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P protein (Melanocyte-specific transporter protein) (Pink-eyed dilution protein homolog)

 P_HUMAN                 Reviewed;         838 AA.
Q04671; Q15211; Q15212; Q96EN1; Q9UMI5;
01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
21-MAR-2006, sequence version 2.
10-OCT-2018, entry version 187.
RecName: Full=P protein;
AltName: Full=Melanocyte-specific transporter protein;
AltName: Full=Pink-eyed dilution protein homolog;
Name=OCA2; Synonyms=D15S12, P;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), AND VARIANT ASP-257.
PubMed=8421497; DOI=10.1038/361072a0;
Rinchik E.M., Bultman S.J., Horsthemke B., Lee S.-T., Strunk K.M.,
Spritz R.A., Avidano K.A., Jong M.T.C., Nicholls R.D.;
"A gene for the mouse pink-eyed dilution locus and for human type II
oculocutaneous albinism.";
Nature 361:72-76(1993).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 3), FUNCTION,
SUBCELLULAR LOCATION, AND VARIANTS TRP-305; GLN-419; PHE-440; ARG-615
AND THR-722.
PubMed=7601462; DOI=10.1016/0888-7543(95)80220-G;
Lee S.-T., Nicholls R.D., Jong M.T.C., Fukai K., Spritz R.A.;
"Organization and sequence of the human P gene and identification of a
new family of transport proteins.";
Genomics 26:354-363(1995).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
TISSUE=Skin;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
NUCLEOTIDE SEQUENCE [MRNA] OF 288-419, AND DISEASE.
TISSUE=Skin;
PubMed=1509264; DOI=10.1126/science.257.5073.1121;
Gardner J.M., Nakatsu Y., Gondo Y., Lee S., Lyon M.F., King R.A.,
Brilliant M.H.;
"The mouse pink-eyed dilution gene: association with human Prader-
Willi and Angelman syndromes.";
Science 257:1121-1124(1992).
[5]
FUNCTION.
PubMed=11310796; DOI=10.1034/j.1600-0749.2001.140203.x;
Brilliant M.H.;
"The mouse p (pink-eyed dilution) and human P genes, oculocutaneous
albinism type 2 (OCA2), and melanosomal pH.";
Pigment Cell Res. 14:86-93(2001).
[6]
POSSIBLE INVOLVEMENT IN SKIN COLOR VARIATION.
PubMed=11601658; DOI=10.1034/j.1600-0749.2001.140508.x;
Manga P., Orlow S.J.;
"Inverse correlation between pink-eyed dilution protein expression and
induction of melanogenesis by bafilomycin A1.";
Pigment Cell Res. 14:362-367(2001).
[7]
FUNCTION.
PubMed=15262401; DOI=10.1016/j.tig.2004.06.010;
Sturm R.A., Frudakis T.N.;
"Eye colour: portals into pigmentation genes and ancestry.";
Trends Genet. 20:327-332(2004).
[8]
REVIEW ON OCA2 VARIANTS.
PubMed=10094567;
DOI=10.1002/(SICI)1098-1004(1999)13:2<99::AID-HUMU2>3.3.CO;2-3;
Oetting W.S., King R.A.;
"Molecular basis of albinism: mutations and polymorphisms of
pigmentation genes associated with albinism.";
Hum. Mutat. 13:99-115(1999).
[9]
FUNCTION, AND INDUCTION.
PubMed=22234890; DOI=10.1101/gr.128652.111;
Visser M., Kayser M., Palstra R.J.;
"HERC2 rs12913832 modulates human pigmentation by attenuating
chromatin-loop formation between a long-range enhancer and the OCA2
promoter.";
Genome Res. 22:446-455(2012).
[10]
VARIANTS OCA2.
PubMed=7874125;
Lee S.-T., Nicholls R.D., Schnur R.E., Guida L.C., Lu-Kuo J.,
Spinner N.B., Zackai E.H., Spritz R.A.;
"Diverse mutations of the P gene among African-Americans with type II
(tyrosinase-positive) oculocutaneous albinism (OCA2).";
Hum. Mol. Genet. 3:2047-2051(1994).
[11]
VARIANTS OCA2.
PubMed=7762554;
Spritz R.A., Fukai K., Holmes S.A., Luande J.;
"Frequent intragenic deletion of the P gene in Tanzanian patients with
type II oculocutaneous albinism (OCA2).";
Am. J. Hum. Genet. 56:1320-1323(1995).
[12]
VARIANTS OCA2.
