Sandbox Reserved 1097: Difference between revisions
From Proteopedia
Jump to navigationJump to search
Stella Glauz (talk | contribs) insertion of similarities and addition of diseases part 1 |
Stella Glauz (talk | contribs) formation changings and standardization of the citation to 'APA' |
||
| Line 2: | Line 2: | ||
<Structure load='5M8L' size='350' frame='true' align='right' caption='Insert caption here' scene='82/829350/Biological_unit/4' /> | <Structure load='5M8L' size='350' frame='true' align='right' caption='Insert caption here' scene='82/829350/Biological_unit/4' /> | ||
'''Human Tyrosinase related protein 1''' ([https://en.wikipedia.org/wiki/TYRP1 TYRP1]) is a Cu2+/Zn2+ metalloenzyme composed of 537 amino acids found in [https://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. TYRP1 can also be called : Catalase B or Glycoprotein 75 (gp75). <ref name="ghanem"/> | '''Human Tyrosinase related protein 1''' ([https://en.wikipedia.org/wiki/TYRP1 TYRP1]) is a Cu2+/Zn2+ metalloenzyme composed of 537 amino acids found in [https://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. TYRP1 can also be called : Catalase B or Glycoprotein 75 (gp75).<ref name="ghanem"/> | ||
== Synthesis and transport == | == Synthesis and transport == | ||
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 name="ghanem"/> | 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 name="ghanem"/> TYRP1 gene is transcripted in the nucleus of melanocytes. Then, the mRNA will be translated by the [https://en.wikipedia.org/wiki/Ribosome ribosomes]and the protein will directly be synthesized in the [http://en.wikipedia.org/wiki/Endoplasmic_reticulum endoplasmic reticulum]which recognizes the signal sequence located on the protein. 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 name="chen"/> 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 [https://fr.wikipedia.org/wiki/Phosphoinositide_3-kinase Phosphoinositide_3-Kinase]<ref name="chen"/>, the [https://www.uniprot.org/uniprot/Q9UMX9 membrane associated transporter protein] (MATP) <ref name="ghanem"/> and the [https://www.uniprot.org/uniprot/Q8TF64 GAIP interacting protein] (GIPC).<ref name= "liu"/> 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). 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 name= "liu"/> TYRP1 is found only in the membrane of mature stage III and IV melanosomes.<ref name="ghanem"/> | ||
== Function == | == Function == | ||
=== Role in melanocytes === | === Role in melanocytes === | ||
First, TYRP1 has a role in [https://en.wikipedia.org/wiki/Melanin melanin] biosynthesis. Indeed, this enzyme has a catalytic function in the melanin biosynthetic pathway. In mouse, when a Cu2+ cation is bound, the protein catalyzes the oxidation of [https://pubchem.ncbi.nlm.nih.gov/compound/5_6-Dihydroxy-1H-indole-2-carboxylic-acid 5,6-dihydroxyindole-2-carboxylic acid (DHICA)] into [https://pubchem.ncbi.nlm.nih.gov/compound/Indole-5_6-quinone-2-carboxylate indole-5,6-quinone-2-carboxylic acid]. This protein is also able to catalyze the oxidation of [https://pubchem.ncbi.nlm.nih.gov/compound/5_6-Dihydroxyindole 5,6-dihydroxyindole (DHI)] into [https://pubchem.ncbi.nlm.nih.gov/compound/Indole-5_6-quinone indole-5,6-quinone]. Both products will allow to obtain eu-melanin, while pheo-melanin is obtained thanks to [https://www.uniprot.org/uniprot/P40126 TYRP2] activity <ref name= "koba"/> | First, TYRP1 has a role in [https://en.wikipedia.org/wiki/Melanin melanin] biosynthesis. Indeed, this enzyme has a catalytic function in the melanin biosynthetic pathway. In mouse, when a Cu2+ cation is bound, the protein catalyzes the oxidation of [https://pubchem.ncbi.nlm.nih.gov/compound/5_6-Dihydroxy-1H-indole-2-carboxylic-acid 5,6-dihydroxyindole-2-carboxylic acid (DHICA)] into [https://pubchem.ncbi.nlm.nih.gov/compound/Indole-5_6-quinone-2-carboxylate indole-5,6-quinone-2-carboxylic acid]. This protein is also able to catalyze the oxidation of [https://pubchem.ncbi.nlm.nih.gov/compound/5_6-Dihydroxyindole 5,6-dihydroxyindole (DHI)] into [https://pubchem.ncbi.nlm.nih.gov/compound/Indole-5_6-quinone indole-5,6-quinone]. Both products will allow to obtain eu-melanin, while pheo-melanin is obtained thanks to [https://www.uniprot.org/uniprot/P40126 TYRP2] activity.<ref name= "koba"/> The activity of the TYRP1 enzyme increases when the serine residues in position 505 and 509 are phosphorylated.<ref name= "liu"/> However, this mechanism does not happened in Humans because Human TYRP1 does not have the DHCIA activity. This can be explained by the fact that the nature of ions in the active site is different. Indeed, two Zn2+ ions bound the active site of the TYRP1 enzyme instead of two Cu2+, which are responsible for a different activity.<ref name= "lai"/> In fact, the incorporation of Cu2+ instead of Zn2+ in human TYRP1 active site, gives to the enzyme the DHICA activity, but no experiment has shown that Cu2+ can replace Zn2+ in vivo conditions.<ref name="Xlai"/> To conclude, the exact role of TYRP1 in pigmentation remains still unclear. Moreover, no gene polymorphism has been observed among caucasian population, despite the variation of hair and skin colors.<ref name= "box"/> | ||
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 name= "vija"/> | 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 name= "vija"/> 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 === | ||
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 name="ghanem"/>. Therefore, the level of expression of TYRP1 mRNA is prognostic marker <ref name= "journe"/> | 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 name="ghanem"/>. Therefore, the level of expression of TYRP1 mRNA is prognostic marker.<ref name= "journe"/> | ||
== Structural highlights == | == Structural highlights == | ||
| Line 21: | Line 21: | ||
The 3D-structure at the top of the page represent the biological unit, it is the working part of the enzyme in-vivo conditions but there is also a 3D-structure for the <scene name='82/829350/Asymmetric_unit/1'>asymmetric unit</scene> of TYRP1. | The 3D-structure at the top of the page represent the biological unit, it is the working part of the enzyme in-vivo conditions but there is also a 3D-structure for the <scene name='82/829350/Asymmetric_unit/1'>asymmetric unit</scene> of TYRP1. | ||
TYRP1 is a globular monomeric protein. It is composed of several domains: a short peptide signal on the N-terminal side followed by a large intra-melanosomal domain. This intra-melanosomal domain contain a cystein-rich domain and a catalytic tyrosinase-like subdomain with two ion-binding sites.<ref name="Xlai">[Xuelei Lai, Harry J. Wichers, Montserrat Soler‐Lopez, Bauke W. Dijkstra. Structure and Function of Human Tyrosinase and Tyrosinase‐Related Proteins. 2018 Jan 2 Epub 2017 Nov 28 PMID: 29052256 https://www.ncbi.nlm.nih.gov/pubmed/29052256 DOI: 10.1002/chem.201704410 https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.201704410]</ref> The next part of the sequence is composed of a transmembrane alpha helix followed by a short cytoplasmic sequence on the C-terminal chain. <ref name = "decker"> [Decker. H, Tuczek.F. The Recent Crystal Structure of Human Tyrosinase Related Protein 1 (HsTYRP1) Solves an Old Problem and Poses a New One. 2017 Nov 13. Epub 2017 Oct 9 PMID: 28990327 https://www.ncbi.nlm.nih.gov/pubmed/28990327 DOI: 10.1002/anie.201708214 https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.201708214]</ref> | TYRP1 is a globular monomeric protein. It is composed of several domains: a short peptide signal on the N-terminal side followed by a large intra-melanosomal domain. This intra-melanosomal domain contain a cystein-rich domain and a catalytic tyrosinase-like subdomain with two ion-binding sites.