1`	`M -> L (in OCA-IA).`	`VAR_021692`
`VARIANT`	`180 180`	`1`	`H -> N (in OCA-IA).`	`VAR_021693`
`VARIANT`	`192 192`	`1`	`S -> Y (associated with SHEP3; light/dark skin; dbSNP:rs1042602 [NCBI]).`	`VAR_007662`
`VARIANT`	`199 199`	`1`	`D -> N (in OCA-IA).`	`VAR_021694`
`VARIANT`	`201 201`	`1`	`A -> S (in OCA-IA).`	`VAR_021695`
`VARIANT`	`205 205`	`1`	`P -> T (in OCA-IA).`	`VAR_021696`
`VARIANT`	`206 206`	`1`	`A -> T (in OCA-IA; dbSNP:rs28940880 [NCBI]).`	`VAR_007663`
`VARIANT`	`216 216`	`1`	`L -> M (in OCA-IA).`	`VAR_007664`
`VARIANT`	`217 217`	`1`	`R -> G (in OCA-IA).`	`VAR_007665`
`VARIANT`	`217 217`	`1`	`R -> Q (in OCA-IA).`	`VAR_007667`
`VARIANT`	`217 217`	`1`	`R -> S (in OCA-IA).`	`VAR_021697`
`VARIANT`	`217 217`	`1`	`R -> W (in OCA-IA).`	`VAR_007666`
`VARIANT`	`217 217`	`1`	`Missing (in OCA-IA).`	`VAR_007926`
`VARIANT`	`227 227`	`1`	`Missing (in OCA-IA).`	`VAR_021698`
`VARIANT`	`236 236`	`1`	`W -> L (in OCA-IA).`	`VAR_021699`
`VARIANT`	`236 236`	`1`	`W -> S (in OCA-IA).`	`VAR_021700`
`VARIANT`	`239 239`	`1`	`R -> W (in OCA-IA).`	`VAR_021701`
`VARIANT`	`240 240`	`1`	`D -> V (in OCA-IA).`	`VAR_021702`
`VARIANT`	`243 243`	`1`	`K -> T (in OCA-IA).`	`VAR_021703`
`VARIANT`	`253 253`	`1`	`G -> R (in OCA-IA).`	`VAR_007668`
`VARIANT`	`256 256`	`1`	`H -> Y (in OCA-IA).`	`VAR_021704`
`VARIANT`	`272 272`	`1`	`W -> C (in OCA-IA).`	`VAR_021705`
`VARIANT`	`275 275`	`1`	`V -> F (in OCA-IB).`	`VAR_007669`
`VARIANT`	`288 288`	`1`	`L -> S (in OCA-IA).`	`VAR_007927`
`VARIANT`	`289 289`	`1`	`C -> G (in OCA-IA).`	`VAR_009237`
`VARIANT`	`289 289`	`1`	`C -> R (in OCA-IA).`	`VAR_007670`
`VARIANT`	`294 294`	`1`	`E -> G (in OCA-IA).`	`VAR_021706`
`VARIANT`	`294 294`	`1`	`E -> K (in OCA-IA/IB).`	`VAR_007928`
`VARIANT`	`299 299`	`1`	`R -> H (in OCA-IA).`	`VAR_007671`
`VARIANT`	`299 299`	`1`	`R -> S (in OCA-IB).`	`VAR_007672`
`VARIANT`	`308 308`	`1`	`R -> T (in dbSNP:rs1042608 [NCBI]).`	`VAR_011825`
`VARIANT`	`312 312`	`1`	`L -> V (in OCA-I).`	`VAR_007673`
`VARIANT`	`313 313`	`1`	`P -> R (in OCA-I).`	`VAR_007674`
`VARIANT`	`318 318`	`1`	`V -> E (in OCA-IA).`	`VAR_021707`
`VARIANT`	`325 325`	`1`	`T -> A (in OCA-IB).`	`VAR_007675`
`VARIANT`	`328 328`	`1`	`E -> Q (in OCA-IA).`	`VAR_007929`
`VARIANT`	`329 329`	`1`	`S -> P (in OCA-IA).`	`VAR_021708`
`VARIANT`	`332 332`	`1`	`M -> T (in OCA-IA).`	`VAR_021709`
`VARIANT`	`339 339`	`1`	`S -> G (in OCA-IA).`	`VAR_007676`
`VARIANT`	`340 340`	`1`	`F -> L (in OCA-I).`	`VAR_007677`
`VARIANT`	`345 345`	`1`	`E -> G (in OCA-IA).`	`VAR_021710`
`VARIANT`	`346 346`	`1`	`G -> E (in OCA-IA).`	`VAR_007930`
`VARIANT`	`355 355`	`1`	`A -> E (in OCA-IA).`	`VAR_007931`
`VARIANT`	`355 355`	`1`	`A -> P (in OCA-IA and OCA-IB).`	`VAR_007678`
`VARIANT`	`361 361`	`1`	`S -> R (in OCA-IA).`	`VAR_007932`
