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ADAM12

{{Short description|Human protein-coding gene}}

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{{For|the television show|Adam-12}}

{{Infobox_gene}}

Disintegrin and metalloproteinase domain-containing protein 12 (previously Meltrin) is an enzyme that in humans is encoded by the ADAM12 gene.{{cite journal | vauthors = Gilpin BJ, Loechel F, Mattei MG, Engvall E, Albrechtsen R, Wewer UM | title = A novel, secreted form of human ADAM 12 (meltrin alpha) provokes myogenesis in vivo | journal = J. Biol. Chem. | volume = 273 | issue = 1 | pages = 157–66 | date = Feb 1998 | pmid = 9417060 | doi = 10.1074/jbc.273.1.157 | doi-access = free }}{{cite journal | vauthors = Kveiborg M, Albrechtsen R, Couchman JR, Wewer UM | title = Cellular roles of ADAM12 in health and disease | journal = Int. J. Biochem. Cell Biol. | volume = 40 | issue = 9 | pages = 1685–702 | date = Jun 2008 | pmid = 18342566 | doi = 10.1016/j.biocel.2008.01.025 }} 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.{{cite journal | vauthors = Yagami-Hiromasa T, Sato T, Kurisaki T, Kamijo K, Nabeshima Y, Fujisawa-Sehara A | title = A metalloprotease-disintegrin participating in myoblast fusion. | journal = Nature | volume = 377 | issue = 6550 | pages = 652–6 | year = 1995 | pmid = 7566181 | doi = 10.1038/377652a0 | bibcode = 1995Natur.377..652Y | s2cid = 4348744 }}

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.{{cite web | title = Entrez Gene: ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8038}}

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%.Danforth's Obstetrics and Gynecology, 10th Edition; Copyright ©2008 Lippincott Williams & Wilkins; Chapter 7: Prenatal Diagnosis, Page 113

ADAM12 has also been implicated in the development of pathology in various cancers, hypertension, liver fibrogenesis, and asthma.{{cite journal | vauthors = Nyren-Erickson EK, Jones JM, Srivastava DK, Mallik S | title = A disintegrin and metalloproteinase-12 (ADAM12): function, roles in disease progression, and clinical implications | journal = Biochim. Biophys. Acta | volume = 1830 | issue = 10 | pages = 4445–55 | year = 2013 | pmid = 23680494 | doi = 10.1016/j.bbagen.2013.05.011 | pmc=3740046}} In asthma, ADAM12 is upregulated in lung epithelium in response to TNF-alpha.{{cite journal | vauthors = Estrella C, Rocks N, Paulissen G, Quesada-Calvo F, Noel A, Vilain E, Lassalle P, Tillie-Leblond I, Cataldo D, Gosset P | title = Role of a disintegrin and metalloprotease-12 in neutrophil recruitment induced by airway epithelium | journal = Am. J. Respir. Cell Mol. Biol. | volume = 41 | issue = 4 | pages = 449–58 | year = 2009 | pmid = 19213876 | doi = 10.1165/rcmb.2008-0124OC | hdl = 2268/5767 | url = http://orbi.ulg.ac.be/handle/2268/5767 | hdl-access = free }}

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.{{cite journal |last=Dzirasa |first=Kafui |date=2017-08-02 |title=A brilliant approach to study the basis of intelligence? |url=https://www.science.org/doi/10.1126/scitranslmed.aao0978 |journal=Science Translational Medicine |language=en |volume=9 |issue=401 |doi=10.1126/scitranslmed.aao0978 |s2cid=44125138 |issn=1946-6234}}

Interactions

ADAM12 has been shown to interact with:

  • ACTN2,{{cite journal | vauthors = Galliano MF, Huet C, Frygelius J, Polgren A, Wewer UM, Engvall E | title = Binding of ADAM12, a marker of skeletal muscle regeneration, to the muscle-specific actin-binding protein, alpha -actinin-2, is required for myoblast fusion | journal = J. Biol. Chem. | volume = 275 | issue = 18 | pages = 13933–9 | date = May 2000 | pmid = 10788519 | doi = 10.1074/jbc.275.18.13933| doi-access = free }}
  • IGFBP3,{{cite journal | vauthors = Shi Z, Xu W, Loechel F, Wewer UM, Murphy LJ | title = ADAM 12, a disintegrin metalloprotease, interacts with insulin-like growth factor-binding protein-3 | journal = J. Biol. Chem. | volume = 275 | issue = 24 | pages = 18574–80 | date = Jun 2000 | pmid = 10849447 | doi = 10.1074/jbc.M002172200 | doi-access = free }}{{cite journal | vauthors = Loechel F, Fox JW, Murphy G, Albrechtsen R, Wewer UM | title = ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3 | journal = Biochem. Biophys. Res. Commun. | volume = 278 | issue = 3 | pages = 511–5 | date = Nov 2000 | pmid = 11095942 | doi = 10.1006/bbrc.2000.3835 }} and
  • PIK3R1.{{cite journal | vauthors = Kang Q, Cao Y, Zolkiewska A | title = Direct interaction between the cytoplasmic tail of ADAM 12 and the Src homology 3 domain of p85alpha activates phosphatidylinositol 3-kinase in C2C12 cells | journal = J. Biol. Chem. | volume = 276 | issue = 27 | pages = 24466–72 | date = Jul 2001 | pmid = 11313349 | doi = 10.1074/jbc.M101162200 | doi-access = free }}

