P_HUMAN
ID P_HUMAN Reviewed; 838 AA.
AC Q04671; Q15211; Q15212; Q96EN1; Q9UMI5;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 209.
DE RecName: Full=P protein;
DE AltName: Full=Melanocyte-specific transporter protein;
DE AltName: Full=Pink-eyed dilution protein homolog;
GN Name=OCA2; Synonyms=D15S12, P;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), AND VARIANT ASP-257.
RX PubMed=8421497; DOI=10.1038/361072a0;
RA Rinchik E.M., Bultman S.J., Horsthemke B., Lee S.-T., Strunk K.M.,
RA Spritz R.A., Avidano K.A., Jong M.T.C., Nicholls R.D.;
RT "A gene for the mouse pink-eyed dilution locus and for human type II
RT oculocutaneous albinism.";
RL Nature 361:72-76(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 3), FUNCTION, SUBCELLULAR
RP LOCATION, AND VARIANTS TRP-305; GLN-419; PHE-440; ARG-615 AND THR-722.
RX PubMed=7601462; DOI=10.1016/0888-7543(95)80220-g;
RA Lee S.-T., Nicholls R.D., Jong M.T.C., Fukai K., Spritz R.A.;
RT "Organization and sequence of the human P gene and identification of a new
RT family of transport proteins.";
RL Genomics 26:354-363(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 288-419, AND DISEASE.
RC TISSUE=Skin;
RX PubMed=1509264; DOI=10.1126/science.257.5073.1121;
RA Gardner J.M., Nakatsu Y., Gondo Y., Lee S., Lyon M.F., King R.A.,
RA Brilliant M.H.;
RT "The mouse pink-eyed dilution gene: association with human Prader-Willi and
RT Angelman syndromes.";
RL Science 257:1121-1124(1992).
RN [5]
RP FUNCTION.
RX PubMed=11310796; DOI=10.1034/j.1600-0749.2001.140203.x;
RA Brilliant M.H.;
RT "The mouse p (pink-eyed dilution) and human P genes, oculocutaneous
RT albinism type 2 (OCA2), and melanosomal pH.";
RL Pigment Cell Res. 14:86-93(2001).
RN [6]
RP POSSIBLE INVOLVEMENT IN SKIN COLOR VARIATION.
RX PubMed=11601658; DOI=10.1034/j.1600-0749.2001.140508.x;
RA Manga P., Orlow S.J.;
RT "Inverse correlation between pink-eyed dilution protein expression and
RT induction of melanogenesis by bafilomycin A1.";
RL Pigment Cell Res. 14:362-367(2001).
RN [7]
RP FUNCTION.
RX PubMed=15262401; DOI=10.1016/j.tig.2004.06.010;
RA Sturm R.A., Frudakis T.N.;
RT "Eye colour: portals into pigmentation genes and ancestry.";
RL Trends Genet. 20:327-332(2004).
RN [8]
RP REVIEW ON OCA2 VARIANTS.
RX PubMed=10094567;
RX DOI=10.1002/(sici)1098-1004(1999)13:2<99::aid-humu2>3.0.co;2-c;
RA Oetting W.S., King R.A.;
RT "Molecular basis of albinism: mutations and polymorphisms of pigmentation
RT genes associated with albinism.";
RL Hum. Mutat. 13:99-115(1999).
RN [9]
RP FUNCTION, AND INDUCTION.
RX PubMed=22234890; DOI=10.1101/gr.128652.111;
RA Visser M., Kayser M., Palstra R.J.;
RT "HERC2 rs12913832 modulates human pigmentation by attenuating chromatin-
RT loop formation between a long-range enhancer and the OCA2 promoter.";
RL Genome Res. 22:446-455(2012).
RN [10]
RP VARIANTS OCA2.
RX PubMed=7874125;
RA Lee S.-T., Nicholls R.D., Schnur R.E., Guida L.C., Lu-Kuo J., Spinner N.B.,
RA Zackai E.H., Spritz R.A.;
RT "Diverse mutations of the P gene among African-Americans with type II
RT (tyrosinase-positive) oculocutaneous albinism (OCA2).";
RL Hum. Mol. Genet. 3:2047-2051(1994).
RN [11]
RP VARIANTS OCA2.
RX PubMed=7762554;
RA Spritz R.A., Fukai K., Holmes S.A., Luande J.;
RT "Frequent intragenic deletion of the P gene in Tanzanian patients with type
RT II oculocutaneous albinism (OCA2).";
RL Am. J. Hum. Genet. 56:1320-1323(1995).
RN [12]
RP VARIANTS OCA2.
RX PubMed=9259203;
RX DOI=10.1002/(sici)1098-1004(1997)10:2<175::aid-humu12>3.0.co;2-x;
RA Spritz R.A., Lee S.-T., Fukai K., Brondum-Nielsen K., Chitayat D.,
RA Lipson M.H., Musarella M.A., Rosenmann A., Weleber R.G.;
RT "Novel mutations of the P gene in type II oculocutaneous albinism (OCA2).";
RL Hum. Mutat. 10:175-177(1997).
RN [13]
RP VARIANTS OCA2 ARG-86; PHE-112; VAL-368; ILE-592; PRO-724 AND VAL-787, AND
RP VARIANT ASP-257.
