Disintegrin and metalloproteinase domain-containing protein 12 (previously Meltrin) is an
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
that in humans is encoded by the ''ADAM12''
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 ...
.
ADAM12 has two splice variants: ADAM12-L, the long form, has a transmembrane region and ADAM12-S, a shorter variant, is soluble and lacks the transmembrane and cytoplasmic domains.
Function
This gene encodes a member of the ADAM (
a disintegrin and metalloprotease
ADAMs (short for a disintegrin and metalloproteinase) are a family of single-pass transmembrane and secreted metalloendopeptidases. All ADAMs are characterized by a particular protein domain, domain organization featuring a pro-domain, a metallo ...
) protein family. Members of this family are membrane-anchored proteins structurally related to snake venom
disintegrin
Disintegrins are a family of small proteins (45–84 amino acids in length) from viper venoms that function as potent inhibitors of both platelet aggregation and integrin-dependent cell adhesion.
Operation
Disintegrins work by countering th ...
s, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. This gene has two alternatively spliced transcripts: a shorter secreted form and a longer membrane-bound form. The shorter form is found to stimulate myogenesis.
Clinical Significance
ADAM 12, a
metalloprotease that binds insulin growth factor binding protein-3 (IGFBP-3), appears to be an effective early
Down syndrome marker. Decreased levels of ADAM 12 may be detected in cases of trisomy 21 as early as 8 to 10 weeks gestation. Maternal serum ADAM 12 and
PAPP-A levels at 8 to 9 weeks gestation in combination with maternal age yielded a 91% detection rate for Down syndrome at a 5% false-positive rate. When
nuchal translucency data from approximately 12 weeks gestation was added, this increased the detection rate to 97%.
ADAM12 has also been implicated in the development of
pathology
Pathology is the study of disease. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in the context of modern medical treatme ...
in various
cancer
Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
s,
hypertension
Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...
,
liver
The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
fibrogenesis, and
asthma
Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...
.
In asthma, ADAM12 is upregulated in
lung
The lungs are the primary Organ (biology), organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the Vertebral column, backbone on either side of the heart. Their ...
epithelium
Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...
in response to
TNF-alpha
Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors o ...
.
In a study of about 1200 persons with extremely high intelligence (IQ about 170), variants of the gene were associated with high IQ compared with a general population.
Interactions
ADAM12 has been shown to
interact with:
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ACTN2,
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IGFBP3
Insulin-like growth factor-binding protein 3, also known as IGFBP-3, is a protein that in humans is encoded by the ''IGFBP3'' gene. IGFBP-3 is one of six insulin-like growth factor-binding protein, IGF binding proteins (IGFBP1, IGFBP-1 to IGFBP6, ...
,
and
*
PIK3R1
Phosphatidylinositol 3-kinase regulatory subunit alpha is an enzyme that in humans is encoded by the ''PIK3R1'' gene.
Function
Phosphatidylinositol 3-kinase phosphorylates the inositol ring of phosphatidylinositol at the 3-prime position. ...
.
References
Further reading
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External links
* The
MEROPS online database for peptidases and their inhibitors
M12.212on the
Atlas of Genetics and Oncology
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{{DEFAULTSORT:Adam12
Proteases
Human proteins
EC 3.4.24