<ref name="Xlai">[Xuelei Lai, Harry J. Wichers, Montserrat Soler‐Lopez, Bauke W. Dijkstra. Structure and Function of Human Tyrosinase and Tyrosinase‐Related Proteins. 2018 Jan 2 Epub 2017 Nov 28 PMID: 29052256 https://www.ncbi.nlm.nih.gov/pubmed/29052256 DOI: 10.1002/chem.201704410 https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.201704410]</ref> The next part of the sequence is composed of a transmembrane alpha helix followed by a short cytoplasmic sequence on the C-terminal chain.<ref name = "decker"> [Decker. H, Tuczek.F. The Recent Crystal Structure of Human Tyrosinase Related Protein 1 (HsTYRP1) Solves an Old Problem and Poses a New One. 2017 Nov 13. Epub 2017 Oct 9 PMID: 28990327 https://www.ncbi.nlm.nih.gov/pubmed/28990327 DOI: 10.1002/anie.201708214 https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.201708214]</ref> | ||
* '''The cystein-rich subdomain''' ''(25-126)'' | * '''The cystein-rich subdomain''' ''(25-126)'' | ||
| Line 42: | Line 42: | ||
== Comparison between enzymes of Tyrosinase family == | == Comparison between enzymes of Tyrosinase family == | ||
In mammals, three enzymes of Tyrosinase family may be involved in biosynthesis of melanin. [[Tyrosinase]] (TYR) reacts two times in the mechanism whereas Tyrosinase Related Protein 1 and 2 (TYRP1 and TYRP2) probably catalyze only one reaction in this biosynthesis. TYR is an oxydoreductase,TYRP2 seems to act as a tautomerase and the exact role in melanin synthesis of human TYRP1 is still under debate. In fact in mices, TYRP1 can especially catalyze the reaction of DHICA in eumelanin but human TYR can also do the same. It is said that TYRP1 can play a significant role in proliferation of melanosomes.<ref name = "decker"/> | In mammals, three enzymes of Tyrosinase family may be involved in biosynthesis of melanin. [[Tyrosinase]] (TYR) reacts two times in the mechanism whereas Tyrosinase Related Protein 1 and 2 (TYRP1 and TYRP2) probably catalyze only one reaction in this biosynthesis. TYR is an oxydoreductase,TYRP2 seems to act as a tautomerase and the exact role in melanin synthesis of human TYRP1 is still under debate. In fact in mices, TYRP1 can especially catalyze the reaction of DHICA in eumelanin but human TYR can also do the same. It is said that TYRP1 can play a significant role in proliferation of melanosomes.<ref name = "decker"/> No human cristal structure is available for TYR, so thanks to cristal structure of TYRP1, it is possible to deduce a good model of TYR. | ||
(Image à faire reaction chimique) | (Image à faire reaction chimique) | ||
| Line 52: | Line 52: | ||
(image à faire) | (image à faire) | ||
According to crystal knowledges, it is said that TYRP1 and TYR can bind the same substrates and even if the composition of the active site is different, it doesn't affect the binding modes of these compounds.<ref name= "lai"/> | According to crystal knowledges, it is said that TYRP1 and TYR can bind the same substrates and even if the composition of the active site is different, it doesn't affect the binding modes of these compounds.<ref name= "lai"/> | ||