RX PubMed=10671067;
RX DOI=10.1002/(sici)1098-1004(1998)12:6<434::aid-humu16>3.0.co;2-7;
RA Oetting W.S., Gardner J.M., Fryer J.P., Ching A., Durham-Pierre D.,
RA King R.A., Brilliant M.H.;
RT "Mutations of the human P gene associated with type II oculocutaneous
RT albinism (OCA2).";
RL Hum. Mutat. 12:434-434(1998).
RN [14]
RP VARIANTS OCA2 GLY-290; ILE-443; GLU-614; LEU-617; CYS-679; CYS-720; ARG-795
RP AND VAL-833 DEL, AND VARIANTS TRP-305 AND GLN-419.
RX PubMed=10987646; DOI=10.1007/s004390051090;
RA Passmore L.A., Kaesmann-Kellner B., Weber B.H.F.;
RT "Novel and recurrent mutations in the tyrosinase gene and the P gene in the
RT German albino population.";
RL Hum. Genet. 105:200-210(1999).
RN [15]
RP VARIANT OCA2 VAL-334, AND VARIANTS UNCLASSIFIED OCA MET-350; THR-370;
RP LYS-678; PHE-688 AND LEU-743.
RX PubMed=10649493;
RX DOI=10.1002/(sici)1098-1004(200002)15:2<166::aid-humu5>3.0.co;2-z;
RA Kerr R., Stevens G., Manga P., Salm S., John P., Haw T., Ramsay M.;
RT "Identification of P gene mutations in individuals with oculocutaneous
RT albinism in sub-Saharan Africa.";
RL Hum. Mutat. 15:166-172(2000).
RN [16]
RP VARIANTS TRP-305 AND GLN-419, AND INVOLVEMENT IN DETERMINATION OF EYE
RP COLOR.
RX PubMed=12163334;
RA Rebbeck T.R., Kanetsky P.A., Walker A.H., Holmes R., Halpern A.C.,
RA Schuchter L.M., Elder D.E., Guerry D.;
RT "P gene as an inherited biomarker of human eye color.";
RL Cancer Epidemiol. Biomarkers Prev. 11:782-784(2002).
RN [17]
RP VARIANTS OCA2 GLY-290; ILE-443; ASP-489; CYS-679 AND LEU-743.
RX PubMed=12876664; DOI=10.1086/377569;
RA King R.A., Willaert R.K., Schmidt R.M., Pietsch J., Savage S., Brott M.J.,
RA Fryer J.P., Summers C.G., Oetting W.S.;
RT "MC1R mutations modify the classic phenotype of oculocutaneous albinism
RT type 2 (OCA2).";
RL Am. J. Hum. Genet. 73:638-645(2003).
RN [18]
RP VARIANTS OCA2 THR-481 AND HIS-799.
RX PubMed=12727022; DOI=10.1016/s0923-1811(03)00005-7;
RA Kato A., Fukai K., Oiso N., Hosomi N., Saitoh S., Wada T., Shimizu H.,
RA Ishii M.;
RT "A novel P gene missense mutation in a Japanese patient with oculocutaneous
RT albinism type II (OCA2).";
RL J. Dermatol. Sci. 31:189-192(2003).
RN [19]
RP VARIANTS OCA2 TRP-10; LEU-198; LEU-211; ILE-394 AND THR-481, AND VARIANTS
RP MET-387 AND ARG-615.
RX PubMed=12713581; DOI=10.1046/j.1523-1747.2003.12127.x;
RA Suzuki T., Miyamura Y., Matsunaga J., Shimizu H., Kawachi Y., Ohyama N.,
RA Ishikawa O., Ishikawa T., Terao H., Tomita Y.;
RT "Six novel P gene mutations and oculocutaneous albinism type 2 frequency in
RT Japanese albino patients.";
RL J. Invest. Dermatol. 120:781-783(2003).
RN [20]
RP VARIANTS TRP-305 AND GLN-419, AND INVOLVEMENT IN SUSCEPTIBILITY TO
RP MELANOMA.
RX PubMed=15889046; DOI=10.1038/sj.ejhg.5201415;
RG Melan-Cohort;
RA Jannot A.-S., Meziani R., Bertrand G., Gerard B., Descamps V.,
RA Archimbaud A., Picard C., Ollivaud L., Basset-Seguin N., Kerob D.,
RA Lanternier G., Lebbe C., Saiag P., Crickx B., Clerget-Darpoux F.,
RA Grandchamp B., Soufir N.;
RT "Allele variations in the OCA2 gene (pink-eyed-dilution locus) are
RT associated with genetic susceptibility to melanoma.";
RL Eur. J. Hum. Genet. 13:913-920(2005).
RN [21]
RP INVOLVEMENT IN SHEP1, AND POLYMORPHISM.
RX PubMed=17236130; DOI=10.1086/510885;
RA Duffy D.L., Montgomery G.W., Chen W., Zhao Z.Z., Le L., James M.R.,
RA Hayward N.K., Martin N.G., Sturm R.A.;
RT "A three-single-nucleotide polymorphism haplotype in intron 1 of OCA2
RT explains most human eye-color variation.";
RL Am. J. Hum. Genet. 80:241-252(2007).
