Tyrosinase oxidises tyrosine to dopaquinone

Stable Identifier
R-HSA-5662662
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

Melanogenesis is initiated with the first step of tyrosine oxidation to dopaquinone, catalyzed by tyrosinase (Mason 1948, Hearing et al. 1980). This first step is the rate-limiting step in melanin synthesis; the remainder of the reaction sequence can proceed spontaneously at a physiological pH value (Halaban et al. 2002, Land et al. 2003).

The melanocyte-specific transporter protein (OCA2, aka P protein, pink-eyed dilution protein homolog) is postulated to play a role in the processing and intracellular trafficking of tyrosinase (TYR) in the melanosome (Potterf et al. 1998, Toyofuku et al. 2002). It is a 110-kDa integral melanosomal protein with 12 predicted transmembrane domains, suggesting a transport function but its exact physiological role is still unknown. In humans, mutations in the OCA2 gene result in oculocutaneous albinism type 2, a disorder of pigmentation characterised by reduced biosynthesis of melanin in the skin, hair and eyes. This disorder is analogous to the pink-eyed dilution phenotype seen in mice with defective Oca2 (Toyofuku et al. 2002). A single SNP in the OCA2 gene is the major determinant of brown and/or blue eye colour (Sturm 2009).

The membrane-associated transporter protein SLC45A2 (melanoma antigen AIM1, MATP) shows sequence and structural similarity to sucrose transport proteins yet its actual physiological substrate and role is still unclear. Mutations in SLC45A2 cause misrouting of tyrosinase similar to the cellular phenotype of OCA2 and cause oculocutaneous albinism type 4 (OCA4) (Cullinane et al. 2011).

Literature References
PubMed ID Title Journal Year
12028586 The etiology of oculocutaneous albinism (OCA) type II: the pink protein modulates the processing and transport of tyrosinase

Toyofuku, K, Valencia, JC, Kushimoto, T, Costin, GE, Virador, VM, Vieira, WD, Ferrans, VJ, Hearing, VJ

Pigment Cell Res. 2002
6766744 Mammalin tyrosinase. Stoichiometry and measurement of reaction products

Hearing, VJ, Ekel, TM, Montague, PM, Nicholson, JM

Biochim. Biophys. Acta 1980
9770375 Normal tyrosine transport and abnormal tyrosinase routing in pink-eyed dilution melanocytes

Potterf, SB, Furumura, M, Sviderskaya, EV, Santis, C, Bennett, DC, Hearing, VJ

Exp. Cell Res. 1998
21677667 Homozygosity mapping and whole-exome sequencing to detect SLC45A2 and G6PC3 mutations in a single patient with oculocutaneous albinism and neutropenia

Cullinane, AR, Vilboux, T, O'Brien, K, Curry, JA, Maynard, DM, Carlson-Donohoe, H, Ciccone, C

J. Invest. Dermatol. 2011
19297406 Molecular genetics of human pigmentation diversity

Sturm, RA

Hum. Mol. Genet. 2009
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
monooxygenase activity of TYR:2xCu2+ [melanosome membrane]
Physical Entity
Activity
This entity is regulated by
Orthologous Events
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