Property Summary

NCBI Gene PubMed Count 55
PubMed Score 65.57
PubTator Score 72.37

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (6)

Protein-protein Interaction (6)

Gene RIF (40)

PMID Text
26356566 Studies suggest that the 3 proteins of the Cerebral Cavernous Malformations (CCM) complex KRIT1/CCM1, CCM2/malcavernin and CCM3/PDCD10 not only require one another for reciprocal stabilization, but also act as a platform for signal transduction.
25869611 a new mutation in MGC4607/CCM2 was identified in several family members with spinal and cutaneous angiomas.
25825518 both CCM2 and CCM3 are required for normal endothelial cell network formation.
25525273 Data find that several disease-associated missense mutations in CCM2 have the potential to interrupt the KRIT1-CCM2 interaction by destabilizing the CCM2 PTB domain and that a KRIT1 mutation also disrupts this interaction
24643410 Cerebral cavernous malformation(CCM)s develop because of loss of heart of glass (HEG)-independent CCM2 signaling in murine transgenic endothelium of central nervous system after birth.
24466005 Prevalence, frequency and characterization of CCM1, CCM2 and CCM3 variants in cerebral cavernous malformation Spanish patients.
24058906 The identification of other four new mutations in 40 sporadic patients with either single or multiple cerebral cavernous malformations, is reported.
24007869 DNA sequencing and deletion/duplication testing of the CCM1, CCM2, and CCM3 genes in the proband revealed a CCM1 c.601CNG mutation.
23485406 CCM2 mutations are associated with cerebral cavernous malformation in some Japanese patients.
23266514 structural characterization of CCM2
23000020 A previously undescribed deletion mutation in CCM2 gene exon 5 is described in an Italian family with multiple cerebral cavernous malformations and epilepsy.
22782892 Down-modulation of STK25, but not STK24, rescued medulloblastoma cells from NGF-induced TrkA-dependent cell death, suggesting that STK25 is part of the death-signaling pathway initiated by TrkA and CCM2.
22684070 Diffraction data were collected from native and selenomethionine-substituted crystals of CCM2-Ct to resolutions of 2.9 and 2.7 A, respectively
22415356 Here we describe the molecular characterization of an Italian child, a symptomatic patient, affected by multiple cerebral cavernous malformations, without a family history of the disease and harbouring a new MGC4607 gene mutation.
22378217 The possible association of CCM2 polymorphisms with sporadic cerebral cavernous malformation, was investigated.
21569831 This study shows for the first time that CCM2 is present in the developing human neocortex.
21543988 Data suggest that the two base pair change in CCM2 has the potential to simplify genetic testing for cerebral cavernous malformation in the Ashkenazi Jewish population.
21029238 Among familial cases of Cerebral cavernous malformations 67% had a mutation in CCM1, 5.5% in CCM2, and 5.5% in CCM3
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20419355 Genetic variations could interfere with the proper CCM1/CCM2/CCM3 protein complex thus explaining the observed clinical variability in cerebral cavernous malformations in a large family.
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
20308363 The KRIT1-CCM2 interaction regulates endothelial junctional stability and vascular barrier function by suppressing activation of the RhoA/ROCK signaling pathway. This pathway is dysregulated in human cerebral cavernous malformation endothelium.
19913121 Observational study of gene-disease association. (HuGE Navigator)
19755102 CCM2 is a key mediator of TrkA-dependent cell death in pediatric neuroblastic tumors
19688696 CCM2 protein contributes to vasculogenesis and angiogenesis in human placenta.
19475721 Aberrant splicing due to a silent nucleotide change in CCM2 gene in a family with cerebral cavernous malformation
19318350 a molecular mechanism for the pathogenesis of cerebral cavernous malformations (CCM) resulting from loss of CCM2-mediated localization of Smurf1, which controls RhoA degradation required for maintenance of normal endothelial cell physiology.
19199464 Methods Multiplex Ligation-dependent Probe Amplification analysis integrates the consecutive sequence analysis of the 3 genes (Krit1/CCM1, MGC4607/CCM2, and PDCD10/CCM3) known to be responsible for cerebral cavernous malformation lesions.
19151728 CCM2 regulates endothelial cytoskeletal architecture, cell-to-cell interactions and lumen formation. Heterozygosity at Ccm2, a genotype equivalent to that in human CCM, results in impaired endothelial barrier function
19088124 Complete localized loss of either CCM1, CCM2 or CCM3 protein expression depend on the inherited mutation in cerebral cavernous malformations.
19088123 Biallelic germline and somatic mutations were identified in CCM1, CCM2 or PDCD10 from all forms of inherited cerebral cavernous malformations.
18300272 data are in agreement with a loss-of-function mechanism for CCM mutations, uncover an N-terminal CCM2 domain required for CCM1 binding, and demonstrate full-length CCM2 as the essential core protein in the CCM1/CCM2/CCM3 complex
17657516 CCM3 (PDCD10) coprecipitates and colocalizes with CCM2. CCM3 directly binds to serine/threonine kinase 25 (STK25, YSK1, SOK1) and the phosphatase domain of Fas-associated phosphatase-1 (FAP-1, PTPN13, PTP-Bas, PTP-BL).
17440989 In a CCM2 affected family, we report a novel causative mutation, (54_55delAC) in exon 2 of the MGC4607 gene, that produces a truncated protein containing only 22 amino acids
17290187 Through its NPXY motifs, Krit1 interacts with malcavernin and may shuttle it through the nucleus via its nuclear localization signal and nuclear export signals, thereby regulating its cellular function.
17160895 The prevalence of CCM2 is much higher than previously predicted, nearly equal to CCM1, and that large genomic deletions in the CCM2 gene represent a major component of this disease.
16769843 Five percent of patients with familial cerebral cavernomas have retinal cavernomas. These lesions are clinically asymptomatic. They can be associated with any of the 3 cerebral cavernous malformation genes.
16373645 CCM1 and CCM2 have similar expression patterns during development and are involved in the same pathway important for central nervous system vascular development
16239636 KRIT1, Malcavernin, and PDCD10 are differentially expressed in cerebral venous malformations and cerebral cavernous malformations
14624391 MGC4607 encodes a protein with a phosphotyrosine-binding domain that may be part of the complex pathway of integrin signaling that, when perturbed, causes abnormal vascular morphogenesis in the brain, leading to CCM formation.