RN [22]
RP VARIANT [LARGE SCALE ANALYSIS] THR-773.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [23]
RP INVOLVEMENT IN SHEP1, AND POLYMORPHISM.
RX PubMed=17952075; DOI=10.1038/ng.2007.13;
RA Sulem P., Gudbjartsson D.F., Stacey S.N., Helgason A., Rafnar T.,
RA Magnusson K.P., Manolescu A., Karason A., Palsson A., Thorleifsson G.,
RA Jakobsdottir M., Steinberg S., Palsson S., Jonasson F., Sigurgeirsson B.,
RA Thorisdottir K., Ragnarsson R., Benediktsdottir K.R., Aben K.K.,
RA Kiemeney L.A., Olafsson J.H., Gulcher J., Kong A., Thorsteinsdottir U.,
RA Stefansson K.;
RT "Genetic determinants of hair, eye and skin pigmentation in Europeans.";
RL Nat. Genet. 39:1443-1452(2007).
RN [24]
RP VARIANTS OCA2 ILE-443; ASP-476; ARG-775 AND HIS-827.
RX PubMed=17385796; DOI=10.1002/pd.1713;
RA Hongyi L., Haiyun W., Hui Z., Qing W., Honglei D., Shu M., Weiying J.;
RT "Prenatal diagnosis of oculocutaneous albinism type II and novel mutations
RT in two Chinese families.";
RL Prenat. Diagn. 27:502-506(2007).
RN [25]
RP INVOLVEMENT IN SHEP1, AND POLYMORPHISM.
RX PubMed=18252221; DOI=10.1016/j.ajhg.2007.10.003;
RA Kayser M., Liu F., Janssens A.C.J.W., Rivadeneira F., Lao O., van Duijn K.,
RA Vermeulen M., Arp P., Jhamai M.M., van Ijcken W.F.J., den Dunnen J.T.,
RA Heath S., Zelenika D., Despriet D.D.G., Klaver C.C.W., Vingerling J.R.,
RA de Jong P.T.V.M., Hofman A., Aulchenko Y.S., Uitterlinden A.G.,
RA Oostra B.A., van Duijn C.M.;
RT "Three genome-wide association studies and a linkage analysis identify
RT HERC2 as a human iris color gene.";
RL Am. J. Hum. Genet. 82:411-423(2008).
RN [26]
RP VARIANT GLN-419, FUNCTION, INDUCTION, INVOLVEMENT IN SHEP1, INVOLVEMENT IN
RP SUSCEPTIBILITY TO MELANOMA, AND POLYMORPHISM.
RX PubMed=18252222; DOI=10.1016/j.ajhg.2007.11.005;
RA Sturm R.A., Duffy D.L., Zhao Z.Z., Leite F.P.M., Stark M.S., Hayward N.K.,
RA Martin N.G., Montgomery G.W.;
RT "A single SNP in an evolutionary conserved region within intron 86 of the
RT HERC2 gene determines human blue-brown eye color.";
RL Am. J. Hum. Genet. 82:424-431(2008).
RN [27]
RP INVOLVEMENT IN SHEP1, POLYMORPHISM, AND INDUCTION.
RX PubMed=18172690; DOI=10.1007/s00439-007-0460-x;
RA Eiberg H., Troelsen J., Nielsen M., Mikkelsen A., Mengel-From J.,
RA Kjaer K.W., Hansen L.;
RT "Blue eye color in humans may be caused by a perfectly associated founder
RT mutation in a regulatory element located within the HERC2 gene inhibiting
RT OCA2 expression.";
RL Hum. Genet. 123:177-187(2008).
RN [28]
RP VARIANTS OCA2 MET-404; TRP-419; ILE-633; CYS-679 AND CYS-684.
RX PubMed=23504663; DOI=10.1002/humu.22315;
RA Simeonov D.R., Wang X., Wang C., Sergeev Y., Dolinska M., Bower M.,
RA Fischer R., Winer D., Dubrovsky G., Balog J.Z., Huizing M., Hart R.,
RA Zein W.M., Gahl W.A., Brooks B.P., Adams D.R.;
RT "DNA variations in oculocutaneous albinism: an updated mutation list and
RT current outstanding issues in molecular diagnostics.";
RL Hum. Mutat. 34:827-835(2013).
CC -!- FUNCTION: Could be involved in the transport of tyrosine, the precursor
CC to melanin synthesis, within the melanocyte. Regulates the pH of
CC melanosome and the melanosome maturation. One of the components of the
CC mammalian pigmentary system. Seems to regulate the post-translational
CC processing of tyrosinase, which catalyzes the limiting reaction in
CC melanin synthesis. May serve as a key control point at which ethnic
CC skin color variation is determined. Major determinant of brown and/or
CC blue eye color. {ECO:0000269|PubMed:11310796,
CC ECO:0000269|PubMed:15262401, ECO:0000269|PubMed:18252222,
CC ECO:0000269|PubMed:22234890, ECO:0000269|PubMed:7601462}.
