ADAM12

For the television show, see Adam-12.

ADAM12
Identifiers
Aliases	ADAM12 , ADAM12-OT1, CAR10, MCMP, MCMPMltna, MLTN, MLTNA, ADAM metallopeptidase domain 12
External IDs	OMIM: 602714; MGI: 105378; HomoloGene: 74862; GeneCards: ADAM12; OMA:ADAM12 - orthologs
Gene location (Human) Chr. Chromosome 10 (human) [1] Band 10q26.2 Start 126,012,381 bp [1] End 126,388,477 bp [1]
Gene location (Mouse) Chr. Chromosome 7 (mouse) [2] Band 7|7 F3 Start 133,484,928 bp [2] End 133,833,875 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in placenta stromal cell of endometrium buccal mucosa cell tibia decidua mucosa of paranasal sinus cartilage tissue gallbladder testicle tendon of biceps brachii Top expressed in gastrula calvaria body of femur mesothelium of peritoneum umbilical cord decidua facial skeleton efferent ductule mandible lesser wing of sphenoid bone More reference expression data BioGPS More reference expression data
Gene ontology Molecular function SH3 domain binding peptidase activity metalloendopeptidase activity protein binding hydrolase activity metal ion binding metallopeptidase activity Cellular component integral component of membrane extracellular region membrane nucleoplasm plasma membrane Biological process cell adhesion myoblast fusion proteolysis extracellular matrix organization positive regulation of angiogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 7: 133.48 – 133.83 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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]

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]

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. ^[12]

Interactions

ADAM12 has been shown to interact with:

• ACTN2, ^[13]
• IGFBP3, ^{[14] [15]} and
• PIK3R1. ^[16]

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. hdl: 2268/5767 . PMID   19213876.
12. Dzirasa K (2017-08-02). "A brilliant approach to study the basis of intelligence?" . Science Translational Medicine. 9 (401). doi:10.1126/scitranslmed.aao0978. ISSN   1946-6234. S2CID   44125138.
13. 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.
14. 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.
15. 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. Bibcode:2000BBRC..278..511L. doi:10.1006/bbrc.2000.3835. PMID   11095942.
16. 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

• Kang Q, Cao Y, Zolkiewska A (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.
• Loechel F, Gilpin BJ, Engvall E, Albrechtsen R, Wewer UM (1998). "Human ADAM 12 (meltrin alpha) is an active metalloprotease". J. Biol. Chem. 273 (27): 16993–7. doi: 10.1074/jbc.273.27.16993 . PMID   9642263.
• Howard L, Nelson KK, Maciewicz RA, Blobel CP (1999). "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. doi: 10.1074/jbc.274.44.31693 . PMID   10531379.
• Galliano MF, Huet C, Frygelius J, Polgren A, Wewer UM, Engvall E (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.
• 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 (2000). "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. doi:10.1083/jcb.149.5.1143. PMC   2174829 . PMID   10831617.
• Shi Z, Xu W, Loechel F, Wewer UM, Murphy LJ (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.
• Eto K, Puzon-McLaughlin W, Sheppard D, Sehara-Fujisawa A, Zhang XP, Takada Y (2001). "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. doi: 10.1074/jbc.M001953200 . PMID   10944520.
• Loechel F, Fox JW, Murphy G, Albrechtsen R, Wewer UM (2001). "ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3". Biochem. Biophys. Res. Commun. 278 (3): 511–5. Bibcode:2000BBRC..278..511L. doi:10.1006/bbrc.2000.3835. PMID   11095942.
• Suzuki A, Kadota N, Hara T, Nakagami Y, Izumi T, Takenawa T, Sabe H, Endo T (2000). "Meltrin alpha cytoplasmic domain interacts with SH3 domains of Src and Grb2 and is phosphorylated by v-Src". Oncogene. 19 (51): 5842–50. doi: 10.1038/sj.onc.1203986 . PMID   11127814.
• Kawaguchi N, Xu X, Tajima R, Kronqvist P, Sundberg C, Loechel F, Albrechtsen R, Wewer UM (2002). "ADAM 12 protease induces adipogenesis in transgenic mice". Am. J. Pathol. 160 (5): 1895–903. doi:10.1016/S0002-9440(10)61136-4. PMC   1850877 . PMID   12000741.
• Cao Y, Kang Q, Zhao Z, Zolkiewska A (2002). "Intracellular processing of metalloprotease disintegrin ADAM12". J. Biol. Chem. 277 (29): 26403–11. doi: 10.1074/jbc.M110814200 . PMID   12000744.
• Abram CL, Seals DF, Pass I, Salinsky D, Maurer L, Roth TM, Courtneidge SA (2003). "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. doi: 10.1074/jbc.M300267200 . PMID   12615925.
• Le Pabic H, Bonnier D, Wewer UM, Coutand A, Musso O, Baffet G, Clément B, Théret N (2003). "ADAM12 in human liver cancers: TGF-beta-regulated expression in stellate cells is associated with matrix remodeling". Hepatology. 37 (5): 1056–66. doi: 10.1053/jhep.2003.50205 . PMID   12717386. S2CID   32722392.
• Kawaguchi N, Sundberg C, Kveiborg M, Moghadaszadeh B, Asmar M, Dietrich N, Thodeti CK, Nielsen FC, Möller P, Mercurio AM, Albrechtsen R, Wewer UM (2004). "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. doi: 10.1242/jcs.00699 . PMID   12915587.
• Mori S, Tanaka M, Nanba D, Nishiwaki E, Ishiguro H, Higashiyama S, Matsuura N (2003). "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. doi: 10.1074/jbc.M306393200 . PMID   12952982.
• Laigaard J, Sørensen T, Fröhlich C, Pedersen BN, Christiansen M, Schiøtt K, Uldbjerg N, Albrechtsen R, Clausen HV, Ottesen B, Wewer UM (2004). "ADAM12: a novel first-trimester maternal serum marker for Down syndrome". Prenat. Diagn. 23 (13): 1086–91. doi:10.1002/pd.762. PMID   14691998. S2CID   32888570.

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 .