(data stored in ACNUC23119 zone)

SWISSPROT: 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   30-AUG-2017, entry version 177.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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,
RP   SUBCELLULAR LOCATION, AND VARIANTS TRP-305; GLN-419; PHE-440; ARG-615
RP   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
RT   new 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
RT   project: 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-
RT   Willi and 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>3.3.CO;2-3;
RA   Oetting W.S., King R.A.;
RT   "Molecular basis of albinism: mutations and polymorphisms of
RT   pigmentation 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
RT   chromatin-loop formation between a long-range enhancer and the OCA2
RT   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.,
RA   Spinner N.B., 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
RT   type 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
RT   (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,
RP   AND VARIANT ASP-257.
RX   PubMed=10671067;
RX   DOI=10.1002/(SICI)1098-1004(1998)12:6<434::AID-HUMU15>3.3.CO;2-1;
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;
RP   ARG-795 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
RT   in the 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.,
RA   Brott M.J., Fryer J.P., Summers C.G., Oetting W.S.;
RT   "MC1R mutations modify the classic phenotype of oculocutaneous
RT   albinism 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
RT   oculocutaneous 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
RP   VARIANTS 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.,
RA   Ohyama N., Ishikawa O., Ishikawa T., Terao H., Tomita Y.;
RT   "Six novel P gene mutations and oculocutaneous albinism type 2
RT   frequency in 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.,
RA   Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA   Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA   Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA   Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal
RT   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.,
RA   Sigurgeirsson B., Thorisdottir K., Ragnarsson R.,
RA   Benediktsdottir K.R., Aben K.K., Kiemeney L.A., Olafsson J.H.,
RA   Gulcher J., Kong A., Thorsteinsdottir U., Stefansson K.;
RT   "Genetic determinants of hair, eye and skin pigmentation in
RT   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
RT   mutations 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.,
RA   van Duijn K., Vermeulen M., Arp P., Jhamai M.M., van Ijcken W.F.J.,
RA   den Dunnen J.T., Heath S., Zelenika D., Despriet D.D.G.,
RA   Klaver C.C.W., Vingerling J.R., de Jong P.T.V.M., Hofman A.,
RA   Aulchenko Y.S., Uitterlinden A.G., 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,
RP   INVOLVEMENT IN 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.,
RA   Hayward N.K., Martin N.G., Montgomery G.W.;
RT   "A single SNP in an evolutionary conserved region within intron 86 of
RT   the 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
RT   founder mutation in a regulatory element located within the HERC2 gene
RT   inhibiting 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
RT   and current outstanding issues in molecular diagnostics.";
RL   Hum. Mutat. 34:827-835(2013).
CC   -!- FUNCTION: Could be involved in the transport of tyrosine, the
CC       precursor to melanin synthesis, within the melanocyte. Regulates
CC       the pH of melanosome and the melanosome maturation. One of the
CC       components of the mammalian pigmentary system. Seems to regulate
CC       the post-translational processing of tyrosinase, which catalyzes
CC       the limiting reaction in melanin synthesis. May serve as a key
CC       control point at which ethnic skin color variation is determined.
CC       Major determinant of brown and/or blue eye color.
CC       {ECO:0000269|PubMed:11310796, ECO:0000269|PubMed:15262401,
CC       ECO:0000269|PubMed:18252222, ECO:0000269|PubMed:22234890,
CC       ECO:0000269|PubMed:7601462}.
CC   -!- SUBCELLULAR LOCATION: Melanosome membrane
CC       {ECO:0000269|PubMed:7601462}; Multi-pass membrane protein
CC       {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         Note=No experimental confirmation available.;
CC   -!- INDUCTION: Expression is under the control of an enhancer element
CC       that is encoded in an intron of the close-by HERC2 gene. The
CC       enhancer element containing the T-allele of the polymorphism
CC       rs12913832 mediates binding of the transcription factors HLTF,
CC       LEF1 and MITF and increases OCA2 expression. In contrast,
CC       transcription factor binding and OCA2 expression are reduced in
CC       carriers of the C-allele of polymorphism rs12913832. Thus, people
CC       homozygous for the C-allele have light-colored eyes, while people
CC       homozygous for the T-allele of polymorphism rs12913832 most often
CC       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
CC       skin/hair/eye pigmentation type 1, blue/brown eyes or
CC       skin/hair/eye pigmentation type 1, blond/brown hair or eye color,
CC       brown/blue or eye color, blue/nonblue or eye color type 3 (EYCL3)
CC       or brown eye color type 2 (BEY2) or hair color type 3 (HCL3).
