P protein
| OCA2 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | OCA2,BEY, BEY1, BEY2, BOCA, D15S12, EYCL, EYCL2, EYCL3, HCL3, PED, SHEP1, OCA2 melanosomal transmembrane protein, P | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM:611409;MGI:97454;HomoloGene:37281;GeneCards:OCA2;OMA:OCA2 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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P protein,also known asmelanocyte-specific transporter proteinorpink-eyed dilution protein homolog,is aproteinthat in humans is encoded by theoculocutaneous albinism II(OCA2)gene.[5]The P protein is believed to be anintegral membrane proteininvolved in small molecule transport, specifically oftyrosine—a precursor ofmelanin.Certain mutations in OCA2 result in type 2oculocutaneous albinism.[5]OCA2 encodes the human homologue of the mouse p (pink-eyed dilution) gene.
The human OCA2 gene is located on the long arm (q) of chromosome 15, specifically from base pair 28,000,020 to base pair 28,344,457 on chromosome 15.
Function[edit]
OCA2 provides instructions for making the protein called P protein which is located inmelanocyteswhich are specialized cells that producemelanin,and in the cells of theretinal pigment epithelium.Melanin is responsible for giving color to the skin, hair, and eyes. Moreover, melanin is found in the light-sensitive tissue of the retina of the eye which plays a role in normal vision.
The exact function of protein P is unknown, but it has been found that it is essential for the normal coloring ofskin,eyes,andhair;and likely involved inmelaninproduction. This gene seems to be the main determinant of eye color depending on the amount of melanin production in theiris stroma(large amounts giving rise to brown eyes; little to no melanin giving rise to blue eyes).
This gene is mutated inAstyanax mexicanus,a Mexican fish which is characterized by a chronicAlbinismin cave's individuals. It exists as a deletion in Pachón and Molino's caves fish that produces the albinism.[6]
Clinical significance[edit]
Mutations in the OCA2 gene cause a disruption in the normal production of melanin; therefore, causing vision problems and reductions inhair,skin,andeye color.Oculocutaneous albinismcaused by mutations in the OCA2 gene is calledoculocutaneous albinism type 2.The prevalence of OCA type 2 is estimated at 1/38,000-1/40,000 in most populations throughout the world, with a higher prevalence in the African population of 1/3,900–1/1,500.[7]Other diseases associated with the deletion of the OCA2 gene areAngelman syndrome(light-colored hair and fair skin) andPrader–Willi syndrome(unusually light-colored hair and fair skin). With both these syndromes, the deletion often occurs in individuals with either syndrome.[8][9]
A mutation in theHERC2gene adjacent to OCA2, affecting OCA2's expression in the human iris, is found common to nearly all people withblue eyes.It has been hypothesized that all blue-eyed humans share a single common ancestor with whom the mutation originated.[10][11][12]
TheHis615Argalleleof OCA2 is involved in the light skin tone and the derived allele is restricted to East Asia with high frequencies, with highest frequencies in Eastern East Asia (49-63%), midrange frequencies in Southeast Asia, and the lowest frequencies in Western China and some Eastern European populations.[13][14]
References[edit]
- ^abcENSG00000277361 GRCh38: Ensembl release 89: ENSG00000104044, ENSG00000277361–Ensembl,May 2017
- ^abcGRCm38: Ensembl release 89: ENSMUSG00000030450–Ensembl,May 2017
- ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ab"Entrez Gene: OCA2 oculocutaneous albinism II (pink-eye dilution homolog, mouse)".Retrieved2015-03-12.
- ^Warren WC, Boggs TE, Borowsky R, Carlson BM, Ferrufino E, Gross JB, et al. (March 2021)."A chromosome-level genome of Astyanax mexicanus surface fish for comparing population-specific genetic differences contributing to trait evolution".Nature Communications.12(1): 1447.Bibcode:2021NatCo..12.1447W.doi:10.1038/s41467-021-21733-z.PMC7933363.PMID33664263.
- ^Hayashi M, Suzuki T (April 2013)."Oculocutaneous albinism type 2".Orphanet.Retrieved2014-11-09.
