Tyrosinase Related Protein 1 (TYRP1) is a melanocyte-specific enzyme involved in the biosynthesis of melanin, the pigment responsible for the color of skin, hair, and eyes . TYRP1 is one of three tyrosinase-like glycoenzymes in human melanocytes, alongside tyrosinase (TYR) and tyrosinase-related protein 2 (TYRP2) . These enzymes play a crucial role in melanogenesis, the process of melanin production within melanosomes .
TYRP1 is an intermembrane enzyme encoded by the TYRP1 gene . It shares approximately 40% amino acid sequence identity with tyrosinase and contains four conserved regions: an N-terminal signal peptide, an intramelanosomal domain, a single transmembrane alpha-helix, and a small, flexible C-terminal cytoplasmic domain . The intramelanosomal domain includes a Cys-rich subdomain unique to mammalian tyrosinases and a tyrosinase-like subdomain with a binuclear metal-ion-binding sequence motif .
Unlike tyrosinase, which contains copper ions in its active site, TYRP1 has two zinc ions . This difference explains why TYRP1 does not exhibit tyrosinase redox activity . Instead, TYRP1 is involved in maintaining the stability of tyrosinase protein and modulating its catalytic activity . It also plays a role in maintaining melanosome ultrastructure and affects melanocyte proliferation and cell death .
TYRP1 is primarily involved in the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) in mice, although this activity has been challenged in humans . The enzyme’s exact role in human melanogenesis remains enigmatic, but it is known to be crucial for the production of melanin . Mutations in the TYRP1 gene can lead to oculocutaneous albinism type 3 (OCA3), an autosomal recessive disorder characterized by reduced melanin production in the skin, hair, and eyes .
Recombinant human TYRP1 has been successfully overexpressed, solubilized, and purified in various studies . The purified recombinant protein is used to further elucidate its function in human melanocytes and to search for suitable activators of mutant variants in the treatment of genetic disorders such as OCA3 . The recombinant form of TYRP1 is also being explored as a potential therapeutic target for melanoma, a malignant tumor of melanocytes .