Tyrosinase-related protein 1, also known as TYRP1, is an intermembrane enzyme which in humans is encoded by the TYRP1gene.[5][6]
Function
Tyrp1 is a melanocyte-specific gene product involved in melanin synthesis within melanosomes.[7] Most Tyrp1 possess 5,6-dihydroxyindole-2-carboxylic acid (melanogenic intermediate) oxidase activity.[8] The catalytic function of Tyrp1 in human melanocytes is less clear. Tyrp1 is involved in stabilizing of tyrosinase protein and modulating its catalytic activity.[7] Tyrp1 is also involved in maintenance of melanosome structure and affects melanocyte proliferation and melanocyte cell death.[9] Melanocytes are derived from the neural crest and migrate into the overlying epidermal ectoderm of a developing organism which forms skin and hair.[10] Therefore, Tyrp1 influences the expression of melanin notably in the skin and hair of an organism.
The Tyrp1 gene also has a non-coding function which indirectly promotes melanoma tumor cell proliferation, especially when highly expressed in a cell.[11] Tyrp1 mRNA interacts with miR-16 and affects its ability to repress genes involved in melanoma cell production.[11]
Clinical significance
Mutations in the mouse Tyrp1 gene are associated with brown pelage and in the human TYRP1 gene with oculocutaneous albinism type 3 (OCA3).[9] An allele of TYRP1 common in Solomon Islanders results in blond hair. Although the phenotype is similar to Northern European blond hair, this allele is not found in Europeans.[12][13] More recent study, Ju et al. 2020 found TYRP1 allele was selected in European population.[14]
Norton et al. 2016 study found TYRP1 is not associated with blond hair color in Melanesians as many populations in Oceania did not carry TYRP1 alleles but still displayed blondism, study indicates that additional unknown alleles contribute to the blondism phenotype in Melanesians.[15]
Alterations of the Tyrp1 gene is responsible for some of the differing phenotypes of skin and coat appearance in various animals. In Dalmatians, black versus "liver" spot color is due to genetic variation of the TYRP1 gene.[16] A particular deletion in the Tyrp1 gene of domestic Chinese-Tibetan swine results in a "brown coloration" of the swine's skin and hair as opposed to the wild-type "black" phenotype.[17] In Oujiang-color carp, mutations of the Tyrp1 gene influenced the expression of "grey" or "brown" phenotypic color of scales.[18]
Elevated levels of Tyrp1 gene expression is also associated with unfavorable patient outcome of those affected by melanoma.[11] The role of Tyrp1 in melanoma progression was determined by comparing "knockout" cell lines which have inactive Tyrp1 to cells with normal and highly expressed Tyrp1.[11] Such studies provide insight to possible clinical usage and treatment of melanoma via regulation of Tyrp1 expression in cells.[11]
^Box NF, Wyeth JR, Mayne CJ, O'Gorman LE, Martin NG, Sturm RA (January 1998). "Complete sequence and polymorphism study of the human TYRP1 gene encoding tyrosinase-related protein 1". Mammalian Genome. 9 (1): 50–53. doi:10.1007/s003359900678. PMID9434945. S2CID10020827.
^Mayer TC (September 1973). "The migratory pathway of neural crest cells into the skin of mouse embryos". Developmental Biology. 34 (1): 39–46. doi:10.1016/0012-1606(73)90337-0. PMID4595498.
^Norton HL, Hanna M, Werren E, Friedlaender J (May 2016). "The rs387907171 SNP in TYRP1 is not associated with blond hair color on the Island of Bougainville". American Journal of Human Biology. 28 (3): 431–435. doi:10.1002/ajhb.22795. PMID26450459. S2CID13727757.
^Chen H, Wang J, Du J, Mandal BK, Si Z, Xu X, et al. (August 2021). "Analysis of recently duplicated TYRP1 genes and their effect on the formation of black patches in Oujiang-color common carp (Cyprinus carpio var. color)". Animal Genetics. 52 (4): 451–460. doi:10.1111/age.13071. PMID33939849. S2CID233720032.
Shibata K, Takeda K, Tomita Y, Tagami H, Shibahara S (April 1992). "Downstream region of the human tyrosinase-related protein gene enhances its promoter activity". Biochemical and Biophysical Research Communications. 184 (2): 568–575. doi:10.1016/0006-291X(92)90627-W. PMID1575733.
Murty VV, Bouchard B, Mathew S, Vijayasaradhi S, Houghton AN (May 1992). "Assignment of the human TYRP (brown) locus to chromosome region 9p23 by nonradioactive in situ hybridization". Genomics. 13 (1): 227–229. doi:10.1016/0888-7543(92)90228-K. PMID1577487.
Abbott C, Jackson IJ, Carritt B, Povey S (October 1991). "The human homolog of the mouse brown gene maps to the short arm of chromosome 9 and extends the known region of homology with mouse chromosome 4". Genomics. 11 (2): 471–473. doi:10.1016/0888-7543(91)90160-G. PMID1769662.
Chintamaneni CD, Ramsay M, Colman MA, Fox MF, Pickard RT, Kwon BS (July 1991). "Mapping the human CAS2 gene, the homologue of the mouse brown (b) locus, to human chromosome 9p22-pter". Biochemical and Biophysical Research Communications. 178 (1): 227–235. doi:10.1016/0006-291X(91)91803-K. PMID1906272.
Box NF, Sturm RA (December 1994). "Dinucleotide repeat polymorphism at the human TYRP1 locus". Human Molecular Genetics. 3 (12): 2270. doi:10.1093/hmg/3.12.2270. PMID7881448.
Sturm RA, O'Sullivan BJ, Box NF, Smith AG, Smit SE, Puttick ER, et al. (September 1995). "Chromosomal structure of the human TYRP1 and TYRP2 loci and comparison of the tyrosinase-related protein gene family". Genomics. 29 (1): 24–34. doi:10.1006/geno.1995.1211. PMID8530077.
Box NF, Wyeth JR, Mayne CJ, O'Gorman LE, Martin NG, Sturm RA (January 1998). "Complete sequence and polymorphism study of the human TYRP1 gene encoding tyrosinase-related protein 1". Mammalian Genome. 9 (1): 50–53. doi:10.1007/s003359900678. PMID9434945. S2CID10020827.
Abe T, Sato M, Tamai M (December 1998). "Dedifferentiation of the retinal pigment epithelium compared to the proliferative membranes of proliferative vitreoretinopathy". Current Eye Research. 17 (12): 1103–1109. doi:10.1076/ceyr.17.12.1103.5126. PMID9872531.
Commo S, Bernard BA (August 2000). "Melanocyte subpopulation turnover during the human hair cycle: an immunohistochemical study". Pigment Cell Research. 13 (4): 253–259. doi:10.1034/j.1600-0749.2000.130407.x. PMID10952393.
External links
Overview of all the structural information available in the PDB for UniProt: P17643 (5,6-dihydroxyindole-2-carboxylic acid oxidase) at the PDBe-KB.
