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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''MLANA'' or "MALENA"
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
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 plat ...
complexes which present it to
T cell
A T cell is a type of lymphocyte. T cells are one of the important white blood cells 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 r ...
s of the immune system. These complexes can be found on the surface of
melanoma
Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
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
A T cell is a type of lymphocyte. T cells are one of the important white blood cells 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 rec ...
s."
Coulie et al. of
Belgium
Belgium, ; french: Belgique ; german: Belgien officially the Kingdom of Belgium, is a country in Northwestern Europe. The country is bordered by the Netherlands to the north, Germany to the east, Luxembourg to the southeast, France to th ...
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 or molecular structure or any foreign particulate matter or a pollen grain 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-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea),
the inner ear,
vaginal epithelium, meninges,
bones,
and heart.
...
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, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
. 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, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
s) with the caveat that it is normally found in benign
nevi
Nevus (plural nevi) is a nonspecific medical term for a visible, circumscribed, chronic lesion of the skin or mucosa. The term originates from ''nævus'', which is Latin for "birthmark"; however, a nevus can be either congenital (present at bir ...
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) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at re ...
transmembrane protein consisting of 118
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
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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