- ^"OCA2 - oculocutaneous albinism II".Genetics Home Reference - Your guide to understanding genetic conditions.U.S. National Library of Medicine.Retrieved30 March2013.
- ^"Don't it make your brown eyes blue?".Understanding Genetics.Archived fromthe originalon 12 May 2018.Retrieved30 March2013.
- ^Bryner J (2008-01-31)."Here's what made those brown eyes blue".Health News.NBC News.Retrieved2008-11-06.;Bryner J (2008-01-31)."One Common Ancestor Behind Blue Eyes".LiveScience.Imaginova Corp.Retrieved2008-11-06.;"Blue-eyed humans have a single, common ancestor".News.University of Copenhagen. 2008-01-30. Archived fromthe originalon 2013-07-02.Retrieved2008-11-06.
- ^Eiberg H, Troelsen J, Nielsen M, Mikkelsen A, Mengel-From J, Kjaer KW, et al. (March 2008). "Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression".Human Genetics.123(2): 177–187.doi:10.1007/s00439-007-0460-x.PMID18172690.S2CID9886658.
- ^Sturm RA, Duffy DL, Zhao ZZ, Leite FP, Stark MS, Hayward NK, et al. (February 2008)."A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color".American Journal of Human Genetics.82(2): 424–431.doi:10.1016/j.ajhg.2007.11.005.PMC2427173.PMID18252222.
- ^Donnelly MP, Paschou P, Grigorenko E, Gurwitz D, Barta C, Lu RB, et al. (May 2012)."A global view of the OCA2-HERC2 region and pigmentation".Human Genetics.131(5): 683–696.doi:10.1007/s00439-011-1110-x.PMC3325407.PMID22065085.
- ^Edwards M, Bigham A, Tan J, Li S, Gozdzik A, Ross K, et al. (March 2010)."Association of the OCA2 polymorphism His615Arg with melanin content in east Asian populations: further evidence of convergent evolution of skin pigmentation".PLOS Genetics.6(3): e1000867.doi:10.1371/journal.pgen.1000867.PMC2832666.PMID20221248.
Further reading[edit]
- Oetting WS, King RA (1999)."Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism".Human Mutation.13(2): 99–115.doi:10.1002/(SICI)1098-1004(1999)13:2<99::AID-HUMU2>3.0.CO;2-C.PMID10094567.S2CID27315644.
- Brilliant MH (April 2001)."The mouse p (pink-eyed dilution) and human P genes, oculocutaneous albinism type 2 (OCA2), and melanosomal pH".Pigment Cell Research.14(2): 86–93.doi:10.1034/j.1600-0749.2001.140203.x.PMID11310796.
- Ramsay M, Colman MA, Stevens G, Zwane E, Kromberg J, Farrall M, et al. (October 1992)."The tyrosinase-positive oculocutaneous albinism locus maps to chromosome 15q11.2-q12".American Journal of Human Genetics.51(4): 879–884.PMC1682821.PMID1415228.
- Gardner JM, Nakatsu Y, Gondo Y, Lee S, Lyon MF, King RA, et al. (August 1992). "The mouse pink-eyed dilution gene: association with human Prader-Willi and Angelman syndromes".Science.257(5073): 1121–1124.Bibcode:1992Sci...257.1121G.doi:10.1126/science.257.5073.1121.PMID1509264.S2CID5800811.
- Ludowese CJ, Thompson KJ, Sekhon GS, Pauli RM (September 1991). "Absence of predictable phenotypic expression in proximal 15q duplications".Clinical Genetics.40(3): 194–201.doi:10.1111/j.1399-0004.1991.tb03076.x.PMID1773534.S2CID28419032.
- Lee ST, Nicholls RD, Jong MT, Fukai K, Spritz RA (March 1995). "Organization and sequence of the human P gene and identification of a new family of transport proteins".Genomics.26(2): 354–363.doi:10.1016/0888-7543(95)80220-G.PMID7601462.
- Spritz RA, Fukai K, Holmes SA, Luande J (June 1995)."Frequent intragenic deletion of the P gene in Tanzanian patients with type II oculocutaneous albinism (OCA2)".American Journal of Human Genetics.56(6): 1320–1323.PMC1801108.PMID7762554.
