Login
Login

CCM2

{{Short description|Protein-coding gene in the species Homo sapiens}}

{{Infobox_gene}}

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.{{Cite journal

| last1 = Liquori | first1 = C. L.

| last2 = Berg | first2 = M. J.

| last3 = Siegel | first3 = A. M.

| last4 = Huang | first4 = E.

| last5 = Zawistowski | first5 = J. S.

| last6 = Stoffer | first6 = T. P.

| last7 = Verlaan | first7 = D.

| last8 = Balogun | first8 = F.

| last9 = Hughes | first9 = L.

| last10 = Leedom | first10 = T. P.

| last11 = Plummer | first11 = N. W.

| last12 = Cannella | first12 = M.

| last13 = Maglione | first13 = V.

| last14 = Squitieri | first14 = F.

| last15 = Johnson | first15 = E. W.

| last16 = Rouleau | first16 = G. A.

| last17 = Ptacek | first17 = L.

| last18 = Marchuk | first18 = D. A.

| title = Mutations in a Gene Encoding a Novel Protein Containing a Phosphotyrosine-Binding Domain Cause Type 2 Cerebral Cavernous Malformations

| doi = 10.1086/380314

| journal = The American Journal of Human Genetics

| volume = 73

| issue = 6

| pages = 1459–1464

| pmc = 1180409

| year = 2003

| pmid = 14624391

}} 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.{{cite journal | vauthors = 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 | title = Multilocus linkage identifies two new loci for a mendelian form of stroke, cerebral cavernous malformation, at 7p15-13 and 3q25.2-27 | journal = Hum Mol Genet | volume = 7 | issue = 12 | pages = 1851–8 |date=Dec 1998 | pmid = 9811928 | doi =10.1093/hmg/7.12.1851 | doi-access = free }}{{cite web | title = Entrez Gene: CCM2 cerebral cavernous malformation 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=83605}} The normal function of malcavernin is to act as a scaffold for a variety of signaling complexes including p38 MAP Kinase.{{Cite journal

| last1 = Uhlik | first1 = M. T.

| last2 = Abell | first2 = A. N.

| last3 = Johnson | first3 = N. L.

| last4 = Sun | first4 = W.

| last5 = Cuevas | first5 = B. D.

| last6 = Lobel-Rice | first6 = K. E.

| last7 = Horne | first7 = E. A.

| last8 = Dell'Acqua | first8 = M. L.

| last9 = Johnson | first9 = G. L.

| doi = 10.1038/ncb1071

| title = Rac–MEKK3–MKK3 scaffolding for p38 MAPK activation during hyperosmotic shock

| journal = Nature Cell Biology

| volume = 5

| issue = 12

| pages = 1104–1110

| year = 2003

| pmid = 14634666

| s2cid = 1897773

}} This protein is also involved in regulating the cellular localization of the KRIT1 protein{{Cite journal

| last1 = Zawistowski | first1 = J. S.

| last2 = Stalheim | first2 = L.

| last3 = Uhlik | first3 = M. T.

| last4 = Abell | first4 = A. N.

| last5 = Ancrile | first5 = B. B.

| last6 = Johnson | first6 = G. L.

| last7 = Marchuk | first7 = D. A.

| doi = 10.1093/hmg/ddi256

| title = CCM1 and CCM2 protein interactions in cell signaling: Implications for cerebral cavernous malformations pathogenesis

| journal = Human Molecular Genetics

| volume = 14

| issue = 17

| pages = 2521–2531

| year = 2005

| pmid = 16037064

| doi-access = free

}} and acts with the Rho Kinase signaling pathway to maintain normal blood vessel structure.{{Cite journal

| last1 = Borikova | first1 = A. L.

| last2 = Dibble | first2 = C. F.

| last3 = Sciaky | first3 = N.

| last4 = Welch | first4 = C. M.

| last5 = Abell | first5 = A. N.

| last6 = Bencharit | first6 = S.

| last7 = Johnson | first7 = G. L.

| title = Rho Kinase Inhibition Rescues the Endothelial Cell Cerebral Cavernous Malformation Phenotype

| journal = The Journal of Biological Chemistry

| volume = 285

| issue = 16

| pages = 11760–11764

| year = 2010

| pmid = 20181950

| pmc = 2852911

| doi = 10.1074/jbc.C109.097220

| doi-access = free

}}{{Cite journal

| last1 = Whitehead | first1 = K. J.

| last2 = Chan | first2 = A. C.

| last3 = Navankasattusas | first3 = S.

| last4 = Koh | first4 = W.

| last5 = London | first5 = N. R.

| last6 = Ling | first6 = J.

| last7 = Mayo | first7 = A. H.

| last8 = Drakos | first8 = S. G.

| last9 = Jones | first9 = D. A.

| last10 = Zhu | first10 = G. E.

| last11 = Marchuk | first11 = D. Y.

| last12 = Davis | first12 = G. E.

| last13 = Li | first13 = D. Y.

