User:Emma Charles/Sandbox 1

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'''Human Tyrosinase related protein 1''' ([https://en.wikipedia.org/wiki/TYRP1 TYRP1]) is a Cu2+/Zn2+ metalloenzyme found in [http://en.wikipedia.org/wiki/Human Humans]. It is expressed in [https://en.wikipedia.org/wiki/Melanocyte melanocytes] where it plays an important role in pigmentation. TYRP1 is also involved in [https://en.wikipedia.org/wiki/Melanoma melanoma] and [https://en.wikipedia.org/wiki/Albinism albinism]. Therefore, it represents an interesting target for therapy <ref>PMID:21324755</ref>. TYRP1 can also be called : 5,6-dihydroxyindole-2-carboxylic acid oxidase (DHICA oxidase); Catalase B or Glycoprotein 75 (gp75).
'''Human Tyrosinase related protein 1''' ([https://en.wikipedia.org/wiki/TYRP1 TYRP1]) is a Cu2+/Zn2+ metalloenzyme found in [http://en.wikipedia.org/wiki/Human Humans]. It is expressed in [https://en.wikipedia.org/wiki/Melanocyte melanocytes] where it plays an important role in pigmentation. TYRP1 is also involved in [https://en.wikipedia.org/wiki/Melanoma melanoma] and [https://en.wikipedia.org/wiki/Albinism albinism]. Therefore, it represents an interesting target for therapy <ref>PMID:21324755</ref>. TYRP1 can also be called : 5,6-dihydroxyindole-2-carboxylic acid oxidase (DHICA oxidase); Catalase B or Glycoprotein 75 (gp75).
== Synthesis and transport ==
== Synthesis and transport ==
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Human Tyrosinase related protein 1 is encoded by the TYRP1 gene, which is located on the chromosome 9p23. The protein is expressed in [https://en.wikipedia.org/wiki/Melanosome melanosomes] and on the surface of melanocytes and melanoma cells. (Ghanem, G and al) TYRP1 protein is synthesized in the nucleus of melanosomes thanks to a signaling sequence. Then, it will be translated by the [https://en.wikipedia.org/wiki/Ribosome ribosomes]and the protein will be directly produced in the [https://en.wikipedia.org/wiki/Endoplasmic_reticulum endoplasmic reticulum]. Then it will be transported through the [https://en.wikipedia.org/wiki/Golgi_apparatus Golgi] to a specific organelles called melanosomes, where pigments are synthesized. (Chen and al) During its maturation, TYRP1 is glycosylated in asparagine in positions 96; 104; 181; 304; 350 and 395. (uniprot). The sorting in the trans-Golgi and transport of the TYRP1 protein to melanosome is dependant of several proteins such as the {{:Phosphoinositide_3-Kinases}} (Chen and al), the [https://www.uniprot.org/uniprot/Q9UMX9 membrane associated transporter protein] (MATP)(Ghanem, G and al) and the [https://www.uniprot.org/uniprot/Q8TF64 GAIP interacting protein] (GIPC) (Liu T.F. and al) The final TYRP1 protein is 537 amino-acids long. (uniprot) TYRP1 is transported to the membrane by the biogenesis of [https://en.wikipedia.org/wiki/Biogenesis_of_lysosome-related_organelles_complex_1 lysosome-related organelles complex 1] (BLOC-1) (wikipedia). The amino-terminal domain will be oriented in the lumen of the melanosome, and the carboxy terminal domain in the cytoplasm of the melanocyte. (Liu T.F. and al) TYRP1 is found only in the membrane of mature stage III and IV melanosomes. (Ghanem, G and al)
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Human Tyrosinase related protein 1 is encoded by the TYRP1 gene, which is located on the chromosome 9p23. The protein is expressed in [https://en.wikipedia.org/wiki/Melanosome melanosomes] and on the surface of melanocytes and melanoma cells <ref>PMID:21324755</ref>. TYRP1 protein is synthesized in the nucleus of melanosomes thanks to a signaling sequence. Then, it will be translated by the [https://en.wikipedia.org/wiki/Ribosome ribosomes]and the protein will be directly produced in the [https://en.wikipedia.org/wiki/Endoplasmic_reticulum endoplasmic reticulum]. Then it will be transported through the [https://en.wikipedia.org/wiki/Golgi_apparatus Golgi] to a specific organelles called melanosomes, where pigments are synthesized <ref>PMID:21324755</ref>. During its maturation, TYRP1 is glycosylated in asparagine in positions 96; 104; 181; 304; 350 and 395. The sorting in the trans-Golgi and transport of the TYRP1 protein to melanosome is dependant of several proteins such as the {{:Phosphoinositide_3-Kinases}} <ref>PMID:21324755</ref>, the [https://www.uniprot.org/uniprot/Q9UMX9 membrane associated transporter protein] (MATP) <ref>PMID:21324755</ref> and the [https://www.uniprot.org/uniprot/Q8TF64 GAIP interacting protein] (GIPC) <ref>PMID:11441007</ref>. The final TYRP1 protein is 537 amino-acids long. TYRP1 is transported to the membrane by the biogenesis of [https://en.wikipedia.org/wiki/Biogenesis_of_lysosome-related_organelles_complex_1 lysosome-related organelles complex 1] (BLOC-1) (wikipedia). The amino-terminal domain will be oriented in the lumen of the melanosome, and the carboxy terminal domain in the cytoplasm of the melanocyte <ref>PMID:11441007</ref>. TYRP1 is found only in the membrane of mature stage III and IV melanosomes <ref>PMID:21324755</ref>.
