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Aliases for CCM2 Gene

Aliases for CCM2 Gene

  • CCM2 Scaffolding Protein 2 3 5
  • Malcavernin 2 3 4
  • Cerebral Cavernous Malformation 2 2 3
  • Osmosensing Scaffold For MEKK3 2 3
  • C7orf22 3 4
  • Cerebral Cavernous Malformations 2 Protein 3
  • Chromosome 7 Open Reading Frame 22 2
  • PP10187 3
  • OSM 3

External Ids for CCM2 Gene

Previous HGNC Symbols for CCM2 Gene

  • C7orf22

Previous GeneCards Identifiers for CCM2 Gene

  • GC07U990144
  • GC00U914335
  • GC07P044781
  • GC07P044813
  • GC07P045006
  • GC07P045039
  • GC07P044924

Summaries for CCM2 Gene

Entrez Gene Summary for CCM2 Gene

  • This gene encodes a scaffold protein that functions in the stress-activated p38 Mitogen-activated protein kinase (MAPK) signaling cascade. The protein interacts with SMAD specific E3 ubiquitin protein ligase 1 (also known as SMURF1) via a phosphotyrosine binding domain to promote RhoA degradation. The protein is required for normal cytoskeletal structure, cell-cell interactions, and lumen formation in endothelial cells. Mutations in this gene result in cerebral cavernous malformations. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2009]

GeneCards Summary for CCM2 Gene

CCM2 (CCM2 Scaffolding Protein) is a Protein Coding gene. Diseases associated with CCM2 include Cerebral Cavernous Malformations-2 and Familial Cerebral Cavernous Malformation 2. Among its related pathways are Regulation of p38-alpha and p38-beta and p38 MAPK signaling pathway (Pathway Interaction Database). An important paralog of this gene is CCM2L.

UniProtKB/Swiss-Prot for CCM2 Gene

  • Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity. May act through the stabilization of endothelial cell junctions (By similarity). May function as a scaffold protein for MAP2K3-MAP3K3 signaling. Seems to play a major role in the modulation of MAP3K3-dependent p38 activation induced by hyperosmotic shock (By similarity).

Gene Wiki entry for CCM2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CCM2 Gene

Genomics for CCM2 Gene

Regulatory Elements for CCM2 Gene

Enhancers for CCM2 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH07F045025 0.2 ENCODE 36.2 +28.6 28606 4.9 ELF3 CTCF KLF1 MAX KLF17 ZBTB40 POLR2A CBX5 EED ETV6 CCM2 ENSG00000260997 MYO1G ENSG00000228596 SNHG15 LINC00957 GC07M045025 LOC102723334
GH07F045020 1.1 Ensembl ENCODE 34.4 +22.1 22126 1.6 HDGF PKNOX1 ZBTB40 POLR2A EED CREM ZNF263 MTA2 TRIM22 JUNB CCM2 ENSG00000260997 MYO1G SNHG15 GC07M045025 LOC102723334
GH07F044975 1 FANTOM5 ENCODE 32.7 -20.6 -20553 6.5 HDGF PKNOX1 WRNIP1 SIN3A FEZF1 ZNF121 ZNF263 JUNB TBX21 PPARG CCM2 MYO1G ENSG00000260997 PURB RAMP3 SNHG15 OGDH ZMIZ2
GH07F044983 0.7 ENCODE 21 -13.8 -13836 5.2 PKNOX1 ARNT CREB3L1 WRNIP1 SIN3A ZNF2 YY1 CBX5 ZNF143 ZNF207 CCM2 SNHG15 ENSG00000260997 TBRG4 DDX56 RAMP3 GC07M044985 SNORA9
GH07F044989 0.9 Ensembl ENCODE 19.2 -8.6 -8639 2.8 TBP HDAC1 NFRKB PTRF FEZF1 RFX5 ZNF680 CEBPB HDAC8 CREB3 CCM2 ENSG00000260997 MIR4649 TBRG4 LINC00957 SNHG15
- Elite enhancer/Elite enhancer-gene association Download Table
Download GeneHancer data dump

