# MLANA
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{{Short description|Protein-coding gene in humans}}
{{Infobox_gene}}
thumb|Immunohistochemistry stain for Melan-A in a poorly differentiated metastatic melanoma to a lymph node, helping in its diagnosis
'''Protein melan-A''' also known as '''melanoma antigen recognized by T cells 1''' or '''MART-1''' is a [protein](/source/protein) that in humans is encoded by the ''MLANA'' or "MALENA" [gene](/source/gene).[{{cite web | title = Entrez Gene: MLANA melan-A| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=2315}}] A fragment of the protein, usually consisting of the nine amino acids 27 to 35, is bound by [MHC class I](/source/MHC_class_I) complexes which present it to [T cell](/source/T_cell)s of the immune system. These complexes can be found on the surface of [melanoma](/source/melanoma) cells. Decameric peptides (26-35) are being investigated as cancer vaccines.
== Discovery and nomenclature ==
The names MART-1 and melan-A were coined by two groups of researchers who independently sequenced the gene for this antigen in 1994. Both names are currently in common use. Kawakami et al. at the [National Cancer Institute](/source/National_Cancer_Institute) coined the term MART-1, which stands for "melanoma antigen recognized by [T-cell](/source/T-cell)s".[{{cite journal |vauthors=Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Rivoltini L, Topalian SL, Miki T, Rosenberg SA | title = Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 91 | issue = 9 | pages = 3515–9 |date=April 1994 | pmid = 8170938 | pmc = 43610 | doi = 10.1073/pnas.91.9.3515 | bibcode = 1994PNAS...91.3515K | doi-access = free }}] Coulie et al. of [Belgium](/source/Belgium) called the gene melan-A, presumably an abbreviation for "melanocyte antigen".[{{cite journal |vauthors=Coulie PG, Brichard V, Van Pel A, Wölfel T, Schneider J, Traversari C, Mattei S, De Plaen E, Lurquin C, Szikora JP, Renauld JC, Boon T | title = A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas | journal = J. Exp. Med. | volume = 180 | issue = 1 | pages = 35–42 |date=July 1994 | pmid = 8006593 | pmc = 2191574 | doi = 10.1084/jem.180.1.35 }}]
== Clinical significance ==
MART-1/melan-A is a protein [antigen](/source/antigen) that is found on the surface of [melanocyte](/source/melanocyte)s. Antibodies against the antigen are used in the medical specialty of [anatomic pathology](/source/anatomic_pathology) in order to recognize cells of melanocytic differentiation, useful for the diagnosis of a [melanoma](/source/melanoma). The same name is also used to refer to the gene which codes for the antigen.
The MART-1/melan-A antigen is specific for the melanocyte lineage, found in normal skin, the retina, and melanocytes, but not in other normal tissues. It is thus useful as a marker for melanocytic tumors ([melanoma](/source/melanoma)s) with the caveat that it is normally found in benign [nevi](/source/nevus) as well.
In many immunological studies melan-A peptides serve as a positive control for T-cell priming experiments. This is due to the fact that its high precursor frequency of about 1/1000 among cytotoxic T-cells makes it easy for antigen presenting cells to evoke peptide-specific responses.[{{cite journal |vauthors=Zippelius A, Pittet MJ, Batard P, etal |title=Thymic selection generates a large T cell pool recognizing a self-peptide in humans |journal=J. Exp. Med. |volume=195 |issue= 4 |pages= 485–94 |year= 2002 |pmid= 11854361 |doi=10.1084/jem.20011658 | pmc=2193620 }}]
== Structure ==
MART-1/melan-A is a putative 13 [kDa](/source/atomic_mass_unit) transmembrane protein consisting of 118 [amino acid](/source/amino_acid)s. It has a single transmembrane domain.
== Regulation ==
Its expression is regulated by the [microphthalmia-associated transcription factor](/source/microphthalmia-associated_transcription_factor).[{{cite journal |vauthors=Du J, Miller AJ, Widlund HR, Horstmann MA, Ramaswamy S, Fisher DE | title = MLANA/MART1 and SILV/PMEL17/GP100 are transcriptionally regulated by MITF in melanocytes and melanoma | journal = Am. J. Pathol. | volume = 163 | issue = 1 | pages = 333–43 | year = 2003 | pmid = 12819038 | doi = 10.1016/S0002-9440(10)63657-7| pmc = 1868174 }}][{{cite journal |vauthors=Hoek KS, Schlegel NC, Eichhoff OM, etal | title = Novel MITF targets identified using a two-step DNA microarray strategy | journal = Pigment Cell Melanoma Res. | volume = 21 | issue = 6 | pages = 665–76 | year = 2008 | pmid = 19067971| doi = 10.1111/j.1755-148X.2008.00505.x | s2cid = 24698373 | doi-access = free }}]
==References==
{{reflist}}
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==Further reading==
{{refbegin | 2}}
*{{cite journal |vauthors=Moritake H, Sugimoto T, Asada Y, etal |title=Newly established clear cell sarcoma (malignant melanoma of soft parts) cell line expressing melanoma-associated Melan-A antigen and overexpressing C-MYC oncogene |journal=Cancer Genet. Cytogenet. |volume=135 |issue= 1 |pages= 48–56 |year= 2002 |pmid= 12072203 |doi=10.1016/S0165-4608(01)00641-0 }}
