CCM2
The CCM2 gene contains 10 coding exons and an alternatively spliced exon 1B. This gene is located on chromosome 7p13 and loss of function mutations on CCM2 lead to the onset of Cerebral Cavernous Malformations (CCM) illness.[1] Cerebral cavernous malformations (CCMs) are vascular malformations in the brain and spinal cord made of dilated capillary vessels.
Protein
Malcavernin is a protein that in humans is encoded by the CCM2 gene.[2][3] The normal function of malcavernin is to act as a scaffold for a variety of signaling complexes including p38 MAP Kinase.[4] This protein is also involved in regulating the cellular localization of the KRIT1 protein[5] and acts with the Rho Kinase signaling pathway to maintain normal blood vessel structure.[6][7]
Advocacy
For more information and support for Cerebral Cavernous Malformations Patients and their families, please visit the Angioma Alliance website: www.angioma.org
References
- ↑ Liquori, C. L.; Berg, M. J.; Siegel, A. M.; Huang, E.; Zawistowski, J. S.; Stoffer, T. P.; Verlaan, D.; Balogun, F.; Hughes, L.; Leedom, T. P.; Plummer, N. W.; Cannella, M.; Maglione, V.; Squitieri, F.; Johnson, E. W.; Rouleau, G. A.; Ptacek, L.; Marchuk, D. A. (2003). "Mutations in a Gene Encoding a Novel Protein Containing a Phosphotyrosine-Binding Domain Cause Type 2 Cerebral Cavernous Malformations". The American Journal of Human Genetics 73 (6): 1459–1464. doi:10.1086/380314. PMC 1180409. PMID 14624391.
- ↑ Craig HD, Gunel M, Cepeda O, Johnson EW, Ptacek L, Steinberg GK, Ogilvy CS, Berg MJ, Crawford SC, Scott RM, Steichen-Gersdorf E, Sabroe R, Kennedy CT, Mettler G, Beis MJ, Fryer A, Awad IA, Lifton RP (Dec 1998). "Multilocus linkage identifies two new loci for a mendelian form of stroke, cerebral cavernous malformation, at 7p15-13 and 3q25.2-27". Hum Mol Genet 7 (12): 1851–8. doi:10.1093/hmg/7.12.1851. PMID 9811928.
- ↑ "Entrez Gene: CCM2 cerebral cavernous malformation 2".
- ↑ Uhlik, M. T.; Abell, A. N.; Johnson, N. L.; Sun, W.; Cuevas, B. D.; Lobel-Rice, K. E.; Horne, E. A.; Dell'Acqua, M. L.; Johnson, G. L. (2003). "Rac–MEKK3–MKK3 scaffolding for p38 MAPK activation during hyperosmotic shock". Nature Cell Biology 5 (12): 1104–1110. doi:10.1038/ncb1071. PMID 14634666.
- ↑ Zawistowski, J. S.; Stalheim, L.; Uhlik, M. T.; Abell, A. N.; Ancrile, B. B.; Johnson, G. L.; Marchuk, D. A. (2005). "CCM1 and CCM2 protein interactions in cell signaling: Implications for cerebral cavernous malformations pathogenesis". Human Molecular Genetics 14 (17): 2521–2531. doi:10.1093/hmg/ddi256. PMID 16037064.
- ↑ Borikova, A. L.; Dibble, C. F.; Sciaky, N.; Welch, C. M.; Abell, A. N.; Bencharit, S.; Johnson, G. L. (2010). "Rho Kinase Inhibition Rescues the Endothelial Cell Cerebral Cavernous Malformation Phenotype". The Journal of Biological Chemistry 285 (16): 11760–11764. doi:10.1074/jbc.C109.097220. PMC 2852911. PMID 20181950.
