TYRP1

Tyrosinase-related protein 1, also known as TYRP1, is an intermembrane enzyme which in humans is encoded by the TYRP1 gene.[5][6]

TYRP1
Identifiers
AliasesTYRP1, CAS2, CATB, GP75, OCA3, TRP, TRP1, TYRP, b-PROTEIN, tyrosinase related protein 1
External IDsOMIM: 115501 MGI: 98881 HomoloGene: 464 GeneCards: TYRP1
Orthologs
SpeciesHumanMouse
Entrez

7306

22178

Ensembl

ENSG00000107165

ENSMUSG00000005994

UniProt

P17643

P07147

RefSeq (mRNA)

NM_000550

NM_001282014
NM_001282015
NM_031202

RefSeq (protein)

NP_000541

NP_001268943
NP_001268944
NP_112479

Location (UCSC)Chr 9: 12.69 – 12.71 MbChr 4: 80.75 – 80.77 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

Regulation

The expression of TYRP1 is regulated by the microphthalmia-associated transcription factor (MITF).[19][20]

Interactions

TYRP1 has been shown to interact with GIPC1.[21]

See also

References
  1. GRCh38: Ensembl release 89: ENSG00000107165 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000005994 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. EntrezGene 7306
  6. 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. PMID 9434945. S2CID 10020827.
  7. Kobayashi T, Imokawa G, Bennett DC, Hearing VJ (November 1998). "Tyrosinase stabilization by Tyrp1 (the brown locus protein)". The Journal of Biological Chemistry. 273 (48): 31801–31805. doi:10.1074/jbc.273.48.31801. PMID 9822646.
  8. Jiménez-Cervantes C, Solano F, Kobayashi T, Urabe K, Hearing VJ, Lozano JA, García-Borrón JC (July 1994). "A new enzymatic function in the melanogenic pathway. The 5,6-dihydroxyindole-2-carboxylic acid oxidase activity of tyrosinase-related protein-1 (TRP1)". The Journal of Biological Chemistry. 269 (27): 17993–18000. doi:10.1016/S0021-9258(17)32408-0. PMID 8027058.
  9. Sarangarajan R, Boissy RE (December 2001). "Tyrp1 and oculocutaneous albinism type 3". Pigment Cell Research. 14 (6): 437–444. doi:10.1034/j.1600-0749.2001.140603.x. PMID 11775055.
  10. 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. PMID 4595498.
  11. Gilot D, Migault M, Bachelot L, Journé F, Rogiers A, Donnou-Fournet E, et al. (November 2017). "A non-coding function of TYRP1 mRNA promotes melanoma growth" (PDF). Nature Cell Biology. 19 (11): 1348–1357. doi:10.1038/ncb3623. PMID 28991221. S2CID 23539385.
  12. Bhanoo SN (3 May 2012). "Another Genetic Quirk of the Solomon Islands: Blond Hair". The New York Times. Retrieved 3 May 2012.
  13. Kenny EE, Timpson NJ, Sikora M, Yee MC, Moreno-Estrada A, Eng C, et al. (May 2012). "Melanesian blond hair is caused by an amino acid change in TYRP1". Science. 336 (6081): 554. Bibcode:2012Sci...336..554K. doi:10.1126/science.1217849. PMC 3481182. PMID 22556244.
  14. Ju, Dan; Mathieson, Iain (December 21, 2020). "The evolution of skin pigmentation-associated variation in West Eurasia". Proceedings of the National Academy of Sciences of the United States of America. 118 (1). doi:10.1073/pnas.2009227118. PMC 7817156. PMID 33443182.
  15. 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. PMID 26450459. S2CID 13727757.
  16. Cargill EJ, Famula TR, Schnabel RD, Strain GM, Murphy KE (July 2005). "The color of a Dalmatian's spots: linkage evidence to support the TYRP1 gene". BMC Veterinary Research. 1 (1): 1. doi:10.1186/1746-6148-1-1. PMC 1192828. PMID 16045797.
  17. Ren J, Mao H, Zhang Z, Xiao S, Ding N, Huang L (May 2011). "A 6-bp deletion in the TYRP1 gene causes the brown colouration phenotype in Chinese indigenous pigs". Heredity. 106 (5): 862–868. doi:10.1038/hdy.2010.129. PMC 3186233. PMID 20978532.
  18. 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. PMID 33939849. S2CID 233720032.
  19. Fang D, Tsuji Y, Setaluri V (July 2002). "Selective down-regulation of tyrosinase family gene TYRP1 by inhibition of the activity of melanocyte transcription factor, MITF". Nucleic Acids Research. 30 (14): 3096–3106. doi:10.1093/nar/gkf424. PMC 135745. PMID 12136092.
  20. Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, et al. (December 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research. 21 (6): 665–676. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
  21. Liu TF, Kandala G, Setaluri V (September 2001). "PDZ domain protein GIPC interacts with the cytoplasmic tail of melanosomal membrane protein gp75 (tyrosinase-related protein-1)". The Journal of Biological Chemistry. 276 (38): 35768–35777. doi:10.1074/jbc.M103585200. PMID 11441007.

Further reading
  • Overview of all the structural information available in the PDB for UniProt: P17643 (5,6-dihydroxyindole-2-carboxylic acid oxidase) at the PDBe-KB.
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