ADAM9 explained

Disintegrin and metalloproteinase domain-containing protein 9 is an enzyme that in humans is encoded by the ADAM9 gene.^{[1] [2]}

Function

This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) 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. The protein encoded by this gene interacts with SH3 domain-containing proteins, binds mitotic arrest deficient 2 beta protein, and is also involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor. Two alternative splice variants have been identified, encoding distinct isoforms.^[2]

Interactions

ADAM9 has been shown to interact with:

• MAD2L2,^[3]
• SH3GL2, and
• SNX9^[4]

Further reading

• Mazzocca A, Coppari R, De Franco R, Cho JY, Libermann TA, Pinzani M, Toker A . A secreted form of ADAM9 promotes carcinoma invasion through tumor-stromal interactions . Cancer Res. . 65 . 11 . 4728–38 . June 2005. 15930291 . 10.1158/0008-5472.CAN-04-4449 . free .
• Nomura N, Miyajima N, Sazuka T . Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1. . DNA Res. . 1 . 1 . 27–35 . 1995 . 7584026 . 10.1093/dnares/1.1.27 . etal. free .
• Nomura N, Miyajima N, Sazuka T . Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1 (supplement). . DNA Res. . 1 . 1 . 47–56 . 1995 . 7584028 . 10.1093/dnares/1.1.47 . etal. free .
• McKie N, Dallas DJ, Edwards T . Cloning of a novel membrane-linked metalloproteinase from human myeloma cells. . Biochem. J. . 318 . 2. 459–62 . 1996 . 8809033 . 10.1042/bj3180459. 1217643 . etal.
• McKie N, Edwards T, Dallas DJ . Expression of members of a novel membrane linked metalloproteinase family (ADAM) in human articular chondrocytes. . Biochem. Biophys. Res. Commun. . 230 . 2 . 335–9 . 1997 . 9016778 . 10.1006/bbrc.1996.5957 . etal.
• Izumi Y, Hirata M, Hasuwa H . A metalloprotease-disintegrin, MDC9/meltrin-gamma/ADAM9 and PKCdelta are involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor. . EMBO J. . 17 . 24 . 7260–72 . 1999 . 9857183 . 10.1093/emboj/17.24.7260 . 1171072 . etal.
• Roghani M, Becherer JD, Moss ML . Metalloprotease-disintegrin MDC9: intracellular maturation and catalytic activity. . J. Biol. Chem. . 274 . 6 . 3531–40 . 1999 . 9920899 . 10.1074/jbc.274.6.3531 . etal. free.
• Nelson KK, Schlöndorff J, Blobel CP . Evidence for an interaction of the metalloprotease-disintegrin tumour necrosis factor alpha convertase (TACE) with mitotic arrest deficient 2 (MAD2), and of the metalloprotease-disintegrin MDC9 with a novel MAD2-related protein, MAD2beta. . Biochem. J. . 343 . 3. 673–80 . 2000 . 10527948 . 10.1042/0264-6021:3430673. 1220601 .
• Howard L, Nelson KK, Maciewicz RA, Blobel CP . 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 . 10531379 . 10.1074/jbc.274.44.31693 . free .
• Zhou M, Graham R, Russell G, Croucher PI . MDC-9 (ADAM-9/Meltrin gamma) functions as an adhesion molecule by binding the alpha(v)beta(5) integrin. . Biochem. Biophys. Res. Commun. . 280 . 2 . 574–80 . 2001 . 11162558 . 10.1006/bbrc.2000.4155 .
• Namba K, Nishio M, Mori K . Involvement of ADAM9 in multinucleated giant cell formation of blood monocytes. . Cell. Immunol. . 213 . 2 . 104–13 . 2002 . 11831872 . 10.1006/cimm.2001.1873 . etal.
• Eto K, Huet C, Tarui T . Functional classification of ADAMs based on a conserved motif for binding to integrin alpha 9beta 1: implications for sperm-egg binding and other cell interactions. . J. Biol. Chem. . 277 . 20 . 17804–10 . 2002 . 11882657 . 10.1074/jbc.M200086200 . etal. free .
• Lim JM, Lee JH, Wee WR, Joo CK . Downregulated expression of ADAM9 in anterior polar cataracts. . Journal of Cataract and Refractive Surgery . 28 . 4 . 697–702 . 2002 . 11955914 . 10.1016/S0886-3350(01)01236-6 . 21982654 .
• Hotoda N, Koike H, Sasagawa N, Ishiura S . A secreted form of human ADAM9 has an alpha-secretase activity for APP. . Biochem. Biophys. Res. Commun. . 293 . 2 . 800–5 . 2002 . 12054541 . 10.1016/S0006-291X(02)00302-9 .
• Amour A, Knight CG, English WR . The enzymatic activity of ADAM8 and ADAM9 is not regulated by TIMPs. . FEBS Lett. . 524 . 1–3 . 154–8 . 2002 . 12135759 . 10.1016/S0014-5793(02)03047-8 . 37423323 . etal. free .
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Mohan S, Thompson GR, Amaar YG . ADAM-9 is an insulin-like growth factor binding protein-5 protease produced and secreted by human osteoblasts . Biochemistry . 41 . 51 . 15394–403 . 2003 . 12484779 . 10.1021/bi026458q . etal.
• Asai M, Hattori C, Szabó B . Putative function of ADAM9, ADAM10, and ADAM17 as APP alpha-secretase . Biochem. Biophys. Res. Commun. . 301 . 1 . 231–5 . 2003 . 12535668 . 10.1016/S0006-291X(02)02999-6 . etal.
• O'Shea C, McKie N, Buggy Y . Expression of ADAM-9 mRNA and protein in human breast cancer . Int. J. Cancer . 105 . 6 . 754–61 . 2003 . 12767059 . 10.1002/ijc.11161 . 19284959 . etal. free .
• Grützmann R, Lüttges J, Sipos B . ADAM9 expression in pancreatic cancer is associated with tumour type and is a prognostic factor in ductal adenocarcinoma . Br. J. Cancer . 90 . 5 . 1053–8 . 2004 . 14997207 . 10.1038/sj.bjc.6601645 . 2409625 . etal.

External links

• ADAM9 on the Atlas of Genetics and Oncology

Notes and References

1. Weskamp G, Kratzschmar J, Reid MS, Blobel CP . MDC9, a widely expressed cellular disintegrin containing cytoplasmic SH3 ligand domains . J Cell Biol . 132 . 4 . 717–26 . Jul 1996. 8647900 . 2199860 . 10.1083/jcb.132.4.717 .
2. Web site: Entrez Gene: ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma).
3. Nov 1999 . Nelson KK, Schlöndorff J, Blobel CP . Evidence for an interaction of the metalloprotease-disintegrin tumour necrosis factor alpha convertase (TACE) with mitotic arrest deficient 2 (MAD2), and of the metalloprotease-disintegrin MDC9 with a novel MAD2-related protein, MAD2beta . Biochem. J. . 343 . Pt 3. 673–80 . 10527948 . 1220601 . 10.1042/0264-6021:3430673.
4. Oct 1999 . Howard L, Nelson KK, Maciewicz RA, Blobel CP . 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 . 10531379 . 10.1074/jbc.274.44.31693. free .