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Human Metabolome Database Version 2.5

 

Showing metabocard for Melanin (HMDB04068)

Legend: metabolite field enzyme field

Version 2.5
Creation Date 2006-08-13 11:15:22
Update Date 2009-11-24 12:31:33
Accession Number HMDB04068
Secondary Accession Numbers Not Available
Common Name Melanin
Description Dermal melanin is produced by melanocytes, which are found in the stratum basale of the epidermis. Although human beings generally possess a similar concentration of melanocytes in their skin, the melanocytes in some individuals and races more frequently or less frequently express the melanin-producing genes, thereby conferring a greater or lesser concentration of skin melanin. Some individual animals and humans have no or very little melanin in their bodies, which is a condition known as albinism. Higher eumelanin levels also can be a disadvantage, however, beyond a higher disposition toward vitamin D deficiency. Dark skin is a complicating factor in the laser removal of port-wine stains. Effective in treating fair skin, lasers generally are less successful in removing port-wine stains in Asians and people of African descent. Higher concentrations of melanin in darker-skinned individuals simply diffuse and absorb the laser radiation, inhibiting light absorption by the targeted tissue. Melanin similarly can complicate laser treatment of other dermatological conditions in people with darker skin. Under the microscope melanin is brown, non-refractile and finely granular with individual granules having a diameter of less than 800 nanometers. This differentiates melanin from common blood breakdown pigments which are larger, chunky and refractile and range in color from green to yellow or red-brown. In heavily pigmented lesions, dense aggregates of melanin can obscure histologic detail. A dilute solution of potassium permanganate is an effective melanin bleach. Pigments causing darkness in skin, hair, feathers, etc. They are irregular polymeric structures and are divided into three groups: allomelanins in the plant kingdom and eumelanins and phaeomelanins in the animal kingdom. When skin pigmentation as a characteristic of race is linked to social status or other human attributes, this phenomenon is known as racialism. Many people and societies overlay racialism with racist perceptions and systems which arbitrarily assign to groups of people a status of inherent superiority or inferiority, privilege or disadvantage based on skin color or racial classification. Apartheid-era South Africa is an example of a white supremacist society based on a system of stratification of power and privilege by skin color, as well as racial admixture. Similar examples can be found in Brazil's highly socially color-stratified society; and, in the U.S., segregation and institutional racism on the part of white-controlled and black-controlled institutions, and internal 'color consciousness' on the part of some ethnic minorities. Prejudice against people with more highly pigmented skin is the most pervasive form of color bias. Many other societies remain informally divided on the basis of skin color and, often, related ethnicity. (See also colonialism, Nazism, pigmentocracy and institutional racism.) Because melanin is an aggregate of smaller component molecules, there are a number of different types of melanin with differing proportions and bonding patterns of these component molecules. Both pheomelanin and eumelanin are found in human skin and hair, but eumelanin is the most abundant melanin in humans, as well as the form most likely to be deficient in albinism. Freckles and moles are formed where there is a localized concentration of melanin in the skin. They are highly associated with pale skin. Melanin is a biopolymer and a neuropeptide. In the early 1970s, John McGinness, Peter Corry, and Peter Proctor reported that melanin is a high-conductivity organic semiconductor (Science, vol 183, 853-855 (1974)). Studies revealed that melanin acted as a voltage-controlled solid-state threshold switch. Further, it emitting a flash of light electroluminescence when it switched. There are approximately ten different types of oculocutaneous albinism, which is mostly an autosomal recessive disorder. Certain ethnicities have higher incidences of different forms. For example, the most common type, called oculocutaneous albinism type 2 (OCA2), is especially frequent among people of indigenous African descent. It is an autosomal recessive disorder characterized by a congenital reduction or absence of melanin pigment in the skin, hair and eyes. The estimated frequency of OCA2 among African-Americans is 1 in 10,000, which contrasts with a frequency of 1 in 36,000 in white Americans . In some African nations, the frequency of the disorder is even higher, ranging from 1 in 2,000 to 1 in 5,000. Another form of Albinism, the 'yellow oculocutaneous albinism', appears to be more prevalent among the Amish, who are of primarily Swiss and German ancestry. People with this IB variant of the disorder commonly have white hair and skin at birth, but rapidly develop normal skin pigmentation in infancy. Broadly, melanin is any of the polyacetylene, polyaniline, and polypyrrole 'blacks' and "browns" or their mixed copolymers. The most common form of biological melanin is a polymer of either or both of two monomer molecules: indolequinone, and dihydroxyindole carboxylic acid. In contrast, some fungal melanin is polyacetylene black. Melanin exists in the plant, animal and protista kingdoms, where it serves as a pigment. The presence of melanin in the archaea and bacteria kingdoms is an issue of ongoing debate amongst researchers in the field.