CC -!- SUBCELLULAR LOCATION: Melanosome membrane {ECO:0000269|PubMed:7601462};
CC Multi-pass membrane protein {ECO:0000269|PubMed:7601462}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q04671-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q04671-2; Sequence=VSP_012284;
CC Name=3;
CC IsoId=Q04671-3; Sequence=VSP_012285, VSP_012286;
CC -!- INDUCTION: Expression is under the control of an enhancer element that
CC is encoded in an intron of the close-by HERC2 gene. The enhancer
CC element containing the T-allele of the polymorphism rs12913832 mediates
CC binding of the transcription factors HLTF, LEF1 and MITF and increases
CC OCA2 expression. In contrast, transcription factor binding and OCA2
CC expression are reduced in carriers of the C-allele of polymorphism
CC rs12913832. Thus, people homozygous for the C-allele have light-colored
CC eyes, while people homozygous for the T-allele of polymorphism
CC rs12913832 most often have brown eyes. {ECO:0000269|PubMed:18172690,
CC ECO:0000269|PubMed:18252222, ECO:0000269|PubMed:22234890}.
CC -!- POLYMORPHISM: Genetic variants in OCA2 define the skin/hair/eye
CC pigmentation variation locus 1 (SHEP1) [MIM:227220]; also known as
CC skin/hair/eye pigmentation type 1, blue/nonblue eyes or skin/hair/eye
CC pigmentation type 1, blue/brown eyes or skin/hair/eye pigmentation type
CC 1, blond/brown hair or eye color, brown/blue or eye color, blue/nonblue
CC or eye color type 3 (EYCL3) or brown eye color type 2 (BEY2) or hair
CC color type 3 (HCL3). Hair, eye and skin pigmentation are among the most
CC visible examples of human phenotypic variation, with a broad normal
CC range that is subject to substantial geographic stratification. In the
CC case of skin, individuals tend to have lighter pigmentation with
CC increasing distance from the equator. By contrast, the majority of
CC variation in human eye and hair color is found among individuals of
CC European ancestry, with most other human populations fixed for brown
CC eyes and black hair. OCA2 polymorphisms may act as a penetrance
CC modifier of the risk of malignant melanoma.
CC {ECO:0000269|PubMed:17236130, ECO:0000269|PubMed:17952075,
CC ECO:0000269|PubMed:18172690, ECO:0000269|PubMed:18252221,
CC ECO:0000269|PubMed:18252222}.
CC -!- DISEASE: Albinism, oculocutaneous, 2 (OCA2) [MIM:203200]: An autosomal
CC recessive disorder in which the biosynthesis of melanin pigment is
CC reduced in skin, hair, and eyes. Although affected infants may appear
CC at birth to have complete absence of melanin pigment, most patients
CC acquire small amounts of pigment with age. Visual anomalies include
CC decreased acuity and nystagmus. The phenotype is highly variable. The
CC hair of affected individuals may turn darker with age, and pigmented
CC nevi or freckles may be seen. African and African American individuals
CC may have yellow hair and blue-gray or hazel irides. One phenotypic
CC variant, 'brown OCA,' has been described in African and African
CC American populations and is characterized by light brown hair and skin
CC color and gray to tan irides. {ECO:0000269|PubMed:10649493,
CC ECO:0000269|PubMed:10671067, ECO:0000269|PubMed:10987646,
CC ECO:0000269|PubMed:12713581, ECO:0000269|PubMed:12727022,
CC ECO:0000269|PubMed:12876664, ECO:0000269|PubMed:17385796,
CC ECO:0000269|PubMed:23504663, ECO:0000269|PubMed:7762554,
CC ECO:0000269|PubMed:7874125, ECO:0000269|PubMed:9259203}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the CitM (TC 2.A.11) transporter family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Mutations of the P gene; Note=Retina International's
CC Scientific Newsletter;
CC URL="https://www.retina-international.org/files/sci-news/pgenemut.htm";
CC -!- WEB RESOURCE: Name=Albinism database (ADB); Note=P mutations;
CC URL="http://www.ifpcs.org/albinism/oca2mut.html";
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Questioning colour - Issue
CC 54 of January 2005;
CC URL="https://web.expasy.org/spotlight/back_issues/054";
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DR EMBL; M99564; AAA36477.1; -; mRNA.
DR EMBL; U19170; AAC13783.1; -; Genomic_DNA.
DR EMBL; U19153; AAC13783.1; JOINED; Genomic_DNA.
DR EMBL; U19154; AAC13783.1; JOINED; Genomic_DNA.
DR EMBL; U19156; AAC13783.1; JOINED; Genomic_DNA.
DR EMBL; U19158; AAC13783.1; JOINED; Genomic_DNA.
DR EMBL; U19160; AAC13783.1; JOINED; Genomic_DNA.
DR EMBL; U19162; AAC13783.1; JOINED; Genomic_DNA.
DR EMBL; U19164; AAC13783.1; JOINED; Genomic_DNA.
DR EMBL; U19166; AAC13783.1; JOINED; Genomic_DNA.
DR EMBL; U19169; AAC13783.1; JOINED; Genomic_DNA.
DR EMBL; U19168; AAC13783.1; JOINED; Genomic_DNA.
DR EMBL; U19167; AAC13783.1; JOINED; Genomic_DNA.
DR EMBL; U19165; AAC13783.1; JOINED; Genomic_DNA.
