MLANA

Protein melan-A also known as melanoma antigen recognized by T cells 1 or MART-1 is a protein that in humans is encoded by the MLANA or "MALENA" gene.[5] A fragment of the protein, usually consisting of the nine amino acids 27 to 35, is bound by MHC class I complexes which present it to T cells of the immune system. These complexes can be found on the surface of melanoma cells. Decameric peptides (26-35) are being investigated as cancer vaccines.

MLANA
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesMLANA, MART-1, MART1, melan-A
External IDsOMIM: 605513 MGI: 108454 HomoloGene: 4026 GeneCards: MLANA
Gene location (Human)
Chr.Chromosome 9 (human)[1]
Band9p24.1Start5,890,889 bp[1]
End5,910,606 bp[1]
RNA expression pattern


More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

2315

77836

Ensembl

ENSG00000120215

ENSMUSG00000024806

UniProt

Q16655

Q2TA50

RefSeq (mRNA)

NM_005511

NM_029993

RefSeq (protein)

NP_005502

NP_084269

Location (UCSC)Chr 9: 5.89 – 5.91 MbChr 19: 29.7 – 29.71 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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 coined the term MART-1, which stands for "melanoma antigen recognized by T-cells."[6] Coulie et al. of Belgium called the gene melan-A, presumably an abbreviation for "melanocyte antigen."[7]

Clinical significance

MART-1/melan-A is a protein antigen that is found on the surface of melanocytes. Antibodies against the antigen are used in the medical specialty of anatomic pathology in order to recognize cells of melanocytic differentiation, useful for the diagnosis of a 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 (melanomas) with the caveat that it is normally found in benign nevi 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.[8]

Structure

MART-1/melan-A is a putative 18 kDa transmembrane protein consisting of 118 amino acids. It has a single transmembrane domain.

Regulation

Its expression is regulated by the Microphthalmia-associated transcription factor.[9][10]

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References
  1. GRCh38: Ensembl release 89: ENSG00000120215 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000024806 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: MLANA melan-A".
  6. Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Rivoltini L, Topalian SL, Miki T, Rosenberg SA (April 1994). "Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor". Proc. Natl. Acad. Sci. U.S.A. 91 (9): 3515–9. doi:10.1073/pnas.91.9.3515. PMC 43610. PMID 8170938.
  7. 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 (July 1994). "A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas". J. Exp. Med. 180 (1): 35–42. doi:10.1084/jem.180.1.35. PMC 2191574. PMID 8006593.
  8. Zippelius A, Pittet MJ, Batard P, et al. (2002). "Thymic selection generates a large T cell pool recognizing a self-peptide in humans". J. Exp. Med. 195 (4): 485–94. doi:10.1084/jem.20011658. PMC 2193620. PMID 11854361.
  9. Du J, Miller AJ, Widlund HR, Horstmann MA, Ramaswamy S, Fisher DE (2003). "MLANA/MART1 and SILV/PMEL17/GP100 are transcriptionally regulated by MITF in melanocytes and melanoma". Am. J. Pathol. 163 (1): 333–43. doi:10.1016/S0002-9440(10)63657-7. PMC 1868174. PMID 12819038.
  10. Hoek KS, Schlegel NC, Eichhoff OM, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.

Further reading


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