Enhancers around CCM2 on UCSC Golden Path with GeneCards custom track

Promoters for CCM2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000625799 525 2801 HDGF PKNOX1 ARNT ARID4B SIN3A BRCA1 YY1 ELK1 GATA2 ZNF143

Genomic Location for CCM2 Gene

Chromosome:
7
Start:
44,999,475 bp from pter
End:
45,076,470 bp from pter
Size:
76,996 bases
Orientation:
Plus strand

Genomic View for CCM2 Gene

Genes around CCM2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CCM2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CCM2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CCM2 Gene

Proteins for CCM2 Gene

  • Protein details for CCM2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9BSQ5-CCM2_HUMAN
    Recommended name:
    Cerebral cavernous malformations 2 protein
    Protein Accession:
    Q9BSQ5
    Secondary Accessions:
    • A4D2L4
    • B3KUV0
    • D3DVL4
    • E9PDJ3
    • F5H0E1
    • F5H551
    • Q71RE5
    • Q8TAT4

    Protein attributes for CCM2 Gene

    Size:
    444 amino acids
    Molecular mass:
    48837 Da
    Quaternary structure:
    • Part of a complex with MAP2K3, MAP3K3 and RAC1. Binds RAC1 directly and independently of its nucleotide-bound state (By similarity). Interacts with HEG1 and KRIT1; KRIT1 greatly facilitates the interaction with HEG1 (By similarity). Interacts with PDCD10.

    Three dimensional structures from OCA and Proteopedia for CCM2 Gene

    Alternative splice isoforms for CCM2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CCM2 Gene

Post-translational modifications for CCM2 Gene

  • Ubiquitination at Lys 96
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for CCM2 Gene

Domains & Families for CCM2 Gene

Protein Domains for CCM2 Gene

Suggested Antigen Peptide Sequences for CCM2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9BSQ5

UniProtKB/Swiss-Prot:

CCM2_HUMAN :
  • The C-terminal region constitutes an independently folded domain that has structural similarity with the USH1C (harmonin) N-terminus, despite very low sequence similarity.
  • Belongs to the CCM2 family.
Domain:
  • The C-terminal region constitutes an independently folded domain that has structural similarity with the USH1C (harmonin) N-terminus, despite very low sequence similarity.
  • Contains 1 PID domain.
Family:
  • Belongs to the CCM2 family.
genes like me logo Genes that share domains with CCM2: view

No data available for Gene Families for CCM2 Gene

Function for CCM2 Gene

Molecular function for CCM2 Gene

UniProtKB/Swiss-Prot Function:
Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity. May act through the stabilization of endothelial cell junctions (By similarity). May function as a scaffold protein for MAP2K3-MAP3K3 signaling. Seems to play a major role in the modulation of MAP3K3-dependent p38 activation induced by hyperosmotic shock (By similarity).

Gene Ontology (GO) - Molecular Function for CCM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 16037064
genes like me logo Genes that share ontologies with CCM2: view
genes like me logo Genes that share phenotypes with CCM2: view

Human Phenotype Ontology for CCM2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CCM2 Gene

MGI Knock Outs for CCM2:

Animal Model Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , miRNA , Transcription Factor Targets and HOMER Transcription for CCM2 Gene

Localization for CCM2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CCM2 Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for CCM2 Gene COMPARTMENTS Subcellular localization image for CCM2 gene
Compartment Confidence
nucleus 4
cytosol 3
mitochondrion 2

Gene Ontology (GO) - Cellular Components for CCM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA,IDA 16037064
GO:0043234 protein complex IEA --
genes like me logo Genes that share ontologies with CCM2: view

Pathways & Interactions for CCM2 Gene

genes like me logo Genes that share pathways with CCM2: view

Pathways by source for CCM2 Gene

Gene Ontology (GO) - Biological Process for CCM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001570 vasculogenesis IMP 14740320
GO:0001701 in utero embryonic development IEA --
GO:0001885 endothelial cell development IEA --
GO:0001944 vasculature development IEA --
GO:0007229 integrin-mediated signaling pathway TAS 16037064
genes like me logo Genes that share ontologies with CCM2: view

No data available for SIGNOR curated interactions for CCM2 Gene

Transcripts for CCM2 Gene

Unigene Clusters for CCM2 Gene

Cerebral cavernous malformation 2:
Representative Sequences:

