Reviewed,
UniProtKB/Swiss-Prot Q04671 (P_HUMAN)
Last modified
November 25, 2008.
Version 92.
History...
Clusters with 100%,
90%,
50% identity |
 Documents (6) |
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Names and origin
| Protein names | Recommended name: P protein Alternative name(s): Melanocyte-specific transporter protein Pink-eyed dilution protein homolog | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 838 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence 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 | |
| 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] |
Ontologies
Keywords | |
|---|---|
| Biological process | Transport |
| Cellular component | Membrane |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Disease | Albinism Disease mutation |
| Domain | Transmembrane |
| PTM | Glycoprotein |
Gene Ontology (GO) | |
| Biological process | citrate transport Inferred from electronic annotation. Source: InterPro eye pigment biosynthetic process Ref.1Traceable author statement. Source: ProtInc |
| Cellular component | integral to membrane Ref.1 Traceable author statement. Source: ProtInc melanosome membraneInferred from electronic annotation. Source: UniProtKB-SubCell |
| Molecular function | L-tyrosine transmembrane transporter activity Ref.2 Traceable author statement. Source: ProtInc arsenite transmembrane transporter activityInferred from electronic annotation. Source: InterPro citrate transmembrane transporter activityInferred from electronic annotation. Source: InterPro |
| Complete GO annotation... | |
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 key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 838 | 838 | P protein | PRO_0000172509 | |||||
Regions | |||||||||
| Topological domain | 1 – 179 | 179 | Cytoplasmic Potential | ||||||
| Transmembrane | 180 – 197 | 18 | Potential | ||||||
| Topological domain | 198 – 330 | 133 | Extracellular Potential | ||||||
| Transmembrane | 331 – 347 | 17 | Potential | ||||||
| Topological domain | 348 – 353 | 6 | Cytoplasmic Potential | ||||||
| Transmembrane | 354 – 370 | 17 | Potential | ||||||
| Topological domain | 371 – 384 | 14 | Extracellular Potential | ||||||
| Transmembrane | 385 – 401 | 17 | Potential | ||||||
| Topological domain | 402 – 423 | 22 | Cytoplasmic Potential | ||||||
| Transmembrane | 424 – 440 | 17 | Potential | ||||||
| Topological domain | 441 – 513 | 73 | Extracellular Potential | ||||||
| Transmembrane | 514 – 530 | 17 | Potential | ||||||
| Topological domain | 531 – 620 | 90 | Cytoplasmic Potential | ||||||
| Transmembrane | 621 – 637 | 17 | Potential | ||||||
| Topological domain | 638 – 647 | 10 | Extracellular Potential | ||||||
| Transmembrane | 648 – 664 | 17 | Potential | ||||||
| Topological domain | 665 – 679 | 15 | Cytoplasmic Potential | ||||||
| Transmembrane | 680 – 696 | 17 | Potential | ||||||
| Topological domain | 697 – 720 | 24 | Extracellular Potential | ||||||
| Transmembrane | 721 – 737 | 17 | Potential | ||||||
| Topological domain | 738 – 760 | 23 | Cytoplasmic Potential | ||||||
| Transmembrane | 761 – 777 | 17 | Potential | ||||||
| Topological domain | 778 – 817 | 40 | Extracellular Potential | ||||||
| Transmembrane | 818 – 834 | 17 | Potential | ||||||
| Topological domain | 835 – 838 | 4 | Cytoplasmic Potential | ||||||
Amino acid modifications | |||||||||
| Glycosylation | 214 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 218 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 273 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 442 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 781 | 1 | N-linked (GlcNAc...) Potential | ||||||
Natural variations | |||||||||
| Alternative sequence | 349 – 372 | 24 | Missing in isoform 2. | VSP_012284 | |||||
| Alternative sequence | 652 – 668 | 17 | WIAIL…LADIH → GLGLVQAGRYYLSTPES in isoform 3. | VSP_012285 | |||||