PubMed=9259203;
DOI=10.1002/(SICI)1098-1004(1997)10:2<175::AID-HUMU12>3.0.CO;2-X;
Spritz R.A., Lee S.-T., Fukai K., Brondum-Nielsen K., Chitayat D.,
Lipson M.H., Musarella M.A., Rosenmann A., Weleber R.G.;
"Novel mutations of the P gene in type II oculocutaneous albinism
(OCA2).";
Hum. Mutat. 10:175-177(1997).
[13]
VARIANTS OCA2 ARG-86; PHE-112; VAL-368; ILE-592; PRO-724 AND VAL-787,
AND VARIANT ASP-257.
PubMed=10671067;
DOI=10.1002/(SICI)1098-1004(1998)12:6<434::AID-HUMU15>3.3.CO;2-1;
Oetting W.S., Gardner J.M., Fryer J.P., Ching A., Durham-Pierre D.,
King R.A., Brilliant M.H.;
"Mutations of the human P gene associated with type II oculocutaneous
albinism (OCA2).";
Hum. Mutat. 12:434-434(1998).
[14]
VARIANTS OCA2 GLY-290; ILE-443; GLU-614; LEU-617; CYS-679; CYS-720;
ARG-795 AND VAL-833 DEL, AND VARIANTS TRP-305 AND GLN-419.
PubMed=10987646; DOI=10.1007/s004390051090;
Passmore L.A., Kaesmann-Kellner B., Weber B.H.F.;
"Novel and recurrent mutations in the tyrosinase gene and the P gene
in the German albino population.";
Hum. Genet. 105:200-210(1999).
[15]
VARIANT OCA2 VAL-334, AND VARIANTS UNCLASSIFIED OCA MET-350; THR-370;
LYS-678; PHE-688 AND LEU-743.
PubMed=10649493;
DOI=10.1002/(SICI)1098-1004(200002)15:2<166::AID-HUMU5>3.0.CO;2-Z;
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. 15:166-172(2000).
[16]
VARIANTS TRP-305 AND GLN-419, AND INVOLVEMENT IN DETERMINATION OF EYE
COLOR.
PubMed=12163334;
Rebbeck T.R., Kanetsky P.A., Walker A.H., Holmes R., Halpern A.C.,
Schuchter L.M., Elder D.E., Guerry D.;
"P gene as an inherited biomarker of human eye color.";
Cancer Epidemiol. Biomarkers Prev. 11:782-784(2002).
[17]
VARIANTS OCA2 GLY-290; ILE-443; ASP-489; CYS-679 AND LEU-743.
PubMed=12876664; DOI=10.1086/377569;
King R.A., Willaert R.K., Schmidt R.M., Pietsch J., Savage S.,
Brott M.J., Fryer J.P., Summers C.G., Oetting W.S.;
"MC1R mutations modify the classic phenotype of oculocutaneous
albinism type 2 (OCA2).";
Am. J. Hum. Genet. 73:638-645(2003).
[18]
VARIANTS OCA2 THR-481 AND HIS-799.
PubMed=12727022; DOI=10.1016/S0923-1811(03)00005-7;
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. 31:189-192(2003).
[19]
VARIANTS OCA2 TRP-10; LEU-198; LEU-211; ILE-394 AND THR-481, AND
VARIANTS MET-387 AND ARG-615.
PubMed=12713581; DOI=10.1046/j.1523-1747.2003.12127.x;
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. 120:781-783(2003).
[20]
VARIANTS TRP-305 AND GLN-419, AND INVOLVEMENT IN SUSCEPTIBILITY TO
MELANOMA.
PubMed=15889046; DOI=10.1038/sj.ejhg.5201415;
Melan-Cohort;
Jannot A.-S., 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.;
"Allele variations in the OCA2 gene (pink-eyed-dilution locus) are
associated with genetic susceptibility to melanoma.";
Eur. J. Hum. Genet. 13:913-920(2005).
[21]
INVOLVEMENT IN SHEP1, AND POLYMORPHISM.
PubMed=17236130; DOI=10.1086/510885;
Duffy D.L., Montgomery G.W., Chen W., Zhao Z.Z., Le L., James M.R.,
Hayward N.K., Martin N.G., Sturm R.A.;
"A three-single-nucleotide polymorphism haplotype in intron 1 of OCA2
explains most human eye-color variation.";
Am. J. Hum. Genet. 80:241-252(2007).
[22]
VARIANT [LARGE SCALE ANALYSIS] THR-773.
PubMed=16959974; DOI=10.1126/science.1133427;
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
Vogelstein B., Kinzler K.W., Velculescu V.E.;
"The consensus coding sequences of human breast and colorectal
cancers.";
Science 314:268-274(2006).
[23]
INVOLVEMENT IN SHEP1, AND POLYMORPHISM.
PubMed=17952075; DOI=10.1038/ng.2007.13;
Sulem P., Gudbjartsson D.F., Stacey S.N., Helgason A., Rafnar T.,
Magnusson K.P., Manolescu A., Karason A., Palsson A., Thorleifsson G.,
Jakobsdottir M., Steinberg S., Palsson S., Jonasson F.,
Sigurgeirsson B., Thorisdottir K., Ragnarsson R.,
Benediktsdottir K.R., Aben K.K., Kiemeney L.A., Olafsson J.H.,
Gulcher J., Kong A., Thorsteinsdottir U., Stefansson K.;
"Genetic determinants of hair, eye and skin pigmentation in
Europeans.";
Nat. Genet. 39:1443-1452(2007).
[24]
VARIANTS OCA2 ILE-443; ASP-476; ARG-775 AND HIS-827.
PubMed=17385796; DOI=10.1002/pd.1713;
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. 27:502-506(2007).
[25]
INVOLVEMENT IN SHEP1, AND POLYMORPHISM.
PubMed=18252221; DOI=10.1016/j.ajhg.2007.10.003;
Kayser M., Liu F., Janssens A.C.J.W., Rivadeneira F., Lao O.,
van Duijn K., Vermeulen M., Arp P., Jhamai M.M., van Ijcken W.F.J.,
den Dunnen J.T., Heath S., Zelenika D., Despriet D.D.G.,
Klaver C.C.W., Vingerling J.R., de Jong P.T.V.M., Hofman A.,
Aulchenko Y.S., Uitterlinden A.G., Oostra B.A., van Duijn C.M.;
"Three genome-wide association studies and a linkage analysis identify
HERC2 as a human iris color gene.";
Am. J. Hum. Genet. 82:411-423(2008).
[26]
VARIANT GLN-419, FUNCTION, INDUCTION, INVOLVEMENT IN SHEP1,
INVOLVEMENT IN SUSCEPTIBILITY TO MELANOMA, AND POLYMORPHISM.
PubMed=18252222; DOI=10.1016/j.ajhg.2007.11.005;
Sturm R.A., Duffy D.L., Zhao Z.Z., Leite F.P.M., Stark M.S.,
Hayward N.K., Martin N.G., Montgomery G.W.;
"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. 82:424-431(2008).
[27]
INVOLVEMENT IN SHEP1, POLYMORPHISM, AND INDUCTION.
PubMed=18172690; DOI=10.1007/s00439-007-0460-x;
Eiberg H., Troelsen J., Nielsen M., Mikkelsen A., Mengel-From J.,
Kjaer K.W., 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. 123:177-187(2008).
[28]
VARIANTS OCA2 MET-404; TRP-419; ILE-633; CYS-679 AND CYS-684.
PubMed=23504663; DOI=10.1002/humu.22315;
Simeonov D.R., Wang X., Wang C., Sergeev Y., Dolinska M., Bower M.,
Fischer R., Winer D., Dubrovsky G., Balog J.Z., Huizing M., Hart R.,
Zein W.M., Gahl W.A., Brooks B.P., Adams D.R.;
"DNA variations in oculocutaneous albinism: an updated mutation list
and current outstanding issues in molecular diagnostics.";
Hum. Mutat. 34:827-835(2013).
-!- 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.
{ECO:0000269|PubMed:11310796, ECO:0000269|PubMed:15262401,
ECO:0000269|PubMed:18252222, ECO:0000269|PubMed:22234890,
ECO:0000269|PubMed:7601462}.
-!- SUBCELLULAR LOCATION: Melanosome membrane
{ECO:0000269|PubMed:7601462}; Multi-pass membrane protein
{ECO:0000269|PubMed:7601462}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=3;
Name=1;
IsoId=Q04671-1; Sequence=Displayed;
Name=2;
IsoId=Q04671-2; Sequence=VSP_012284;
Name=3;
IsoId=Q04671-3; Sequence=VSP_012285, VSP_012286;
Note=No experimental confirmation available.;
-!- INDUCTION: Expression is under the control of an enhancer element
that is encoded in an intron of the close-by HERC2 gene. The
enhancer element containing the T-allele of the polymorphism
rs12913832 mediates binding of the transcription factors HLTF,
LEF1 and MITF and increases OCA2 expression. In contrast,
transcription factor binding and OCA2 expression are reduced in
carriers of the C-allele of polymorphism rs12913832. Thus, people
homozygous for the C-allele have light-colored eyes, while people
homozygous for the T-allele of polymorphism rs12913832 most often
have brown eyes. {ECO:0000269|PubMed:18172690,
ECO:0000269|PubMed:18252222, ECO:0000269|PubMed:22234890}.
-!- POLYMORPHISM: Genetic variants in OCA2 define the skin/hair/eye
pigmentation variation locus 1 (SHEP1) [MIM:227220]; also known as
skin/hair/eye pigmentation type 1, blue/nonblue eyes or
skin/hair/eye pigmentation type 1, blue/brown eyes or
skin/hair/eye pigmentation type 1, blond/brown hair or eye color,
brown/blue or eye color, blue/nonblue or eye color type 3 (EYCL3)
or brown eye color type 2 (BEY2) or hair color type 3 (HCL3).
Hair, eye and skin pigmentation are among the most visible
examples of human phenotypic variation, with a broad normal range
that is subject to substantial geographic stratification. In the
case of skin, individuals tend to have lighter pigmentation with
increasing distance from the equator. By contrast, the majority of
variation in human eye and hair color is found among individuals
of European ancestry, with most other human populations fixed for
brown eyes and black hair. OCA2 polymorphisms may act as a
penetrance modifier of the risk of malignant melanoma.
{ECO:0000269|PubMed:17236130, ECO:0000269|PubMed:17952075,
ECO:0000269|PubMed:18172690, ECO:0000269|PubMed:18252221,
ECO:0000269|PubMed:18252222}.
-!- DISEASE: Albinism, oculocutaneous, 2 (OCA2) [MIM:203200]: An
autosomal recessive disorder in which the biosynthesis of melanin
pigment is reduced in skin, hair, and eyes. Although affected
infants may appear at birth to have complete absence of melanin
pigment, most patients acquire small amounts of pigment with age.
Visual anomalies include decreased acuity and nystagmus. The
phenotype is highly variable. The hair of affected individuals may
turn darker with age, and pigmented nevi or freckles may be seen.
African and African American individuals may have yellow hair and
blue-gray or hazel irides. One phenotypic variant, 'brown OCA,'
has been described in African and African American populations and
is characterized by light brown hair and skin color and gray to
tan irides. {ECO:0000269|PubMed:10649493,
ECO:0000269|PubMed:10671067, ECO:0000269|PubMed:10987646,
ECO:0000269|PubMed:12713581, ECO:0000269|PubMed:12727022,
ECO:0000269|PubMed:12876664, ECO:0000269|PubMed:17385796,
ECO:0000269|PubMed:23504663, ECO:0000269|PubMed:7762554,
ECO:0000269|PubMed:7874125, ECO:0000269|PubMed:9259203}. Note=The
disease is caused by mutations affecting the gene represented in
this entry.
-!- SIMILARITY: Belongs to the CitM (TC 2.A.11) transporter family.
{ECO:0000305}.
-!- WEB RESOURCE: Name=Mutations of the P gene; Note=Retina
International's Scientific Newsletter;
URL="http://www.retina-international.org/files/sci-news/pgenemut.htm";
-!- WEB RESOURCE: Name=Albinism database (ADB); Note=P mutations;
URL="http://www.ifpcs.org/albinism/oca2mut.html";
-!- WEB RESOURCE: Name=Protein Spotlight; Note=Questioning colour
- Issue 54 of January 2005;
URL="https://web.expasy.org/spotlight/back_issues/054";
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EMBL; M99564; AAA36477.1; -; mRNA.
EMBL; U19170; AAC13783.1; -; Genomic_DNA.
EMBL; U19153; AAC13783.1; JOINED; Genomic_DNA.
EMBL; U19154; AAC13783.1; JOINED; Genomic_DNA.
EMBL; U19156; AAC13783.1; JOINED; Genomic_DNA.
EMBL; U19158; AAC13783.1; JOINED; Genomic_DNA.
EMBL; U19160; AAC13783.1; JOINED; Genomic_DNA.
EMBL; U19162; AAC13783.1; JOINED; Genomic_DNA.
EMBL; U19164; AAC13783.1; JOINED; Genomic_DNA.
EMBL; U19166; AAC13783.1; JOINED; Genomic_DNA.
EMBL; U19169; AAC13783.1; JOINED; Genomic_DNA.
EMBL; U19168; AAC13783.1; JOINED; Genomic_DNA.
EMBL; U19167; AAC13783.1; JOINED; Genomic_DNA.
EMBL; U19165; AAC13783.1; JOINED; Genomic_DNA.
EMBL; U19163; AAC13783.1; JOINED; Genomic_DNA.
EMBL; U19161; AAC13783.1; JOINED; Genomic_DNA.
EMBL; U19159; AAC13783.1; JOINED; Genomic_DNA.
EMBL; U19157; AAC13783.1; JOINED; Genomic_DNA.
EMBL; U19155; AAC13783.1; JOINED; Genomic_DNA.
EMBL; U19176; AAC13784.1; -; Genomic_DNA.
EMBL; U19153; AAC13784.1; JOINED; Genomic_DNA.
EMBL; U19154; AAC13784.1; JOINED; Genomic_DNA.
EMBL; U19155; AAC13784.1; JOINED; Genomic_DNA.
EMBL; U19157; AAC13784.1; JOINED; Genomic_DNA.
EMBL; U19158; AAC13784.1; JOINED; Genomic_DNA.
EMBL; U19159; AAC13784.1; JOINED; Genomic_DNA.
EMBL; U19160; AAC13784.1; JOINED; Genomic_DNA.
EMBL; U19161; AAC13784.1; JOINED; Genomic_DNA.
EMBL; U19162; AAC13784.1; JOINED; Genomic_DNA.
EMBL; U19163; AAC13784.1; JOINED; Genomic_DNA.
EMBL; U19164; AAC13784.1; JOINED; Genomic_DNA.
EMBL; U19165; AAC13784.1; JOINED; Genomic_DNA.
EMBL; U19166; AAC13784.1; JOINED; Genomic_DNA.
EMBL; U19167; AAC13784.1; JOINED; Genomic_DNA.
EMBL; U19168; AAC13784.1; JOINED; Genomic_DNA.
EMBL; U19169; AAC13784.1; JOINED; Genomic_DNA.
EMBL; U19171; AAC13784.1; JOINED; Genomic_DNA.
EMBL; U19172; AAC13784.1; JOINED; Genomic_DNA.
EMBL; U19173; AAC13784.1; JOINED; Genomic_DNA.
EMBL; U19174; AAC13784.1; JOINED; Genomic_DNA.
EMBL; U19175; AAC13784.1; JOINED; Genomic_DNA.
EMBL; BC012097; AAH12097.1; -; mRNA.
EMBL; M97901; AAA36430.1; -; mRNA.
CCDS; CCDS10020.1; -. [Q04671-1]
CCDS; CCDS73701.1; -. [Q04671-2]
PIR; A57173; A57173.
PIR; S28911; S28911.
RefSeq; NP_000266.2; NM_000275.2. [Q04671-1]
RefSeq; NP_001287913.1; NM_001300984.1. [Q04671-2]
UniGene; Hs.654411; -.
ProteinModelPortal; Q04671; -.
SMR; Q04671; -.
BioGrid; 111002; 3.
IntAct; Q04671; 1.
STRING; 9606.ENSP00000346659; -.
TCDB; 2.A.45.2.1; the arsenite-antimonite (arsb) efflux family.
iPTMnet; Q04671; -.
PhosphoSitePlus; Q04671; -.
BioMuta; OCA2; -.
DMDM; 90110050; -.
PaxDb; Q04671; -.
PeptideAtlas; Q04671; -.
PRIDE; Q04671; -.
ProteomicsDB; 58261; -.
ProteomicsDB; 58262; -. [Q04671-2]
ProteomicsDB; 58263; -. [Q04671-3]
Ensembl; ENST00000353809; ENSP00000261276; ENSG00000104044. [Q04671-2]
Ensembl; ENST00000354638; ENSP00000346659; ENSG00000104044. [Q04671-1]
GeneID; 4948; -.
KEGG; hsa:4948; -.
UCSC; uc001zbh.6; human. [Q04671-1]
CTD; 4948; -.
DisGeNET; 4948; -.
EuPathDB; HostDB:ENSG00000104044.15; -.
GeneCards; OCA2; -.
GeneReviews; OCA2; -.
H-InvDB; HIX0012054; -.
HGNC; HGNC:8101; OCA2.
MalaCards; OCA2; -.
MIM; 203200; phenotype.
MIM; 227220; phenotype.
MIM; 611409; gene.
neXtProt; NX_Q04671; -.
OpenTargets; ENSG00000104044; -.
Orphanet; 72; Angelman syndrome.
Orphanet; 79432; Oculocutaneous albinism type 2.
Orphanet; 98754; Prader-Willi syndrome due to maternal uniparental disomy of chromosome 15.
Orphanet; 177901; Prader-Willi syndrome due to paternal deletion of 15q11q13 type 1.
Orphanet; 177904; Prader-Willi syndrome due to paternal deletion of 15q11q13 type 2.
PharmGKB; PA31890; -.
eggNOG; KOG2639; Eukaryota.
eggNOG; COG1055; LUCA.
GeneTree; ENSGT00390000017120; -.
HOGENOM; HOG000047303; -.
HOVERGEN; HBG008343; -.
InParanoid; Q04671; -.
OMA; QVTHNWT; -.
OrthoDB; EOG091G03O6; -.
PhylomeDB; Q04671; -.
TreeFam; TF323556; -.
Reactome; R-HSA-5662702; Melanin biosynthesis.
SIGNOR; Q04671; -.
ChiTaRS; OCA2; human.
GeneWiki; OCA2; -.
GenomeRNAi; 4948; -.
PRO; PR:Q04671; -.
Proteomes; UP000005640; Chromosome 15.
Bgee; ENSG00000104044; Expressed in 146 organ(s), highest expression level in pigmented layer of retina.
CleanEx; HS_OCA2; -.
ExpressionAtlas; Q04671; baseline and differential.
Genevisible; Q04671; HS.
GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
GO; GO:0033162; C:melanosome membrane; IDA:UniProtKB.
GO; GO:0005302; F:L-tyrosine transmembrane transporter activity; TAS:ProtInc.
GO; GO:0005215; F:transporter activity; TAS:ProtInc.
GO; GO:0008283; P:cell proliferation; IEA:Ensembl.
GO; GO:0006726; P:eye pigment biosynthetic process; TAS:ProtInc.
GO; GO:0042438; P:melanin biosynthetic process; IEA:Ensembl.
GO; GO:0030318; P:melanocyte differentiation; IEA:Ensembl.
GO; GO:0007286; P:spermatid development; IEA:Ensembl.
InterPro; IPR004680; Cit_transptr-like_dom.
Pfam; PF03600; CitMHS; 1.
1: Evidence at protein level;
Albinism; Alternative splicing; Complete proteome; Disease mutation;
Glycoprotein; Membrane; Polymorphism; Reference proteome;
Transmembrane; Transmembrane helix; Transport.
CHAIN 1 838 P protein.
/FTId=PRO_0000172509.
TOPO_DOM 1 179 Cytoplasmic. {ECO:0000255}.
TRANSMEM 180 197 Helical. {ECO:0000255}.
TOPO_DOM 198 330 Extracellular. {ECO:0000255}.
TRANSMEM 331 347 Helical. {ECO:0000255}.
TOPO_DOM 348 353 Cytoplasmic. {ECO:0000255}.
TRANSMEM 354 370 Helical. {ECO:0000255}.
TOPO_DOM 371 384 Extracellular. {ECO:0000255}.
TRANSMEM 385 401 Helical. {ECO:0000255}.
TOPO_DOM 402 423 Cytoplasmic. {ECO:0000255}.
TRANSMEM 424 440 Helical. {ECO:0000255}.
TOPO_DOM 441 513 Extracellular. {ECO:0000255}.
TRANSMEM 514 530 Helical. {ECO:0000255}.
TOPO_DOM 531 620 Cytoplasmic. {ECO:0000255}.
TRANSMEM 621 637 Helical. {ECO:0000255}.
TOPO_DOM 638 647 Extracellular. {ECO:0000255}.
TRANSMEM 648 664 Helical. {ECO:0000255}.
TOPO_DOM 665 679 Cytoplasmic. {ECO:0000255}.
TRANSMEM 680 696 Helical. {ECO:0000255}.
TOPO_DOM 697 720 Extracellular. {ECO:0000255}.
TRANSMEM 721 737 Helical. {ECO:0000255}.
TOPO_DOM 738 760 Cytoplasmic. {ECO:0000255}.
TRANSMEM 761 777 Helical. {ECO:0000255}.
TOPO_DOM 778 817 Extracellular. {ECO:0000255}.
TRANSMEM 818 834 Helical. {ECO:0000255}.
TOPO_DOM 835 838 Cytoplasmic. {ECO:0000255}.
CARBOHYD 214 214 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 218 218 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 273 273 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 442 442 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 781 781 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
VAR_SEQ 349 372 Missing (in isoform 2).
{ECO:0000303|PubMed:15489334}.
/FTId=VSP_012284.
VAR_SEQ 652 668 WIAILGAIWLLILADIH -> GLGLVQAGRYYLSTPES
(in isoform 3).
{ECO:0000303|PubMed:8421497}.
/FTId=VSP_012285.
VAR_SEQ 669 838 Missing (in isoform 3).
{ECO:0000303|PubMed:8421497}.
/FTId=VSP_012286.
VARIANT 10 10 R -> W (in OCA2; dbSNP:rs554862186).
{ECO:0000269|PubMed:12713581}.
/FTId=VAR_020622.
VARIANT 27 27 G -> R (in OCA2; dbSNP:rs61738394).
/FTId=VAR_006117.
VARIANT 86 86 S -> R (in OCA2; dbSNP:rs772243109).
{ECO:0000269|PubMed:10671067}.
/FTId=VAR_006118.
VARIANT 112 112 C -> F (in OCA2; dbSNP:rs562649990).
{ECO:0000269|PubMed:10671067}.
/FTId=VAR_006119.
VARIANT 198 198 P -> L (in OCA2; dbSNP:rs183487020).
{ECO:0000269|PubMed:12713581}.
/FTId=VAR_020623.
VARIANT 206 211 Missing (in OCA2; severe).
/FTId=VAR_006120.
VARIANT 211 211 P -> L (in OCA2; dbSNP:rs190612616).
{ECO:0000269|PubMed:12713581}.
/FTId=VAR_020624.
VARIANT 241 241 P -> R (in dbSNP:rs2305253).
/FTId=VAR_022019.
VARIANT 257 257 A -> D (in dbSNP:rs1050968).
{ECO:0000269|PubMed:10671067,
ECO:0000269|PubMed:8421497}.
/FTId=VAR_006121.
VARIANT 266 266 R -> W (in dbSNP:rs33929465).
/FTId=VAR_032094.
VARIANT 273 274 NW -> KV (in OCA2; dbSNP:rs797044784).
/FTId=VAR_006122.
VARIANT 290 290 R -> G (in OCA2; dbSNP:rs769408559).
{ECO:0000269|PubMed:10987646,
ECO:0000269|PubMed:12876664}.
/FTId=VAR_020625.
VARIANT 305 305 R -> W (polymorphism associated with
nonblue eye color; could be a biomarker
of cutaneous cancer risk;
dbSNP:rs1800401).
{ECO:0000269|PubMed:10987646,
ECO:0000269|PubMed:12163334,
ECO:0000269|PubMed:15889046,
ECO:0000269|PubMed:7601462}.
/FTId=VAR_006123.
VARIANT 334 334 A -> V (in OCA2; dbSNP:rs121918168).
{ECO:0000269|PubMed:10649493}.
/FTId=VAR_020626.
VARIANT 336 336 A -> V (in dbSNP:rs34010619).
/FTId=VAR_032095.
VARIANT 350 350 V -> M (in unclassified OCA;
dbSNP:rs533478642).
{ECO:0000269|PubMed:10649493}.
/FTId=VAR_020627.
VARIANT 368 368 A -> V (in OCA2; dbSNP:rs61745150).
{ECO:0000269|PubMed:10671067}.
/FTId=VAR_006124.
VARIANT 370 370 I -> T (in unclassified OCA;
dbSNP:rs34731820).
{ECO:0000269|PubMed:10649493}.
/FTId=VAR_020628.
VARIANT 385 385 F -> I (in OCA2; severe;
dbSNP:rs137956605).
/FTId=VAR_006125.
VARIANT 387 387 T -> M (in dbSNP:rs150335311).
{ECO:0000269|PubMed:12713581}.
/FTId=VAR_020629.
VARIANT 394 394 M -> I (in OCA2; dbSNP:rs121918171).
{ECO:0000269|PubMed:12713581}.
/FTId=VAR_020630.
VARIANT 395 395 M -> L (in OCA2; severe;
dbSNP:rs757286784).
/FTId=VAR_006126.
VARIANT 404 404 T -> M (in OCA2; dbSNP:rs144812594).
{ECO:0000269|PubMed:23504663}.
/FTId=VAR_006127.
VARIANT 419 419 R -> Q (polymorphism associated with
green/hazel eye color; dbSNP:rs1800407).
{ECO:0000269|PubMed:10987646,
ECO:0000269|PubMed:12163334,
ECO:0000269|PubMed:15889046,
ECO:0000269|PubMed:18252222,
ECO:0000269|PubMed:7601462}.
/FTId=VAR_006128.
VARIANT 419 419 R -> W (in OCA2; dbSNP:rs143218168).
{ECO:0000269|PubMed:23504663}.
/FTId=VAR_006129.
VARIANT 425 425 Missing (in OCA2; mild).
/FTId=VAR_006130.
VARIANT 440 440 L -> F (in dbSNP:rs1800408).
{ECO:0000269|PubMed:7601462}.
/FTId=VAR_007939.
VARIANT 440 440 L -> H.
/FTId=VAR_006131.
VARIANT 443 443 V -> I (in OCA2; dbSNP:rs121918166).
{ECO:0000269|PubMed:10987646,
ECO:0000269|PubMed:12876664,
ECO:0000269|PubMed:17385796}.
/FTId=VAR_006132.
VARIANT 446 446 M -> V (in OCA2; mild; AROA form;
dbSNP:rs140566426).
/FTId=VAR_006133.
VARIANT 473 473 I -> S (in OCA2).