References

{{Reflist|33em}}

Further reading

{{Refbegin|33em}}

  • {{cite journal | vauthors = Kang Q, Cao Y, Zolkiewska A | title = Direct interaction between the cytoplasmic tail of ADAM 12 and the Src homology 3 domain of p85alpha activates phosphatidylinositol 3-kinase in C2C12 cells. | journal = J. Biol. Chem. | volume = 276 | issue = 27 | pages = 24466–72 | year = 2001 | pmid = 11313349 | doi = 10.1074/jbc.M101162200 | doi-access = free }}
  • {{cite journal | vauthors = Loechel F, Gilpin BJ, Engvall E, Albrechtsen R, Wewer UM | title = Human ADAM 12 (meltrin alpha) is an active metalloprotease. | journal = J. Biol. Chem. | volume = 273 | issue = 27 | pages = 16993–7 | year = 1998 | pmid = 9642263 | doi = 10.1074/jbc.273.27.16993 | doi-access = free }}
  • {{cite journal | vauthors = Howard L, Nelson KK, Maciewicz RA, Blobel CP | title = Interaction of the metalloprotease disintegrins MDC9 and MDC15 with two SH3 domain-containing proteins, endophilin I and SH3PX1. | journal = J. Biol. Chem. | volume = 274 | issue = 44 | pages = 31693–9 | year = 1999 | pmid = 10531379 | doi = 10.1074/jbc.274.44.31693 | doi-access = free }}
  • {{cite journal | vauthors = Galliano MF, Huet C, Frygelius J, Polgren A, Wewer UM, Engvall E | title = Binding of ADAM12, a marker of skeletal muscle regeneration, to the muscle-specific actin-binding protein, alpha -actinin-2, is required for myoblast fusion. | journal = J. Biol. Chem. | volume = 275 | issue = 18 | pages = 13933–9 | year = 2000 | pmid = 10788519 | doi = 10.1074/jbc.275.18.13933 | doi-access = free }}
  • {{cite journal | vauthors = Iba K, Albrechtsen R, Gilpin B, Fröhlich C, Loechel F, Zolkiewska A, Ishiguro K, Kojima T, Liu W, Langford JK, Sanderson RD, Brakebusch C, Fässler R, Wewer UM | title = 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. | journal = J. Cell Biol. | volume = 149 | issue = 5 | pages = 1143–56 | year = 2000 | pmid = 10831617 | pmc = 2174829 | doi = 10.1083/jcb.149.5.1143 }}
  • {{cite journal | vauthors = Shi Z, Xu W, Loechel F, Wewer UM, Murphy LJ | title = ADAM 12, a disintegrin metalloprotease, interacts with insulin-like growth factor-binding protein-3. | journal = J. Biol. Chem. | volume = 275 | issue = 24 | pages = 18574–80 | year = 2000 | pmid = 10849447 | doi = 10.1074/jbc.M002172200 | doi-access = free }}
  • {{cite journal | vauthors = Eto K, Puzon-McLaughlin W, Sheppard D, Sehara-Fujisawa A, Zhang XP, Takada Y | title = RGD-independent binding of integrin alpha9beta1 to the ADAM-12 and -15 disintegrin domains mediates cell-cell interaction. | journal = J. Biol. Chem. | volume = 275 | issue = 45 | pages = 34922–30 | year = 2001 | pmid = 10944520 | doi = 10.1074/jbc.M001953200 | doi-access = free }}
  • {{cite journal | vauthors = Loechel F, Fox JW, Murphy G, Albrechtsen R, Wewer UM | title = ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3. | journal = Biochem. Biophys. Res. Commun. | volume = 278 | issue = 3 | pages = 511–5 | year = 2001 | pmid = 11095942 | doi = 10.1006/bbrc.2000.3835 }}
  • {{cite journal | vauthors = Suzuki A, Kadota N, Hara T, Nakagami Y, Izumi T, Takenawa T, Sabe H, Endo T | title = Meltrin alpha cytoplasmic domain interacts with SH3 domains of Src and Grb2 and is phosphorylated by v-Src. | journal = Oncogene | volume = 19 | issue = 51 | pages = 5842–50 | year = 2000 | pmid = 11127814 | doi = 10.1038/sj.onc.1203986 | doi-access = free }}
