CCM2

CCM2
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	4FQN, 4TVQ, 4WJ7, 4Y5O, 4YKC, 4YKD, 4YL6
Identifiers
Aliases	CCM2, C7orf22, OSM, PP10187, CCM2 scaffolding protein, CCM2 scaffold protein
External IDs	OMIM: 607929 MGI: 2384924 HomoloGene: 12868 GeneCards: CCM2
Gene location (Human)
Chr.	Chromosome 7 (human)
End	45,076,469 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	6,546,744 bp
RNA expression pattern
	Top expressed in
	putamen; ; nucleus accumbens; ; cingulate gyrus; ; caudate nucleus; ; prefrontal cortex; ; Brodmann area 9; ; amygdala; ; hypothalamus; ; blood; ; right lobe of liver;
	Top expressed in
	olfactory tubercle; ; medial geniculate nucleus; ; barrel cortex; ; thymus; ; otic placode; ; fossa; ; medial dorsal nucleus; ; Paneth cell; ; lateral geniculate nucleus; ; internal carotid artery;
	More reference expression data
	n/a
Gene ontology
Molecular function	protein binding;
Cellular component	cytoplasm; mitochondrion; protein-containing complex;
Biological process	vasculogenesis; integrin-mediated signaling pathway; inner ear development; endothelial tube morphogenesis; multicellular organism development; heart development; cell-cell junction organization; blood vessel endothelial cell differentiation; blood vessel development; vasculature development; in utero embryonic development; stress-activated MAPK cascade; endothelial cell development; venous blood vessel morphogenesis; multicellular organism growth; pericardium development;
	Sources:Amigo / QuickGO
Orthologs
	83605
	216527
	ENSG00000136280
	ENSMUSG00000000378
	Q9BSQ5
	Q8K2Y9
NM_001029835; NM_001167934; NM_001167935; NM_031443; NM_001363458;
	NM_001363459
	NM_001190343; NM_001190344; NM_146014
NP_001025006; NP_001161406; NP_001161407; NP_113631; NP_001350387;
	NP_001350388
	NP_001177272; NP_001177273; NP_666126
	Wikidata
View/Edit Human	View/Edit Mouse

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.^[5] 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.^[6]^[7] The normal function of malcavernin is to act as a scaffold for a variety of signaling complexes including p38 MAP Kinase.^[8] This protein is also involved in regulating the cellular localization of the KRIT1 protein^[9] and acts with the Rho Kinase signaling pathway to maintain normal blood vessel structure.^[10]^[11]

Advocacy

For more information and support for Cerebral Cavernous Malformations Patients and their families, please visit the Angioma Alliance website: www.angioma.org

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000136280 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000000378 - 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.
↑ 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. S2CID 1897773.
↑ 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.

External links

Human CCM2 genome location and CCM2 gene details page in the UCSC Genome Browser.
Human OSM genome location and OSM gene details page in the UCSC Genome Browser.

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. Bibcode:2002PNAS...9916899M. 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. Bibcode:2003Sci...300..767S. 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. 30 (2): 122–8. doi:10.1017/S0317167100053385. 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. Bibcode:2004PNAS..10115724W. 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. S2CID 42858113.
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. S2CID 25509373.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000136280 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000000378 - 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] 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.

[pmid9811928-6] 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-7] "Entrez Gene: CCM2 cerebral cavernous malformation 2".

[8] 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. S2CID 1897773.

[9] 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.

[10] 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.

[11] 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.

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Protein

Advocacy

References

External links

Further reading