AA Sequence

MEEEGKKGKKPGIVSPFKRVFLKGEKSRDKKAHEKVTERRPLHTVVLSLPERVEPDRLLSDYIEKEVKYL      1 - 70
GQLTSIPGYLNPSSRTEILHFIDNAKRAHQLPGHLTQEHDAVLSLSAYNVKLAWRDGEDIILRVPIHDIA     71 - 140
AVSYVRDDAAHLVVLKTAQDPGISPSQSLCAESSRGLSAGSLSESAVGPVEACCLVILAAESKVAAEELC    141 - 210
CLLGQVFQVVYTESTIDFLDRAIFDGASTPTHHLSLHSDDSSTKVDIKETYEVEASTFCFPESVDVGGAS    211 - 280
PHSKTISESELSASATELLQDYMLTLRTKLSSQEIQQFAALLHEYRNGASIHEFCINLRQLYGDSRKFLL    281 - 350
LGLRPFIPEKDSQHFENFLETIGVKDGRGIITDSFGRHRRALSTTSSSTTNGNRATGSSDDRSAPSEGDE    351 - 420
WDRMISDISSDIEALGCSMDQDSA                                                  421 - 444
//

Text Mined References (57)

PMID Year Title
26356566 2015 The cerebral cavernous malformations proteins.
25869611 2015 A Novel MGC4607/CCM2 Gene Mutation Associated with Cerebral Spinal and Cutaneous Cavernous Angiomas.
25825518 2015 CCM2-CCM3 interaction stabilizes their protein expression and permits endothelial network formation.
25814554 2015 Phospho-tyrosine dependent protein-protein interaction network.
25525273 2015 Structural basis for the disruption of the cerebral cavernous malformations 2 (CCM2) interaction with Krev interaction trapped 1 (KRIT1) by disease-associated mutations.
24643410 2014 Cerebral cavernous malformations arise independent of the heart of glass receptor.
24466005 2014 Mutation prevalence of cerebral cavernous malformation genes in Spanish patients.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24058906 2013 Sporadic cerebral cavernous malformations: report of further mutations of CCM genes in 40 Italian patients.
24007869 2013 Identification of a c.601C>G mutation in the CCM1 gene in a kindred with multiple skin, spinal and cerebral cavernous malformations.
23485406 2013 Genomic causes of multiple cerebral cavernous malformations in a Japanese population.
23266514 2013 Structural studies of cerebral cavernous malformations 2 (CCM2) reveal a folded helical domain at its C-terminus.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23000020 2013 Identification of a novel CCM2 gene mutation in an Italian family with multiple cerebral cavernous malformations and epilepsy: a causative mutation?
22782892 2012 STK25 protein mediates TrkA and CCM2 protein-dependent death in pediatric tumor cells of neural origin.
22684070 2012 Crystallization and preliminary X-ray analysis of the C-terminal domain of CCM2, part of a novel adaptor protein involved in cerebral cavernous malformations.
22415356 2012 De novo MGC4607 gene heterozygous missense variants in a child with multiple cerebral cavernous malformations.
22378217 2012 CCM2 gene polymorphisms in Italian sporadic patients with cerebral cavernous malformation: a case-control study.
21569831 2011 CCM2 expression during prenatal development and adult human neocortex.
21543988 2011 A founder mutation in the Ashkenazi Jewish population affecting messenger RNA splicing of the CCM2 gene causes cerebral cavernous malformations.
21029238 2011 Mutation analysis of CCM1, CCM2 and CCM3 genes in a cohort of Italian patients with cerebral cavernous malformation.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20489202 2010 Crystal structure of CCM3, a cerebral cavernous malformation protein critical for vascular integrity.