DR EMBL; U19163; AAC13783.1; JOINED; Genomic_DNA.
DR EMBL; U19161; AAC13783.1; JOINED; Genomic_DNA.
DR EMBL; U19159; AAC13783.1; JOINED; Genomic_DNA.
DR EMBL; U19157; AAC13783.1; JOINED; Genomic_DNA.
DR EMBL; U19155; AAC13783.1; JOINED; Genomic_DNA.
DR EMBL; U19176; AAC13784.1; -; Genomic_DNA.
DR EMBL; U19153; AAC13784.1; JOINED; Genomic_DNA.
DR EMBL; U19154; AAC13784.1; JOINED; Genomic_DNA.
DR EMBL; U19155; AAC13784.1; JOINED; Genomic_DNA.
DR EMBL; U19157; AAC13784.1; JOINED; Genomic_DNA.
DR EMBL; U19158; AAC13784.1; JOINED; Genomic_DNA.
DR EMBL; U19159; AAC13784.1; JOINED; Genomic_DNA.
DR EMBL; U19160; AAC13784.1; JOINED; Genomic_DNA.
DR EMBL; U19161; AAC13784.1; JOINED; Genomic_DNA.
DR EMBL; U19162; AAC13784.1; JOINED; Genomic_DNA.
DR EMBL; U19163; AAC13784.1; JOINED; Genomic_DNA.
DR EMBL; U19164; AAC13784.1; JOINED; Genomic_DNA.
DR EMBL; U19165; AAC13784.1; JOINED; Genomic_DNA.
DR EMBL; U19166; AAC13784.1; JOINED; Genomic_DNA.
DR EMBL; U19167; AAC13784.1; JOINED; Genomic_DNA.
DR EMBL; U19168; AAC13784.1; JOINED; Genomic_DNA.
DR EMBL; U19169; AAC13784.1; JOINED; Genomic_DNA.
DR EMBL; U19171; AAC13784.1; JOINED; Genomic_DNA.
DR EMBL; U19172; AAC13784.1; JOINED; Genomic_DNA.
DR EMBL; U19173; AAC13784.1; JOINED; Genomic_DNA.
DR EMBL; U19174; AAC13784.1; JOINED; Genomic_DNA.
DR EMBL; U19175; AAC13784.1; JOINED; Genomic_DNA.
DR EMBL; BC012097; AAH12097.1; -; mRNA.
DR EMBL; M97901; AAA36430.1; -; mRNA.
DR CCDS; CCDS10020.1; -. [Q04671-1]
DR CCDS; CCDS73701.1; -. [Q04671-2]
DR PIR; A57173; A57173.
DR PIR; S28911; S28911.
DR RefSeq; NP_000266.2; NM_000275.2. [Q04671-1]
DR RefSeq; NP_001287913.1; NM_001300984.1. [Q04671-2]
DR AlphaFoldDB; Q04671; -.
DR BioGRID; 111002; 5.
DR IntAct; Q04671; 3.
DR STRING; 9606.ENSP00000346659; -.
DR TCDB; 2.A.45.2.1; the arsenite-antimonite (arsb) efflux family.
DR GlyGen; Q04671; 6 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q04671; -.
DR PhosphoSitePlus; Q04671; -.
DR BioMuta; OCA2; -.
DR DMDM; 90110050; -.
DR MassIVE; Q04671; -.
DR PaxDb; Q04671; -.
DR PeptideAtlas; Q04671; -.
DR PRIDE; Q04671; -.
DR Antibodypedia; 22329; 196 antibodies from 25 providers.
DR DNASU; 4948; -.
DR Ensembl; ENST00000353809.9; ENSP00000261276.8; ENSG00000104044.16. [Q04671-2]
DR Ensembl; ENST00000354638.8; ENSP00000346659.3; ENSG00000104044.16. [Q04671-1]
DR GeneID; 4948; -.
DR KEGG; hsa:4948; -.
DR MANE-Select; ENST00000354638.8; ENSP00000346659.3; NM_000275.3; NP_000266.2.
DR UCSC; uc001zbh.6; human. [Q04671-1]
DR CTD; 4948; -.
DR DisGeNET; 4948; -.
DR GeneCards; OCA2; -.
DR GeneReviews; OCA2; -.
DR HGNC; HGNC:8101; OCA2.
DR HPA; ENSG00000104044; Tissue enhanced (choroid plexus, skin).
DR MalaCards; OCA2; -.
DR MIM; 203200; phenotype.
DR MIM; 227220; phenotype.
DR MIM; 611409; gene.
DR neXtProt; NX_Q04671; -.
DR OpenTargets; ENSG00000104044; -.
DR Orphanet; 98794; Angelman syndrome due to maternal 15q11q13 deletion.
DR Orphanet; 79432; Oculocutaneous albinism type 2.
DR Orphanet; 98754; Prader-Willi syndrome due to maternal uniparental disomy of chromosome 15.
DR Orphanet; 177901; Prader-Willi syndrome due to paternal deletion of 15q11q13 type 1.
DR Orphanet; 177904; Prader-Willi syndrome due to paternal deletion of 15q11q13 type 2.
DR PharmGKB; PA31890; -.