Synonyms Not Available
Chemical IUPAC Name Not Available
Chemical Formula C18H10N2O4
Chemical Structure Structure
Chemical Taxonomy
Kingdom
  • Organic
Super Class
  • Heterocyclic molecules
Class
  • Indoles and Indole Derivatives
Sub Class
  • Melatonins
Family
  • Mammalian Metabolite
Species
  • ketone
  • enamine
  • alkene
  • heterocyclic compound
Biofunction
—
Application
—
Source
  • Endogenous
Average Molecular Weight 318.283
Monoisotopic Molecular Weight 318.064056
Isomeric SMILES CC1=C2NC=C3C4=C5C(NC=C5C(C(=O)C1=O)=C23)=C(C)C(=O)C4=O
Canonical SMILES CC1=C2NC=C3C4=C5C(NC=C5C(C(=O)C1=O)=C23)=C(C)C(=O)C4=O
KEGG Compound ID C05606 Link Image
BioCyc ID MELANIN Link Image
BiGG ID 46115 Link Image
Wikipedia Link Melanin Link Image
NuGOwiki Link HMDB04068 Link Image
Metagene Link HMDB04068 Link Image
METLIN ID 7011 Link Image
PubChem Compound 6325610 Link Image
PubChem Substance 7991501 Link Image
ChEBI ID Not Available
CAS Registry Number 8049-97-6
InChI Identifier InChI=1/C18H10N2O4/c1-5-13-9-7(3-19-13)12-10-8(11(9)17(23)15(5)21)4-20-14(10)6(2)16(22)18(12)24/h3-4,19-20H,1-2H3
Synthesis Reference Not Available
Melting Point (Experimental) Not Available
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility 0.31300002 mg/mL [Predicted by ALOGPS] Calculated using ALOGPS
Physiological Charge 0
State Solid
Experimental LogP/Hydrophobicity Not Available Source: PhysProp
Predicted LogP/Hydrophobicity 1.76 [Predicted by ALOGPS]; -0.626 [Predicted by PubChem via XLOGP] Calculated using ALOGPS
Material Safety Data Sheet (MSDS) Not Available
MOL File Show Link Image
SDF File Show Link Image
PDB File Show Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Experimental 1H NMR Spectrum Not Available
Experimental 13C NMR Spectrum Not Available
Experimental 13C HSQC Spectrum Not Available
Predicted 1H NMR Spectrum Show Image
Show Peaklist
Predicted 13C NMR Spectrum Show Image
Show Peaklist
Mass Spectrum Not Available
Simplified TOCSY Spectrum Not Available
BMRB Spectrum Not Available
Cellular Location
  • Cytoplasm
Biofluid Location
  • Blood
Tissue Location
Tissue References
Adrenal Gland —
Adrenal Medulla —
Bladder —
Dermis —
Fibroblasts —
Hair —
Keratinocyte —
Melanocyte —
Myelin —
Nerve Cells —
Neuron —
Skin —
Spleen —
Stratum Corneum —
Thyroid Gland —
Concentrations (Normal)
Biofluid Blood
Value 5030.0 +/- 314.0 uM
Age Adult:>18 yrs old
Sex Both
Patient information Normal
Comments The concentration refers to the mean quantity of plasma soluble melanins (1.61 +/- 0.1 mg/ml)
References
  • Hegedus ZL: The probable involvement of soluble and deposited melanins, their intermediates and the reactive oxygen side-products in human diseases and aging. Toxicology. 2000 Apr 14;145(2-3):85-101. [PubMed Link Image]
Biofluid Blood
Value 5345 +/- 318 uM
Age Adult:>18 yrs old
Sex Both
Patient information Normal
Comments The concentration refers to the total plasma concentration of melanins: (1.70 +/- 0.10) mg/ml
References
  • Hegedus ZL, Frank HA, Steinman TI, Altschule MD, Nayak U: Elevated levels of plasma lipofuscins in patients with chronic renal failure. Arch Int Physiol Biochim. 1988 Dec;96(5):211-21. [PubMed Link Image]
Concentrations (Abnormal)
Biofluid Blood
Value 8551 +/- 1194 uM
Age Adult:>18 yrs old
Sex Both
Condition Chronic renal failure
Comments The concentration refers to the total plasma concentration of melanins (2.72 +/- 0.38 mg/ml)
References
  • Hegedus ZL, Frank HA, Steinman TI, Altschule MD, Nayak U: Elevated levels of plasma lipofuscins in patients with chronic renal failure. Arch Int Physiol Biochim. 1988 Dec;96(5):211-21. [PubMed Link Image]
Associated Disorders
Condition References
Chronic renal failure