CC       Hair, eye and skin pigmentation are among the most visible
CC       examples of human phenotypic variation, with a broad normal range
CC       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
CC       of European ancestry, with most other human populations fixed for
CC       brown eyes and black hair. OCA2 polymorphisms may act as a
CC       penetrance 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
CC       autosomal recessive disorder in which the biosynthesis of melanin
CC       pigment is reduced in skin, hair, and eyes. Although affected
CC       infants may appear at birth to have complete absence of melanin
CC       pigment, most patients acquire small amounts of pigment with age.
CC       Visual anomalies include decreased acuity and nystagmus. The
CC       phenotype is highly variable. The hair of affected individuals may
CC       turn darker with age, and pigmented nevi or freckles may be seen.
CC       African and African American individuals may have yellow hair and
CC       blue-gray or hazel irides. One phenotypic variant, 'brown OCA,'
CC       has been described in African and African American populations and
CC       is characterized by light brown hair and skin color and gray to
CC       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 mutations affecting the gene represented in
CC       this 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
CC       International's Scientific Newsletter;
CC       URL="http://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 -
CC       Issue 54 of January 2005;
CC       URL="http://web.expasy.org/spotlight/back_issues/054";
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   UniGene; Hs.654411; -.
DR   ProteinModelPortal; Q04671; -.
DR   BioGrid; 111002; 3.
DR   IntAct; Q04671; 1.
DR   STRING; 9606.ENSP00000346659; -.
DR   TCDB; 2.A.45.2.1; the arsenite-antimonite (arsb) efflux family.
DR   iPTMnet; Q04671; -.
DR   PhosphoSitePlus; Q04671; -.
DR   BioMuta; OCA2; -.
DR   DMDM; 90110050; -.
DR   PaxDb; Q04671; -.
DR   PeptideAtlas; Q04671; -.
DR   PRIDE; Q04671; -.
DR   Ensembl; ENST00000353809; ENSP00000261276; ENSG00000104044. [Q04671-2]
DR   Ensembl; ENST00000354638; ENSP00000346659; ENSG00000104044. [Q04671-1]
DR   GeneID; 4948; -.
DR   KEGG; hsa:4948; -.
DR   UCSC; uc001zbh.6; human. [Q04671-1]
DR   CTD; 4948; -.
DR   DisGeNET; 4948; -.
DR   GeneCards; OCA2; -.
DR   GeneReviews; OCA2; -.
DR   H-InvDB; HIX0012054; -.
DR   HGNC; HGNC:8101; OCA2.
DR   MalaCards; OCA2; -.
DR   MIM; 203200; phenotype.
DR   MIM; 227220; phenotype.
DR   MIM; 611409; gene.
DR   neXtProt; NX_Q04671; -.
DR   OpenTargets; ENSG00000104044; -.
DR   Orphanet; 72; Angelman syndrome.
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   eggNOG; KOG2639; Eukaryota.
DR   eggNOG; COG1055; LUCA.
DR   GeneTree; ENSGT00390000017120; -.
DR   HOGENOM; HOG000047303; -.
DR   HOVERGEN; HBG008343; -.
DR   InParanoid; Q04671; -.
DR   OMA; QVTHNWT; -.
DR   OrthoDB; EOG091G03O6; -.
DR   PhylomeDB; Q04671; -.
DR   TreeFam; TF323556; -.
DR   Reactome; R-HSA-5662702; Melanin biosynthesis.
DR   GeneWiki; OCA2; -.
DR   GenomeRNAi; 4948; -.
DR   PRO; PR:Q04671; -.
DR   Proteomes; UP000005640; Chromosome 15.
DR   Bgee; ENSG00000104044; -.
DR   CleanEx; HS_OCA2; -.
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:0005215; F:transporter activity; TAS:ProtInc.
DR   GO; GO:0008283; P:cell proliferation; IEA:Ensembl.
DR   GO; GO:0006726; P:eye pigment biosynthetic process; TAS:ProtInc.
DR   GO; GO:0042438; P:melanin biosynthetic process; IEA:Ensembl.
DR   GO; GO:0030318; P:melanocyte differentiation; IEA:Ensembl.
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;
DR   PRODOM; Q04671.
DR   SWISS-2DPAGE; Q04671.
KW   Albinism; Alternative splicing; Complete proteome; Disease mutation;
KW   Glycoprotein; Membrane; Polymorphism; Reference proteome;
KW   Transmembrane; Transmembrane helix; Transport.
FT   CHAIN         1    838       P protein.
FT                                /FTId=PRO_0000172509.
