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

Summary

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; gonad; 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, Nov 2024]
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

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_000077.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
Novel Chronic Mouse Model of Cerebral Cavernous Malformations.
Title: Novel Chronic Mouse Model of Cerebral Cavernous Malformations.
Loss of CCM2 is associated with Cerebral Cavernous Malformations.
Title: Micro-CT Imaging Reveals Mekk3 Heterozygosity Prevents Cerebral Cavernous Malformations in Ccm2-Deficient Mice.
CCM2 expression and it's role during ovary and testis development
Title: Expression of CCM2 and CCM3 during mouse gonadogenesis.
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.
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.
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.
Developmental timing of CCM2 loss influences cerebral cavernous malformations in mice.
Title: Developmental timing of CCM2 loss influences cerebral cavernous malformations in mice.
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.
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)

Endonuclease-mediated (4)
Gene trapped (1) 1 citation
Targeted (7) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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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	IEA Inferred from Electronic Annotation 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)

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
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
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

NC_000077.7 Reference GRCm39 C57BL/6J

Range

6496887..6546761

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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