  • Hegedus ZL, Frank HA, Steinman TI, Altschule MD, Nayak U: Elevated levels of plasma lipofuscins in patients with chronic renal failure. Arch Int Physiol Biochim. 1988 Dec;96(5):211-21. [PubMed Link Image]
OMIM ID Not Available
Pathways
Name SMPDB Link KEGG Link
Tyrosine Metabolism SMP00006 Link Image map00350 Link Image
General References
  1. Pugh ND, Balachandran P, Lata H, Dayan FE, Joshi V, Bedir E, Makino T, Moraes R, Khan I, Pasco DS: Melanin: dietary mucosal immune modulator from Echinacea and other botanical supplements. Int Immunopharmacol. 2005 Apr;5(4):637-47. [PubMed Link Image]
  2. Borges CR, Roberts JC, Wilkins DG, Rollins DE: Relationship of melanin degradation products to actual melanin content: application to human hair. Anal Biochem. 2001 Mar 1;290(1):116-25. [PubMed Link Image]
  3. Alaluf S, Atkins D, Barrett K, Blount M, Carter N, Heath A: The impact of epidermal melanin on objective measurements of human skin colour. Pigment Cell Res. 2002 Apr;15(2):119-26. [PubMed Link Image]
  4. Wenczl E, Van der Schans GP, Roza L, Kolb RM, Timmerman AJ, Smit NP, Pavel S, Schothorst AA: (Pheo)melanin photosensitizes UVA-induced DNA damage in cultured human melanocytes. J Invest Dermatol. 1998 Oct;111(4):678-82. [PubMed Link Image]
  5. Nielsen KP, Zhao L, Stamnes JJ, Stamnes K, Moan J: The importance of the depth distribution of melanin in skin for DNA protection and other photobiological processes. J Photochem Photobiol B. 2006 Mar 1;82(3):194-8. Epub 2006 Jan 4. [PubMed Link Image]
  6. Watanabe T, Tamura A, Yoshimura Y, Nakazawa H: Determination of melanin in human hair by photoacoustic spectroscopy. Anal Biochem. 1997 Dec 15;254(2):267-71. [PubMed Link Image]
  7. Claridge E, Cotton S, Hall P, Moncrieff M: From colour to tissue histology: Physics-based interpretation of images of pigmented skin lesions. Med Image Anal. 2003 Dec;7(4):489-502. [PubMed Link Image]
  8. Schmidt R, Krien P, Regnier M: The use of diethylaminoethyl-cellulose-membrane filters in a bioassay to quantify melanin synthesis. Anal Biochem. 1996 Mar 15;235(2):113-8. [PubMed Link Image]
  9. Lu H, Edwards C, Gaskell S, Pearse A, Marks R: Melanin content and distribution in the surface corneocyte with skin phototypes. Br J Dermatol. 1996 Aug;135(2):263-7. [PubMed Link Image]
  10. Kronstrand R, Forstberg-Peterson S, Kagedal B, Ahlner J, Larson G: Codeine concentration in hair after oral administration is dependent on melanin content. Clin Chem. 1999 Sep;45(9):1485-94. [PubMed Link Image]
  11. Bartosik J, Wulf HC, Kobayasi T: Melanin and melanosome complexes in long standing stable vitiligo--an ultrastructural study. Eur J Dermatol. 1998 Mar;8(2):95-7. [PubMed Link Image]
  12. Svensson SP, Lindgren S, Powell W, Green H: Melanin inhibits cytotoxic effects of doxorubicin and daunorubicin in MOLT 4 cells. Pigment Cell Res. 2003 Aug;16(4):351-4. [PubMed Link Image]
  13. Dwyer T, Muller HK, Blizzard L, Ashbolt R, Phillips G: The use of spectrophotometry to estimate melanin density in Caucasians. Cancer Epidemiol Biomarkers Prev. 1998 Mar;7(3):203-6. [PubMed Link Image]
  14. Shimada M, Yamada Y, Itoh M, Yatagai T: Melanin and blood concentration in human skin studied by multiple regression analysis: experiments. Phys Med Biol. 2001 Sep;46(9):2385-95. [PubMed Link Image]
  15. Yamashita T, Kuwahara T, Gonzalez S, Takahashi M: Non-invasive visualization of melanin and melanocytes by reflectance-mode confocal microscopy. J Invest Dermatol. 2005 Jan;124(1):235-40. [PubMed Link Image]
  16. Huang Z, Zeng H, Hamzavi I, Alajlan A, Tan E, McLean DI, Lui H: Cutaneous melanin exhibiting fluorescence emission under near-infrared light excitation. J Biomed Opt. 2006 May-Jun;11(3):34010. [PubMed Link Image]
