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    Ccm2 cerebral cavernous malformation 2 [ Mus musculus (house mouse) ]

    Gene ID: 216527, updated on 10-Mar-2024

    Summary

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    Official Symbol
    Ccm2provided by MGI
    Official Full Name
    cerebral cavernous malformation 2provided by MGI
    Primary source
    MGI:MGI:2384924
    See related
    Ensembl:ENSMUSG00000000378 AllianceGenome:MGI:2384924
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Summary
    Acts upstream of or within several processes, including circulatory system development; endothelial cell development; and in utero embryonic development. Part of protein-containing complex. Is expressed in several structures, including cardiovascular system; central nervous system; early conceptus; gut; and retina layer. Used to study cerebral cavernous malformation 2. Human ortholog(s) of this gene implicated in cerebral cavernous malformation 2. Orthologous to human CCM2 (CCM2 scaffold protein). [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Ubiquitous expression in thymus adult (RPKM 84.9), spleen adult (RPKM 58.8) and 28 other tissues See more
    Orthologs
    human all
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    Genomic context

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    Location:
    11 A1; 11 4.45 cM
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 11 NC_000077.7 (6496887..6546761)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 11 NC_000077.6 (6546887..6596761)

    Chromosome 11 - NC_000077.7Genomic Context describing neighboring genes Neighboring gene STARR-seq mESC enhancer starr_28469 Neighboring gene small nucleolar RNA host gene 15 Neighboring gene small nucleolar RNA, H/ACA box 9 Neighboring gene predicted gene, 24000 Neighboring gene STARR-positive B cell enhancer mm9_chr11:6481502-6481803 Neighboring gene NAC alpha domain containing Neighboring gene transforming growth factor beta regulated gene 4 Neighboring gene predicted gene, 24313

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. Impaired retinoic acid signaling in cerebral cavernous malformations. Grdseloff N, et al. Sci Rep, 2023 Apr 5. PMID 37019926, Free PMC Article
    2. Novel Chronic Mouse Model of Cerebral Cavernous Malformations. Cardoso C, et al. Stroke, 2020 Apr. PMID 31992178
    3. Low fluid shear stress conditions contribute to activation of cerebral cavernous malformation signalling pathways. Li J, et al. Biochim Biophys Acta Mol Basis Dis, 2019 Nov 1. PMID 31369819
    4. Strategy for identifying repurposed drugs for the treatment of cerebral cavernous malformation. Gibson CC, et al. Circulation, 2015 Jan 20. PMID 25486933, Free PMC Article
    5. Study of cerebral cavernous malformation in Spain and Portugal: high prevalence of a 14 bp deletion in exon 5 of MGC4607 (CCM2 gene). Ortiz L, et al. J Neurol, 2007 Mar. PMID 17345049

    See all (59) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Cerebral cavernous malformation proteins, CCM1, CCM2 and CCM3, are decreased in metastatic lesions in a murine breast carcinoma model.
      Title: Cerebral cavernous malformation proteins, CCM1, CCM2 and CCM3, are decreased in metastatic lesions in a murine breast carcinoma model.
    2. Novel Chronic Mouse Model of Cerebral Cavernous Malformations.
      Title: Novel Chronic Mouse Model of Cerebral Cavernous Malformations.
    3. Loss of CCM2 is associated with Cerebral Cavernous Malformations.
      Title: Micro-CT Imaging Reveals Mekk3 Heterozygosity Prevents Cerebral Cavernous Malformations in Ccm2-Deficient Mice.
    4. CCM2 expression and it's role during ovary and testis development
      Title: Expression of CCM2 and CCM3 during mouse gonadogenesis.
    5. CCM2:MEKK3-mediated regulation of Rho-ROCK signalling is required for maintenance of neurovascular integrity, a mechanism by which CCM2 loss leads to disease.
      Title: Structure and vascular function of MEKK3-cerebral cavernous malformations 2 complex.
    6. 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.
      Title: STK25 protein mediates TrkA and CCM2 protein-dependent death in pediatric tumor cells of neural origin.
    7. The inducible deletion of Ccm2 in adult mice recapitulates the cerebral cavernous malformations-like brain lesions in humans.
      Title: Conditional deletion of Ccm2 causes hemorrhage in the adult brain: a mouse model of human cerebral cavernous malformations.
    8. Developmental timing of CCM2 loss influences cerebral cavernous malformations in mice.
      Title: Developmental timing of CCM2 loss influences cerebral cavernous malformations in mice.
    9. Rac1/osmosensing scaffold for MEKK3 contributes via phospholipase C-gamma1 to activation of the osmoprotective transcription factor NFAT5.
      Title: Rac1/osmosensing scaffold for MEKK3 contributes via phospholipase C-gamma1 to activation of the osmoprotective transcription factor NFAT5.
    10. Pdcd10 has a different role in cerebral cavernous malformation than Ccm2 and Krit1
      Title: Mutations in 2 distinct genetic pathways result in cerebral cavernous malformations in mice.
    Submit: New GeneRIF Correction See all GeneRIFs (19)

