Hmdb loader

Showing Protein P protein (HMDBP10790)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP10790
Secondary Accession Numbers
  • 17062
Name P protein
Synonyms
  1. Melanocyte-specific transporter protein
  2. Pink-eyed dilution protein homolog
Gene Name OCA2
Protein Type Unknown
Biological Properties
General Function Involved in arsenite transmembrane transporter activity
Specific Function Could be involved in the transport of tyrosine, the precursor to melanin synthesis, within the melanocyte. Regulates the pH of melanosome and the melanosome maturation. One of the components of the mammalian pigmentary system. Seems to regulate the post-translational processing of tyrosinase, which catalyzes the limiting reaction in melanin synthesis. May serve as a key control point at which ethnic skin color variation is determined. Major determinant of brown and/or blue eye color
Pathways Not Available
Reactions Not Available
GO Classification
Component
cell part
membrane part
intrinsic to membrane
integral to membrane
Function
inorganic anion transmembrane transporter activity
transmembrane transporter activity
substrate-specific transmembrane transporter activity
ion transmembrane transporter activity
transporter activity
tricarboxylic acid transmembrane transporter activity
citrate transmembrane transporter activity
arsenite transmembrane transporter activity
organic acid transmembrane transporter activity
carboxylic acid transmembrane transporter activity
anion transmembrane transporter activity
Process
establishment of localization
transport
tricarboxylic acid transport
citrate transport
transmembrane transport
organic acid transport
carboxylic acid transport
Cellular Location
  1. Melanosome membrane
  2. Multi-pass membrane protein
Gene Properties
Chromosome Location Chromosome:1
Locus 15q
SNPs OCA2
Gene Sequence 
>2517 bp
ATGCATCTGGAGGGCAGAGACGGCAGGCGGTACCCCGGCGCGCCGGCGGTGGAGCTCCTG
CAGACGTCCGTGCCCAGCGGACTCGCTGAACTTGTGGCCGGCAAGCGCAGGCTTCCTCGG
GGAGCCGGTGGAGCTGACCCCTCGCACTCCTGCCCCAGGGGGGCTGCCGGGCAGAGCTCT
TGGGCTCCTGCAGGCCAGGAGTTTGCTTCATTCCTCACAAAAGGGAGGTCTCACTCTTCT
TTGCCCCAGATGTCCAGCTCCAGGTCTAAAGATTCCTGCTTTACAGAAAACACTCCTTTG
CTGAGGAATTCCTTACAGGAGAAAGGGTCACGGTGCATACCTGTTTACCATCCAGAGTTC
ATCACTGCTGAAGAGTCTTGGGAAGACAGCTCTGCTGACTGGGAGCGAAGATACCTGCTA
AGCAGGGAGGTGTCTGGTCTGTCTGCATCTGCCTCCTCCGAGAAGGGAGACCTTCTGGAC
AGCCCGCACATCCGACTCCGTCTTTCCAAGCTGAGGCGCTGTGTGCAGTGGCTGAAAGTC
ATGGGCCTGTTTGCCTTTGTGGTGCTGTGTTCTATTTTGTTCAGCCTATATCCGGATCAA
GGAAAGCTCTGGCAGCTGTTGGCCTTATCACCGCTGGAGAACTACTCCGTGAACCTTAGC
AGCCACGTGGACTCCACGCTGCTGCAGGTGGACCTGGCAGGGGCCCTAGTGGCCAGTGGG
CCGAGTCGTCCTGGGAGGGAAGAGCACATCGTGGTGGAGCTGACCCAGGCTGACGCTTTG
GGCTCCAGGTGGCGGCGGCCACAGCAGGTCACTCACAACTGGACGGTGTATTTAAATCCG
AGGAGAAGCGAGCACTCAGTGATGAGCAGGACCTTTGAGGTACTGACCAGAGAGACGGTG
TCCATCAGCATCCGGGCCTCCCTGCAGCAGACCCAGGCTGTCCCTCTTTTGATGGCTCAT
CAGTACCTCCGCGGAAGTGTAGAAACCCAGGTGACCATCGCGACGGCCATCCTCGCGGGC
GTCTACGCGCTGATCATATTTGAGATCGTGCACAGAACTCTGGCGGCCATGCTGGGTTCC