  17. Eng HL, Chen WJ: Melanin-producing medullary carcinoma of the thyroid gland. Arch Pathol Lab Med. 1989 Apr;113(4):377-80. [PubMed Link Image]
  18. Mammone T, Marenus K, Muizzuddin N, Maes D: Evidence and utility of melanin degrading enzymes. J Cosmet Sci. 2004 Jan-Feb;55(1):116-7. [PubMed Link Image]
  19. Shimada M, Yamada Y, Itoh M, Yatagai T: Melanin and blood concentration in a human skin model studied by multiple regression analysis: assessment by Monte Carlo simulation. Phys Med Biol. 2001 Sep;46(9):2397-406. [PubMed Link Image]
  20. Nishidate I, Aizu Y, Mishina H: Depth visualization of a local blood region in skin tissue by use of diffuse reflectance images. Opt Lett. 2005 Aug 15;30(16):2128-30. [PubMed Link Image]
  21. Wikipedia Link Image
Metabolic Enzymes
  1. 5,6-dihydroxyindole-2-carboxylic acid oxidase
  2. P protein
Enzyme 1 [top]
Enzyme 1 ID 7622
Enzyme 1 Name 5,6-dihydroxyindole-2-carboxylic acid oxidase
Enzyme 1 Synonyms
  1. DHICA oxidase
  2. Catalase B
  3. Glycoprotein 75
  4. Melanoma antigen gp75
  5. Tyrosinase-related protein 1
  6. TRP
  7. TRP-1
  8. TRP1
Enzyme 1 Gene Name TYRP1
Enzyme 1 Protein Sequence >5,6-dihydroxyindole-2-carboxylic acid oxidase 
MSAPKLLSLGCIFFPLLLFQQARAQFPRQCATVEALRSGMCCPDLSPVSGPGTDRCGSSS
GRGRCEAVTADSRPHSPQYPHDGRDDREVWPLRFFNRTCHCNGNFSGHNCGTCRPGWRGA
ACDQRVLIVRRNLLDLSKEEKNHFVRALDMAKRTTHPLFVIATRRSEEILGPDGNTPQFE
NISIYNYFVWTHYYSVKKTFLGVGQESFGEVDFSHEGPAFLTWHRYHLLRLEKDMQEMLQ
EPSFSLPYWNFATGKNVCDICTDDLMGSRSNFDSTLISPNSVFSQWRVVCDSLEDYDTLG
TLCNSTEDGPIRRNPAGNVARPMVQRLPEPQDVAQCLEVGLFDTPPFYSNSTNSFRNTVE
GYSDPTGKYDPAVRSLHNLAHLFLNGTGGQTHLSPNDPIFVLLHTFTDAVFDEWLRRYNA
DISTFPLENAPIGHNRQYNMVPFWPPVTNTEMFVTAPDNLGYTYEIQWPSREFSVPEIIA
IAVVGALLLVALIFGTASYLIRARRSMDEANQPLLTDQYQCYAEEYEKLQNPNQSVV
Enzyme 1 Number of Residues 537
Enzyme 1 Molecular Weight 60723.8
Enzyme 1 Theoretical pI 5.86
Enzyme 1 GO Classification
Function
  • binding
  • catalytic activity
  • cation binding
  • copper ion binding
  • ion binding
  • metal ion binding
  • monooxygenase activity
  • oxidoreductase activity
  • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, another compound as one donor, and incorporation of one atom of oxygen
  • transition metal ion binding
Process
  • melanin biosynthetic process
  • melanin metabolic process
  • metabolic process
  • oxidation reduction
  • secondary metabolic process
Component
  • cell part
  • cytoplasmic vesicle membrane
  • melanosome membrane
  • membrane
  • organelle membrane
  • vesicle membrane
Enzyme 1 General Function Involved in copper ion binding
Enzyme 1 Specific Function Oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into indole-5,6-quinone-2-carboxylic acid. May regulate or influence the type of melanin synthesized
Enzyme 1 Pathways Not Available
Enzyme 1 Reactions Not Available
Enzyme 1 Pfam Domain Function
Enzyme 1 Signals
  • 1-24
Enzyme 1 Transmembrane Regions
  • 478-501
Enzyme 1 Essentiality Not Available
Enzyme 1 GenBank ID Protein 2735662 Link Image
Enzyme 1 UniProtKB/Swiss-Prot ID P17643 Link Image
Enzyme 1 UniProtKB/Swiss-Prot Entry Name TYRP1_HUMAN Link Image
Enzyme 1 PDB ID Not Available
Enzyme 1 Cellular Location Not Available
Enzyme 1 Gene Sequence >1614 bp 
ATGAGTGCTCCTAAACTCCTCTCTCTGGGCTGTATCTTCTTCCCCTTGCTACTTTTTCAG
CAGGCCCGGGCTCAATTCCCAAGACAGTGTGCCACTGTTGAGGCTTTGAGAAGTGGTATG
TGTTGCCCAGACCTGTCCCCTGTGTCTGGGCCTGGGACAGACCGCTGTGGCTCATCATCA
GGGAGGGGCAGATGTGAGGCAGTGACTGCAGACTCCCGGCCCCACAGCCCTCAGTATCCC
CATGATGGCAGAGATGATCGGGAGGTCTGGCCCTTGCGCTTCTTCAATAGGACATGTCAC
TGCAACGGCAATTTCTCAGGACACAACTGTGGGACGTGCCGTCCTGGCTGGAGAGGAGCT
GCCTGTGACCAGAGGGTTCTCATAGTCAGGAGAAATCTTCTGGACTTAAGTAAAGAAGAA
AAGAACCACTTTGTCCGGGCCCTGGATATGGCAAAGCGCACAACTCACCCTTTATTTGTC
ATTGCCACCAGGAGATCAGAAGAAATACTGGGGCCAGATGGCAACACGCCACAATTTGAG
AACATTTCCATTTATAACTACTTTGTTTGGACACACTATTACTCAGTCAAAAAGACTTTC