  • {{cite journal | vauthors = Kawaguchi N, Xu X, Tajima R, Kronqvist P, Sundberg C, Loechel F, Albrechtsen R, Wewer UM | title = ADAM 12 protease induces adipogenesis in transgenic mice. | journal = Am. J. Pathol. | volume = 160 | issue = 5 | pages = 1895–903 | year = 2002 | pmid = 12000741 | pmc = 1850877 | doi = 10.1016/S0002-9440(10)61136-4 }}
  • {{cite journal | vauthors = Cao Y, Kang Q, Zhao Z, Zolkiewska A | title = Intracellular processing of metalloprotease disintegrin ADAM12 | journal = J. Biol. Chem. | volume = 277 | issue = 29 | pages = 26403–11 | year = 2002 | pmid = 12000744 | doi = 10.1074/jbc.M110814200 | doi-access = free }}
  • {{cite journal | vauthors = Abram CL, Seals DF, Pass I, Salinsky D, Maurer L, Roth TM, Courtneidge SA | title = The adaptor protein fish associates with members of the ADAMs family and localizes to podosomes of Src-transformed cells | journal = J. Biol. Chem. | volume = 278 | issue = 19 | pages = 16844–51 | year = 2003 | pmid = 12615925 | doi = 10.1074/jbc.M300267200 | doi-access = free }}
  • {{cite journal | vauthors = Le Pabic H, Bonnier D, Wewer UM, Coutand A, Musso O, Baffet G, Clément B, Théret N | title = ADAM12 in human liver cancers: TGF-beta-regulated expression in stellate cells is associated with matrix remodeling | journal = Hepatology | volume = 37 | issue = 5 | pages = 1056–66 | year = 2003 | pmid = 12717386 | doi = 10.1053/jhep.2003.50205 | s2cid = 32722392 | doi-access = free }}
  • {{cite journal | vauthors = Kawaguchi N, Sundberg C, Kveiborg M, Moghadaszadeh B, Asmar M, Dietrich N, Thodeti CK, Nielsen FC, Möller P, Mercurio AM, Albrechtsen R, Wewer UM | title = ADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating beta1 integrin function | journal = J. Cell Sci. | volume = 116 | issue = Pt 19 | pages = 3893–904 | year = 2004 | pmid = 12915587 | doi = 10.1242/jcs.00699 | doi-access = free }}
  • {{cite journal | vauthors = Mori S, Tanaka M, Nanba D, Nishiwaki E, Ishiguro H, Higashiyama S, Matsuura N | title = PACSIN3 binds ADAM12/meltrin alpha and up-regulates ectodomain shedding of heparin-binding epidermal growth factor-like growth factor | journal = J. Biol. Chem. | volume = 278 | issue = 46 | pages = 46029–34 | year = 2003 | pmid = 12952982 | doi = 10.1074/jbc.M306393200 | doi-access = free }}
  • {{cite journal | vauthors = Laigaard J, Sørensen T, Fröhlich C, Pedersen BN, Christiansen M, Schiøtt K, Uldbjerg N, Albrechtsen R, Clausen HV, Ottesen B, Wewer UM | title = ADAM12: a novel first-trimester maternal serum marker for Down syndrome | journal = Prenat. Diagn. | volume = 23 | issue = 13 | pages = 1086–91 | year = 2004 | pmid = 14691998 | doi = 10.1002/pd.762 | s2cid = 32888570 }}

{{Refend}}

External links

  • The MEROPS online database for peptidases and their inhibitors: [http://merops.sanger.ac.uk/cgi-bin/merops.cgi?id=M12.212 M12.212]
  • [http://atlasgeneticsoncology.org/Genes/ADAM12ID44084ch10q26.html ADAM12] on the Atlas of Genetics and Oncology
  • {{UCSC gene info|ADAM12}}

{{Metalloendopeptidases}}

{{Enzymes}}

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{{DEFAULTSORT:Adam12}}

Category:Proteases

Category:Human proteins

Category:EC 3.4.24