20419355 2010 Genetic variations within KRIT1/CCM1, MGC4607/CCM2 and PDCD10/CCM3 in a large Italian family harbouring a Krit1/CCM1 mutation.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20308363 2010 Cerebral cavernous malformations proteins inhibit Rho kinase to stabilize vascular integrity.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19755102 2009 CCM2 mediates death signaling by the TrkA receptor tyrosine kinase.
19688696 2009 CCM2 and CCM3 proteins contribute to vasculogenesis and angiogenesis in human placenta.
19475721 2009 Aberrant splicing due to a silent nucleotide change in CCM2 gene in a family with cerebral cavernous malformation.
19318350 2009 Cerebral cavernous malformation 2 protein promotes smad ubiquitin regulatory factor 1-mediated RhoA degradation in endothelial cells.
19199464 2009 Molecular screening test in familial forms of cerebral cavernous malformation: the impact of the Multiplex Ligation-dependent Probe Amplification approach.
19151728 2009 The cerebral cavernous malformation signaling pathway promotes vascular integrity via Rho GTPases.
19151727 2009 Regulation of cardiovascular development and integrity by the heart of glass-cerebral cavernous malformation protein pathway.
19088124 2009 A two-hit mechanism causes cerebral cavernous malformations: complete inactivation of CCM1, CCM2 or CCM3 in affected endothelial cells.
19088123 2009 Biallelic somatic and germline mutations in cerebral cavernous malformations (CCMs): evidence for a two-hit mechanism of CCM pathogenesis.
18469344 2008 ccm1 cell autonomously regulates endothelial cellular morphogenesis and vascular tubulogenesis in zebrafish.
18300272 2008 Novel CCM1, CCM2, and CCM3 mutations in patients with cerebral cavernous malformations: in-frame deletion in CCM2 prevents formation of a CCM1/CCM2/CCM3 protein complex.
17657516 2007 CCM3 interacts with CCM2 indicating common pathogenesis for cerebral cavernous malformations.
17440989 2007 Highly variable penetrance in subjects affected with cavernous cerebral angiomas (CCM) carrying novel CCM1 and CCM2 mutations.
17290187 2007 Interaction between krit1 and malcavernin: implications for the pathogenesis of cerebral cavernous malformations.
17160895 2007 Deletions in CCM2 are a common cause of cerebral cavernous malformations.
16769843 2006 Frequency of retinal cavernomas in 60 patients with familial cerebral cavernomas: a clinical and genetic study.
16373645 2006 CCM2 expression parallels that of CCM1.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16239636 2005 Cerebral venous malformations have distinct genetic origin from cerebral cavernous malformations.
16037064 2005 CCM1 and CCM2 protein interactions in cell signaling: implications for cerebral cavernous malformations pathogenesis.
15498874 2004 Large-scale cDNA transfection screening for genes related to cancer development and progression.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
14740320 2004 Mutations within the MGC4607 gene cause cerebral cavernous malformations.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14624391 2003 Mutations in a gene encoding a novel protein containing a phosphotyrosine-binding domain cause type 2 cerebral cavernous malformations.
12853948 2003 The DNA sequence of human chromosome 7.
12774951 2003 Linkage to the CCM2 locus and genetic heterogeneity in familial cerebral cavernous malformation.
12690205 2003 Human chromosome 7: DNA sequence and biology.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
9811928 1998 Multilocus linkage identifies two new loci for a mendelian form of stroke, cerebral cavernous malformation, at 7p15-13 and 3q25.2-27.