- ↑ Whitehead, K. J.; Chan, A. C.; Navankasattusas, S.; Koh, W.; London, N. R.; Ling, J.; Mayo, A. H.; Drakos, S. G.; Jones, D. A.; Zhu, G. E.; Marchuk, D. Y.; Davis, G. E.; Li, D. Y. (2009). "The Cerebral Cavernous Malformation signaling pathway promotes vascular integrity via Rho GTPases". Nature Medicine 15 (2): 177–184. doi:10.1038/nm.1911. PMC 2767168. PMID 19151728.
Further reading
- Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "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. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Scherer SW, Cheung J, MacDonald JR; et al. (2003). "Human Chromosome 7: DNA Sequence and Biology". Science 300 (5620): 767–72. doi:10.1126/science.1083423. PMC 2882961. PMID 12690205.
- Dupré N, Verlaan DJ, Hand CK; et al. (2003). "Linkage to the CCM2 locus and genetic heterogeneity in familial cerebral cavernous malformation". The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 30 (2): 122–8. PMID 12774951.
- Liquori CL, Berg MJ, Siegel AM; et al. (2004). "Mutations in a Gene Encoding a Novel Protein Containing a Phosphotyrosine-Binding Domain Cause Type 2 Cerebral Cavernous Malformations". Am. J. Hum. Genet. 73 (6): 1459–64. doi:10.1086/380314. PMC 1180409. PMID 14624391.
- Ota T, Suzuki Y, Nishikawa T; et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Denier C, Goutagny S, Labauge P; et al. (2004). "Mutations within the MGC4607 Gene Cause Cerebral Cavernous Malformations". Am. J. Hum. Genet. 74 (2): 326–37. doi:10.1086/381718. PMC 1181930. PMID 14740320.
- Gerhard DS, Wagner L, Feingold EA; et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Wan D, Gong Y, Qin W; et al. (2004). "Large-scale cDNA transfection screening for genes related to cancer development and progression". Proc. Natl. Acad. Sci. U.S.A. 101 (44): 15724–9. doi:10.1073/pnas.0404089101. PMC 524842. PMID 15498874.
- Zawistowski JS, Stalheim L, Uhlik MT; et al. (2005). "CCM1 and CCM2 protein interactions in cell signaling: implications for cerebral cavernous malformations pathogenesis". Hum. Mol. Genet. 14 (17): 2521–31. doi:10.1093/hmg/ddi256. PMID 16037064.
- Guclu B, Ozturk AK, Pricola KL; et al. (2006). "Cerebral venous malformations have distinct genetic origin from cerebral cavernous malformations". Stroke 36 (11): 2479–80. doi:10.1161/01.STR.0000183616.99139.d3. PMID 16239636.
- Seker A, Pricola KL, Guclu B; et al. (2006). "CCM2 expression parallels that of CCM1". Stroke 37 (2): 518–23. doi:10.1161/01.STR.0000198835.49387.25. PMID 16373645.
- Labauge P, Krivosic V, Denier C; et al. (2006). "Frequency of retinal cavernomas in 60 patients with familial cerebral cavernomas: a clinical and genetic study". Arch. Ophthalmol. 124 (6): 885–6. doi:10.1001/archopht.124.6.885. PMID 16769843.
- Liquori CL, Berg MJ, Squitieri F; et al. (2007). "Deletions in CCM2 Are a Common Cause of Cerebral Cavernous Malformations". Am. J. Hum. Genet. 80 (1): 69–75. doi:10.1086/510439. PMC 1785317. PMID 17160895.
- Zhang J, Rigamonti D, Dietz HC, Clatterbuck RE (2007). "Interaction between krit1 and malcavernin: implications for the pathogenesis of cerebral cavernous malformations". Neurosurgery 60 (2): 353–9; discussion 359. doi:10.1227/01.NEU.0000249268.11074.83. PMID 17290187.
- Gianfrancesco F, Cannella M, Martino T; et al. (2007). "Highly variable penetrance in subjects affected with cavernous cerebral angiomas (CCM) carrying novel CCM1 and CCM2 mutations". Am. J. Med. Genet. B Neuropsychiatr. Genet. 144 (5): 691–5. doi:10.1002/ajmg.b.30381. PMID 17440989.
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