`VARIANT`	`367 367`	`1`	`H -> Y (in OCA).`	`VAR_007933`
`VARIANT`	`370 370`	`1`	`M -> T (in OCA-IA).`	`VAR_007934`
`VARIANT`	`371 371`	`1`	`N -> T (in OCA-IA).`	`VAR_007679`
`VARIANT`	`371 371`	`1`	`N -> Y (in OCA-IA).`	`VAR_007935`
`VARIANT`	`373 373`	`1`	`T -> K (in OCA-IA).`	`VAR_007680`
`VARIANT`	`378 378`	`1`	`Q -> K (in OCA-IA).`	`VAR_021711`
`VARIANT`	`380 380`	`1`	`S -> P (in OCA-IB).`	`VAR_007681`
`VARIANT`	`382 382`	`1`	`N -> K (in OCA-IA).`	`VAR_007682`
`VARIANT`	`383 383`	`1`	`D -> N (in OCA-IA).`	`VAR_007683`
`VARIANT`	`390 390`	`1`	`H -> D (in OCA-IB).`	`VAR_007684`
`VARIANT`	`393 393`	`1`	`V -> F (in OCA-IA).`	`VAR_007936`
`VARIANT`	`395 395`	`1`	`S -> N (in OCA-IA).`	`VAR_007685`
`VARIANT`	`395 395`	`1`	`S -> R (in OCA-IA).`	`VAR_021712`
`VARIANT`	`398 398`	`1`	`E -> A (in OCA-IA).`	`VAR_021713`
`VARIANT`	`398 398`	`1`	`E -> V (in OCA-IA).`	`VAR_021714`
`VARIANT`	`400 400`	`1`	`W -> L (in OCA-IA).`	`VAR_009238`
`VARIANT`	`402 402`	`1`	`R -> G (in OCA-IB).`	`VAR_007937`
`VARIANT`	`402 402`	`1`	`R -> L (in OCA-IA).`	`VAR_021715`
`VARIANT`	`402 402`	`1`	`R -> Q (in dbSNP:rs1126809 [NCBI]).`	`VAR_007686`
`VARIANT`	`403 403`	`1`	`R -> S (in OCA-IA and OCA-IB).`	`VAR_007687`
`VARIANT`	`404 404`	`1`	`H -> N (in OCA-IA).`	`VAR_021716`
`VARIANT`	`404 404`	`1`	`H -> P (in OCA-I).`	`VAR_007688`
`VARIANT`	`405 405`	`1`	`R -> L (in OCA-IA).`	`VAR_021717`
`VARIANT`	`406 406`	`1`	`P -> L (in OCA-IA and OCA-IB).`	`VAR_007689`
`VARIANT`	`408 408`	`1`	`Q -> H (in OCA-IA).`	`VAR_021718`
`VARIANT`	`409 409`	`1`	`E -> D (in OCA-IA).`	`VAR_021719`
`VARIANT`	`416 416`	`1`	`A -> S (in OCA-IA).`	`VAR_021720`
`VARIANT`	`417 417`	`1`	`P -> H (in OCA-IA).`	`VAR_021721`
`VARIANT`	`419 419`	`1`	`G -> R (in OCA-IA).`	`VAR_007690`
`VARIANT`	`422 422`	`1`	`R -> Q (in OCA-ITS and OCA-IA).`	`VAR_007691`
`VARIANT`	`424 424`	`1`	`S -> F (in OCA-IA).`	`VAR_021722`
`VARIANT`	`426 426`	`1`	`M -> K (in OCA-IA).`	`VAR_021723`
`VARIANT`	`427 427`	`1`	`V -> G (in OCA-IA).`	`VAR_021724`
`VARIANT`	`431 431`	`1`	`P -> L (in OCA-IA).`	`VAR_007938`
`VARIANT`	`434 434`	`1`	`R -> I (in OCA-IA).`	`VAR_021725`
`VARIANT`	`435 435`	`1`	`N -> D (in OCA-IA).`	`VAR_021726`
`VARIANT`	`439 439`	`1`	`F -> V (in OCA-IA).`	`VAR_021727`
`VARIANT`	`444 444`	`1`	`D -> G (in OCA-IA).`	`VAR_021728`
`VARIANT`	`446 446`	`1`	`G -> S (in OCA-IA).`	`VAR_007692`
`VARIANT`	`448 448`	`1`	`D -> N (in OCA-IA and OCA-IB).`	`VAR_007693`
`CONFLICT`	`42 45`		`DRSP -> TGV (in Ref. 2; AAA61241).`
`CONFLICT`	`179 179`		`M -> I (in Ref. 4; CAA68756).`
`CONFLICT`	`373 378`		`TMSQVQ -> HVPGT (in Ref. 2; AAA61241).`
`CONFLICT`	`495 495`		`L -> P (in Ref. 2; AAA61241/AAA61244).`
`CONFLICT`	`520 523`		`DYHS -> GLPQ (in Ref. 2).`
`CONFLICT`	`525 528`		`YQSH -> VSEPFIKGLGNRVGPKSPDLTLTQSNVQVPENICWYFL (in Ref. 2).`