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC37115

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    acts_upstream_of_or_within blood vessel development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within blood vessel endothelial cell differentiation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within cell-cell junction organization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within endothelial cell development IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    acts_upstream_of_or_within endothelial cell development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within endothelial tube morphogenesis ISO
    Inferred from Sequence Orthology
    more info
    		 PubMed 
    involved_in endothelium development NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in heart development IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    acts_upstream_of_or_within heart development IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    acts_upstream_of_or_within heart development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within heart development ISO
    Inferred from Sequence Orthology
    more info
    		 PubMed 
    acts_upstream_of_or_within in utero embryonic development IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    acts_upstream_of_or_within in utero embryonic development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within inner ear development IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within multicellular organism growth IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    acts_upstream_of_or_within multicellular organism growth IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within pericardium development IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    acts_upstream_of_or_within pericardium development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of angiogenesis NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    acts_upstream_of_or_within vasculature development IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    acts_upstream_of_or_within vasculature development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in vasculogenesis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    acts_upstream_of_or_within vasculogenesis IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in vasculogenesis ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within venous blood vessel morphogenesis IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    acts_upstream_of_or_within venous blood vessel morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytoplasm ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in mitochondrion ISO
    Inferred from Sequence Orthology
    more info
    		  
    part_of protein-containing complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    cerebral cavernous malformations protein 2 homolog
    Names
    cerebral cavernous malformation 2 homolog
    malcavernin
    osmosensing scaffold for MEKK3

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001190343.1 → NP_001177272.1  cerebral cavernous malformations protein 2 homolog isoform 2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) lacks an in-frame exon in the coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.
      Source sequence(s)
      AL603787, AL646047
      UniProtKB/TrEMBL
      Q3TM53
      Conserved Domains (2) summary
      cd13166
      Location:10 → 179
      PTB_CCM2; Cerebral cavernous malformation 2 FERM domain C-lobe
      pfam16545
      Location:238 → 328
      CCM2_C; Cerebral cavernous malformation protein, harmonin-homology

    2. NM_001190344.1 → NP_001177273.1  cerebral cavernous malformations protein 2 homolog isoform 3

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The resulting protein (isoform 3) has a distinct N-terminus and is shorter than isoform 1.
      Source sequence(s)
      AL603787, AL646047
      Consensus CDS
      CCDS48751.1
      UniProtKB/TrEMBL
      F7AVU1, F8WJD3, Q3TM53
      Related
      ENSMUSP00000105344.3, ENSMUST00000109722.9
      Conserved Domains (2) summary
      cd13166
      Location:2 → 173
      PTB_CCM2; Cerebral cavernous malformation 2 FERM domain C-lobe
      pfam16545
      Location:232 → 322
      CCM2_C; Cerebral cavernous malformation protein, harmonin-homology

    3. NM_146014.3 → NP_666126.1  cerebral cavernous malformations protein 2 homolog isoform 1

      See identical proteins and their annotated locations for NP_666126.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AL603787, AL646047
      Consensus CDS
      CCDS24422.1
      UniProtKB/Swiss-Prot
      Q5SUA3, Q8K2Y9
      Related
      ENSMUSP00000000388.9, ENSMUST00000000388.15
      Conserved Domains (2) summary
      cd13516
      Location:291 → 386
      HHD_CCM2; harmonin-homology domain (harmonin_N_like domain) of malcavernin (CCM2)
      cd13166
      Location:43 → 237
      PTB_CCM2; Cerebral cavernous malformation 2 FERM domain C-lobe

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000077.7 Reference GRCm39 C57BL/6J

      Range
      6496887..6546761
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006514622.3 → XP_006514685.1  cerebral cavernous malformations protein 2 homolog isoform X1

      Conserved Domains (2) summary
      cd13516
      Location:285 → 380
      HHD_CCM2; harmonin-homology domain (harmonin_N_like domain) of malcavernin (CCM2)
      cd13166
      Location:37 → 231
      PTB_CCM2; Cerebral cavernous malformation 2 FERM domain C-lobe

    2. XM_036156517.1 → XP_036012410.1  cerebral cavernous malformations protein 2 homolog isoform X2

      Conserved Domains (2) summary
      pfam16545
      Location:99 → 189
      CCM2_C; Cerebral cavernous malformation protein, harmonin-homology
      cl17171
      Location:1 → 40
      PH-like; Pleckstrin homology-like domain
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8K2Y9.1 GenPept UniProtKB/Swiss-Prot:Q8K2Y9

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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