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for CCM2 Gene

ExUns: 1 ^ 2a · 2b · 2c · 2d ^ 3 ^ 4a · 4b ^ 5a · 5b ^ 6 ^ 7a · 7b ^ 8 ^ 9 ^ 10 ^ 11 ^ 12a · 12b · 12c · 12d ^ 13a · 13b ^ 14a · 14b · 14c ^
SP1: - - - - - - - - - -
SP2: - - - - -
SP3: - - - - - - - - - - - - - -
SP4: - - - - - - - - - - - - -
SP5: - - - - - - - - - - - -
SP6: - - - - - - -
SP7: - - - - - - - - - -
SP8: - - - - - - - - - -
SP9: - - - - - - -
SP10: - - - - - - - - - - - - - - -
SP11: - - - - - - - - - - -
SP12: - - - - - - - - - - - -
SP13: - - - - - - - - - - - - - - - -
SP14:
SP15: - - - - - - - - - - - - - -
SP16: - - - - - - - - - - - - - - - -
SP17: - - - - - - - - -
SP18:
SP19:
SP20: - - - - - - - - - - - - - - -
SP21: - - - - - - - -
SP22: - - - - - -
SP23: - - - - - -
SP24: - -
SP25: - - - - - -
SP26: - - - - - - - - - - - - - - - - - - -
SP27:
SP28:

ExUns: 15a · 15b · 15c ^ 16a · 16b ^ 17a · 17b ^ 18 ^ 19a · 19b · 19c ^ 20a · 20b · 20c · 20d ^ 21a · 21b · 21c · 21d · 21e · 21f · 21g
SP1: - - - - -
SP2: - - - - -
SP3: - - - - - - - -
SP4: - - - -
SP5: - - - - -
SP6: - - -
SP7: - - - - -
SP8: - - - - - - -
SP9: - - - - - - - - -
SP10: - - - -
SP11:
SP12:
SP13: - - - -
SP14: - - - - -
SP15:
SP16:
SP17: - - - - - - - - -
SP18: - - - - - -
SP19: - - -
SP20:
SP21:
SP22:
SP23:
SP24:
SP25:
SP26:
SP27:
SP28: -

Relevant External Links for CCM2 Gene

GeneLoc Exon Structure for
CCM2
ECgene alternative splicing isoforms for
CCM2

Expression for CCM2 Gene

mRNA expression in normal human tissues for CCM2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CCM2 Gene

This gene is overexpressed in Whole Blood (x4.9).

Protein differential expression in normal tissues from HIPED for CCM2 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (23.6), CD8 Tcells (6.3), and Blymphocyte (6.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CCM2 Gene



Protein tissue co-expression partners for CCM2 Gene

NURSA nuclear receptor signaling pathways regulating expression of CCM2 Gene:

CCM2

SOURCE GeneReport for Unigene cluster for CCM2 Gene:

Hs.148272
genes like me logo Genes that share expression patterns with CCM2: view

Primer Products

No data available for mRNA Expression by UniProt/SwissProt for CCM2 Gene

Orthologs for CCM2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for CCM2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CCM2 34 35
  • 99.39 (n)
mouse
(Mus musculus)
Mammalia Ccm2 34 16 35
  • 89.53 (n)
rat
(Rattus norvegicus)
Mammalia Ccm2 34
  • 88.91 (n)
cow
(Bos Taurus)
Mammalia CCM2 34 35
  • 88.89 (n)
dog
(Canis familiaris)
Mammalia LOC100856167 34
  • 87.23 (n)
CCM2 35
  • 87 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia CCM2 35
  • 81 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CCM2 35
  • 63 (a)
OneToOne
chicken
(Gallus gallus)
Aves CCM2 34 35
  • 80.23 (n)
lizard
(Anolis carolinensis)
Reptilia CCM2 35
  • 79 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia ccm2 34
  • 76.02 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.6991 34
zebrafish
(Danio rerio)
Actinopterygii ccm2 34 35
  • 70.99 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 34 (a)
OneToMany
Species where no ortholog for CCM2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for CCM2 Gene