CTTGGGGTAGGACAGGAAAGCTTTGGTGAAGTGGATTTCTCTCATGAGGGACCAGCTTTT
CTCACATGGCACAGGTACCACCTCCTGCGTCTGGAGAAAGACATGCAGGAAATGTTGCAA
GAGCCTTCTTTCTCCCTTCCTTACTGGAATTTTGCAACGGGGAAAAATGTCTGTGATATC
TGCACGGATGACTTGATGGGATCCAGAAGCAACTTTGATTCCACTCTAATAAGCCCAAAC
TCTGTCTTTTCTCAATGGCGAGTGGTCTGTGACTCCTTGGAAGATTATGATACCCTGGGA
ACACTTTGTAACAGCACCGAGGATGGGCCAATTAGGAGAAATCCAGCTGGAAATGTGGCC
AGACCAATGGTGCAACGTCTTCCTGAACCACAGGATGTCGCTCAGTGCTTGGAAGTTGGT
TTATTTGACACGCCTCCTTTTTATTCCAACTCTACAAACAGTTTCCGAAACACAGTGGAA
GGTTACAGTGACCCCACGGGAAAGTATGACCCTGCTGTTCGAAGTCTTCACAATTTGGCT
CATCTATTCCTGAATGGAACAGGGGGACAAACCCATTTGTCTCCAAATGATCCTATTTTT
GTCCTCCTGCACACCTTCACAGATGCAGTCTTTGATGAATGGCTGAGGAGATACAATGCT
GATATATCCACATTTCCATTGGAAAATGCCCCTATTGGACATAATAGACAATACAACATG
GTGCCATTCTGGCCCCCAGTCACCAACACAGAAATGTTTGTTACTGCTCCAGACAACCTG
GGATACACTTATGAAATTCAATGGCCAAGTCGGGAGTTTAGTGTACCTGAGATAATTGCC
ATAGCAGTAGTTGGCGCTTTGTTACTGGTTGCACTCATTTTTGGGACTGCTTCTTATCTG
ATTCGTGCCAGACGCAGTATGGATGAAGCTAACCAGCCTCTCCTCACTGATCAGTATCAA
TGCTATGCTGAAGAATATGAAAAACTCCAGAATCCTAATCAGTCTGTGGTCTAA
Enzyme 1 GenBank Gene ID AF001295 Link Image
Enzyme 1 GeneCard ID TYRP1 Link Image
Enzyme 1 GenAtlas ID TYRP1 Link Image
Enzyme 1 HGNC ID HGNC:12450 Link Image
Enzyme 1 Chromosome Location 9
Enzyme 1 Locus 9p23
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 General References
  1. Cohen T, Muller RM, Tomita Y, Shibahara S: Nucleotide sequence of the cDNA encoding human tyrosinase-related protein. Nucleic Acids Res. 1990 May 11;18(9):2807-8. [PubMed Link Image]
  2. Chintamaneni CD, Ramsay M, Colman MA, Fox MF, Pickard RT, Kwon BS: Mapping the human CAS2 gene, the homologue of the mouse brown (b) locus, to human chromosome 9p22-pter. Biochem Biophys Res Commun. 1991 Jul 15;178(1):227-35. [PubMed Link Image]
  3. Box NF, Wyeth JR, Mayne CJ, O'Gorman LE, Martin NG, Sturm RA: Complete sequence and polymorphism study of the human TYRP1 gene encoding tyrosinase-related protein 1. Mamm Genome. 1998 Jan;9(1):50-3. [PubMed Link Image]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed Link Image]
  5. Sturm RA, O'Sullivan BJ, Box NF, Smith AG, Smit SE, Puttick ER, Parsons PG, Dunn IS: Chromosomal structure of the human TYRP1 and TYRP2 loci and comparison of the tyrosinase-related protein gene family. Genomics. 1995 Sep 1;29(1):24-34. [PubMed Link Image]
  6. Shibata K, Takeda K, Tomita Y, Tagami H, Shibahara S: Downstream region of the human tyrosinase-related protein gene enhances its promoter activity. Biochem Biophys Res Commun. 1992 Apr 30;184(2):568-75. [PubMed Link Image]
  7. Vijayasaradhi S, Bouchard B, Houghton AN: The melanoma antigen gp75 is the human homologue of the mouse b (brown) locus gene product. J Exp Med. 1990 Apr 1;171(4):1375-80. [PubMed Link Image]
  8. Urquhart A: Human tyrosinase-like protein (TYRL) carboxy terminus: closer homology with the mouse protein than previously reported. Nucleic Acids Res. 1991 Oct 25;19(20):5803. [PubMed Link Image]
  9. Halaban R, Moellmann G: Murine and human b locus pigmentation genes encode a glycoprotein (gp75) with catalase activity. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4809-13. [PubMed Link Image]
  10. Basrur V, Yang F, Kushimoto T, Higashimoto Y, Yasumoto K, Valencia J, Muller J, Vieira WD, Watabe H, Shabanowitz J, Hearing VJ, Hunt DF, Appella E: Proteomic analysis of early melanosomes: identification of novel melanosomal proteins. J Proteome Res. 2003 Jan-Feb;2(1):69-79. [PubMed Link Image]
  11. Chi A, Valencia JC, Hu ZZ, Watabe H, Yamaguchi H, Mangini NJ, Huang H, Canfield VA, Cheng KC, Yang F, Abe R, Yamagishi S, Shabanowitz J, Hearing VJ, Wu C, Appella E, Hunt DF: Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes. J Proteome Res. 2006 Nov;5(11):3135-44. [PubMed Link Image]
