Tyrosinase

Tyrosinase
Identifiers
Symbols	TYR ; ATN; CMM8; OCA1; OCA1A; OCAIA; SHEP3
External IDs	OMIM: 606933 MGI: 98880 HomoloGene: 30969 ChEMBL: 1973 GeneCards: TYR Gene
EC number	1.14.18.1
Gene ontology Molecular function • monooxygenase activity • monophenol monooxygenase activity • copper ion binding • protein binding • protein homodimerization activity • protein heterodimerization activity Cellular component • nucleus • cytoplasm • lysosome • Golgi-associated vesicle • cytosol • integral component of membrane • melanosome membrane • melanosome • perinuclear region of cytoplasm Biological process • melanin biosynthetic process from tyrosine • eye pigment biosynthetic process • visual perception • cell proliferation • response to UV • response to vitamin D • cellular nitrogen compound metabolic process • melanin biosynthetic process • small molecule metabolic process • thymus development • response to cAMP • oxidation-reduction process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7299	22173
Ensembl	ENSG00000077498	ENSMUSG00000004651
UniProt	P14679	P11344
RefSeq (mRNA)	NM_000372	NM_011661
RefSeq (protein)	NP_000363	NP_035791
Location (UCSC)	Chr 11: 89.18 – 89.3 Mb	Chr 7: 87.43 – 87.49 Mb
PubMed search	[1]	[2]

Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin. It is mainly involved in two distinct reactions of melanin synthesis; firstly, the hydroxylation of a monophenol and secondly, the conversion of an o-diphenol to the corresponding o-quinone. o-Quinone undergoes several reactions to eventually form melanin. Tyrosinase is a copper-containing enzyme present in plant and animal tissues that catalyzes the production of melanin and other pigments from tyrosine by oxidation, as in the blackening of a peeled or sliced potato exposed to air. It is found inside melanosomes which are synthesised in the skin melanocytes. In humans, the tyrosinase enzyme is encoded by the TYR gene.

Significance

Clinical significance

A mutation in the tyrosinase gene resulting in impaired tyrosinase production leads to type I oculocutaneous albinism, a hereditary disorder that affects one in every 17,000 people.

Tyrosinase activity is very important. If uncontrolled during melanoma, it results in increased melanin synthesis. Decreasing tyrosinase activity has been targeted for the betterment or prevention of conditions related to the hyperpigmentation of the skin, such as melasma and age spots.

Several polyphenols, including flavonoids or stilbenoid, substrate analogues, free radical scavengers, and copper chelators, have been known to inhibit tyrosinase. Henceforth, the medical and cosmetic industries are focusing research on tyrosinase inhibitors to treat skin disorders.

Significance in food industry

In food industry, tyrosinase inhibition is desired as tyrosinase catalyzes the oxidation of phenolic compounds found in fruits and vegetables into quinones, which gives an undesirable taste and color and also decreases the availability of certain essential amino acids as well as the digestibility of the products. As such, highly effective tyrosinase inhibitors are also needed in agriculture and the food industry. Well known tyrosinase inhibitors include kojic acid, tropolone, coumarins, vanillic acid, vanillin, and vanillic alcohol.

Significance in insects

Tyrosinase has a wide range of functions in insects, including wound healing, sclerotization, melanin synthesis and parasite encapsulation. As a result, it is an important enzyme is the defensive mechanisms of insects and some insecticides are aimed to inhibit tyrosinase.

Catalyzed reaction

monophenol monooxygenase Catechol-Quinone Identifiers EC number 1.14.18.1 CAS number Template:CAS Databases IntEnz IntEnz view BRENDA BRENDA entry ExPASy NiceZyme view KEGG KEGG entry MetaCyc metabolic pathway PRIAM profile PDB structures RCSB PDB PDBe PDBsum Gene Ontology AmiGO / EGO Search PMC articles PubMed articles NCBI proteins

Tyrosinase carries out the oxidation of phenols such as tyrosine and dopamine using dioxygen (O₂). In the presence of catechol, benzoquinone is formed (see reaction below). Hydrogens removed from catechol combine with oxygen to form water.

The substrate specificity becomes dramatically restricted in mammalian tyrosinase which uses only L-form of tyrosine or DOPA as substrates, and has restricted requirement for L-DOPA as cofactor.

Structure

Tyrosinase
Tridimensional structure of a functional unit from octopus hemocyanin
Identifiers
Symbol	Tyrosinase
Pfam	PF00264
Pfam clan	CL0205
InterPro	IPR002227
PROSITE	PDOC00398
SCOP	1hc2
SUPERFAMILY	1hc2
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Common central domain of tyrosinase
Identifiers
Symbol	Tyrosinase
Pfam	PF00264
InterPro	IPR002227
PROSITE	PDOC00398
SCOP	1hc2
SUPERFAMILY	1hc2
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Tyrosinases have been isolated and studied from a wide variety of plant, animal, and fungal species. Tyrosinases from different species are diverse in terms of their structural properties, tissue distribution, and cellular location. No common tyrosinase protein structure occurring across all species has been found. The enzymes found in plant, animal, and fungal tissue frequently differ with respect to their primary structure, size, glycosylation pattern, and activation characteristics. However, all tyrosinases have in common a binuclear, type 3 copper centre within their active sites. Here, two copper atoms are each coordinated with three histidine residues.

Human tyrosinase

Human tyrosinase is a single membrane-spanning transmembrane protein. In humans, tyrosinase is sorted into melanosomes and the catalytically active domain of the protein resides within melanosomes. Only a small, enzymatically inessential part of the protein extends into the cytoplasm of the melanocyte.

As opposed to fungal tyrosinase, human tyrosinase is a membrane-bound glycoprotein and has 13% carbohydrate content.

Active site

Crystallographic structure of a Streptomyces-derived tyrosinase in complex with a so-called "caddie protein" In all models, only the tyrosinase molecule is shown, copper atoms are shown in green and the molecular surface is shown in red. In models D and E, histidine amino acids are shown as a blue line representation. From model E, each copper atom within the active site is indeed complexed with three histidine residues, forming a type 3 copper center. From models C and D, the active site for this protein can be seen to sit within a pillus formed on the molecular surface of the molecule.

The two copper atoms within the active site of tyrosinase enzymes interact with dioxygen to form a highly reactive chemical intermediate that then oxidizes the substrate. The activity of tyrosinase is similar to catechol oxidase, a related class of copper oxidase. Tyrosinases and catechol oxidases are collectively termed polyphenol oxidases.

Gene regulation

The gene for tyrosinase is regulated by the microphthalmia-associated transcription factor (MITF).

External links

• GeneReviews/NCBI/NIH/UW entry on Oculocutaneous Albinism Type 1
• Tyrosinase at the US National Library of Medicine Medical Subject Headings (MeSH)