ENSEMBL:
Gene Tree for CCM2 (if available)
TreeFam:
Gene Tree for CCM2 (if available)

Paralogs for CCM2 Gene

Paralogs for CCM2 Gene

(1) SIMAP similar genes for CCM2 Gene using alignment to 5 proteins:

genes like me logo Genes that share paralogs with CCM2: view

Variants for CCM2 Gene

Sequence variations from dbSNP and Humsavar for CCM2 Gene

SNP ID Clin Chr 07 pos Sequence Context AA Info Type
rs137852843 Cerebral cavernous malformations 2 (CCM2) [MIM:603284], Pathogenic 45,068,563(+) CATCC(G/T)GGCTG intron-variant, nc-transcript-variant, reference, missense
VAR_067352 Cerebral cavernous malformations 2 (CCM2) [MIM:603284]
VAR_067353 Cerebral cavernous malformations 2 (CCM2) [MIM:603284]
rs137852841 Pathogenic 45,064,493(+) TGACT(C/T)AGGAG nc-transcript-variant, reference, stop-gained
rs137852842 Pathogenic 45,000,334(+) GCGAT(A/G)TGGAA intron-variant, upstream-variant-2KB, reference, missense

Structural Variations from Database of Genomic Variants (DGV) for CCM2 Gene

Variant ID Type Subtype PubMed ID
nsv1117709 CNV deletion 24896259
nsv1144173 CNV deletion 24896259
nsv366390 CNV deletion 16902084
nsv473655 CNV novel sequence insertion 20440878
nsv951641 CNV deletion 24416366

Variation tolerance for CCM2 Gene

Residual Variation Intolerance Score: 27.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.60; 78.10% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for CCM2 Gene

Human Gene Mutation Database (HGMD)
CCM2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CCM2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CCM2 Gene

Disorders for CCM2 Gene

MalaCards: The human disease database

(10) MalaCards diseases for CCM2 Gene - From: OMIM, ClinVar, GeneTests, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
cerebral cavernous malformations-2
  • cerebral cavernous malformation 2
familial cerebral cavernous malformation 2
  • ccm2
cavernous malformation
cerebral cavernous malformations-1
  • hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations
human venous malformation
  • malformation venous
- elite association - COSMIC cancer census association via MalaCards
Search CCM2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

CCM2_HUMAN
  • Cerebral cavernous malformations 2 (CCM2) [MIM:603284]: A congenital vascular anomaly of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. The lesions are characterized by grossly enlarged blood vessels consisting of a single layer of endothelium and without any intervening neural tissue, ranging in diameter from a few millimeters to several centimeters. {ECO:0000269 PubMed:14624391, ECO:0000269 PubMed:14740320, ECO:0000269 PubMed:22415356}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for CCM2

Genetic Association Database (GAD)
CCM2
Human Genome Epidemiology (HuGE) Navigator
CCM2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
CCM2
genes like me logo Genes that share disorders with CCM2: view

No data available for Genatlas for CCM2 Gene

Publications for CCM2 Gene

  1. Mutations within the MGC4607 gene cause cerebral cavernous malformations. (PMID: 14740320) Denier C. … Tournier-Lasserve E. (Am. J. Hum. Genet. 2004) 3 4 22 64
  2. Mutations in a gene encoding a novel protein containing a phosphotyrosine-binding domain cause type 2 cerebral cavernous malformations. (PMID: 14624391) Liquori C.L. … Marchuk D.A. (Am. J. Hum. Genet. 2003) 3 4 22 64
  3. Structural studies of cerebral cavernous malformations 2 (CCM2) reveal a folded helical domain at its C-terminus. (PMID: 23266514) Fisher O.S. … Boggon T.J. (FEBS Lett. 2013) 3 4 64
  4. De Novo MGC4607 gene heterozygous missense variants in a child with multiple cerebral cavernous malformations. (PMID: 22415356) Mosca L. … Penco S. (J. Mol. Neurosci. 2012) 3 4 64
  5. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose J.E. … Uhl G.R. (Mol. Med. 2010) 3 46 64

Products for CCM2 Gene

Sources for CCM2 Gene

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