DR VEuPathDB; HostDB:ENSG00000104044; -.
DR eggNOG; KOG2639; Eukaryota.
DR GeneTree; ENSGT01030000234550; -.
DR HOGENOM; CLU_011920_2_1_1; -.
DR InParanoid; Q04671; -.
DR OMA; ISWIDFE; -.
DR OrthoDB; 495573at2759; -.
DR PhylomeDB; Q04671; -.
DR TreeFam; TF323556; -.
DR PathwayCommons; Q04671; -.
DR Reactome; R-HSA-5662702; Melanin biosynthesis.
DR SignaLink; Q04671; -.
DR SIGNOR; Q04671; -.
DR BioGRID-ORCS; 4948; 8 hits in 1062 CRISPR screens.
DR ChiTaRS; OCA2; human.
DR GeneWiki; OCA2; -.
DR GenomeRNAi; 4948; -.
DR Pharos; Q04671; Tbio.
DR PRO; PR:Q04671; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q04671; protein.
DR Bgee; ENSG00000104044; Expressed in pigmented layer of retina and 146 other tissues.
DR ExpressionAtlas; Q04671; baseline and differential.
DR Genevisible; Q04671; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0033162; C:melanosome membrane; IDA:UniProtKB.
DR GO; GO:0005302; F:L-tyrosine transmembrane transporter activity; TAS:ProtInc.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0006726; P:eye pigment biosynthetic process; TAS:ProtInc.
DR GO; GO:0042438; P:melanin biosynthetic process; IBA:GO_Central.
DR GO; GO:0030318; P:melanocyte differentiation; IBA:GO_Central.
DR GO; GO:0007286; P:spermatid development; IEA:Ensembl.
DR InterPro; IPR004680; Cit_transptr-like_dom.
DR Pfam; PF03600; CitMHS; 1.
PE 1: Evidence at protein level;
KW Albinism; Alternative splicing; Disease variant; Glycoprotein; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..838
FT /note="P protein"
FT /id="PRO_0000172509"
FT TOPO_DOM 1..179
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 180..197
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 198..330
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 331..347
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 348..353
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 354..370
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 371..384
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 385..401
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 402..423
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 424..440
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 441..513
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 514..530
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 531..620
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 621..637
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 638..647
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 648..664
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 665..679
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 680..696
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 697..720
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 721..737
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 738..760
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 761..777
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 778..817
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 818..834
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 835..838
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 38..60
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 74..94
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 214
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 218
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 273
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 442
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 781
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 349..372
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_012284"
FT VAR_SEQ 652..668
FT /note="WIAILGAIWLLILADIH -> GLGLVQAGRYYLSTPES (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:8421497"
FT /id="VSP_012285"
FT VAR_SEQ 669..838
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:8421497"
FT /id="VSP_012286"
FT VARIANT 10
FT /note="R -> W (in OCA2; dbSNP:rs554862186)"
FT /evidence="ECO:0000269|PubMed:12713581"
FT /id="VAR_020622"
FT VARIANT 27