  12. Rooryck C, Roudaut C, Robine E, Musebeck J, Arveiler B: Oculocutaneous albinism with TYRP1 gene mutations in a Caucasian patient. Pigment Cell Res. 2006 Jun;19(3):239-42. [PubMed Link Image]
Enzyme 1 Metabolite References Not Available
Enzyme 2 [top]
Enzyme 2 ID 17062
Enzyme 2 Name P protein
Enzyme 2 Synonyms
  1. Melanocyte-specific transporter protein
  2. Pink-eyed dilution protein homolog
Enzyme 2 Gene Name OCA2
Enzyme 2 Protein Sequence >P protein 
MHLEGRDGRRYPGAPAVELLQTSVPSGLAELVAGKRRLPRGAGGADPSHSCPRGAAGQSS
WAPAGQEFASFLTKGRSHSSLPQMSSSRSKDSCFTENTPLLRNSLQEKGSRCIPVYHPEF
ITAEESWEDSSADWERRYLLSREVSGLSASASSEKGDLLDSPHIRLRLSKLRRCVQWLKV
MGLFAFVVLCSILFSLYPDQGKLWQLLALSPLENYSVNLSSHVDSTLLQVDLAGALVASG
PSRPGREEHIVVELTQADALGSRWRRPQQVTHNWTVYLNPRRSEHSVMSRTFEVLTRETV
SISIRASLQQTQAVPLLMAHQYLRGSVETQVTIATAILAGVYALIIFEIVHRTLAAMLGS
LAALAALAVIGDRPSLTHVVEWIDFETLALLFGMMILVAIFSETGFFDYCAVKAYRLSRG
RVWAMIIMLCLIAAVLSAFLDNVTTMLLFTPVTIRLCEVLNLDPRQVLIAEVIFTNIGGA
ATAIGDPPNVIIVSNQELRKMGLDFAGFTAHMFIGICLVLLVCFPLLRLLYWNRKLYNKE
PSEIVELKHEIHVWRLTAQRISPASREETAVRRLLLGKVLALEHLLARRLHTFHRQISQE
DKNWETNIQELQKKHRISDGILLAKCLTVLGFVIFMFFLNSFVPGIHLDLGWIAILGAIW
LLILADIHDFEIILHRVEWATLLFFAALFVLMEALAHLHLIEYVGEQTALLIKMVPEEQR
LIAAIVLVVWVSALASSLIDNIPFTATMIPVLLNLSHDPEVGLPAPPLMYALAFGACLGG
NGTLIGASANVVCAGIAEQHGYGFSFMEFFRLGFPMMVVSCTVGMCYLLVAHVVVGWN
Enzyme 2 Number of Residues 838
Enzyme 2 Molecular Weight 92848.5
Enzyme 2 Theoretical pI 7.28
Enzyme 2 GO Classification
Function
  • anion transmembrane transporter activity
  • arsenite transmembrane transporter activity
  • carboxylic acid transmembrane transporter activity
  • citrate transmembrane transporter activity
  • inorganic anion transmembrane transporter activity
  • ion transmembrane transporter activity
  • organic acid transmembrane transporter activity
  • substrate-specific transmembrane transporter activity
  • transmembrane transporter activity
  • transporter activity
  • tricarboxylic acid transmembrane transporter activity
Process
  • carboxylic acid transport
  • citrate transport
  • establishment of localization
  • organic acid transport
  • transmembrane transport
  • transport
  • tricarboxylic acid transport
Component
  • cell part
  • integral to membrane
  • intrinsic to membrane
  • membrane part
Enzyme 2 General Function Involved in arsenite transmembrane transporter activity
Enzyme 2 Specific 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
Enzyme 2 Pathways Not Available
Enzyme 2 Reactions Not Available
Enzyme 2 Pfam Domain Function
Enzyme 2 Signals
  • None
Enzyme 2 Transmembrane Regions
  • 180-197 331-347 354-370 385-401 424-440 514-530 621-637 648-664 680-696 721-737 761-777 818-834
Enzyme 2 Essentiality Not Available
Enzyme 2 GenBank ID Protein 157266326 Link Image
Enzyme 2 UniProtKB/Swiss-Prot ID Q04671 Link Image
Enzyme 2 UniProtKB/Swiss-Prot Entry Name P_HUMAN Link Image
Enzyme 2 PDB ID Not Available
Enzyme 2 Cellular Location Not Available
Enzyme 2 Gene Sequence >2517 bp 
ATGCATCTGGAGGGCAGAGACGGCAGGCGGTACCCCGGCGCGCCGGCGGTGGAGCTCCTG
CAGACGTCCGTGCCCAGCGGACTCGCTGAACTTGTGGCCGGCAAGCGCAGGCTTCCTCGG
GGAGCCGGTGGAGCTGACCCCTCGCACTCCTGCCCCAGGGGGGCTGCCGGGCAGAGCTCT
TGGGCTCCTGCAGGCCAGGAGTTTGCTTCATTCCTCACAAAAGGGAGGTCTCACTCTTCT
TTGCCCCAGATGTCCAGCTCCAGGTCTAAAGATTCCTGCTTTACAGAAAACACTCCTTTG
CTGAGGAATTCCTTACAGGAGAAAGGGTCACGGTGCATACCTGTTTACCATCCAGAGTTC
ATCACTGCTGAAGAGTCTTGGGAAGACAGCTCTGCTGACTGGGAGCGAAGATACCTGCTA
AGCAGGGAGGTGTCTGGTCTGTCTGCATCTGCCTCCTCCGAGAAGGGAGACCTTCTGGAC
AGCCCGCACATCCGACTCCGTCTTTCCAAGCTGAGGCGCTGTGTGCAGTGGCTGAAAGTC
ATGGGCCTGTTTGCCTTTGTGGTGCTGTGTTCTATTTTGTTCAGCCTATATCCGGATCAA
GGAAAGCTCTGGCAGCTGTTGGCCTTATCACCGCTGGAGAACTACTCCGTGAACCTTAGC
AGCCACGTGGACTCCACGCTGCTGCAGGTGGACCTGGCAGGGGCCCTAGTGGCCAGTGGG
CCGAGTCGTCCTGGGAGGGAAGAGCACATCGTGGTGGAGCTGACCCAGGCTGACGCTTTG
