Reactome | Tyrosinase oxidises tyrosine to dopaquinone

Tyrosinase oxidises tyrosine to dopaquinone

Stable Identifier

R-HSA-5662662

Type

Reaction [transition]

Species

Homo sapiens

Compartment

melanosome membrane, melanosome lumen

ReviewStatus

5/5

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Tyrosinase oxidises tyrosine to dopaquinone

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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
6766744	Mammalin tyrosinase. Stoichiometry and measurement of reaction products Montague, PM, Hearing, VJ, Ekel, TM, Nicholson, JM	Biochim. Biophys. Acta	1980
12028586	The etiology of oculocutaneous albinism (OCA) type II: the pink protein modulates the processing and transport of tyrosinase Kushimoto, T, Vieira, WD, Toyofuku, K, Virador, VM, Valencia, JC, Hearing, VJ, Costin, GE, Ferrans, VJ	Pigment Cell Res.	2002
9770375	Normal tyrosine transport and abnormal tyrosinase routing in pink-eyed dilution melanocytes Furumura, M, Hearing, VJ, Sviderskaya, EV, Bennett, DC, Santis, C, Potterf, SB	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 Vilboux, T, Cullinane, AR, Maynard, DM, Carlson-Donohoe, H, Ciccone, C, O'Brien, K, Curry, JA	J. Invest. Dermatol.	2011
19297406	Molecular genetics of human pigmentation diversity Sturm, RA	Hum. Mol. Genet.	2009