TYR (tyrosinase (oculocutaneous albinism IA))

2012-06-01   Erin E Mendoza , Randy Burd 

Department of Nutritional Sciences, University of Arizona, Tucson, AZ 85721, USA




Atlas Image
Diagram of Tyrosinase promoter region adapted from Ray et al. 2007. H5URS(human 5 upstream regulatory sequence), TDE (Tyrosinase distal element), and TPE (Tyrosinase proximal element).


Gene encompasses 80 kb of DNA, 5 exons.


2082 bp.


Tyrosinase Like Gene (TRYL 11p11.2) shares 98,55% sequence identity with the 3 region of Tyrosinase. The sequence similarity lies in exons IV and V and lacks exons I, II, and III (Chaki et al., 2005).


Atlas Image
Schematic of Tyrosinase Polypeptide adapted from Mashima 1994. SP (signal peptide), EGF (Epidermal growth factor)-like domain, CuA and CuB (Copper binding domains) and TM (transmembrane domain).


529 amino acids; nascent protein is 60 kDa; Posttranslationally modified by glycosylation giving an 80 kDa protein. Contains an 18 amino acid long signal peptide, six N glycosylation sites, two copper binding sites (CuA and CuB) and a transmembrane domain (Mashima, 1994; Kosmadaki et al., 2010).


Expressed mainly in neural crest derived melanocytes and is sorted into the melanosomes within the melanocyte. Tyrosinase is also found in retinal pigment epithelium cells (Hearing, 2011).


Transmembrane protein.


Tyrosinase catalyzes conversion of tyrosine to DOPA; the rate limiting step of melanin biosynthesis and subsequently DOPA to dopaquinone (Olivares et al., 2009).
Atlas Image
Tyrosinase catalyzes the conversion of tyrosine to DOPA in the rate-limiting step of melanin biosynthesis.


The protein tyrosinase related protein 1 (TRP1) is a member of the tyrosinase protein family and utilizes copper as its cofactor. Its function in humans is not well elucidated but is thought to aid in maintaining tyrosinase catalytic activity and stability. It is also involved in maintaining melanosome structure as well as proliferation and cell death of melanocytes (Sarangarajan et al., 2000; Ghanem et al., 2011). Tyrosinase related protein 2 (TRP2), which is also known as DOPAchrome tautomerase catalyzes the conversion of DOPAchrome to 5,6-dihydroxy indole-2-carboxylic acid (DHICA). TRP2 binds 2 zinc ions as cofactors instead of copper (Olivares et al., 2001; Wan et al., 2011).



Partial or complete deletion of Tyrosinase leads to dysregulation of melanin synthesis within the melanosomes leading to oculocutaneous albinism (OCA1). The presence of non-pathologic polymorphisms results in variations in skin pigmentation. There are a total of 189 reported OCA1 mutations including 148 missense or nonsense, 23 small deletions, 8 small insertions, 2 insertion/deletion type 1, 1 complex rearrangement, and 7 splice site alterations (Ray et al., 2007; Ko et al., 2011).

Implicated in

Entity name
Highly aggressive neoplasma arising from melanocytes. Melanoma is responsible for the majority of skin cancer related deaths with a very high probability of metastasis. This neoplasm is greatly resistant to most conventional therapies. Due to the longevity of melanocytes, these cells are considered to have a greater mutagenic burden. This burden is also greater due to the position of melanocytes within the skin and their exposure to UV light. Tyrosinase enzymatic activity has been found to be associated with a better prognosis due to its association with functional activity of the tumor supressor p53. Tyrosinase-mediated melanin production signaled by p53 activation is a key protective response to UV damage (Flaherty, 2012; Gilcrest, 2011).
Several environmental and genetic factors are involved in the complex process of melanocytic tumorigenesis. Melanin production involving tyrosinase as the rate-limiting step has been shown to protect keratinocytes from DNA damage and oxidative stress from ultra violet radiation; A low incidence of melanoma in darker skinned populations has been observed, indicating a photoprotective role of melanin (Kanavy, 2011).
Entity name
Oculocutaneous albinism 1A
Autosomal recessive condition that results in partial or complete loss of tyrosinase activity. Complete loss of activity results in the absence of melanin in the skin and eyes and is classified as OCA1A and the presence of only reduced tyrosinase activity is classified as OCA1B. Complete loss of tyrosinase activity results in the total absence of melanin in the skin and hair. The iris in patients with OCA1A is light blue or gray and the retina lacks pigmentation as well. Tyrosinase null patients have greatly reduced visual acuity accompanied by nystagmus, strabismus, and usually photophobia (Ray et al., 2007). Patients with OCA1B present with varying levels of pigment. The hair in these patients is often yellow. The yellow color is a result of the pheomelanin synthesis. Dopaquinone has a high affinity for sulfhydryl compounds and produces pheomelanin as a result, causing yellow pigmentation. Patients with OCA1B often develop pigmentation in the cooler regions of the body, like the extremities (Chiang et al., 2008).
Prognosis in patients is generally good with no system abnormalities other than the loss or reduction in pigmentation. Patients are advised to protect their skin from sun to prevent sunburn (Ray et al., 2007).
Transcription of tyrosinase has been shown to increase with activation of the tumor suppressor p53, linking both to the tanning response following exposure to UV damage (Khlgatian et al., 2002 and Cui et al., 2007).