FT   TOPO_DOM      1    179       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    180    197       Helical. {ECO:0000255}.
FT   TOPO_DOM    198    330       Extracellular. {ECO:0000255}.
FT   TRANSMEM    331    347       Helical. {ECO:0000255}.
FT   TOPO_DOM    348    353       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    354    370       Helical. {ECO:0000255}.
FT   TOPO_DOM    371    384       Extracellular. {ECO:0000255}.
FT   TRANSMEM    385    401       Helical. {ECO:0000255}.
FT   TOPO_DOM    402    423       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    424    440       Helical. {ECO:0000255}.
FT   TOPO_DOM    441    513       Extracellular. {ECO:0000255}.
FT   TRANSMEM    514    530       Helical. {ECO:0000255}.
FT   TOPO_DOM    531    620       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    621    637       Helical. {ECO:0000255}.
FT   TOPO_DOM    638    647       Extracellular. {ECO:0000255}.
FT   TRANSMEM    648    664       Helical. {ECO:0000255}.
FT   TOPO_DOM    665    679       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    680    696       Helical. {ECO:0000255}.
FT   TOPO_DOM    697    720       Extracellular. {ECO:0000255}.
FT   TRANSMEM    721    737       Helical. {ECO:0000255}.
FT   TOPO_DOM    738    760       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    761    777       Helical. {ECO:0000255}.
FT   TOPO_DOM    778    817       Extracellular. {ECO:0000255}.
FT   TRANSMEM    818    834       Helical. {ECO:0000255}.
FT   TOPO_DOM    835    838       Cytoplasmic. {ECO:0000255}.
FT   CARBOHYD    214    214       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    218    218       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    273    273       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    442    442       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    781    781       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   VAR_SEQ     349    372       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_012284.
FT   VAR_SEQ     652    668       WIAILGAIWLLILADIH -> GLGLVQAGRYYLSTPES
FT                                (in isoform 3).
FT                                {ECO:0000303|PubMed:8421497}.
FT                                /FTId=VSP_012285.
FT   VAR_SEQ     669    838       Missing (in isoform 3).
FT                                {ECO:0000303|PubMed:8421497}.
FT                                /FTId=VSP_012286.
FT   VARIANT      10     10       R -> W (in OCA2; dbSNP:rs554862186).
FT                                {ECO:0000269|PubMed:12713581}.
FT                                /FTId=VAR_020622.
FT   VARIANT      27     27       G -> R (in OCA2; dbSNP:rs61738394).
FT                                /FTId=VAR_006117.
FT   VARIANT      86     86       S -> R (in OCA2; dbSNP:rs772243109).
FT                                {ECO:0000269|PubMed:10671067}.
FT                                /FTId=VAR_006118.
FT   VARIANT     112    112       C -> F (in OCA2; dbSNP:rs562649990).
FT                                {ECO:0000269|PubMed:10671067}.
FT                                /FTId=VAR_006119.
FT   VARIANT     198    198       P -> L (in OCA2; dbSNP:rs183487020).
FT                                {ECO:0000269|PubMed:12713581}.
FT                                /FTId=VAR_020623.
FT   VARIANT     206    211       Missing (in OCA2; severe).
FT                                /FTId=VAR_006120.
FT   VARIANT     211    211       P -> L (in OCA2; dbSNP:rs190612616).
FT                                {ECO:0000269|PubMed:12713581}.
FT                                /FTId=VAR_020624.
FT   VARIANT     241    241       P -> R (in dbSNP:rs2305253).
FT                                /FTId=VAR_022019.
FT   VARIANT     257    257       A -> D (in dbSNP:rs1050968).
FT                                {ECO:0000269|PubMed:10671067,
FT                                ECO:0000269|PubMed:8421497}.
FT                                /FTId=VAR_006121.
FT   VARIANT     266    266       R -> W (in dbSNP:rs33929465).
FT                                /FTId=VAR_032094.
FT   VARIANT     273    274       NW -> KV (in OCA2; dbSNP:rs797044784).
FT                                /FTId=VAR_006122.
FT   VARIANT     290    290       R -> G (in OCA2; dbSNP:rs769408559).
FT                                {ECO:0000269|PubMed:10987646,
FT                                ECO:0000269|PubMed:12876664}.
FT                                /FTId=VAR_020625.
FT   VARIANT     305    305       R -> W (polymorphism associated with
FT                                nonblue eye color; could be a biomarker
FT                                of cutaneous cancer risk;
FT                                dbSNP:rs1800401).
