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discounted EARLY registration ends Dec 31, 2014
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MetaCyc Enzyme: tyrosinase

Gene: TYR Accession Number: HS01248 (MetaCyc)

Synonyms: OCAIA, OCA1A

Species: Homo sapiens

Summary:
Tyrosinases use molecular oxygen to catalyze two different enzymatic reactions, (i) the ortho-hydroxylation of monophenols to ortho-diphenols (monophenolase, cresolase acticity) and (ii) the oxidation of ortho-diphenols to ortho-quinones (diphenolase, catecholase activity) [Decker00].

In addition, the human enzyme was shown to catalyze the oxidation of a different melanin intermediate, 5,6-dihydroxyindole-2-carboxylate [Olivares01].

The mammalian tyrosinase is a melanocyte-specific enzyme critical for the synthesis of melanin, which takes place in a post-Golgi compartment termed the melanosome. It converts L-tyrosine to L-dopa and L-dopa to dopaquinone.

Tyrosinase has been purified from human skin [Vijayan82]. A cDNA encoding the human tyrosinase gene has been cloned and sequenced [Kwon87], and the chromosomal gene has been sequenced and mapped to chromosome 11 (q14-q21) [Barton88, Giebel91].

Expression of the human tyrosinase precursor cDNA in mouse cells led to synthesis and expression of active tyrosinase, and to stable production of melanin. [Takeda89, Bouchard89].

Oculocutaneous albinism (OCA) types 1, 2 and 3 are caused by mutations in the genes encoding tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1; also known as TRP1 and gp75), and the P protein (OCA2), respectively [Takeda90, Halaban00, Nakamura02]. The P protein modulates the processing and transport of tyrosinase [MercadoBlanco93]. Mutations in TYR can also cause autosomal recessive ocular albinism (AROA), a disorder that affects vision [Fukai95]

Gene Citations: [Shibahara88]

Map Position: [90,457,708 -> 90,575,914]

Molecular Weight of Polypeptide: 60.393 kD (from nucleotide sequence)

Unification Links: ArrayExpress:P14679 , Entrez-Nucleotide:M27160 , PhosphoSite:P14679 , PhylomeDB:P14679 , Pride:P14679 , Protein Model Portal:P14679 , SMR:P14679 , String:9606.ENSP00000263321 , UniProt:P14679

Relationship Links: InterPro:IN-FAMILY:IPR002227 , InterPro:IN-FAMILY:IPR008922 , Pfam:IN-FAMILY:PF00264 , Prints:IN-FAMILY:PR00092 , Prosite:IN-FAMILY:PS00497 , Prosite:IN-FAMILY:PS00498

Gene-Reaction Schematic: ?

Credits:
Created 09-Apr-2010 by Caspi R , SRI International


Enzymatic reaction of: L-dopa oxidase (tyrosinase)

EC Number: 1.10.3.-

L-dopa + 0.5 oxygen <=> dopaquinone + H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

Cofactors or Prosthetic Groups: Cu2+ [Spritz97]


Enzymatic reaction of: L-tyrosine monooxygenase (tyrosinase)

L-tyrosine + 0.5 oxygen <=> L-dopa

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: (S)-reticuline biosynthesis II

Cofactors or Prosthetic Groups: Cu2+ [Spritz97]

Kinetic Parameters:

Substrate
Km (μM)
Citations
L-tyrosine
500.0
[Vijayan82]


Enzymatic reaction of: 5,6-dihydroxyindole monooxygenase (tyrosinase)

5,6-dihydroxyindole + 2 H+ + oxygen <=> indole-5,6-quinone + 2 H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: eumelanin biosynthesis


Enzymatic reaction of: 5,6-dihydroxyindole-2-carboxylate monooxygenase (tyrosinase)

Synonyms: 5,6-dihydroxyindole-2-carboxylate oxidase, DHICA oxidase

5,6-dihydroxyindole-2-carboxylate + 2 H+ + oxygen <=> indole-5,6-quinone-2-carboxylate + 2 H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: eumelanin biosynthesis

Summary:
Two different approaches, comparison of the catalytic activities of human melanocytic cell lines expressing the full set of melanogenic enzymes or deficient in TYRP1, and transient expression of human TYR and murine tyr genes in COS7 cells, were used to demonstrate that the human tyrosinase functions as a DHICA oxidase. On the other hand, in mice the product of Tyrp1 catalyzes this function [Olivares01].