Sequence information

Length: 529 AA [This is the length of the unprocessed precursor]

Molecular weight: 60393 Da [This is the MW of the unprocessed precursor]

CRC64: 67211A91608A59E1 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MLLAVLYCLL WSFQTSAGHF PRACVSSKNL MEKECCPPWS GDRSPCGQLS GRGSCQNILL 

        70         80         90        100        110        120 
SNAPLGPQFP FTGVDDRESW PSVFYNRTCQ CSGNFMGFNC GNCKFGFWGP NCTERRLLVR 

       130        140        150        160        170        180 
RNIFDLSAPE KDKFFAYLTL AKHTISSDYV IPIGTYGQMK NGSTPMFNDI NIYDLFVWMH 

       190        200        210        220        230        240 
YYVSMDALLG GSEIWRDIDF AHEAPAFLPW HRLFLLRWEQ EIQKLTGDEN FTIPYWDWRD 

       250        260        270        280        290        300 
AEKCDICTDE YMGGQHPTNP NLLSPASFFS SWQIVCSRLE EYNSHQSLCN GTPEGPLRRN 

       310        320        330        340        350        360 
PGNHDKSRTP RLPSSADVEF CLSLTQYESG SMDKAANFSF RNTLEGFASP LTGIADASQS 

       370        380        390        400        410        420 
SMHNALHIYM NGTMSQVQGS ANDPIFLLHH AFVDSIFEQW LRRHRPLQEV YPEANAPIGH 

       430        440        450        460        470        480 
NRESYMVPFI PLYRNGDFFI SSKDLGYDYS YLQDSDPDSF QDYIKSYLEQ ASRIWSWLLG 

       490        500        510        520 
AAMVGAVLTA LLAGLVSLLC RHKRKQLPEE KQPLLMEKED YHSLYQSHL

P14679 in FASTA format

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	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools