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Reviewed, UniProtKB/Swiss-Prot Q04671 (P_HUMAN)

Last modified November 25, 2008. Version 92. Feed History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    P protein
Alternative name(s):
    Melanocyte-specific transporter protein
    Pink-eyed dilution protein homolog
Gene names
Name: OCA2
Synonyms: D15S12, P
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length838 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

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.

Subcellular location

Melanosome membrane; Multi-pass membrane protein.

Polymorphism

Genetic variations in OCA2 are associated with skin/hair/eye pigmentation variability type 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.

Involvement in disease

Defects in OCA2 are the cause of oculocutaneous albinism type 2 (OCA2) [MIM:203200]. OCA2 is an autosomal recessive form of albinism, a disorder of pigmentation in the skin, hair, and eyes. The phenotype of patients with OCA2 is typically somewhat less severe than in those with tyrosinase-deficient OCA1. There are several forms of OCA2, from typical OCA to relatively mild 'autosomal recessive ocular albinism' (AROA). OCA2 is the most prevalent type of albinism throughout the world.

The gene OCA2 is localized to chromosome 15 at 15q11.2-q12, a region associated with Prader-Willi and Angelman syndromes, suggesting that altered expression of the OCA2 gene may be responsible for the hypopygmentation phenotype exhibited by certain individuals with these disorders.

Human pigmentation, including eye color, has been associated with skin cancer risk.

Sequence similarities

Belongs to the SLC13A transporter (TC 2.A.47) family. P subfamily. [View classification]

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q04671-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q04671-2)

The sequence of this isoform differs from the canonical sequence as follows:
     349-372: Missing.
Isoform 3 (identifier: Q04671-3)

The sequence of this isoform differs from the canonical sequence as follows:
     652-668: WIAILGAIWLLILADIH → GLGLVQAGRYYLSTPES
     669-838: Missing.
Notes: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 838838P protein
PRO_0000172509

Regions

Topological domain1 – 179179Cytoplasmic Potential
Transmembrane180 – 19718 Potential
Topological domain198 – 330133Extracellular Potential
Transmembrane331 – 34717 Potential
Topological domain348 – 3536Cytoplasmic Potential
Transmembrane354 – 37017 Potential
Topological domain371 – 38414Extracellular Potential
Transmembrane385 – 40117 Potential
Topological domain402 – 42322Cytoplasmic Potential
Transmembrane424 – 44017 Potential
Topological domain441 – 51373Extracellular Potential
Transmembrane514 – 53017 Potential
Topological domain531 – 62090Cytoplasmic Potential
Transmembrane621 – 63717 Potential
Topological domain638 – 64710Extracellular Potential
Transmembrane648 – 66417 Potential
Topological domain665 – 67915Cytoplasmic Potential
Transmembrane680 – 69617 Potential
Topological domain697 – 72024Extracellular Potential
Transmembrane721 – 73717 Potential
Topological domain738 – 76023Cytoplasmic Potential
Transmembrane761 – 77717 Potential
Topological domain778 – 81740Extracellular Potential
Transmembrane818 – 83417 Potential
Topological domain835 – 8384Cytoplasmic Potential

Amino acid modifications

Glycosylation2141N-linked (GlcNAc...) Potential
Glycosylation2181N-linked (GlcNAc...) Potential
Glycosylation2731N-linked (GlcNAc...) Potential
Glycosylation4421N-linked (GlcNAc...) Potential
Glycosylation7811N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence349 – 37224Missing in isoform 2.
VSP_012284
Alternative sequence652 – 66817WIAIL…LADIH → GLGLVQAGRYYLSTPES in isoform 3.
VSP_012285
Alternative sequence669 – 838170Missing in isoform 3.
VSP_012286
Natural variant101R → W in OCA2.
VAR_020622
Natural variant271G → R in OCA2.
VAR_006117
Natural variant861S → R in OCA2.
VAR_006118
Natural variant1121C → F in OCA2.
VAR_006119
Natural variant1981P → L in OCA2.
VAR_020623
Natural variant206 – 2116Missing in OCA2; severe.
VAR_006120
Natural variant2111P → L in OCA2.
VAR_020624
Natural variant2411P → R: dbSNP rs2305253.
VAR_022019
Natural variant2571A → D: dbSNP rs1050968.
VAR_006121
Natural variant2661R → W: dbSNP rs33929465.
VAR_032094
Natural variant273 – 2742NW → KV in OCA2.
VAR_006122
Natural variant2901R → G in OCA2.
VAR_020625
Natural variant3051R → W Polymorphism associated with nonblue eye color; could be a biomarker of cutaneous cancer risk. dbSNP rs1800401.
VAR_006123
Natural variant3341A → V in OCA2.
VAR_020626
Natural variant3361A → V: dbSNP rs34010619.
VAR_032095
Natural variant3501V → M in unclassified OCA.
VAR_020627
Natural variant3681A → V in OCA2.
VAR_006124
Natural variant3701I → T in unclassified OCA. dbSNP rs34731820.
VAR_020628
Natural variant3851F → I in OCA2; severe.
VAR_006125
Natural variant3871T → M
VAR_020629
Natural variant3941M → I in OCA2.
VAR_020630
Natural variant3951M → L in OCA2; severe.
VAR_006126
Natural variant4041T → M in OCA2.
VAR_006127
Natural variant4191R → Q Polymorphism associated with green/hazel eye color. dbSNP rs1800407.
VAR_006128
Natural variant4191R → W in OCA2.
VAR_006129
Natural variant4251Missing in OCA2; mild.
VAR_006130
Natural variant4401L → F: dbSNP rs1800408.
VAR_007939
Natural variant4401L → H
VAR_006131
Natural variant4431V → I in OCA2.
VAR_006132
Natural variant4461M → V in OCA2; mild; AROA form.
VAR_006133
Natural variant4731I → S in OCA2.
VAR_006134
Natural variant4761N → D in OCA2.
VAR_043700
Natural variant4811A → T in OCA2.
VAR_007940
Natural variant4891N → D in OCA2; mild/severe.
VAR_006135
Natural variant5191V → A: dbSNP rs41446944.
VAR_032096
Natural variant5491H → Q in OCA2.
VAR_006136
Natural variant5601R → H: dbSNP rs35110389.
VAR_032097
Natural variant5921T → I in OCA2. dbSNP rs1800413.
VAR_006137
Natural variant6141K → E in OCA2.
VAR_020631
Natural variant6141K → N in OCA2.
VAR_006138
Natural variant6151H → R: dbSNP rs1800414.
VAR_006139
Natural variant6171I → L in OCA2.
VAR_020632
Natural variant6521W → R in OCA2.
VAR_006140
Natural variant6781E → K in unclassified OCA.
VAR_020633
Natural variant6791W → C in OCA2.
VAR_020634
Natural variant6791W → R in OCA2; severe.
VAR_006141
Natural variant6881L → F in unclassified OCA.
VAR_020635
Natural variant7201R → C in OCA2.
VAR_020636
Natural variant7221I → T: dbSNP rs1800417.
VAR_006142
Natural variant7241A → P in OCA2.
VAR_006143
Natural variant7361S → L in OCA2.
VAR_006144
Natural variant7431P → L in OCA2 and unclassified OCA.