FT /note="G -> R (in OCA2; dbSNP:rs61738394)"
FT /id="VAR_006117"
FT VARIANT 86
FT /note="S -> R (in OCA2; dbSNP:rs772243109)"
FT /evidence="ECO:0000269|PubMed:10671067"
FT /id="VAR_006118"
FT VARIANT 112
FT /note="C -> F (in OCA2; dbSNP:rs562649990)"
FT /evidence="ECO:0000269|PubMed:10671067"
FT /id="VAR_006119"
FT VARIANT 198
FT /note="P -> L (in OCA2; dbSNP:rs183487020)"
FT /evidence="ECO:0000269|PubMed:12713581"
FT /id="VAR_020623"
FT VARIANT 206..211
FT /note="Missing (in OCA2; severe)"
FT /id="VAR_006120"
FT VARIANT 211
FT /note="P -> L (in OCA2; dbSNP:rs190612616)"
FT /evidence="ECO:0000269|PubMed:12713581"
FT /id="VAR_020624"
FT VARIANT 241
FT /note="P -> R (in dbSNP:rs2305253)"
FT /id="VAR_022019"
FT VARIANT 257
FT /note="A -> D (in dbSNP:rs1050968)"
FT /evidence="ECO:0000269|PubMed:10671067,
FT ECO:0000269|PubMed:8421497"
FT /id="VAR_006121"
FT VARIANT 266
FT /note="R -> W (in dbSNP:rs33929465)"
FT /id="VAR_032094"
FT VARIANT 273..274
FT /note="NW -> KV (in OCA2; dbSNP:rs797044784)"
FT /id="VAR_006122"
FT VARIANT 290
FT /note="R -> G (in OCA2; dbSNP:rs769408559)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:12876664"
FT /id="VAR_020625"
FT VARIANT 305
FT /note="R -> W (associated with nonblue eye color; could be
FT a biomarker of cutaneous cancer risk; dbSNP:rs1800401)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:12163334, ECO:0000269|PubMed:15889046,
FT ECO:0000269|PubMed:7601462"
FT /id="VAR_006123"
FT VARIANT 334
FT /note="A -> V (in OCA2; dbSNP:rs121918168)"
FT /evidence="ECO:0000269|PubMed:10649493"
FT /id="VAR_020626"
FT VARIANT 336
FT /note="A -> V (in dbSNP:rs34010619)"
FT /id="VAR_032095"
FT VARIANT 350
FT /note="V -> M (in unclassified OCA; dbSNP:rs533478642)"
FT /evidence="ECO:0000269|PubMed:10649493"
FT /id="VAR_020627"
FT VARIANT 368
FT /note="A -> V (in OCA2; dbSNP:rs61745150)"
FT /evidence="ECO:0000269|PubMed:10671067"
FT /id="VAR_006124"
FT VARIANT 370
FT /note="I -> T (in unclassified OCA; dbSNP:rs34731820)"
FT /evidence="ECO:0000269|PubMed:10649493"
FT /id="VAR_020628"
FT VARIANT 385
FT /note="F -> I (in OCA2; severe; dbSNP:rs137956605)"
FT /id="VAR_006125"
FT VARIANT 387
FT /note="T -> M (in dbSNP:rs150335311)"
FT /evidence="ECO:0000269|PubMed:12713581"
FT /id="VAR_020629"
FT VARIANT 394
FT /note="M -> I (in OCA2; dbSNP:rs121918171)"
FT /evidence="ECO:0000269|PubMed:12713581"
FT /id="VAR_020630"
FT VARIANT 395
FT /note="M -> L (in OCA2; severe; dbSNP:rs757286784)"
FT /id="VAR_006126"
FT VARIANT 404
FT /note="T -> M (in OCA2; dbSNP:rs144812594)"
FT /evidence="ECO:0000269|PubMed:23504663"
FT /id="VAR_006127"
FT VARIANT 419
FT /note="R -> Q (associated with green/hazel eye color;
FT dbSNP:rs1800407)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:12163334, ECO:0000269|PubMed:15889046,
FT ECO:0000269|PubMed:18252222, ECO:0000269|PubMed:7601462"
FT /id="VAR_006128"
FT VARIANT 419
FT /note="R -> W (in OCA2; dbSNP:rs143218168)"
FT /evidence="ECO:0000269|PubMed:23504663"
FT /id="VAR_006129"
FT VARIANT 425
FT /note="Missing (in OCA2; mild; dbSNP:rs752510351)"
FT /id="VAR_006130"
FT VARIANT 440
FT /note="L -> F (in dbSNP:rs1800408)"
FT /evidence="ECO:0000269|PubMed:7601462"
FT /id="VAR_007939"
FT VARIANT 440
FT /note="L -> H"
FT /id="VAR_006131"
FT VARIANT 443
FT /note="V -> I (in OCA2; dbSNP:rs121918166)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:12876664, ECO:0000269|PubMed:17385796"
FT /id="VAR_006132"
FT VARIANT 446
FT /note="M -> V (in OCA2; mild; AROA form;
FT dbSNP:rs140566426)"
FT /id="VAR_006133"
FT VARIANT 473
FT /note="I -> S (in OCA2)"
FT /id="VAR_006134"
FT VARIANT 476
FT /note="N -> D (in OCA2)"
FT /evidence="ECO:0000269|PubMed:17385796"
FT /id="VAR_043700"
FT VARIANT 481
FT /note="A -> T (in OCA2; dbSNP:rs74653330)"
FT /evidence="ECO:0000269|PubMed:12713581,
FT ECO:0000269|PubMed:12727022"
FT /id="VAR_007940"
FT VARIANT 489
FT /note="N -> D (in OCA2; mild/severe; dbSNP:rs121918170)"
FT /evidence="ECO:0000269|PubMed:12876664"
FT /id="VAR_006135"
FT VARIANT 519