The three enzymes have several sites of N-glycosylation which are important for their maturation, two of these sites are shared by the three enzymes. TYRP1 and 2 have both six sites and among them, four are exactly the same. <ref name="Xlai"/> | The three enzymes have several sites of N-glycosylation which are important for their maturation, two of these sites are shared by the three enzymes. TYRP1 and 2 have both six sites and among them, four are exactly the same.<ref name="Xlai"/> | ||
==== Differences ==== | ==== Differences ==== | ||
| Line 61: | Line 61: | ||
Interet des ions !!! | Interet des ions !!! | ||
The binds between the protein and its inhibitors are not affected by change in hydrogen bounds. It can be interesting to study this property to design better inhibitors. The future discovery of TRP1 role in melanin synthesis may be a breakthrough for cosmetic industry. <ref name = "decker"/> | The binds between the protein and its inhibitors are not affected by change in hydrogen bounds. It can be interesting to study this property to design better inhibitors. The future discovery of TRP1 role in melanin synthesis may be a breakthrough for cosmetic industry.<ref name = "decker"/> | ||
==Diseases== | ==Diseases== | ||
===Oculocutaneous albinism 3=== | ===Oculocutaneous albinism 3=== | ||
| Line 75: | Line 75: | ||
The phenotypical expression of the missense mutations T253M and M452V are yet to be confirmed whereas the other point mutations are pathological.<ref name= "lai"/> Affected individuals have red coloured hair and rufous skin complexion. However, since OCA3 permits some melanin accumulation over time, the hypopigmentation does not suffice to alter the eye development. Thus, feature bearers may possess a green iris but no significant visual anomalies.<ref name = "grønskov"/> | The phenotypical expression of the missense mutations T253M and M452V are yet to be confirmed whereas the other point mutations are pathological.<ref name= "lai"/> Affected individuals have red coloured hair and rufous skin complexion. However, since OCA3 permits some melanin accumulation over time, the hypopigmentation does not suffice to alter the eye development. Thus, feature bearers may possess a green iris but no significant visual anomalies.<ref name = "grønskov"/> | ||
==References== | ==References== | ||
<ref name="ghanem"/> Ghanem, G., | <ref name="ghanem"/> Ghanem, G., & Fabrice, J. (2011). Tyrosinase related protein 1 (TYRP1/gp75) in human cutaneous melanoma. Molecular oncology, 5(2), 150–155. doi:10.1016/j.molonc.2011.01.006 | ||
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5528278/ | |||
<ref name="chen"/> Chen H., Salopek T.G., Jimbow K., 2001. The role of phosphoinositide 3-kinase in the sorting and transport of newly synthesized tyrosinase related protein-1 (TRP1). J. Investig. Dermatol. Symp. Proc.. 6, (1) 105–114 PMID: 21324755 | <ref name="chen"/> Chen H., Salopek T.G., Jimbow K., 2001. The role of phosphoinositide 3-kinase in the sorting and transport of newly synthesized tyrosinase related protein-1 (TRP1). J. Investig. Dermatol. Symp. Proc.. 6, (1) 105–114 PMID: 21324755 | ||
https://www.jidsponline.org/article/S0022-202X(15)52884-4/fulltext | |||
<ref name= "liu"/> Liu T.F., Kandala G., Setaluri V., 2001. PDZ-domain protein GIPC interacts with the cytoplasmic tail of melanosomal membrane protein gp75 (tyrosinase related protein-1). J. Biol. Chem.. 276, 35768–35777 PMID: 11441007 | <ref name= "liu"/> Liu T.F., Kandala G., Setaluri V., 2001. PDZ-domain protein GIPC interacts with the cytoplasmic tail of melanosomal membrane protein gp75 (tyrosinase related protein-1). J. Biol. Chem.. 276, 35768–35777 PMID: 11441007 doi: 10.1074/jbc.M103585200 | ||
http://www.jbc.org/content/276/38/35768.full | |||
