TYR

Fig1. Pathway of melanogenesis. (i) Monophenolase activity of tyrosinase. (ii) Diphenolase activity of tyrosinase. (Thanh-Nhat Pham, 2024)

What is TYR protein?

TYR (tyrosinase) gene is a protein coding gene which situated on the long arm of chromosome 11 at locus 11q14. Nitrotyrosine is a product of tyrosine nitration mediated by reactive nitrogen species such as peroxynitrite anion and nitrogen dioxide. It is detected in large number of pathological conditions and is considered a marker of NO-dependent, reactive nitrogen species-induced nitrative stress. Nitrotyrosine is found in numerous disease-affected tissues, such as the cornea in keratoconus. The TYR protein is consisted of 529 amino acids and its molecular mass is approximately 60.4 kDa.

What is the function of TYR protein?

This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the initial and rate limiting step in the cascade of reactions leading to melanin production from tyrosine. In addition to hydroxylating tyrosine to DOPA (3,4-dihydroxyphenylalanine), it also catalyzes the oxidation of DOPA to DOPA-quinone, and possibly the oxidation of DHI (5,6-dihydroxyindole) to indole-5,6 quinone

TYR Related Signaling Pathway

TYR protein is mainly involved in the signaling pathway of tyrosine metabolism, its main role is to catalyze the metabolism of tyrosine enzyme and tyrosine, and participate in the synthesis process of melanin. In this process, the Tyrosinase protein promotes melanin synthesis by oxidizing tyrosine, which in turn affects skin, hair and eye color. TYR is a rate-limiting enzyme that regulates the production of melanin. It influences the synthesis of melanin by catalyzing the oxidation of tyrosine

TYR Related Diseases

The Tyrosinase protein has been implicated ina variety of diseases, especially those related to melanin. These include: Vitiligo, Acanthosis nigricans, Pigmented disorders, Melanoma and other diseases such as certain hereditary eye diseases, cataracts, etc.

Bioapplications of TYR

The application of TYR protein mainly takes advantage of its role in regulating melanin production, and achieves whitening and anti-browning effects by inhibiting its activity. Cosmetics industry: TYR inhibitors can reduce skin pigmentation and help improve uneven skin tone. Pharmaceutical industry: Research and application of TYR inhibitors are also ongoing, especially in the treatment of pigment-related diseases such as melasma and freckles. Food and agricultural products: In order to prevent Browning of fruits, vegetables and other agricultural products during processing and storage, affecting appearance and nutritional value, inhibitors of Tyrosinase are also used as anti-browning compounds.

Fig2. Potential applications of natural tyrosinase inhibitors issued from biomass waste valorization. (Thanh-Nhat Pham, 2024)

Case study 1: Chen Hong, 2024

Epimedin B (EB) is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim., a traditional herb widely used in China. The researchers's previous study showed that EB was a stronger inducer of melanogenesis and an activator of tyrosinase (TYR). However, the role of EB in melanogenesis and the mechanism underlying the regulation remain unclear.

Herein, as an extension to the previous investigation, they provide comprehensive evidence of EB-induced pigmentation in vivo and in vitro and elucidate the melanogenesis mechanism by assessing its effects on the TYR family of proteins (TYRs) in terms of expression, activity, and stability. The results showed that EB increased TYRs expression through microphthalmia-associated transcription factor-mediated p-Akt (referred to as protein kinase B (PKB))/glycogen synthase kinase 3β (GSK3β)/β-catenin, p-p70 S6 kinase cascades, and protein 38 (p38)/mitogen-activated protein (MAP) kinase (MAPK) and extracellular regulated protein kinases (ERK)/MAPK pathways. Furthermore, EB exerted repigmentation by stimulating TYR activity in hydroquinone- and N-phenylthiourea-induced TYR inhibitive models, including melanoma cells, zebrafish, and mice. Finally, EB ameliorated monobenzone-induced depigmentation in vitro and in vivo through the enhancement of TYRs stability by inhibiting TYR misfolding, TYR-related protein 1 formation, and retention in the endoplasmic reticulum and then by downregulating the ubiquitination and proteolysis processes.

Fig1. The protein expression levels of p-MITF, MITF, TYR, TYR-related protein 1 (TYRP1), dopachrome tautomerase (DCT), and melanoma antigen (Melan-A) (72 h on B16F10 cells).

Fig2. The protein expression levels of protein kinase A (PKA), phosphoinositide 3-kinase (PI3K), p-AKT, AKT, GSK-3β, β-catenin, p-p70 S6, p70 S6, p-c-Jun N-terminal kinase (JNK), JNK, p-p38, p38, p-ERK, and ERK (24 h on B16F10 cells).

Case study 2: Zi-Yi Xia, 2024

Resina Draconis is a traditional Chinese medicine, with the in-depth research, its medicinal value in anti-tumor has been revealed. Loureirin A is extracted from Resina Draconis, however, research on the anti-tumor efficacy of Loureirin A is rare.

This research demonstrated that Loureirin A inhibited the proliferation of and caused G0/G1 cell cycle arrest in melanoma cells in a concentration-dependent manner. Further study showed that the melanin content and tyrosinase activity was enhanced after Loureirin A treatment, demonstrated that Loureirin A promoted melanoma cell differentiation. The activity and the expression of tyrosinase was measured. Taken together, this study demonstrated for the first time the anti-tumor effects of Loureirin A in melanoma cells, which provided a novel therapeutic strategy against melanoma.

Fig3. Loureirin A promotes the differentiation of B16 cells. The tyrosinase activity in B16 cells.

Fig4. The protein levels of Tyrosinase, TRP1, TRP2, and MITF in B16 cells were measured by western blot.

TYR has several biochemical functions, for example, copper ion binding,monooxygenase activity,monophenol monooxygenase activity. Some of the functions are cooperated with other proteins, some of the functions could acted by TYR itself. We selected most functions TYR had, and list some proteins which have the same functions with TYR. You can find most of the proteins on our site.

TYR has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with TYR here. Most of them are supplied by our site. Hope this information will be useful for your research of TYR.