**Acknowledgements**

This work was supported by Grant Application 156, Exploratory Research Projects PN-II-ID-PCE-2011-3-0492-1, funded by Ministerul Educației și Cercetării Științifice and by the Academia Română Project 1/2011 of the Institute of Biochemistry. Molecular simulations were performed using the high-performance computational capabilities of the HPC Linux cluster at IBAR and the High-Performance Computing Infrastructure for South East Europe's Research Communities (HP-SEE), a project cofunded by the European Commission (under contract number 261499) through the Seventh Framework Programme. Gabriela Negroiu acknowledges Dr. Sabina Zurac, Department of Pathology, Colentina University Hospital, Bucharest, Romania for providing the image of the specimen in **Figure 9** and for sharing her valuable expertise in melanoma pathology during our collaborative research. Adina Milac is grateful to Dr. Andriy Anishkin, Department of Biology, University of Maryland, College Park, MD, USA for advice and discussions on molecular simulations of cholesterol-containing membranes.

[6] Dadras, SS. Molecular diagnostics in melanoma, current status and perspectives. Archives of Pathology and Laboratory Medicine. 2011;**135**:860-869. DOI: 10.1200/

The Multiple Roles of Tyrosinase-Related Protein-2/L-Dopachrome Tautomerase in Melanoma...

http://dx.doi.org/10.5772/intechopen.70513

75

[7] Ko JM, Fisher DE. A new era: Melanoma genetics and therapeutics. Journal of Pathology.

[8] Melanoma Molecular Map Project [Internet]. 2017. Available from: www.mmmp.org/

[9] Cioaca D, Ghenea S, Spiridon LN, et al. C-terminus glycans with critical functional role in the maturation of secretory glycoproteins. PLoS One. 2011;**6**(5):e19979. DOI: 10.1371/

[10] Sendovski M, Kanteev M, Ben-Yosef VS, et al. First structures of an active bacterial tyrosinase reveal copper plasticity. Journal of Molecular Biology. 2011;**405**:227-237

[11] Matoba Y, Bando N, Oda K, et al. A molecular mechanism for copper transportation to tyrosinase that is assisted by ametallochaperone, caddie protein. Journal of Biological

[12] Olivares C, Solano F. New insights into the active site structure and catalytic mechanism of tyrosinase and its related proteins. Pigment Cell & Melanoma Research. 2009;**22**:750-

[13] Solano F, Jimenez-Cervantes C, Martinez-Liarte J-H, et al. Molecular mechanism for catalysis by a new zinc-enzyme, dopachrome tautomerase. The Biochemical Journal

[14] Orlow SJ, Zhou BK, Chakraborty AK. High-molecular-weight forms of tyrosinase and the tyrosinase-related proteins: Evidence for a melanogenic complex. Journal of

[15] Vavricka CJ, Ray KW, Christensen BM, et al. Purification and N-glycosylation analysis of melanoma antigen dopachrome tautomerase. Protein Journal. 2010;**29**:204-212

[16] Wang N, Daniels R, Hebert DN. The cotranslational maturation of the type imembrane glycoprotein tyrosinase: The heat shock protein 70 system hands off tothe lectin-based

[17] Geoghegan V, Guo A, Trudgian D, et al. Comprehensive identification of arginine methylation in primary T cells reveals regulatory roles in cell signalling. Nature

[18] Paschen A, Song M, Osen W, et al. Detection of spontaneous CD4+ T-cell responses in melanoma patients against a tyrosinase-related protein-2-derived epitope identified in

[19] Parkhurst MR, Fitzgerald EB, Southwood S, et al. Identification of a shared HLA-A\*0201 restricted T-cell epitope from the melanoma antigen tyrosinase-related protein 2 (TRP2).

HLA-DRB1\*0301 transgenic mice. Clinical Cancer Research. 2005;**11**:5241-5247

chaperone system. Molecular Biology of the Cell. 2005;**16**:3740-3752

Communications. 2015;**6**:6758. DOI: 10.1038/ncomms7758

JCO.2006.06.0442

2011;**223**:241-250. DOI: 10.1002/path.2804

MMMP [Accessed: 01-06-2017]

Chemistry. 2011;**286**:30219-30231

760. DOI: 10.1111/j.1755-148X.2009.00636.x

Investigative Dermatology. 1994;**103**:196-201

Cancer Research. 1998;**58**(21):4895-4901

journal.pone.0019979

1996;**313**:447-453
