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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 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"/>

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 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.  

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"/>

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>

The cystein-rich domain has an epidermal growth factor‐like fold formed by two pairs of short antiparallel beta-strands (62-66/98-102 and 116-118/124-126)<ref name= "lai"/> . This previous domain strongly interact with the tyrosinase-like subdomain by the lastloop of the cystein-rich domain preceding the N-terminal domain. The role of the cystein-rich domain is still unknown, it is only found in mammalians. This domain is stabilized by three (42-65/56-99/101-110) disulfide bounds and is located at the opposite of the active site. It is said that the cystein-rich domain might help to the formation of a complexe between TYR and TYRP2.<ref name="Xlai"/><ref name= "lai"/>  

TYRP1 has six sites of N-glygosylation which are important for maturation of the protein (Asn 96, 104,181,304,350,385). On our 3D structure all these sites are glycosylated.  

The active site is located in the tyrosinase-like subdomain. It is delimited by four helices and contains the binuclear metal-binding site. It looks like type-3 binuclear copper-binding site of Tyrosinases. The two ions are bound with planar trigonal geometry and the distance between them is : 3,5 ± 0,1 Ā. A molecule of water located at the same distance (2,1 ± 0,1 Ā) from the two ions can make a bridge between them. Mutations on amino acids of the active site have no significant affect on TYRP1 activity.<ref name= "lai"/>  

The crystal structure of TYRP1 shows that TYRP1 can bind tyrosine, mimosine (DOPA equivalent), kojic acid, tropolone. DOPA and tyrosine can interact with the active site by their aromatic hydroxy or keto groups through hydrogen bounds with water molecule between the ions. Aromatic stacking interactions with H381 and hydrogen bonds between carboxylate group, ARG374 and Ser 394 represent other interactions between these substrates and the active site. Tropolone have direct interactions with one of the Zn2+ ion because  of its metal-chelating property. The interactions between tropolone and Zn2+ show that the binuclear site is flexible. The ring hydroxy and keto groups of kojic acid bind the Zinc ion away from 3Ā. All these non specific interactions may confirm that TYRP1 can have several roles.<ref name= "lai"/>  

== 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"/> 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.   

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 main difference between these three enzymes is the nature of metal ions they bind on the active site. TYRP1 and TYRP2 bind two zinc ions whereas TYR binds two copper ions. Therefore these enzymes catalyze different reactions: TYR catalyzes the conversion of tyrosine into L-DOPA and then in Dopaquinone,TYRP2 isomerizes dopachrome to DHICA. Moreover, the active site of TYRP2 contains two molecules of water and a substrate interacting with both Zn2+ during reactions, whereas TYRP1 active site's contains only one molecule of water and a substrate which are interacting with only one Zn2+ ion. However, no 3D-structure of TYRP2 is now available so the exact coordination of metal ions in the active site stay unclear.<ref name="Xlai"/>