Human protein-coding gene
For the television show, see
Adam-12 .
Disintegrin and metalloproteinase domain-containing protein 12 (previously Meltrin) is anenzyme that in humans is encoded by theADAM12 gene .[ 5] [ 6] [ 7]
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 venomdisintegrins , 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 [ edit ] ADAM 12, ametalloprotease that binds insulin growth factor binding protein-3 (IGFBP-3), appears to be an effective earlyDown 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 andPAPP-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. Whennuchal 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 ofpathology in variouscancers ,hypertension ,liver fibrogenesis, andasthma .[ 10] lung epithelium in response toTNF-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]
ADAM12 has been shown tointeract with:
^a b c GRCh38: Ensembl release 89: ENSG00000148848 –Ensembl , May 2017^a b c GRCm38: Ensembl release 89: ENSMUSG00000054555 –Ensembl , May 2017^ "Human PubMed Reference:" .National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" .National Center for Biotechnology Information, U.S. National Library of Medicine .^ 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 . ^ 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 . ^ 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 . ^ "Entrez Gene: ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha)" .^ Danforth's Obstetrics and Gynecology, 10th Edition; Copyright ©2008 Lippincott Williams & Wilkins; Chapter 7: Prenatal Diagnosis, Page 113 ^ 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 . ^ 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 . ^ 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 . ^ 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 . ^ 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 . ^ 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 . ^ 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 . 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 .
Activity Regulation Classification Kinetics Types