CTTGCAGCACTGGCAGCACTGGCTGTGATTGGCGATAGACCCAGCCTGACCCATGTGGTG
GAGTGGATTGATTTTGAGACGCTGGCCCTGCTGTTTGGCATGATGATCTTAGTAGCCATA
TTTTCAGAAACGGGATTTTTCGATTATTGTGCTGTAAAGGCATACCGGCTCTCCCGGGGA
CGGGTGTGGGCCATGATCATCATGCTCTGTCTCATCGCGGCCGTCCTCTCTGCCTTCTTG
GACAACGTCACCACCATGCTCCTCTTCACGCCTGTGACCATAAGGTTGTGTGAGGTGCTC
AACCTTGATCCAAGACAAGTCCTGATTGCAGAAGTGATCTTCACAAACATTGGAGGAGCT
GCCACTGCCATCGGGGACCCTCCAAATGTCATTATTGTTTCCAACCAAGAGCTGAGGAAG
ATGGGCCTGGACTTTGCCGGATTCACTGCACACATGTTCATTGGGATTTGCCTTGTTCTC
CTGGTCTGCTTTCCGCTCCTCAGACTCCTTTACTGGAACAGAAAGCTTTATAACAAGGAA
CCCAGTGAGATTGTTGAACTGAAGCACGAGATTCACGTCTGGCGCCTGACTGCTCAGCGC
ATCAGCCCGGCCAGCCGCGAGGAGACAGCTGTGCGCCGCCTGCTGCTGGGGAAGGTGCTG
GCACTGGAGCACCTGCTCGCCCGGAGGCTGCACACCTTCCACAGACAGATCTCACAGGAG
GACAAAAATTGGGAGACCAATATCCAAGAACTCCAAAAAAAGCATAGGATATCTGACGGG
ATTCTGCTCGCCAAATGCCTGACAGTGTTGGGATTTGTTATCTTCATGTTTTTCCTCAAT
TCGTTTGTCCCTGGCATTCATCTTGATCTTGGATGGATTGCTATTCTGGGTGCCATCTGG
TTGCTAATTTTAGCTGATATTCATGATTTTGAGATAATTCTACACAGAGTGGAATGGGCA
ACCCTTCTGTTTTTTGCAGCGCTCTTTGTTCTGATGGAGGCATTGGCACATCTCCACTTA
ATAGAATATGTTGGAGAACAAACTGCTTTGCTAATAAAGATGGTCCCAGAGGAGCAGCGC
CTCATAGCCGCCATTGTCCTGGTGGTGTGGGTCTCAGCCCTGGCGTCGTCCCTGATTGAC
AACATCCCGTTCACTGCTACCATGATTCCCGTGCTCCTGAACCTGAGCCACGACCCTGAG
GTTGGCCTGCCCGCACCGCCGCTCATGTATGCCCTGGCCTTCGGTGCTTGCCTGGGAGGT
AACGGGACACTGATTGGCGCGTCGGCAAACGTCGTGTGTGCAGGGATTGCAGAACAGCAT
GGATATGGGTTCTCCTTCATGGAATTTTTCAGGCTGGGCTTCCCAATGATGGTTGTGTCC
TGCACTGTTGGGATGTGTTATCTCCTTGTGGCTCATGTGGTGGTGGGATGGAATTAA
Protein Properties
Number of Residues 838
Molecular Weight 92848.5
Theoretical pI 7.28
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • 180-197
  • 331-347
  • 354-370
  • 385-401
  • 424-440
  • 514-530
  • 621-637
  • 648-664
  • 680-696
  • 721-737
  • 761-777
  • 818-834
Protein Sequence 
>P protein
MHLEGRDGRRYPGAPAVELLQTSVPSGLAELVAGKRRLPRGAGGADPSHSCPRGAAGQSS
WAPAGQEFASFLTKGRSHSSLPQMSSSRSKDSCFTENTPLLRNSLQEKGSRCIPVYHPEF
ITAEESWEDSSADWERRYLLSREVSGLSASASSEKGDLLDSPHIRLRLSKLRRCVQWLKV
MGLFAFVVLCSILFSLYPDQGKLWQLLALSPLENYSVNLSSHVDSTLLQVDLAGALVASG
PSRPGREEHIVVELTQADALGSRWRRPQQVTHNWTVYLNPRRSEHSVMSRTFEVLTRETV
SISIRASLQQTQAVPLLMAHQYLRGSVETQVTIATAILAGVYALIIFEIVHRTLAAMLGS
LAALAALAVIGDRPSLTHVVEWIDFETLALLFGMMILVAIFSETGFFDYCAVKAYRLSRG
RVWAMIIMLCLIAAVLSAFLDNVTTMLLFTPVTIRLCEVLNLDPRQVLIAEVIFTNIGGA
ATAIGDPPNVIIVSNQELRKMGLDFAGFTAHMFIGICLVLLVCFPLLRLLYWNRKLYNKE
PSEIVELKHEIHVWRLTAQRISPASREETAVRRLLLGKVLALEHLLARRLHTFHRQISQE
DKNWETNIQELQKKHRISDGILLAKCLTVLGFVIFMFFLNSFVPGIHLDLGWIAILGAIW
LLILADIHDFEIILHRVEWATLLFFAALFVLMEALAHLHLIEYVGEQTALLIKMVPEEQR
LIAAIVLVVWVSALASSLIDNIPFTATMIPVLLNLSHDPEVGLPAPPLMYALAFGACLGG
NGTLIGASANVVCAGIAEQHGYGFSFMEFFRLGFPMMVVSCTVGMCYLLVAHVVVGWN
GenBank ID Protein 157266326
UniProtKB/Swiss-Prot ID Q04671
UniProtKB/Swiss-Prot Entry Name P_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_000275.2
GeneCard ID OCA2
GenAtlas ID OCA2
HGNC ID HGNC:8101
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [PubMed:16959974 ]
  3. Oetting WS, King RA: Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism. Hum Mutat. 1999;13(2):99-115. [PubMed:10094567 ]