| title = The Cerebral Cavernous Malformation signaling pathway promotes vascular integrity via Rho GTPases

| doi = 10.1038/nm.1911

| journal = Nature Medicine

| volume = 15

| issue = 2

| pages = 177–184

| pmc = 2767168

| year = 2009

| pmid = 19151728

}}

References

{{reflist}}

External links

  • {{UCSC gene info|CCM2}}
  • {{UCSC gene info|OSM}}

Further reading

{{refbegin | 2}}

  • {{cite journal | vauthors=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |bibcode=2002PNAS...9916899M |display-authors=etal|doi-access=free }}
  • {{cite journal | vauthors=Scherer SW, Cheung J, MacDonald JR |title=Human Chromosome 7: DNA Sequence and Biology |journal=Science |volume=300 |issue= 5620 |pages= 767–72 |year= 2003 |pmid= 12690205 |doi= 10.1126/science.1083423 | pmc=2882961 |bibcode=2003Sci...300..767S |display-authors=etal}}
  • {{cite journal | vauthors=Dupré N, Verlaan DJ, Hand CK |title=Linkage to the CCM2 locus and genetic heterogeneity in familial cerebral cavernous malformation |journal=The Canadian Journal of Neurological Sciences |volume=30 |issue= 2 |pages= 122–8 |year= 2003 |pmid= 12774951 |doi= 10.1017/S0317167100053385|display-authors=etal|doi-access=free }}
  • {{cite journal | vauthors=Liquori CL, Berg MJ, Siegel AM |title=Mutations in a Gene Encoding a Novel Protein Containing a Phosphotyrosine-Binding Domain Cause Type 2 Cerebral Cavernous Malformations |journal=Am. J. Hum. Genet. |volume=73 |issue= 6 |pages= 1459–64 |year= 2004 |pmid= 14624391 |doi=10.1086/380314 | pmc=1180409 |display-authors=etal}}
  • {{cite journal | vauthors=Ota T, Suzuki Y, Nishikawa T |title=Complete sequencing and characterization of 21,243 full-length human cDNAs |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 |display-authors=etal|doi-access=free }}
  • {{cite journal | vauthors=Denier C, Goutagny S, Labauge P |title=Mutations within the MGC4607 Gene Cause Cerebral Cavernous Malformations |journal=Am. J. Hum. Genet. |volume=74 |issue= 2 |pages= 326–37 |year= 2004 |pmid= 14740320 |doi=10.1086/381718 | pmc=1181930 |display-authors=etal}}
  • {{cite journal | vauthors=Gerhard DS, Wagner L, Feingold EA |title=The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 |display-authors=etal}}
  • {{cite journal | vauthors=Wan D, Gong Y, Qin W |title=Large-scale cDNA transfection screening for genes related to cancer development and progression |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 44 |pages= 15724–9 |year= 2004 |pmid= 15498874 |doi= 10.1073/pnas.0404089101 | pmc=524842 |bibcode=2004PNAS..10115724W |display-authors=etal|doi-access=free }}
  • {{cite journal | vauthors=Zawistowski JS, Stalheim L, Uhlik MT |title=CCM1 and CCM2 protein interactions in cell signaling: implications for cerebral cavernous malformations pathogenesis |journal=Hum. Mol. Genet. |volume=14 |issue= 17 |pages= 2521–31 |year= 2005 |pmid= 16037064 |doi= 10.1093/hmg/ddi256 |display-authors=etal|doi-access=free }}
  • {{cite journal | vauthors=Guclu B, Ozturk AK, Pricola KL |title=Cerebral venous malformations have distinct genetic origin from cerebral cavernous malformations |journal=Stroke |volume=36 |issue= 11 |pages= 2479–80 |year= 2006 |pmid= 16239636 |doi= 10.1161/01.STR.0000183616.99139.d3 |display-authors=etal|doi-access=free |hdl=11424/244289 |hdl-access=free }}
  • {{cite journal | vauthors=Seker A, Pricola KL, Guclu B |title=CCM2 expression parallels that of CCM1 |journal=Stroke |volume=37 |issue= 2 |pages= 518–23 |year= 2006 |pmid= 16373645 |doi= 10.1161/01.STR.0000198835.49387.25 |display-authors=etal|doi-access=free }}
  • {{cite journal | vauthors=Labauge P, Krivosic V, Denier C |title=Frequency of retinal cavernomas in 60 patients with familial cerebral cavernomas: a clinical and genetic study |journal=Arch. Ophthalmol. |volume=124 |issue= 6 |pages= 885–6 |year= 2006 |pmid= 16769843 |doi= 10.1001/archopht.124.6.885 |display-authors=etal|doi-access=free }}
  • {{cite journal | vauthors=Liquori CL, Berg MJ, Squitieri F |title=Deletions in CCM2 Are a Common Cause of Cerebral Cavernous Malformations |journal=Am. J. Hum. Genet. |volume=80 |issue= 1 |pages= 69–75 |year= 2007 |pmid= 17160895 |doi= 10.1086/510439 | pmc=1785317 |display-authors=etal}}
  • {{cite journal | vauthors=Zhang J, Rigamonti D, Dietz HC, Clatterbuck RE |title=Interaction between krit1 and malcavernin: implications for the pathogenesis of cerebral cavernous malformations |journal=Neurosurgery |volume=60 |issue= 2 |pages= 353–9; discussion 359 |year= 2007 |pmid= 17290187 |doi= 10.1227/01.NEU.0000249268.11074.83 |s2cid=42858113 }}
  • {{cite journal | vauthors=Gianfrancesco F, Cannella M, Martino T |title=Highly variable penetrance in subjects affected with cavernous cerebral angiomas (CCM) carrying novel CCM1 and CCM2 mutations |journal=Am. J. Med. Genet. B Neuropsychiatr. Genet. |volume=144 |issue= 5 |pages= 691–5 |year= 2007 |pmid= 17440989 |doi= 10.1002/ajmg.b.30381 |s2cid=25509373 |display-authors=etal}}

{{refend}}

{{gene-7-stub}}