/FTId=VAR_006134.
VARIANT 476 476 N -> D (in OCA2).
{ECO:0000269|PubMed:17385796}.
/FTId=VAR_043700.
VARIANT 481 481 A -> T (in OCA2; dbSNP:rs74653330).
{ECO:0000269|PubMed:12713581,
ECO:0000269|PubMed:12727022}.
/FTId=VAR_007940.
VARIANT 489 489 N -> D (in OCA2; mild/severe;
dbSNP:rs121918170).
{ECO:0000269|PubMed:12876664}.
/FTId=VAR_006135.
VARIANT 519 519 V -> A (in dbSNP:rs41446944).
/FTId=VAR_032096.
VARIANT 549 549 H -> Q (in OCA2).
/FTId=VAR_006136.
VARIANT 560 560 R -> H (in dbSNP:rs35110389).
/FTId=VAR_032097.
VARIANT 592 592 T -> I (in OCA2; dbSNP:rs1800413).
{ECO:0000269|PubMed:10671067}.
/FTId=VAR_006137.
VARIANT 614 614 K -> E (in OCA2).
{ECO:0000269|PubMed:10987646}.
/FTId=VAR_020631.
VARIANT 614 614 K -> N (in OCA2).
/FTId=VAR_006138.
VARIANT 615 615 H -> R (in dbSNP:rs1800414).
{ECO:0000269|PubMed:12713581,
ECO:0000269|PubMed:7601462}.
/FTId=VAR_006139.
VARIANT 617 617 I -> L (in OCA2; dbSNP:rs763016773).
{ECO:0000269|PubMed:10987646}.
/FTId=VAR_020632.
VARIANT 633 633 V -> I (in OCA2; dbSNP:rs1372200062).
{ECO:0000269|PubMed:23504663}.
/FTId=VAR_072600.
VARIANT 652 652 W -> R (in OCA2; dbSNP:rs886043514).
/FTId=VAR_006140.
VARIANT 678 678 E -> K (in unclassified OCA).
{ECO:0000269|PubMed:10649493}.
/FTId=VAR_020633.
VARIANT 679 679 W -> C (in OCA2; dbSNP:rs121918169).
{ECO:0000269|PubMed:10987646,
ECO:0000269|PubMed:12876664,
ECO:0000269|PubMed:23504663}.
/FTId=VAR_020634.
VARIANT 679 679 W -> R (in OCA2; severe;
dbSNP:rs751822606).
/FTId=VAR_006141.
VARIANT 684 684 F -> C (in OCA2; dbSNP:rs772754008).
{ECO:0000269|PubMed:23504663}.
/FTId=VAR_072601.
VARIANT 688 688 L -> F (in unclassified OCA).
{ECO:0000269|PubMed:10649493}.
/FTId=VAR_020635.
VARIANT 720 720 R -> C (in OCA2; dbSNP:rs141545475).
{ECO:0000269|PubMed:10987646}.
/FTId=VAR_020636.
VARIANT 722 722 I -> T (in dbSNP:rs1800417).
{ECO:0000269|PubMed:7601462}.
/FTId=VAR_006142.
VARIANT 724 724 A -> P (in OCA2).
{ECO:0000269|PubMed:10671067}.
/FTId=VAR_006143.
VARIANT 736 736 S -> L (in OCA2; dbSNP:rs780296175).
/FTId=VAR_006144.
VARIANT 743 743 P -> L (in OCA2 and unclassified OCA;
dbSNP:rs121918167).
{ECO:0000269|PubMed:10649493,
ECO:0000269|PubMed:12876664}.
/FTId=VAR_006145.
VARIANT 773 773 A -> T (in a breast cancer sample;
somatic mutation).
{ECO:0000269|PubMed:16959974}.
/FTId=VAR_036468.
VARIANT 775 775 G -> R (in OCA2).
{ECO:0000269|PubMed:17385796}.
/FTId=VAR_043701.
VARIANT 787 787 A -> V (in OCA2; dbSNP:rs200457227).
{ECO:0000269|PubMed:10671067}.
/FTId=VAR_006146.
VARIANT 795 795 G -> R (in OCA2).
{ECO:0000269|PubMed:10987646}.
/FTId=VAR_020637.
VARIANT 799 799 Q -> H (in OCA2).
{ECO:0000269|PubMed:12727022}.
/FTId=VAR_020638.
VARIANT 827 827 Y -> H (in OCA2).
{ECO:0000269|PubMed:17385796}.
/FTId=VAR_043702.
VARIANT 833 833 Missing (in OCA2).
{ECO:0000269|PubMed:10987646}.
/FTId=VAR_021682.
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


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