ADAM12

Disintegrin and metalloproteinase domain-containing protein 12 (previously Meltrin) is an enzyme that in humans is encoded by the ADAM12 gene.[5][6] 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.[7]

For the television show, see Adam-12.
ADAM12
Identifiers
AliasesADAM12, ADAM12-OT1, CAR10, MCMP, MCMPMltna, MLTN, MLTNA, ADAM metallopeptidase domain 12
External IDsOMIM: 602714 MGI: 105378 HomoloGene: 74862 GeneCards: ADAM12
Gene location (Human)
Chr.Chromosome 10 (human)[1]
Band10q26.2Start126,012,381 bp[1]
End126,388,455 bp[1]
RNA expression pattern




More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

8038

11489

Ensembl

ENSG00000148848

ENSMUSG00000054555

UniProt

O43184

Q61824

RefSeq (mRNA)

NM_021641
NM_001288973
NM_001288974
NM_001288975
NM_003474

NM_007400

RefSeq (protein)

NP_001275902
NP_001275903
NP_001275904
NP_003465
NP_067673

NP_031426

Location (UCSC)Chr 10: 126.01 – 126.39 MbChr 7: 133.88 – 134.23 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[8]

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%.[9]

ADAM12 has also been implicated in the development of pathology in various cancers, hypertension, liver fibrogenesis, and asthma.[10] In asthma, ADAM12 is upregulated in lung epithelium in response to TNF-alpha.[11]

Interactions

ADAM12 has been shown to interact with:

References
  1. GRCh38: Ensembl release 89: ENSG00000148848 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000054555 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Gilpin BJ, Loechel F, Mattei MG, Engvall E, Albrechtsen R, Wewer UM (Feb 1998). "A novel, secreted form of human ADAM 12 (meltrin alpha) provokes myogenesis in vivo". J. Biol. Chem. 273 (1): 157–66. doi:10.1074/jbc.273.1.157. PMID 9417060.
  6. Kveiborg M, Albrechtsen R, Couchman JR, Wewer UM (Jun 2008). "Cellular roles of ADAM12 in health and disease". Int. J. Biochem. Cell Biol. 40 (9): 1685–702. doi:10.1016/j.biocel.2008.01.025. PMID 18342566.
  7. Yagami-Hiromasa T, Sato T, Kurisaki T, Kamijo K, Nabeshima Y, Fujisawa-Sehara A (1995). "A metalloprotease-disintegrin participating in myoblast fusion". Nature. 377 (6550): 652–6. Bibcode:1995Natur.377..652Y. doi:10.1038/377652a0. PMID 7566181. S2CID 4348744.
  8. "Entrez Gene: ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha)".
  9. Danforth's Obstetrics and Gynecology, 10th Edition; Copyright ©2008 Lippincott Williams & Wilkins; Chapter 7: Prenatal Diagnosis, Page 113
  10. Nyren-Erickson EK, Jones JM, Srivastava DK, Mallik S (2013). "A disintegrin and metalloproteinase-12 (ADAM12): function, roles in disease progression, and clinical implications". Biochim. Biophys. Acta. 1830 (10): 4445–55. doi:10.1016/j.bbagen.2013.05.011. PMC 3740046. PMID 23680494.
  11. Estrella C, Rocks N, Paulissen G, Quesada-Calvo F, Noel A, Vilain E, Lassalle P, Tillie-Leblond I, Cataldo D, Gosset P (2009). "Role of a disintegrin and metalloprotease-12 in neutrophil recruitment induced by airway epithelium". Am. J. Respir. Cell Mol. Biol. 41 (4): 449–58. doi:10.1165/rcmb.2008-0124OC. PMID 19213876.
  12. Galliano MF, Huet C, Frygelius J, Polgren A, Wewer UM, Engvall E (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. 275 (18): 13933–9. doi:10.1074/jbc.275.18.13933. PMID 10788519.
  13. Shi Z, Xu W, Loechel F, Wewer UM, Murphy LJ (Jun 2000). "ADAM 12, a disintegrin metalloprotease, interacts with insulin-like growth factor-binding protein-3". J. Biol. Chem. 275 (24): 18574–80. doi:10.1074/jbc.M002172200. PMID 10849447.
  14. Loechel F, Fox JW, Murphy G, Albrechtsen R, Wewer UM (Nov 2000). "ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3". Biochem. Biophys. Res. Commun. 278 (3): 511–5. doi:10.1006/bbrc.2000.3835. PMID 11095942.
  15. Kang Q, Cao Y, Zolkiewska A (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. 276 (27): 24466–72. doi:10.1074/jbc.M101162200. PMID 11313349.

Further reading
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