tyrosinase

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/11/22 18:28:10」(JST)

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TYR
Identifiers
Aliases	TYR, ATN, CMM8, OCA1, OCA1A, OCAIA, SHEP3, tyrosinase, Tyrosinase
External IDs	OMIM: 606933 MGI: 98880 HomoloGene: 30969 GeneCards: TYR
Genetically Related Diseases
age related macular degeneration, melanoma, Vitiligo
Gene ontology Molecular function • metal ion binding • copper ion binding • monooxygenase activity • protein homodimerization activity • monophenol monooxygenase activity • oxidoreductase activity • protein heterodimerization activity • protein binding Cellular component • cytoplasm • integral component of membrane • cytosol • nucleus • membrane • perinuclear region of cytoplasm • lysosome • melanosome membrane • Golgi-associated vesicle • melanosome Biological process • response to UV • response to cAMP • metabolic process • melanin biosynthetic process from tyrosine • response to vitamin D • pigmentation • thymus development • oxidation-reduction process • eye pigment biosynthetic process • cell proliferation • visual perception • melanin biosynthetic 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 NM_001317397
RefSeq (protein)	NP_000363.1	NP_035791.1
Location (UCSC)	Chr 11: 89.18 – 89.3 Mb	Chr 7: 87.42 – 87.49 Mb
PubMed search
Wikidata
View/Edit Human		View/Edit Mouse

Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin. The enzyme 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 20,000 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 as it is the defensive mechanism of insects. Some insecticides are aimed to inhibit tyrosinase.

Catalyzed reaction

monophenol monooxygenase Catechol-Quinone Identifiers EC number 1.14.18.1 CAS number 9002-10-2 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.

The derived TYR allele (rs2733832) is associated with lighter skin pigmentation in human populations. It is most common in Europe, but is also found at lower, moderate frequencies in Central Asia, the Middle East, North Africa, and among the San and Mbuti Pygmies.

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).

References

External links

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

UpToDate Contents

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• 1. 黒色腫（メラノーマ）における所属リンパ節の病理学的評価 pathologic evaluation of regional lymph nodes in melanoma
• 2. 遺伝性皮膚症 the genodermatoses
• 3. 黒色腫（メラノーマ）における所属リンパ節の評価および治療 evaluation and treatment of regional lymph nodes in melanoma
• 4. 皮膚黒色腫におけるtumor node metastasis（TNM）病期分類法およびその他の予後因子 tumor node metastasis tnm staging system and other prognostic factors in cutaneous melanoma
• 5. 肝斑 melasma

English Journal

• Preparation of tyrosinase inhibitors and antibrowning agents using green technology.

• Dong X1, Zhang Y2, He JL1, Zhang S1, Zeng MM1, Chen J3, Zheng ZP4.
• Food chemistry.Food Chem.2016 Apr 15;197(Pt A):589-96. doi: 10.1016/j.foodchem.2015.11.007. Epub 2015 Nov 3.
• Chalcones and their derivatives have attracted great interests in recent years for their comprehensive biological activities. In this study, 2,4,2',4'-tetrahydroxychalcone and its two derivatives, 1,3,5-tris-(2,4-dihydroxy-phenyl)pentane-1,5-dione (new compound) and 7,2',4'-trihydroxyflavanone, were
• PMID 26616992

• Inhibitory effects of Na7PMo11CuO40 on mushroom tyrosinase and melanin formation and its antimicrobial activities.

• Xing R1, Wang F2, Dong L3, Zheng AP1, Wang L4, Su WJ1, Lin T3.
• Food chemistry.Food Chem.2016 Apr 15;197(Pt A):205-11. doi: 10.1016/j.foodchem.2015.10.119. Epub 2015 Nov 11.
• Keggin-type Cu-substituted phosphomolybdic acid (Na7PMo11CuO40, abbreviated as PMo11Cu) was synthesized and characterized. The inhibitory effects of PMo11Cu on mushroom tyrosinase and melanin formation in B16 melanoma cells were studied. The results showed that PMo11Cu could strongly inhibit the act
• PMID 26616942

• Characterization of polyphenol oxidase from Cape gooseberry (Physalis peruviana L.) fruit.

• Bravo K1, Osorio E2.
• Food chemistry.Food Chem.2016 Apr 15;197(Pt A):185-90. doi: 10.1016/j.foodchem.2015.10.126. Epub 2015 Oct 26.
• Cape gooseberry (Physalis peruviana) is an exotic fruit highly valued, however it is a very rich source of polyphenol oxidase (PPO). In this study, Cape gooseberry PPO was isolated and biochemically characterized. The enzyme was extracted and purified using acetone and aqueous two-phase systems. The
• PMID 26616939

Japanese Journal

• カテコール電流計測のためのチロシナーゼ修飾ポリチオニンを電着したグラッシーカーボン電極

• 電気化学および工業物理化学 85(1), 17-22, 2017-01
• NAID 40021047311

• Generation of hydroxyl radicals and singlet oxygen during oxidation of rhododendrol and rhododendrol-catechol

• Ｊｏｕｒｎａｌ　ｏｆ　Ｃｌｉｎｉｃａｌ　Ｂｉｏｃｈｅｍｉｓｔｒｙ　ａｎｄ　Ｎｕｔｒｉｔｉｏｎ 60(2), 86-92, 2017
• NAID 130005398534

• Tyrosinase Modified Poly(thionine) Electrodeposited Glassy Carbon Electrode for Amperometric Determination of Catechol

• Electrochemistry 85(1), 17-22, 2017
• NAID 130005180913

Related Links

• Tyrosinaseとは - goo Wikipedia (ウィキペディア)

Crystallographic structure of a Streptomyces-derived tyrosinase in complex with a so-called "caddie protein" [11] In all models, only the tyrosinase molecule is shown, copper atoms are shown in green and the molecular surface is ...

• Tyrosinase (T311) Mouse mAb (IHC Specific) #9319 | CST 抗体

米国CST社の日本法人CSTジャパン株式会社【公式サイト】Tyrosinase (T311) Mouse mAb (IHC Specific)ページ。高品質の研究用試薬、米国本社の開発研究者による技術的サポートをご提供しております。

Related Pictures

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★リンクテーブル★

リンク元	「チロシナーゼ」「phenoloxidase」「monophenol monooxygenase」

「チロシナーゼ」

　　[★]

英

tyrosinase

同

モノフェノールモノオキシゲナーゼ monophenol monooxygenase、モノフェノールオキシダーゼ monophenol oxidase、フェノラーゼ phenolase

「phenoloxidase」

　　[★]

フェノール酸化酵素、フェノールオキシダーゼ

関

monophenol monooxygenase、tyrosinase

「monophenol monooxygenase」

　　[★]

モノフェノールモノオキシゲナーゼ

関

phenoloxidase、tyrosinase