ADAM12

Function

This gene encodes a member of the ADAM (a disintegrin and metalloprotease) protein family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, 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 in various cancers, hypertension, liver fibrogenesis, and asthma. In asthma, ADAM12 is upregulated in lung epithelium in response to TNF-alpha.

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:

• ACTN2,
• IGFBP3, and
• PIK3R1.

References

References

1. (Feb 1998). "A novel, secreted form of human ADAM 12 (meltrin alpha) provokes myogenesis in vivo". J. Biol. Chem..
2. (Jun 2008). "Cellular roles of ADAM12 in health and disease". Int. J. Biochem. Cell Biol..
3. (1995). "A metalloprotease-disintegrin participating in myoblast fusion.". Nature.
4. "Entrez Gene: ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha)".
5. Danforth's Obstetrics and Gynecology, 10th Edition; Copyright ©2008 Lippincott Williams & Wilkins; Chapter 7: Prenatal Diagnosis, Page 113
6. (2013). "A disintegrin and metalloproteinase-12 (ADAM12): function, roles in disease progression, and clinical implications". Biochim. Biophys. Acta.
7. (2009). "Role of a disintegrin and metalloprotease-12 in neutrophil recruitment induced by airway epithelium". Am. J. Respir. Cell Mol. Biol..
8. Dzirasa, Kafui. (2017-08-02). "A brilliant approach to study the basis of intelligence?". Science Translational Medicine.
9. (May 2000). "Binding of ADAM12, a marker of skeletal muscle regeneration, to the muscle-specific actin-binding protein, alpha -actinin-2, is required for myoblast fusion". J. Biol. Chem..
10. (Jun 2000). "ADAM 12, a disintegrin metalloprotease, interacts with insulin-like growth factor-binding protein-3". J. Biol. Chem..
11. (Nov 2000). "ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3". Biochem. Biophys. Res. Commun..
12. (Jul 2001). "Direct interaction between the cytoplasmic tail of ADAM 12 and the Src homology 3 domain of p85alpha activates phosphatidylinositol 3-kinase in C2C12 cells". J. Biol. Chem..