  4. Passmore LA, Kaesmann-Kellner B, Weber BH: Novel and recurrent mutations in the tyrosinase gene and the P gene in the German albino population. Hum Genet. 1999 Sep;105(3):200-10. [PubMed:10987646 ]
  5. Sulem P, Gudbjartsson DF, Stacey SN, Helgason A, Rafnar T, Magnusson KP, Manolescu A, Karason A, Palsson A, Thorleifsson G, Jakobsdottir M, Steinberg S, Palsson S, Jonasson F, Sigurgeirsson B, Thorisdottir K, Ragnarsson R, Benediktsdottir KR, Aben KK, Kiemeney LA, Olafsson JH, Gulcher J, Kong A, Thorsteinsdottir U, Stefansson K: Genetic determinants of hair, eye and skin pigmentation in Europeans. Nat Genet. 2007 Dec;39(12):1443-52. Epub 2007 Oct 21. [PubMed:17952075 ]
  6. Kayser M, Liu F, Janssens AC, Rivadeneira F, Lao O, van Duijn K, Vermeulen M, Arp P, Jhamai MM, van Ijcken WF, den Dunnen JT, Heath S, Zelenika D, Despriet DD, Klaver CC, Vingerling JR, de Jong PT, Hofman A, Aulchenko YS, Uitterlinden AG, Oostra BA, van Duijn CM: Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene. Am J Hum Genet. 2008 Feb;82(2):411-23. doi: 10.1016/j.ajhg.2007.10.003. Epub 2008 Jan 25. [PubMed:18252221 ]
  7. Sturm RA, Duffy DL, Zhao ZZ, Leite FP, Stark MS, Hayward NK, Martin NG, Montgomery GW: A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color. Am J Hum Genet. 2008 Feb;82(2):424-31. doi: 10.1016/j.ajhg.2007.11.005. Epub 2008 Jan 24. [PubMed:18252222 ]
  8. Eiberg H, Troelsen J, Nielsen M, Mikkelsen A, Mengel-From J, Kjaer KW, Hansen L: 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. Hum Genet. 2008 Mar;123(2):177-87. doi: 10.1007/s00439-007-0460-x. Epub 2008 Jan 3. [PubMed:18172690 ]
  9. Rinchik EM, Bultman SJ, Horsthemke B, Lee ST, Strunk KM, Spritz RA, Avidano KM, Jong MT, Nicholls RD: A gene for the mouse pink-eyed dilution locus and for human type II oculocutaneous albinism. Nature. 1993 Jan 7;361(6407):72-6. [PubMed:8421497 ]
  10. Lee ST, Nicholls RD, Jong MT, Fukai K, Spritz RA: Organization and sequence of the human P gene and identification of a new family of transport proteins. Genomics. 1995 Mar 20;26(2):354-63. [PubMed:7601462 ]
  11. Gardner JM, Nakatsu Y, Gondo Y, Lee S, Lyon MF, King RA, Brilliant MH: The mouse pink-eyed dilution gene: association with human Prader-Willi and Angelman syndromes. Science. 1992 Aug 21;257(5073):1121-4. [PubMed:1509264 ]
  12. Brilliant MH: The mouse p (pink-eyed dilution) and human P genes, oculocutaneous albinism type 2 (OCA2), and melanosomal pH. Pigment Cell Res. 2001 Apr;14(2):86-93. [PubMed:11310796 ]
  13. Manga P, Orlow SJ: Inverse correlation between pink-eyed dilution protein expression and induction of melanogenesis by bafilomycin A1. Pigment Cell Res. 2001 Oct;14(5):362-7. [PubMed:11601658 ]
  14. Sturm RA, Frudakis TN: Eye colour: portals into pigmentation genes and ancestry. Trends Genet. 2004 Aug;20(8):327-32. [PubMed:15262401 ]