FT                                {ECO:0000269|PubMed:10987646,
FT                                ECO:0000269|PubMed:12163334,
FT                                ECO:0000269|PubMed:15889046,
FT                                ECO:0000269|PubMed:7601462}.
FT                                /FTId=VAR_006123.
FT   VARIANT     334    334       A -> V (in OCA2; dbSNP:rs121918168).
FT                                {ECO:0000269|PubMed:10649493}.
FT                                /FTId=VAR_020626.
FT   VARIANT     336    336       A -> V (in dbSNP:rs34010619).
FT                                /FTId=VAR_032095.
FT   VARIANT     350    350       V -> M (in unclassified OCA;
FT                                dbSNP:rs533478642).
FT                                {ECO:0000269|PubMed:10649493}.
FT                                /FTId=VAR_020627.
FT   VARIANT     368    368       A -> V (in OCA2; dbSNP:rs61745150).
FT                                {ECO:0000269|PubMed:10671067}.
FT                                /FTId=VAR_006124.
FT   VARIANT     370    370       I -> T (in unclassified OCA;
FT                                dbSNP:rs34731820).
FT                                {ECO:0000269|PubMed:10649493}.
FT                                /FTId=VAR_020628.
FT   VARIANT     385    385       F -> I (in OCA2; severe;
FT                                dbSNP:rs137956605).
FT                                /FTId=VAR_006125.
FT   VARIANT     387    387       T -> M (in dbSNP:rs150335311).
FT                                {ECO:0000269|PubMed:12713581}.
FT                                /FTId=VAR_020629.
FT   VARIANT     394    394       M -> I (in OCA2; dbSNP:rs121918171).
FT                                {ECO:0000269|PubMed:12713581}.
FT                                /FTId=VAR_020630.
FT   VARIANT     395    395       M -> L (in OCA2; severe;
FT                                dbSNP:rs757286784).
FT                                /FTId=VAR_006126.
FT   VARIANT     404    404       T -> M (in OCA2; dbSNP:rs144812594).
FT                                {ECO:0000269|PubMed:23504663}.
FT                                /FTId=VAR_006127.
FT   VARIANT     419    419       R -> Q (polymorphism associated with
FT                                green/hazel eye color; dbSNP:rs1800407).
FT                                {ECO:0000269|PubMed:10987646,
FT                                ECO:0000269|PubMed:12163334,
FT                                ECO:0000269|PubMed:15889046,
FT                                ECO:0000269|PubMed:18252222,
FT                                ECO:0000269|PubMed:7601462}.
FT                                /FTId=VAR_006128.
FT   VARIANT     419    419       R -> W (in OCA2; dbSNP:rs143218168).
FT                                {ECO:0000269|PubMed:23504663}.
FT                                /FTId=VAR_006129.
FT   VARIANT     425    425       Missing (in OCA2; mild).
FT                                /FTId=VAR_006130.
FT   VARIANT     440    440       L -> F (in dbSNP:rs1800408).
FT                                {ECO:0000269|PubMed:7601462}.
FT                                /FTId=VAR_007939.
FT   VARIANT     440    440       L -> H.
FT                                /FTId=VAR_006131.
FT   VARIANT     443    443       V -> I (in OCA2; dbSNP:rs28934272).
FT                                {ECO:0000269|PubMed:10987646,
FT                                ECO:0000269|PubMed:12876664,
FT                                ECO:0000269|PubMed:17385796}.
FT                                /FTId=VAR_006132.
FT   VARIANT     446    446       M -> V (in OCA2; mild; AROA form;
FT                                dbSNP:rs140566426).
FT                                /FTId=VAR_006133.
FT   VARIANT     473    473       I -> S (in OCA2).
FT                                /FTId=VAR_006134.
FT   VARIANT     476    476       N -> D (in OCA2).
FT                                {ECO:0000269|PubMed:17385796}.
FT                                /FTId=VAR_043700.
FT   VARIANT     481    481       A -> T (in OCA2; dbSNP:rs74653330).
FT                                {ECO:0000269|PubMed:12713581,
FT                                ECO:0000269|PubMed:12727022}.
FT                                /FTId=VAR_007940.
FT   VARIANT     489    489       N -> D (in OCA2; mild/severe;
FT                                dbSNP:rs121918170).
FT                                {ECO:0000269|PubMed:12876664}.
FT                                /FTId=VAR_006135.
FT   VARIANT     519    519       V -> A (in dbSNP:rs41446944).
FT                                /FTId=VAR_032096.
FT   VARIANT     549    549       H -> Q (in OCA2).
FT                                /FTId=VAR_006136.