<ref name= "koba"/> Kobayashi T., Urabe K., Winder A., Jiménez-Cervantes C., Imokawa G., Brewington T., | <ref name= "koba"/> Kobayashi, T., Urabe, K., Winder, A., Jiménez-Cervantes, C., Imokawa, G., Brewington, T., … Hearing, V. J. (1994). Tyrosinase related protein 1 (TRP1) functions as a DHICA oxidase in melanin biosynthesis. The EMBO journal, 13(24), 5818–5825. | ||
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC395555/ | |||
<ref name= "lai"/> Lai X, Wichers | <ref name= "lai"/> Lai, X., Wichers, H. J., Soler-Lopez, M., & Dijkstra, B. W. (2017). Structure of Human Tyrosinase Related Protein 1 Reveals a Binuclear Zinc Active Site Important for Melanogenesis. Angewandte Chemie (International ed. in English), 56(33), 9812–9815. doi:10.1002/anie.201704616 | ||
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601231/ | |||
<ref name="Xlai"/> Xuelei Lai, Harry J. Wichers, Montserrat Soler‐Lopez, Bauke W. Dijkstra. Structure and Function of Human Tyrosinase and Tyrosinase‐Related Proteins. 2018 Jan 2 Epub 2017 Nov 28 PMID: 29052256 https://www.ncbi.nlm.nih.gov/pubmed/29052256 | <ref name="Xlai"/> Xuelei Lai, Harry J. Wichers, Montserrat Soler‐Lopez, Bauke W. Dijkstra. Structure and Function of Human Tyrosinase and Tyrosinase‐Related Proteins. 2018 Jan 2 Epub 2017 Nov 28 PMID: 29052256 https://www.ncbi.nlm.nih.gov/pubmed/29052256 doi: 10.1002/chem.201704410 | ||
https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.201704410 | |||
<ref name= "box"/> Box N.F., Wyeth J.R., Mayne C.J., O'Gorman L.E., Martin N.G., Sturm R.A., 1998. Complete sequence and polymorphism study of the human TYRP1 gene encoding tyrosinase-related protein. Mamm. Genome. 9, 50–53 PMID:9434945 | <ref name= "box"/> Box N.F., Wyeth J.R., Mayne C.J., O'Gorman L.E., Martin N.G., Sturm R.A., 1998. Complete sequence and polymorphism study of the human TYRP1 gene encoding tyrosinase-related protein. Mamm. Genome. 9, 50–53 PMID:9434945 doi:10.1007/s003359900678 | ||
https://link.springer.com/article/10.1007/s003359900678#citeas | |||
<ref name= "vija"/> Vijayasaradhi S., Bouchard B., Houghton A.N. | <ref name= "vija"/> Vijayasaradhi, S., Bouchard, B., & Houghton, A. N. (1990). The melanoma antigen gp75 is the human homologue of the mouse b (brown) locus gene product. The Journal of experimental medicine, 171(4), 1375–1380. doi:10.1084/jem.171.4.1375 | ||
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2187848/ | |||
<ref name= "journe"/> Journe F. , | <ref name= "journe"/> Journe, F., Id Boufker, H., Van Kempen, L., Galibert, M. D., Wiedig, M., Salès, F., … Ghanem, G. (2011). TYRP1 mRNA expression in melanoma metastases correlates with clinical outcome. British journal of cancer, 105(11), 1726–1732. doi:10.1038/bjc.2011.451 | ||
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242608/ | |||
<ref name = "decker"/> Decker H., Tuczek F. The Recent Crystal Structure of Human Tyrosinase Related Protein 1 (HsTYRP1) Solves an Old Problem and Poses a New One. 2017 Nov 13. Epub 2017 Oct 9 PMID: 28990327 https://www.ncbi.nlm.nih.gov/pubmed/28990327 | <ref name = "decker"/> Decker H., Tuczek F. The Recent Crystal Structure of Human Tyrosinase Related Protein 1 (HsTYRP1) Solves an Old Problem and Poses a New One. 2017 Nov 13. Epub 2017 Oct 9 PMID: 28990327 https://www.ncbi.nlm.nih.gov/pubmed/28990327 doi: 10.1002/anie.201708214 | ||
https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.201708214 | |||
<ref name = "grønskov"/> Grønskov K, Ek J, Brondum-Nielsen K. Oculocutaneous albinism. Orphanet | <ref name = "grønskov"/> Grønskov, K., Ek, J., & Brondum-Nielsen, K. (2007). Oculocutaneous albinism. Orphanet journal of rare diseases, 2, 43. doi:10.1186/1750-1172-2-43 | ||
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211462/ | |||