== Function ==
== Function ==
'''Role in melanocytes'''
'''Role in melanocytes'''
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First, TYRP1 has a role in melanin biosynthesis. Indeed, this enzyme has a catalytic function in the melanin biosynthetic pathway. When a Cu2+ cation is bound, the protein catalyzes the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into indole-5,6-quinone-2-carboxylic acid. This protein is also able to catalyze the oxidation of 5,6-dihydroxyindole (DHI) into indole-5,6-quinone. Both products will allow to obtain eu-melanin, while pheo-melanin is obtain thanks to [https://www.uniprot.org/uniprot/P40126 TYRP2] activity. (Kobayashi T. and al) The activity of the TYRP1 enzyme increase when the serine residues in position 505 and 509 are phosphorylated. (Liu T.F. and al)
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First, TYRP1 has a role in melanin biosynthesis. Indeed, this enzyme has a catalytic function in the melanin biosynthetic pathway. When a Cu2+ cation is bound, the protein catalyzes the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into indole-5,6-quinone-2-carboxylic acid. This protein is also able to catalyze the oxidation of 5,6-dihydroxyindole (DHI) into indole-5,6-quinone. Both products will allow to obtain eu-melanin, while pheo-melanin is obtain thanks to [https://www.uniprot.org/uniprot/P40126 TYRP2] activity <ref>PMID:7813420</ref>. The activity of the TYRP1 enzyme increase when the serine residues in position 505 and 509 are phosphorylated <ref>PMID:11441007 </ref>.
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However, the exact role of TYRP1 in pigmentation remains still unclear. Indeed, no gene polymorphism has been observed among caucasian population, despite the variation of hair and skin colors. (Box N.F. and al)
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However, the exact role of TYRP1 in pigmentation remains still unclear. Indeed, no gene polymorphism has been observed among caucasian population, despite the variation of hair and skin colors <ref>DOI 10.1007/s003359900678</ref>.
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In addition, the [https://www.uniprot.org/uniprot/P07147 mouse homolog of the TYRP1] is involved in melanocytes differenciation too. Therefore, it could be used as a differentiation marker. (Vijayasaradhi S. and al) In humans, the exact role of TYRP1 in differentiation of melanocyte is unclear. However, it is supposed that the protein is involved in the mechanism, as it is involved in pigmentation.
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In addition, the [https://www.uniprot.org/uniprot/P07147 mouse homolog of the TYRP1] is involved in melanocytes differenciation too. Therefore, it could be used as a differentiation marker <ref>PMID:2324688</ref>. In humans, the exact role of TYRP1 in differentiation of melanocyte is unclear. However, it is supposed that the protein is involved in the mechanism, as it is involved in pigmentation.
'''Role in melanoma'''
'''Role in melanoma'''
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TYRP1 also have a role in progression of melanoma. In fact, as TYRP1 is involved in the proliferation and differentiation of melanocytes, a mutation of the protein is associated with a higher risk for melanoma. (Ghanem, G and al) Therefore, the level of expression of TYRP1 mRNA is prognostic marker (Journe F. and al)
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TYRP1 also have a role in progression of melanoma. In fact, as TYRP1 is involved in the proliferation and differentiation of melanocytes, a mutation of the protein is associated with a higher risk for melanoma <ref>PMID:21324755</ref>. Therefore, the level of expression of TYRP1 mRNA is prognostic marker <ref>PMID:22045183 </ref>.
== References ==
== References ==

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Emma Charles

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