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Protein melan-A also known as melanoma antigen recognized by T cells 1 or MART-1 is a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''MLANA'' or "MALENA"
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
. A fragment of the protein, usually consisting of the nine amino acids 27 to 35, is bound by
MHC class I MHC class I molecules are one of two primary classes of major histocompatibility complex (MHC) molecules (the other being MHC class II) and are found on the cell surface of all nucleated cells in the bodies of vertebrates. They also occur on ...
complexes which present it to
T cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...
s of the immune system. These complexes can be found on the surface of
melanoma Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...
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 The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...
coined the term MART-1, which stands for "melanoma antigen recognized by
T-cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their ce ...
s". Coulie et al. of
Belgium Belgium, officially the Kingdom of Belgium, is a country in Northwestern Europe. Situated in a coastal lowland region known as the Low Countries, it is bordered by the Netherlands to the north, Germany to the east, Luxembourg to the southeas ...
called the gene melan-A, presumably an abbreviation for "melanocyte antigen".


Clinical significance

MART-1/melan-A is a protein
antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
that is found on the surface of
melanocyte Melanocytes are melanin-producing neural-crest, neural crest-derived cell (biology), cells located in the bottom layer (the stratum basale) of the skin's epidermis (skin), epidermis, the middle layer of the eye (the uvea), the inner ear, vagina ...
s. Antibodies against the antigen are used in the medical specialty of
anatomic pathology Anatomical pathology (''Commonwealth'') or anatomic pathology (''U.S.'') is a medical specialty that is concerned with the diagnosis of disease based on the macroscopic, microscopic, biochemical, immunologic and molecular examination ...
in order to recognize cells of melanocytic differentiation, useful for the diagnosis of a
melanoma Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...
. 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 Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...
s) with the caveat that it is normally found in benign
nevi The Infrastructure Investment and Jobs Act (IIJA), also known as the Bipartisan Infrastructure Law (BIL),H.R. 3684 is a United States federal statute enacted by the 117th United States Congress and signed into law by President Joe Biden on Nove ...
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.


Structure

MART-1/melan-A is a putative 13
kDa The dalton or unified atomic mass unit (symbols: Da or u, respectively) is a unit of mass defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at rest. It is a non-SI unit accepted f ...
transmembrane protein consisting of 118
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
s. It has a single transmembrane domain.


Regulation

Its expression is regulated by the
microphthalmia-associated transcription factor Microphthalmia-associated transcription factor also known as class E basic helix-loop-helix protein 32 or bHLHe32 is a protein that in humans is encoded by the ''MITF'' gene. MITF is a basic helix-loop-helix leucine zipper transcription factor ...
.


References


Further reading

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