| Alternative sequence | 669 – 838 | 170 | Missing in isoform 3. | VSP_012286 | |||||
| Natural variant | 10 | 1 | R → W in OCA2. | VAR_020622 | |||||
| Natural variant | 27 | 1 | G → R in OCA2. | VAR_006117 | |||||
| Natural variant | 86 | 1 | S → R in OCA2. | VAR_006118 | |||||
| Natural variant | 112 | 1 | C → F in OCA2. | VAR_006119 | |||||
| Natural variant | 198 | 1 | P → L in OCA2. | VAR_020623 | |||||
| Natural variant | 206 – 211 | 6 | Missing in OCA2; severe. | VAR_006120 | |||||
| Natural variant | 211 | 1 | P → L in OCA2. | VAR_020624 | |||||
| Natural variant | 241 | 1 | P → R: dbSNP rs2305253. | VAR_022019 | |||||
| Natural variant | 257 | 1 | A → D: dbSNP rs1050968. | VAR_006121 | |||||
| Natural variant | 266 | 1 | R → W: dbSNP rs33929465. | VAR_032094 | |||||
| Natural variant | 273 – 274 | 2 | NW → KV in OCA2. | VAR_006122 | |||||
| Natural variant | 290 | 1 | R → G in OCA2. | VAR_020625 | |||||
| Natural variant | 305 | 1 | R → W Polymorphism associated with nonblue eye color; could be a biomarker of cutaneous cancer risk. dbSNP rs1800401. | VAR_006123 | |||||
| Natural variant | 334 | 1 | A → V in OCA2. | VAR_020626 | |||||
| Natural variant | 336 | 1 | A → V: dbSNP rs34010619. | VAR_032095 | |||||
| Natural variant | 350 | 1 | V → M in unclassified OCA. | VAR_020627 | |||||
| Natural variant | 368 | 1 | A → V in OCA2. | VAR_006124 | |||||
| Natural variant | 370 | 1 | I → T in unclassified OCA. dbSNP rs34731820. | VAR_020628 | |||||
| Natural variant | 385 | 1 | F → I in OCA2; severe. | VAR_006125 | |||||
| Natural variant | 387 | 1 | T → M | VAR_020629 | |||||
| Natural variant | 394 | 1 | M → I in OCA2. | VAR_020630 | |||||
| Natural variant | 395 | 1 | M → L in OCA2; severe. | VAR_006126 | |||||
| Natural variant | 404 | 1 | T → M in OCA2. | VAR_006127 | |||||
| Natural variant | 419 | 1 | R → Q Polymorphism associated with green/hazel eye color. dbSNP rs1800407. | VAR_006128 | |||||
| Natural variant | 419 | 1 | R → W in OCA2. | VAR_006129 | |||||
| Natural variant | 425 | 1 | Missing in OCA2; mild. | VAR_006130 | |||||
| Natural variant | 440 | 1 | L → F: dbSNP rs1800408. | VAR_007939 | |||||
| Natural variant | 440 | 1 | L → H | VAR_006131 | |||||
| Natural variant | 443 | 1 | V → I in OCA2. | VAR_006132 | |||||
| Natural variant | 446 | 1 | M → V in OCA2; mild; AROA form. | VAR_006133 | |||||
| Natural variant | 473 | 1 | I → S in OCA2. | VAR_006134 | |||||
| Natural variant | 476 | 1 | N → D in OCA2. | VAR_043700 | |||||
| Natural variant | 481 | 1 | A → T in OCA2. | VAR_007940 | |||||
| Natural variant | 489 | 1 | N → D in OCA2; mild/severe. | VAR_006135 | |||||
| Natural variant | 519 | 1 | V → A: dbSNP rs41446944. | VAR_032096 | |||||
| Natural variant | 549 | 1 | H → Q in OCA2. | VAR_006136 | |||||
| Natural variant | 560 | 1 | R → H: dbSNP rs35110389. | VAR_032097 | |||||
| Natural variant | 592 | 1 | T → I in OCA2. dbSNP rs1800413. | VAR_006137 | |||||
| Natural variant | 614 | 1 | K → E in OCA2. | VAR_020631 | |||||
| Natural variant | 614 | 1 | K → N in OCA2. | VAR_006138 | |||||
| Natural variant | 615 | 1 | H → R: dbSNP rs1800414. | VAR_006139 | |||||
| Natural variant | 617 | 1 | I → L in OCA2. | VAR_020632 | |||||
| Natural variant | 652 | 1 | W → R in OCA2. | VAR_006140 | |||||
| Natural variant | 678 | 1 | E → K in unclassified OCA. | VAR_020633 | |||||
| Natural variant | 679 | 1 | W → C in OCA2. | VAR_020634 | |||||
| Natural variant | 679 | 1 | W → R in OCA2; severe. | VAR_006141 | |||||
| Natural variant | 688 | 1 | L → F in unclassified OCA. | VAR_020635 | |||||
| Natural variant | 720 | 1 | R → C in OCA2. | VAR_020636 | |||||
| Natural variant | 722 | 1 | I → T: dbSNP rs1800417. | VAR_006142 | |||||
| Natural variant | 724 | 1 | A → P in OCA2. | VAR_006143 | |||||
| Natural variant | 736 | 1 | S → L in OCA2. | VAR_006144 | |||||
| Natural variant | 743 | 1 | P → L in OCA2 and unclassified OCA. | ||||||