FT /note="V -> A (in dbSNP:rs41446944)"
FT /id="VAR_032096"
FT VARIANT 549
FT /note="H -> Q (in OCA2)"
FT /id="VAR_006136"
FT VARIANT 560
FT /note="R -> H (in dbSNP:rs35110389)"
FT /id="VAR_032097"
FT VARIANT 592
FT /note="T -> I (in OCA2; dbSNP:rs1800413)"
FT /evidence="ECO:0000269|PubMed:10671067"
FT /id="VAR_006137"
FT VARIANT 614
FT /note="K -> E (in OCA2)"
FT /evidence="ECO:0000269|PubMed:10987646"
FT /id="VAR_020631"
FT VARIANT 614
FT /note="K -> N (in OCA2)"
FT /id="VAR_006138"
FT VARIANT 615
FT /note="H -> R (in dbSNP:rs1800414)"
FT /evidence="ECO:0000269|PubMed:12713581,
FT ECO:0000269|PubMed:7601462"
FT /id="VAR_006139"
FT VARIANT 617
FT /note="I -> L (in OCA2; dbSNP:rs763016773)"
FT /evidence="ECO:0000269|PubMed:10987646"
FT /id="VAR_020632"
FT VARIANT 633
FT /note="V -> I (in OCA2; dbSNP:rs1372200062)"
FT /evidence="ECO:0000269|PubMed:23504663"
FT /id="VAR_072600"
FT VARIANT 652
FT /note="W -> R (in OCA2; dbSNP:rs886043514)"
FT /id="VAR_006140"
FT VARIANT 678
FT /note="E -> K (in unclassified OCA)"
FT /evidence="ECO:0000269|PubMed:10649493"
FT /id="VAR_020633"
FT VARIANT 679
FT /note="W -> C (in OCA2; dbSNP:rs121918169)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:12876664, ECO:0000269|PubMed:23504663"
FT /id="VAR_020634"
FT VARIANT 679
FT /note="W -> R (in OCA2; severe; dbSNP:rs751822606)"
FT /id="VAR_006141"
FT VARIANT 684
FT /note="F -> C (in OCA2; dbSNP:rs772754008)"
FT /evidence="ECO:0000269|PubMed:23504663"
FT /id="VAR_072601"
FT VARIANT 688
FT /note="L -> F (in unclassified OCA)"
FT /evidence="ECO:0000269|PubMed:10649493"
FT /id="VAR_020635"
FT VARIANT 720
FT /note="R -> C (in OCA2; dbSNP:rs141545475)"
FT /evidence="ECO:0000269|PubMed:10987646"
FT /id="VAR_020636"
FT VARIANT 722
FT /note="I -> T (in dbSNP:rs1800417)"
FT /evidence="ECO:0000269|PubMed:7601462"
FT /id="VAR_006142"
FT VARIANT 724
FT /note="A -> P (in OCA2)"
FT /evidence="ECO:0000269|PubMed:10671067"
FT /id="VAR_006143"
FT VARIANT 736
FT /note="S -> L (in OCA2; dbSNP:rs780296175)"
FT /id="VAR_006144"
FT VARIANT 743
FT /note="P -> L (in OCA2 and unclassified OCA;
FT dbSNP:rs121918167)"
FT /evidence="ECO:0000269|PubMed:10649493,
FT ECO:0000269|PubMed:12876664"
FT /id="VAR_006145"
FT VARIANT 773
FT /note="A -> T (in a breast cancer sample; somatic mutation;
FT dbSNP:rs1184589806)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036468"
FT VARIANT 775
FT /note="G -> R (in OCA2)"
FT /evidence="ECO:0000269|PubMed:17385796"
FT /id="VAR_043701"
FT VARIANT 787
FT /note="A -> V (in OCA2; dbSNP:rs200457227)"
FT /evidence="ECO:0000269|PubMed:10671067"
FT /id="VAR_006146"
FT VARIANT 795
FT /note="G -> R (in OCA2)"
FT /evidence="ECO:0000269|PubMed:10987646"
FT /id="VAR_020637"
FT VARIANT 799
FT /note="Q -> H (in OCA2)"
FT /evidence="ECO:0000269|PubMed:12727022"
FT /id="VAR_020638"
FT VARIANT 827
FT /note="Y -> H (in OCA2; dbSNP:rs1255943449)"
FT /evidence="ECO:0000269|PubMed:17385796"
FT /id="VAR_043702"
FT VARIANT 833
FT /note="Missing (in OCA2; dbSNP:rs751440917)"
FT /evidence="ECO:0000269|PubMed:10987646"
FT /id="VAR_021682"
SQ SEQUENCE 838 AA; 92850 MW; A6158B9E55BD7199 CRC64;
MHLEGRDGRR YPGAPAVELL QTSVPSGLAE LVAGKRRLPR GAGGADPSHS CPRGAAGQSS
WAPAGQEFAS FLTKGRSHSS LPQMSSSRSK DSCFTENTPL LRNSLQEKGS RCIPVYHPEF
ITAEESWEDS SADWERRYLL SREVSGLSAS ASSEKGDLLD SPHIRLRLSK LRRCVQWLKV
MGLFAFVVLC SILFSLYPDQ GKLWQLLALS PLENYSVNLS SHVDSTLLQV DLAGALVASG
PSRPGREEHI VVELTQADAL GSRWRRPQQV THNWTVYLNP RRSEHSVMSR TFEVLTRETV
SISIRASLQQ TQAVPLLMAH QYLRGSVETQ VTIATAILAG VYALIIFEIV HRTLAAMLGS
LAALAALAVI GDRPSLTHVV EWIDFETLAL LFGMMILVAI FSETGFFDYC AVKAYRLSRG
RVWAMIIMLC LIAAVLSAFL DNVTTMLLFT PVTIRLCEVL NLDPRQVLIA EVIFTNIGGA
ATAIGDPPNV IIVSNQELRK MGLDFAGFTA HMFIGICLVL LVCFPLLRLL YWNRKLYNKE
PSEIVELKHE IHVWRLTAQR ISPASREETA VRRLLLGKVL ALEHLLARRL HTFHRQISQE
DKNWETNIQE LQKKHRISDG ILLAKCLTVL GFVIFMFFLN SFVPGIHLDL GWIAILGAIW
LLILADIHDF EIILHRVEWA TLLFFAALFV LMEALAHLHL IEYVGEQTAL LIKMVPEEQR
LIAAIVLVVW VSALASSLID NIPFTATMIP VLLNLSHDPE VGLPAPPLMY ALAFGACLGG
NGTLIGASAN VVCAGIAEQH GYGFSFMEFF RLGFPMMVVS CTVGMCYLLV AHVVVGWN