GGCTCCAGGTGGCGGCGGCCACAGCAGGTCACTCACAACTGGACGGTGTATTTAAATCCG
AGGAGAAGCGAGCACTCAGTGATGAGCAGGACCTTTGAGGTACTGACCAGAGAGACGGTG
TCCATCAGCATCCGGGCCTCCCTGCAGCAGACCCAGGCTGTCCCTCTTTTGATGGCTCAT
CAGTACCTCCGCGGAAGTGTAGAAACCCAGGTGACCATCGCGACGGCCATCCTCGCGGGC
GTCTACGCGCTGATCATATTTGAGATCGTGCACAGAACTCTGGCGGCCATGCTGGGTTCC
CTTGCAGCACTGGCAGCACTGGCTGTGATTGGCGATAGACCCAGCCTGACCCATGTGGTG
GAGTGGATTGATTTTGAGACGCTGGCCCTGCTGTTTGGCATGATGATCTTAGTAGCCATA
TTTTCAGAAACGGGATTTTTCGATTATTGTGCTGTAAAGGCATACCGGCTCTCCCGGGGA
CGGGTGTGGGCCATGATCATCATGCTCTGTCTCATCGCGGCCGTCCTCTCTGCCTTCTTG
GACAACGTCACCACCATGCTCCTCTTCACGCCTGTGACCATAAGGTTGTGTGAGGTGCTC
AACCTTGATCCAAGACAAGTCCTGATTGCAGAAGTGATCTTCACAAACATTGGAGGAGCT
GCCACTGCCATCGGGGACCCTCCAAATGTCATTATTGTTTCCAACCAAGAGCTGAGGAAG
ATGGGCCTGGACTTTGCCGGATTCACTGCACACATGTTCATTGGGATTTGCCTTGTTCTC
CTGGTCTGCTTTCCGCTCCTCAGACTCCTTTACTGGAACAGAAAGCTTTATAACAAGGAA
CCCAGTGAGATTGTTGAACTGAAGCACGAGATTCACGTCTGGCGCCTGACTGCTCAGCGC
ATCAGCCCGGCCAGCCGCGAGGAGACAGCTGTGCGCCGCCTGCTGCTGGGGAAGGTGCTG
GCACTGGAGCACCTGCTCGCCCGGAGGCTGCACACCTTCCACAGACAGATCTCACAGGAG
GACAAAAATTGGGAGACCAATATCCAAGAACTCCAAAAAAAGCATAGGATATCTGACGGG
ATTCTGCTCGCCAAATGCCTGACAGTGTTGGGATTTGTTATCTTCATGTTTTTCCTCAAT
TCGTTTGTCCCTGGCATTCATCTTGATCTTGGATGGATTGCTATTCTGGGTGCCATCTGG
TTGCTAATTTTAGCTGATATTCATGATTTTGAGATAATTCTACACAGAGTGGAATGGGCA
ACCCTTCTGTTTTTTGCAGCGCTCTTTGTTCTGATGGAGGCATTGGCACATCTCCACTTA
ATAGAATATGTTGGAGAACAAACTGCTTTGCTAATAAAGATGGTCCCAGAGGAGCAGCGC
CTCATAGCCGCCATTGTCCTGGTGGTGTGGGTCTCAGCCCTGGCGTCGTCCCTGATTGAC
AACATCCCGTTCACTGCTACCATGATTCCCGTGCTCCTGAACCTGAGCCACGACCCTGAG
GTTGGCCTGCCCGCACCGCCGCTCATGTATGCCCTGGCCTTCGGTGCTTGCCTGGGAGGT
AACGGGACACTGATTGGCGCGTCGGCAAACGTCGTGTGTGCAGGGATTGCAGAACAGCAT
GGATATGGGTTCTCCTTCATGGAATTTTTCAGGCTGGGCTTCCCAATGATGGTTGTGTCC
TGCACTGTTGGGATGTGTTATCTCCTTGTGGCTCATGTGGTGGTGGGATGGAATTAA
Enzyme 2 GenBank Gene ID NM_000275.2 Link Image
Enzyme 2 GeneCard ID OCA2 Link Image
Enzyme 2 GenAtlas ID OCA2 Link Image
Enzyme 2 HGNC ID HGNC:8101 Link Image
Enzyme 2 Chromosome Location 1
Enzyme 2 Locus 15q
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 General References
  1. Rinchik EM, Bultman SJ, Horsthemke B, Lee ST, Strunk KM, Spritz RA, Avidano KM, Jong MT, Nicholls RD: A gene for the mouse pink-eyed dilution locus and for human type II oculocutaneous albinism. Nature. 1993 Jan 7;361(6407):72-6. [PubMed Link Image]
  2. Lee ST, Nicholls RD, Jong MT, Fukai K, Spritz RA: Organization and sequence of the human P gene and identification of a new family of transport proteins. Genomics. 1995 Mar 20;26(2):354-63. [PubMed Link Image]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed Link Image]
  4. Gardner JM, Nakatsu Y, Gondo Y, Lee S, Lyon MF, King RA, Brilliant MH: The mouse pink-eyed dilution gene: association with human Prader-Willi and Angelman syndromes. Science. 1992 Aug 21;257(5073):1121-4. [PubMed Link Image]
  5. Brilliant MH: The mouse p (pink-eyed dilution) and human P genes, oculocutaneous albinism type 2 (OCA2), and melanosomal pH. Pigment Cell Res. 2001 Apr;14(2):86-93. [PubMed Link Image]
  6. Manga P, Orlow SJ: Inverse correlation between pink-eyed dilution protein expression and induction of melanogenesis by bafilomycin A1. Pigment Cell Res. 2001 Oct;14(5):362-7. [PubMed Link Image]
  7. Sturm RA, Frudakis TN: Eye colour: portals into pigmentation genes and ancestry. Trends Genet. 2004 Aug;20(8):327-32. [PubMed Link Image]
  8. Oetting WS, King RA: Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism. Hum Mutat. 1999;13(2):99-115. [PubMed Link Image]
  9. Lee ST, Nicholls RD, Schnur RE, Guida LC, Lu-Kuo J, Spinner NB, Zackai EH, Spritz RA: Diverse mutations of the P gene among African-Americans with type II (tyrosinase-positive) oculocutaneous albinism (OCA2). Hum Mol Genet. 1994 Nov;3(11):2047-51. [PubMed Link Image]
