Biology:ADAM12
 Generic protein structure example |
Disintegrin and metalloproteinase domain-containing protein 12 (previously Meltrin) is an enzyme that in humans is encoded by the ADAM12 gene.[1][2] 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.[3]
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.[4]
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%.[5]
ADAM12 has also been implicated in the development of pathology in various cancers, hypertension, liver fibrogenesis, and asthma.[6] In asthma, ADAM12 is upregulated in lung epithelium in response to TNF-alpha.[7]
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.[8]
Interactions
ADAM12 has been shown to interact with:
References
- ↑ "A novel, secreted form of human ADAM 12 (meltrin alpha) provokes myogenesis in vivo". J. Biol. Chem. 273 (1): 157–66. Feb 1998. doi:10.1074/jbc.273.1.157. PMID 9417060.
- ↑ "Cellular roles of ADAM12 in health and disease". Int. J. Biochem. Cell Biol. 40 (9): 1685–702. Jun 2008. doi:10.1016/j.biocel.2008.01.025. PMID 18342566.
- ↑ "A metalloprotease-disintegrin participating in myoblast fusion.". Nature 377 (6550): 652–6. 1995. doi:10.1038/377652a0. PMID 7566181. Bibcode: 1995Natur.377..652Y.
- ↑ "Entrez Gene: ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8038.
- ↑ Danforth's Obstetrics and Gynecology, 10th Edition; Copyright ©2008 Lippincott Williams & Wilkins; Chapter 7: Prenatal Diagnosis, Page 113
- ↑ "A disintegrin and metalloproteinase-12 (ADAM12): function, roles in disease progression, and clinical implications". Biochim. Biophys. Acta 1830 (10): 4445–55. 2013. doi:10.1016/j.bbagen.2013.05.011. PMID 23680494.
- ↑ "Role of a disintegrin and metalloprotease-12 in neutrophil recruitment induced by airway epithelium". Am. J. Respir. Cell Mol. Biol. 41 (4): 449–58. 2009. doi:10.1165/rcmb.2008-0124OC. PMID 19213876. http://orbi.ulg.ac.be/handle/2268/5767.
- ↑ Dzirasa, Kafui (2017-08-02). "A brilliant approach to study the basis of intelligence?" (in en). Science Translational Medicine 9 (401). doi:10.1126/scitranslmed.aao0978. ISSN 1946-6234. https://www.science.org/doi/10.1126/scitranslmed.aao0978.
- ↑ "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. 275 (18): 13933–9. May 2000. doi:10.1074/jbc.275.18.13933. PMID 10788519.
- ↑ "ADAM 12, a disintegrin metalloprotease, interacts with insulin-like growth factor-binding protein-3". J. Biol. Chem. 275 (24): 18574–80. Jun 2000. doi:10.1074/jbc.M002172200. PMID 10849447.
- ↑ "ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3". Biochem. Biophys. Res. Commun. 278 (3): 511–5. Nov 2000. doi:10.1006/bbrc.2000.3835. PMID 11095942.
- ↑ "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. 276 (27): 24466–72. Jul 2001. doi:10.1074/jbc.M101162200. PMID 11313349.
Further reading
- "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. 276 (27): 24466–72. 2001. doi:10.1074/jbc.M101162200. PMID 11313349.
- "Human ADAM 12 (meltrin alpha) is an active metalloprotease.". J. Biol. Chem. 273 (27): 16993–7. 1998. doi:10.1074/jbc.273.27.16993. PMID 9642263.
- "Interaction of the metalloprotease disintegrins MDC9 and MDC15 with two SH3 domain-containing proteins, endophilin I and SH3PX1.". J. Biol. Chem. 274 (44): 31693–9. 1999. doi:10.1074/jbc.274.44.31693. PMID 10531379.
- "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. 275 (18): 13933–9. 2000. doi:10.1074/jbc.275.18.13933. PMID 10788519.
- "The cysteine-rich domain of human ADAM 12 supports cell adhesion through syndecans and triggers signaling events that lead to beta1 integrin-dependent cell spreading.". J. Cell Biol. 149 (5): 1143–56. 2000. doi:10.1083/jcb.149.5.1143. PMID 10831617.
- "ADAM 12, a disintegrin metalloprotease, interacts with insulin-like growth factor-binding protein-3.". J. Biol. Chem. 275 (24): 18574–80. 2000. doi:10.1074/jbc.M002172200. PMID 10849447.
- "RGD-independent binding of integrin alpha9beta1 to the ADAM-12 and -15 disintegrin domains mediates cell-cell interaction.". J. Biol. Chem. 275 (45): 34922–30. 2001. doi:10.1074/jbc.M001953200. PMID 10944520.
- "ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3.". Biochem. Biophys. Res. Commun. 278 (3): 511–5. 2001. doi:10.1006/bbrc.2000.3835. PMID 11095942.
- "Meltrin alpha cytoplasmic domain interacts with SH3 domains of Src and Grb2 and is phosphorylated by v-Src.". Oncogene 19 (51): 5842–50. 2000. doi:10.1038/sj.onc.1203986. PMID 11127814.
- "ADAM 12 protease induces adipogenesis in transgenic mice.". Am. J. Pathol. 160 (5): 1895–903. 2002. doi:10.1016/S0002-9440(10)61136-4. PMID 12000741.
- "Intracellular processing of metalloprotease disintegrin ADAM12". J. Biol. Chem. 277 (29): 26403–11. 2002. doi:10.1074/jbc.M110814200. PMID 12000744.
- "The adaptor protein fish associates with members of the ADAMs family and localizes to podosomes of Src-transformed cells". J. Biol. Chem. 278 (19): 16844–51. 2003. doi:10.1074/jbc.M300267200. PMID 12615925.
- "ADAM12 in human liver cancers: TGF-beta-regulated expression in stellate cells is associated with matrix remodeling". Hepatology 37 (5): 1056–66. 2003. doi:10.1053/jhep.2003.50205. PMID 12717386.
- "ADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating beta1 integrin function". J. Cell Sci. 116 (Pt 19): 3893–904. 2004. doi:10.1242/jcs.00699. PMID 12915587.
- "PACSIN3 binds ADAM12/meltrin alpha and up-regulates ectodomain shedding of heparin-binding epidermal growth factor-like growth factor". J. Biol. Chem. 278 (46): 46029–34. 2003. doi:10.1074/jbc.M306393200. PMID 12952982.
- "ADAM12: a novel first-trimester maternal serum marker for Down syndrome". Prenat. Diagn. 23 (13): 1086–91. 2004. doi:10.1002/pd.762. PMID 14691998.
External links
- The MEROPS online database for peptidases and their inhibitors: M12.212
- ADAM12 on the Atlas of Genetics and Oncology
- Human ADAM12 genome location and ADAM12 gene details page in the UCSC Genome Browser.
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