Enzymatic reaction of: tyrosinase

EC Number: 1.14.18.1

L-tyrosine + oxygen <=> dopaquinone + H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

In Pathways: (S)-reticuline biosynthesis II , L-dopachrome biosynthesis

Cofactors or Prosthetic Groups: Cu2+ [Spritz97, Akyilmaz10]

Kinetic Parameters:

Substrate
Km (μM)
Citations
L-tyrosine
500.0
[Vijayan82]


References

Akyilmaz10: Akyilmaz E, Yorganci E, Asav E (2010). "Do copper ions activate tyrosinase enzyme? A biosensor model for the solution." Bioelectrochemistry 78(2);155-60. PMID: 19840905

Barton88: Barton DE, Kwon BS, Francke U (1988). "Human tyrosinase gene, mapped to chromosome 11 (q14----q21), defines second region of homology with mouse chromosome 7." Genomics 3(1);17-24. PMID: 3146546

Bouchard89: Bouchard B, Fuller BB, Vijayasaradhi S, Houghton AN (1989). "Induction of pigmentation in mouse fibroblasts by expression of human tyrosinase cDNA." J Exp Med 169(6);2029-42. PMID: 2499655

Decker00: Decker H, Dillinger R, Tuczek F (2000). "How Does Tyrosinase Work? Recent Insights from Model Chemistry and Structural Biology This work was supported by the Medicine and Science Center of the University of Mainz (H.D.) and the Deutsche Forschungsgemeinschaft (F.T., R.D.). The authors thank M.Moller for help with the graphical artwork." Angew Chem Int Ed Engl 39(9);1591-1595. PMID: 10820445

Fukai95: Fukai K, Holmes SA, Lucchese NJ, Siu VM, Weleber RG, Schnur RE, Spritz RA (1995). "Autosomal recessive ocular albinism associated with a functionally significant tyrosinase gene polymorphism." Nat Genet 9(1);92-5. PMID: 7704033

Giebel91: Giebel LB, Strunk KM, Spritz RA (1991). "Organization and nucleotide sequences of the human tyrosinase gene and a truncated tyrosinase-related segment." Genomics 9(3);435-45. PMID: 1903356

Halaban00: Halaban R, Svedine S, Cheng E, Smicun Y, Aron R, Hebert DN (2000). "Endoplasmic reticulum retention is a common defect associated with tyrosinase-negative albinism." Proc Natl Acad Sci U S A 97(11);5889-94. PMID: 10823941

Kwon87: Kwon BS, Haq AK, Pomerantz SH, Halaban R (1987). "Isolation and sequence of a cDNA clone for human tyrosinase that maps at the mouse c-albino locus." Proc Natl Acad Sci U S A 84(21);7473-7. PMID: 2823263

MercadoBlanco93: Mercado-Blanco J, Garcia F, Fernandez-Lopez M, Olivares J (1993). "Melanin production by Rhizobium meliloti GR4 is linked to nonsymbiotic plasmid pRmeGR4b: cloning, sequencing, and expression of the tyrosinase gene mepA." J Bacteriol 175(17);5403-10. PMID: 8366027

Nakamura02: Nakamura E, Miyamura Y, Matsunaga J, Kano Y, Dakeishi-Hara M, Tanita M, Kono M, Tomita Y (2002). "A novel mutation of the tyrosinase gene causing oculocutaneous albinism type 1 (OCA1)." J Dermatol Sci 28(2);102-5. PMID: 11858948

Olivares01: Olivares C, Jimenez-Cervantes C, Lozano JA, Solano F, Garcia-Borron JC (2001). "The 5,6-dihydroxyindole-2-carboxylic acid (DHICA) oxidase activity of human tyrosinase." Biochem J 354(Pt 1);131-9. PMID: 11171088

Shibahara88: Shibahara S, Tomita Y, Tagami H, Muller RM, Cohen T (1988). "Molecular basis for the heterogeneity of human tyrosinase." Tohoku J Exp Med 156(4);403-14. PMID: 2854305

Spritz97: Spritz RA, Ho L, Furumura M, Hearing VJ (1997). "Mutational analysis of copper binding by human tyrosinase." J Invest Dermatol 109(2);207-12. PMID: 9242509

Takeda89: Takeda A, Tomita Y, Okinaga S, Tagami H, Shibahara S (1989). "Functional analysis of the cDNA encoding human tyrosinase precursor." Biochem Biophys Res Commun 162(3);984-90. PMID: 2504160

Takeda90: Takeda A, Tomita Y, Matsunaga J, Tagami H, Shibahara S (1990). "Molecular basis of tyrosinase-negative oculocutaneous albinism. A single base mutation in the tyrosinase gene causing arginine to glutamine substitution at position 59." J Biol Chem 265(29);17792-7. PMID: 2120217

Vijayan82: Vijayan E, Husain I, Ramaiah A, Madan NC (1982). "Purification of human skin tyrosinase and its protein inhibitor: properties of the enzyme and the mechanism of inhibition by protein." Arch Biochem Biophys 217(2);738-47. PMID: 6814365


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Thu Nov 27, 2014, BIOCYC14B.