FT   VARIANT     560    560       R -> H (in dbSNP:rs35110389).
FT                                /FTId=VAR_032097.
FT   VARIANT     592    592       T -> I (in OCA2; dbSNP:rs1800413).
FT                                {ECO:0000269|PubMed:10671067}.
FT                                /FTId=VAR_006137.
FT   VARIANT     614    614       K -> E (in OCA2).
FT                                {ECO:0000269|PubMed:10987646}.
FT                                /FTId=VAR_020631.
FT   VARIANT     614    614       K -> N (in OCA2).
FT                                /FTId=VAR_006138.
FT   VARIANT     615    615       H -> R (in dbSNP:rs1800414).
FT                                {ECO:0000269|PubMed:12713581,
FT                                ECO:0000269|PubMed:7601462}.
FT                                /FTId=VAR_006139.
FT   VARIANT     617    617       I -> L (in OCA2; dbSNP:rs763016773).
FT                                {ECO:0000269|PubMed:10987646}.
FT                                /FTId=VAR_020632.
FT   VARIANT     633    633       V -> I (in OCA2).
FT                                {ECO:0000269|PubMed:23504663}.
FT                                /FTId=VAR_072600.
FT   VARIANT     652    652       W -> R (in OCA2).
FT                                /FTId=VAR_006140.
FT   VARIANT     678    678       E -> K (in unclassified OCA).
FT                                {ECO:0000269|PubMed:10649493}.
FT                                /FTId=VAR_020633.
FT   VARIANT     679    679       W -> C (in OCA2; dbSNP:rs121918169).
FT                                {ECO:0000269|PubMed:10987646,
FT                                ECO:0000269|PubMed:12876664,
FT                                ECO:0000269|PubMed:23504663}.
FT                                /FTId=VAR_020634.
FT   VARIANT     679    679       W -> R (in OCA2; severe;
FT                                dbSNP:rs751822606).
FT                                /FTId=VAR_006141.
FT   VARIANT     684    684       F -> C (in OCA2; dbSNP:rs772754008).
FT                                {ECO:0000269|PubMed:23504663}.
FT                                /FTId=VAR_072601.
FT   VARIANT     688    688       L -> F (in unclassified OCA).
FT                                {ECO:0000269|PubMed:10649493}.
FT                                /FTId=VAR_020635.
FT   VARIANT     720    720       R -> C (in OCA2; dbSNP:rs141545475).
FT                                {ECO:0000269|PubMed:10987646}.
FT                                /FTId=VAR_020636.
FT   VARIANT     722    722       I -> T (in dbSNP:rs1800417).
FT                                {ECO:0000269|PubMed:7601462}.
FT                                /FTId=VAR_006142.
FT   VARIANT     724    724       A -> P (in OCA2).
FT                                {ECO:0000269|PubMed:10671067}.
FT                                /FTId=VAR_006143.
FT   VARIANT     736    736       S -> L (in OCA2; dbSNP:rs780296175).
FT                                /FTId=VAR_006144.
FT   VARIANT     743    743       P -> L (in OCA2 and unclassified OCA;
FT                                dbSNP:rs121918167).
FT                                {ECO:0000269|PubMed:10649493,
FT                                ECO:0000269|PubMed:12876664}.
FT                                /FTId=VAR_006145.
FT   VARIANT     773    773       A -> T (in a breast cancer sample;
FT                                somatic mutation).
FT                                {ECO:0000269|PubMed:16959974}.
FT                                /FTId=VAR_036468.
FT   VARIANT     775    775       G -> R (in OCA2).
FT                                {ECO:0000269|PubMed:17385796}.
FT                                /FTId=VAR_043701.
FT   VARIANT     787    787       A -> V (in OCA2; dbSNP:rs200457227).
FT                                {ECO:0000269|PubMed:10671067}.
FT                                /FTId=VAR_006146.
FT   VARIANT     795    795       G -> R (in OCA2).
FT                                {ECO:0000269|PubMed:10987646}.
FT                                /FTId=VAR_020637.
FT   VARIANT     799    799       Q -> H (in OCA2).
FT                                {ECO:0000269|PubMed:12727022}.
FT                                /FTId=VAR_020638.
FT   VARIANT     827    827       Y -> H (in OCA2).
FT                                {ECO:0000269|PubMed:17385796}.
FT                                /FTId=VAR_043702.
FT   VARIANT     833    833       Missing (in OCA2).
FT                                {ECO:0000269|PubMed:10987646}.
FT                                /FTId=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
//

If you have problems or comments...

PBIL Back to PBIL home page