- Lee ST, Nicholls RD, Schnur RE, Guida LC, Lu-Kuo J, Spinner NB, et al. (November 1994). "Diverse mutations of the P gene among African-Americans with type II (tyrosinase-positive) oculocutaneous albinism (OCA2)".Human Molecular Genetics.3(11): 2047–2051.PMID7874125.
- Durham-Pierre D, Gardner JM, Nakatsu Y, King RA, Francke U, Ching A, et al. (June 1994). "African origin of an intragenic deletion of the human P gene in tyrosinase positive oculocutaneous albinism".Nature Genetics.7(2): 176–179.doi:10.1038/ng0694-176.PMID7920637.S2CID6185436.
- Lee ST, Nicholls RD, Bundey S, Laxova R, Musarella M, Spritz RA (February 1994)."Mutations of the P gene in oculocutaneous albinism, ocular albinism, and Prader-Willi syndrome plus albinism".The New England Journal of Medicine.330(8): 529–534.doi:10.1056/NEJM199402243300803.PMID8302318.
- Rinchik EM, Bultman SJ, Horsthemke B, Lee ST, Strunk KM, Spritz RA, et al. (January 1993). "A gene for the mouse pink-eyed dilution locus and for human type II oculocutaneous albinism".Nature.361(6407): 72–76.Bibcode:1993Natur.361...72R.doi:10.1038/361072a0.PMID8421497.S2CID21794972.
- Spritz RA, Lee ST, Fukai K, Brondum-Nielsen K, Chitayat D, Lipson MH, et al. (1997)."Novel mutations of the P gene in type II oculocutaneous albinism (OCA2)".Human Mutation.10(2): 175–177.doi:10.1002/(SICI)1098-1004(1997)10:2<175::AID-HUMU12>3.0.CO;2-X.PMID9259203.S2CID5762140.
- Kerr R, Stevens G, Manga P, Salm S, John P, Haw T, et al. (2000)."Identification of P gene mutations in individuals with oculocutaneous albinism in sub-Saharan Africa".Human Mutation.15(2): 166–172.doi:10.1002/(SICI)1098-1004(200002)15:2<166::AID-HUMU5>3.0.CO;2-Z.PMID10649493.S2CID1306686.
- Oetting WS, Gardner JM, Fryer JP, Ching A, Durham-Pierre D, King RA, et al. (1998)."Mutations of the human P gene associated with Type II oculocutaneous albinism (OCA2). Mutations in brief no. 205. Online".Human Mutation.12(6): 434.doi:10.1002/(SICI)1098-1004(1998)12:6<434::AID-HUMU16>3.0.CO;2-7.PMID10671067.S2CID34505863.
- Passmore LA, Kaesmann-Kellner B, Weber BH (September 1999). "Novel and recurrent mutations in the tyrosinase gene and the P gene in the German albino population".Human Genetics.105(3): 200–210.doi:10.1007/s004390051090(inactive 2024-04-08).PMID10987646.
{{cite journal}}:CS1 maint: DOI inactive as of April 2024 (link) - Manga P, Kromberg J, Turner A, Jenkins T, Ramsay M (March 2001)."In Southern Africa, brown oculocutaneous albinism (BOCA) maps to the OCA2 locus on chromosome 15q: P-gene mutations identified".American Journal of Human Genetics.68(3): 782–787.doi:10.1086/318800.PMC1274491.PMID11179026.
- Manga P, Orlow SJ (October 2001). "Inverse correlation between pink-eyed dilution protein expression and induction of melanogenesis by bafilomycin A1".Pigment Cell Research.14(5): 362–367.doi:10.1034/j.1600-0749.2001.140508.x.PMID11601658.
- Toyofuku K, Valencia JC, Kushimoto T, Costin GE, Virador VM, Vieira WD, et al. (June 2002). "The etiology of oculocutaneous albinism (OCA) type II: the pink protein modulates the processing and transport of tyrosinase".Pigment Cell Research.15(3): 217–224.doi:10.1034/j.1600-0749.2002.02007.x.PMID12028586.
External links[edit]