  10. Spritz RA, Fukai K, Holmes SA, Luande J: Frequent intragenic deletion of the P gene in Tanzanian patients with type II oculocutaneous albinism (OCA2). Am J Hum Genet. 1995 Jun;56(6):1320-3. [PubMed Link Image]
  11. Spritz RA, Lee ST, Fukai K, Brondum-Nielsen K, Chitayat D, Lipson MH, Musarella MA, Rosenmann A, Weleber RG: Novel mutations of the P gene in type II oculocutaneous albinism (OCA2). Hum Mutat. 1997;10(2):175-7. [PubMed Link Image]
  12. Oetting WS, Gardner JM, Fryer JP, Ching A, Durham-Pierre D, King RA, Brilliant MH: Mutations of the human P gene associated with Type II oculocutaneous albinism (OCA2). Mutations in brief no. 205. Online. Hum Mutat. 1998;12(6):434. [PubMed Link Image]
  13. Passmore LA, Kaesmann-Kellner B, Weber BH: Novel and recurrent mutations in the tyrosinase gene and the P gene in the German albino population. Hum Genet. 1999 Sep;105(3):200-10. [PubMed Link Image]
  14. 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. 2000;15(2):166-72. [PubMed Link Image]
  15. Rebbeck TR, Kanetsky PA, Walker AH, Holmes R, Halpern AC, Schuchter LM, Elder DE, Guerry D: P gene as an inherited biomarker of human eye color. Cancer Epidemiol Biomarkers Prev. 2002 Aug;11(8):782-4. [PubMed Link Image]
  16. King RA, Willaert RK, Schmidt RM, Pietsch J, Savage S, Brott MJ, Fryer JP, Summers CG, Oetting WS: MC1R mutations modify the classic phenotype of oculocutaneous albinism type 2 (OCA2). Am J Hum Genet. 2003 Sep;73(3):638-45. Epub 2003 Jul 22. [PubMed Link Image]
  17. 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. 2003 May;31(3):189-92. [PubMed Link Image]
  18. 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. 2003 May;120(5):781-3. [PubMed Link Image]
  19. Jannot AS, 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, Melan-Cohort: Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma. Eur J Hum Genet. 2005 Aug;13(8):913-20. [PubMed Link Image]
  20. Duffy DL, Montgomery GW, Chen W, Zhao ZZ, Le L, James MR, Hayward NK, Martin NG, Sturm RA: A three-single-nucleotide polymorphism haplotype in intron 1 of OCA2 explains most human eye-color variation. Am J Hum Genet. 2007 Feb;80(2):241-52. Epub 2006 Dec 20. [PubMed Link Image]
  21. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [PubMed Link Image]
  22. Sulem P, Gudbjartsson DF, Stacey SN, Helgason A, Rafnar T, Magnusson KP, Manolescu A, Karason A, Palsson A, Thorleifsson G, Jakobsdottir M, Steinberg S, Palsson S, Jonasson F, Sigurgeirsson B, Thorisdottir K, Ragnarsson R, Benediktsdottir KR, Aben KK, Kiemeney LA, Olafsson JH, Gulcher J, Kong A, Thorsteinsdottir U, Stefansson K: Genetic determinants of hair, eye and skin pigmentation in Europeans. Nat Genet. 2007 Dec;39(12):1443-52. Epub 2007 Oct 21. [PubMed Link Image]
  23. 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. 2007 Jun;27(6):502-6. [PubMed Link Image]
  24. Kayser M, Liu F, Janssens AC, Rivadeneira F, Lao O, van Duijn K, Vermeulen M, Arp P, Jhamai MM, van Ijcken WF, den Dunnen JT, Heath S, Zelenika D, Despriet DD, Klaver CC, Vingerling JR, de Jong PT, Hofman A, Aulchenko YS, Uitterlinden AG, Oostra BA, van Duijn CM: Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene. Am J Hum Genet. 2008 Feb;82(2):411-23. Epub 2008 Jan 25. [PubMed Link Image]
  25. Sturm RA, Duffy DL, Zhao ZZ, Leite FP, Stark MS, Hayward NK, Martin NG, Montgomery GW: 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. 2008 Feb;82(2):424-31. Epub 2008 Jan 24. [PubMed Link Image]
  26. Eiberg H, Troelsen J, Nielsen M, Mikkelsen A, Mengel-From J, Kjaer KW, 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. 2008 Mar;123(2):177-87. Epub 2008 Jan 3. [PubMed Link Image]
Enzyme 2 Metabolite References Not Available