  15. Lee ST, Nicholls RD, Schnur RE, Guida LC, Lu-Kuo J, Spinner NB, Zackai EH, Spritz RA: Diverse mutations of the P gene among African-Americans with type II (tyrosinase-positive) oculocutaneous albinism (OCA2). Hum Mol Genet. 1994 Nov;3(11):2047-51. [PubMed:7874125 ]
  16. Spritz RA, Fukai K, Holmes SA, Luande J: Frequent intragenic deletion of the P gene in Tanzanian patients with type II oculocutaneous albinism (OCA2). Am J Hum Genet. 1995 Jun;56(6):1320-3. [PubMed:7762554 ]
  17. Spritz RA, Lee ST, Fukai K, Brondum-Nielsen K, Chitayat D, Lipson MH, Musarella MA, Rosenmann A, Weleber RG: Novel mutations of the P gene in type II oculocutaneous albinism (OCA2). Hum Mutat. 1997;10(2):175-7. [PubMed:9259203 ]
  18. Oetting WS, Gardner JM, Fryer JP, Ching A, Durham-Pierre D, King RA, Brilliant MH: Mutations of the human P gene associated with Type II oculocutaneous albinism (OCA2). Mutations in brief no. 205. Online. Hum Mutat. 1998;12(6):434. [PubMed:10671067 ]
  19. Kerr R, Stevens G, Manga P, Salm S, John P, Haw T, Ramsay M: Identification of P gene mutations in individuals with oculocutaneous albinism in sub-Saharan Africa. Hum Mutat. 2000;15(2):166-72. [PubMed:10649493 ]
  20. Rebbeck TR, Kanetsky PA, Walker AH, Holmes R, Halpern AC, Schuchter LM, Elder DE, Guerry D: P gene as an inherited biomarker of human eye color. Cancer Epidemiol Biomarkers Prev. 2002 Aug;11(8):782-4. [PubMed:12163334 ]
  21. King RA, Willaert RK, Schmidt RM, Pietsch J, Savage S, Brott MJ, Fryer JP, Summers CG, Oetting WS: MC1R mutations modify the classic phenotype of oculocutaneous albinism type 2 (OCA2). Am J Hum Genet. 2003 Sep;73(3):638-45. Epub 2003 Jul 22. [PubMed:12876664 ]
  22. Kato A, Fukai K, Oiso N, Hosomi N, Saitoh S, Wada T, Shimizu H, Ishii M: A novel P gene missense mutation in a Japanese patient with oculocutaneous albinism type II (OCA2). J Dermatol Sci. 2003 May;31(3):189-92. [PubMed:12727022 ]
  23. Suzuki T, Miyamura Y, Matsunaga J, Shimizu H, Kawachi Y, Ohyama N, Ishikawa O, Ishikawa T, Terao H, Tomita Y: Six novel P gene mutations and oculocutaneous albinism type 2 frequency in Japanese albino patients. J Invest Dermatol. 2003 May;120(5):781-3. [PubMed:12713581 ]
  24. Jannot AS, Meziani R, Bertrand G, Gerard B, Descamps V, Archimbaud A, Picard C, Ollivaud L, Basset-Seguin N, Kerob D, Lanternier G, Lebbe C, Saiag P, Crickx B, Clerget-Darpoux F, Grandchamp B, Soufir N, Melan-Cohort: Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma. Eur J Hum Genet. 2005 Aug;13(8):913-20. [PubMed:15889046 ]
  25. Duffy DL, Montgomery GW, Chen W, Zhao ZZ, Le L, James MR, Hayward NK, Martin NG, Sturm RA: A three-single-nucleotide polymorphism haplotype in intron 1 of OCA2 explains most human eye-color variation. Am J Hum Genet. 2007 Feb;80(2):241-52. Epub 2006 Dec 20. [PubMed:17236130 ]
  26. Hongyi L, Haiyun W, Hui Z, Qing W, Honglei D, Shu M, Weiying J: Prenatal diagnosis of oculocutaneous albinism type II and novel mutations in two Chinese families. Prenat Diagn. 2007 Jun;27(6):502-6. [PubMed:17385796 ]