Pubmed IDLast YearTitleAuthors
158954602005Determination of variants in the 3'-region of the tyrosinase gene requires locus specific amplification.Chaki M et al
189256682008A new hypothesis of OCA1B.Chiang PW et al
173505732007Central role of p53 in the suntan response and pathologic hyperpigmentation.Cui R et al
220348652012Targeting metastatic melanoma.Flaherty KT et al
213247552011Tyrosinase related protein 1 (TYRP1/gp75) in human cutaneous melanoma.Ghanem G et al
220944002011Molecular aspects of tanning.Gilchrest BA et al
220944042011Determination of melanin synthetic pathways.Hearing VJ et al
221234202011Ultraviolet radiation and melanoma.Kanavy HE et al
118518852002Tyrosinase gene expression is regulated by p53.Khlgatian MK et al
222941962012Mutation spectrum of the TYR and SLC45A2 genes in patients with oculocutaneous albinism.Ko JM et al
201977452010Recent progresses in understanding pigmentation.Kosmadaki MG et al
77613451994Molecular and biological control of melanogenesis through tyrosinase genes and intrinsic and extrinsic regulatory factors.Mishima Y et al
197354572009New insights into the active site structure and catalytic mechanism of tyrosinase and its related proteins.Olivares C et al
173559132007Tyrosinase and ocular diseases: some novel thoughts on the molecular basis of oculocutaneous albinism type 1.Ray K et al
110412102000Mutant alleles at the brown locus encoding tyrosinase-related protein-1 (TRP-1) affect proliferation of mouse melanocytes in culture.Sarangarajan R et al
15373331992A second tyrosinase-related protein, TRP-2, is a melanogenic enzyme termed DOPAchrome tautomerase.Tsukamoto K et al
215199232011Regulation of melanocyte pivotal transcription factor MITF by some other transcription factors.Wan P et al

Other Information

Locus ID:

NCBI: 7299
MIM: 606933
HGNC: 12442
Ensembl: ENSG00000077498


dbSNP: 7299
ClinVar: 7299
TCGA: ENSG00000077498


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Tyrosine metabolismKEGGko00350
Tyrosine metabolismKEGGhsa00350
Metabolic pathwaysKEGGhsa01100
Catecholamine biosynthesis, tyrosine => dopamine => noradrenaline => adrenalineKEGGhsa_M00042
Catecholamine biosynthesis, tyrosine => dopamine => noradrenaline => adrenalineKEGGM00042
Metabolism of amino acids and derivativesREACTOMER-HSA-71291
Melanin biosynthesisREACTOMER-HSA-5662702

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
128175912003Control of confounding of genetic associations in stratified populations.228
195783642009Genome-wide association study identifies three loci associated with melanoma risk.185
205856272010Web-based, participant-driven studies yield novel genetic associations for common traits.155
125794162003Skin pigmentation, biogeographical ancestry and admixture mapping.141
184880272008ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma.118
184880272008ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma.118
204105012010Variant of TYR and autoimmunity susceptibility loci in generalized vitiligo.102
204105012010Variant of TYR and autoimmunity susceptibility loci in generalized vitiligo.102
179993552007A genomewide association study of skin pigmentation in a South Asian population.90
193849532009Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians.67


Erin E Mendoza ; Randy Burd

TYR (tyrosinase (oculocutaneous albinism IA))

Atlas Genet Cytogenet Oncol Haematol. 2012-06-01

Online version: http://atlasgeneticsoncology.org/gene/42738/tyr