*{{cite journal |vauthors=Dutoit V, Rubio-Godoy V, Pittet MJ, etal |title=Degeneracy of antigen recognition as the molecular basis for the high frequency of naive A2/Melan-a peptide multimer(+) CD8(+) T cells in humans |journal=J. Exp. Med. |volume=196 |issue= 2 |pages= 207–16 |year= 2002 |pmid= 12119345 |doi=10.1084/jem.20020242 | pmc=2193921 }}
*{{cite journal |vauthors=Mantovani S, Palermo B, Garbelli S, etal |title=Dominant TCR-alpha requirements for a self antigen recognition in humans |journal=J. Immunol. |volume=169 |issue= 11 |pages= 6253–60 |year= 2002 |pmid= 12444131 |doi= 10.4049/jimmunol.169.11.6253|s2cid=6143069 |doi-access= }}
*{{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |bibcode=2002PNAS...9916899M |doi-access=free }}
*{{cite journal |vauthors=Du J, Miller AJ, Widlund HR, etal |title=MLANA/MART1 and SILV/PMEL17/GP100 are transcriptionally regulated by MITF in melanocytes and melanoma |journal=Am. J. Pathol. |volume=163 |issue= 1 |pages= 333–43 |year= 2003 |pmid= 12819038 |doi= 10.1016/S0002-9440(10)63657-7| pmc=1868174 }}
*{{cite journal |vauthors=Mandelcorn-Monson RL, Shear NH, Yau E, etal |title=Cytotoxic T lymphocyte reactivity to gp100, MelanA/MART-1, and tyrosinase, in HLA-A2-positive vitiligo patients |journal=J. Invest. Dermatol. |volume=121 |issue= 3 |pages= 550–6 |year= 2003 |pmid= 12925214 |doi= 10.1046/j.1523-1747.2003.12413.x |doi-access= free }}
*{{cite journal |vauthors=Ghorab Z, Jorda M, Ganjei P, Nadji M |title=Melan A (A103) is expressed in adrenocortical neoplasms but not in renal cell and hepatocellular carcinomas |journal=Appl. Immunohistochem. Mol. Morphol. |volume=11 |issue= 4 |pages= 330–3 |year= 2004 |pmid= 14663359 |doi= 10.1097/00129039-200312000-00009|s2cid=37758396 }}
*{{cite journal |vauthors=Murer K, Urosevic M, Willers J, etal |title=Expression of Melan-A/MART-1 in primary melanoma cell cultures has prognostic implication in metastatic melanoma patients |journal=Melanoma Res. |volume=14 |issue= 4 |pages= 257–62 |year= 2005 |pmid= 15305155 |doi=10.1097/01.cmr.0000136713.21029.56 |s2cid=19261422 }}
*{{cite journal |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 }}
*{{cite journal |vauthors=Kucher C, Zhang PJ, Pasha T, etal |title=Expression of Melan-A and Ki-67 in desmoplastic melanoma and desmoplastic nevi |journal=The American Journal of Dermatopathology |volume=26 |issue= 6 |pages= 452–7 |year= 2005 |pmid= 15618925 |doi=10.1097/00000372-200412000-00002 |s2cid=22909579 }}
*{{cite journal |vauthors=Hoashi T, Watabe H, Muller J, etal |title=MART-1 is required for the function of the melanosomal matrix protein PMEL17/GP100 and the maturation of melanosomes |journal=J. Biol. Chem. |volume=280 |issue= 14 |pages= 14006–16 |year= 2005 |pmid= 15695812 |doi= 10.1074/jbc.M413692200 |s2cid=31894507 |doi-access=free }}
*{{cite journal |vauthors=Godefroy E, Scotto L, Souleimanian NE, etal |title=Identification of two Melan-A CD4+ T cell epitopes presented by frequently expressed MHC class II alleles |journal=Clin. Immunol. |volume=121 |issue= 1 |pages= 54–62 |year= 2006 |pmid= 16814609 |doi= 10.1016/j.clim.2006.05.007 }}
*{{cite journal |vauthors=Kono M, Dunn IS, Durda PJ, etal |title=Role of the mitogen-activated protein kinase signaling pathway in the regulation of human melanocytic antigen expression |journal=Mol. Cancer Res. |volume=4 |issue= 10 |pages= 779–92 |year= 2007 |pmid= 17050671 |doi= 10.1158/1541-7786.MCR-06-0077 |s2cid=7499391 |doi-access=free }}
*{{cite journal |vauthors=Bioley G, Jandus C, Tuyaerts S, etal |title=Melan-A/MART-1-specific CD4 T cells in melanoma patients: identification of new epitopes and ex vivo visualization of specific T cells by MHC class II tetramers |journal=J. Immunol. |volume=177 |issue= 10 |pages= 6769–79 |year= 2007 |pmid= 17082590 |doi= 10.4049/jimmunol.177.10.6769|s2cid=27014057 |doi-access=free }}
*{{cite journal |vauthors=Roma AA, Magi-Galluzzi C, Zhou M |title=Differential expression of melanocytic markers in myoid, lipomatous, and vascular components of renal angiomyolipomas |journal=Arch. Pathol. Lab. Med. |volume=131 |issue= 1 |pages= 122–5 |year= 2007 |pmid= 17227112 |doi= 10.5858/2007-131-122-DEOMMI }}
*{{cite journal |vauthors=Yuan F, Georgiou T, Hillon T, etal |title=Crystallization and preliminary X-ray structural studies of a Melan-A pMHC-TCR complex |journal=Acta Crystallographica Section F |volume=63 |issue= Pt 9 |pages= 758–60 |year= 2007 |pmid= 17768347 |doi= 10.1107/S1744309107037244 | pmc=2376329 }}
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{{gene-9-stub}}
Category:Genes on human chromosome 9
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Adapted from the Wikipedia article [MLANA](https://en.wikipedia.org/wiki/MLANA) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/MLANA?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.