CCM2 (CCM2 scaffold protein)

Gene

• Entrez ID: 83605
• Gene name: CCM2 scaffold protein
• Gene symbol: CCM2
• Synonyms: C7orf22, OSM, PP10187
• Chromosome: 7
• Chromosome location: 7p13
• Summary: 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs137852841	C>T	Pathogenic	Non coding transcript variant, coding sequence variant, stop gained
rs137852843	T>G	Pathogenic	Non coding transcript variant, intron variant, coding sequence variant, missense variant
rs755800734	C>T	Pathogenic	Intron variant, coding sequence variant, non coding transcript variant, stop gained
rs765548101	C>G,T	Pathogenic	Non coding transcript variant, coding sequence variant, stop gained, synonymous variant
rs886041157	C>T	Pathogenic	Stop gained, coding sequence variant, non coding transcript variant
rs1057520070	C>-	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant, intron variant
rs1131691312	->AG	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant, intron variant
rs1131691538	TTCT>-	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant, intron variant
rs1204653825	C>-	Likely-pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs1331484727	->C	Likely-pathogenic, pathogenic	Non coding transcript variant, coding sequence variant, genic downstream transcript variant, frameshift variant
rs1554365507	A>G	Likely-pathogenic	Splice acceptor variant, intron variant
rs1554365511	->ATTTAAACGAGTATTTAAA	Pathogenic	Coding sequence variant, non coding transcript variant, inframe indel, intron variant, stop gained
rs1554365577	->G	Pathogenic	Coding sequence variant, intron variant, non coding transcript variant, frameshift variant
rs1554375233	C>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1554377652	T>C	Likely-pathogenic	Missense variant, coding sequence variant, intron variant, non coding transcript variant
rs1562881854	G>-	Pathogenic	Coding sequence variant, non coding transcript variant, intron variant, frameshift variant
rs1562881859	AG>-	Likely-pathogenic	Coding sequence variant, non coding transcript variant, intron variant, stop gained
rs1562881980	TG>-	Likely-pathogenic	Coding sequence variant, non coding transcript variant, intron variant, frameshift variant
rs1562882045	AGAC>-	Pathogenic	Coding sequence variant, non coding transcript variant, intron variant, frameshift variant
rs1562882049	A>T	Likely-pathogenic	Coding sequence variant, non coding transcript variant, intron variant, stop gained
rs1562906798	AA>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1562906981	G>A	Pathogenic	Splice donor variant
rs1562907331	GCCCTGTGGTTCCTTCCAGAGAGCCCACCAGCTTCCGGGACACTTGACTCAGGAGCACGATGCTGTGCTCAGCCTGTCTGCGT>-	Likely-pathogenic	Splice acceptor variant, non coding transcript variant, intron variant, coding sequence variant
rs1562907365	G>A,T	Pathogenic, likely-pathogenic	Splice acceptor variant
rs1562907455	T>-	Pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs1562912426	T>G	Likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant, intron variant
rs1562912441	G>-	Likely-pathogenic	Coding sequence variant, non coding transcript variant, intron variant, frameshift variant
rs1562912528	G>A	Likely-pathogenic	Coding sequence variant, synonymous variant, non coding transcript variant, intron variant
rs1562913873	G>A	Pathogenic	Splice acceptor variant, intron variant
rs1562917629	G>-	Likely-pathogenic	Non coding transcript variant, genic downstream transcript variant, coding sequence variant, intron variant, frameshift variant
rs1562921605	AG>-	Pathogenic-likely-pathogenic, pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant, genic downstream transcript variant
rs1583901813	ATGAGAAGGTGACAGAGAGGCGCCCT>-	Pathogenic	Coding sequence variant, non coding transcript variant, intron variant, frameshift variant
rs1583970495	->GCCC	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1583983649	T>C	Uncertain-significance, likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant, intron variant
rs1583984070	G>C	Pathogenic	Intron variant, splice donor variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001570	Process	Vasculogenesis	IMP	14740320
GO:0001701	Process	In utero embryonic development	IEA
GO:0001885	Process	Endothelial cell development	IEA
GO:0005515	Function	Protein binding	IPI	16037064, 17657516, 20489202, 23007647, 23266514, 25525273, 25814554, 25910212, 32296183
GO:0005737	Component	Cytoplasm	IDA	16037064
GO:0005739	Component	Mitochondrion	IDA
GO:0007229	Process	Integrin-mediated signaling pathway	TAS	16037064
GO:0032991	Component	Protein-containing complex	IEA
GO:0035264	Process	Multicellular organism growth	IEA
GO:0045216	Process	Cell-cell junction organization	IEA
GO:0048839	Process	Inner ear development	IEA
GO:0048845	Process	Venous blood vessel morphogenesis	IEA
GO:0051403	Process	Stress-activated MAPK cascade	TAS	16037064
GO:0060039	Process	Pericardium development	IEA
GO:0060837	Process	Blood vessel endothelial cell differentiation	IEA
GO:0061154	Process	Endothelial tube morphogenesis	IMP	19151727

Other IDs

• MIM: 607929
• HGNC: 21708
• e!Ensembl: ENSG00000136280

Protein

• UniProt ID: Q9BSQ5
• Protein name: Cerebral cavernous malformations 2 protein (Malcavernin)
• Protein 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).
• PDB: 4FQN, 4TVQ, 4WJ7, 4Y5O, 4YKC, 4YKD, 4YL6
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF16545	CCM2_C	287 → 387	Cerebral cavernous malformation protein, harmonin-homology	Domain

• Sequence:

  MEEEGKKGKKPGIVSPFKRVFLKGEKSRDKKAHEKVTERRPLHTVVLSLPERVEPDRLLS
  DYIEKEVKYLGQLTSIPGYLNPSSRTEILHFIDNAKRAHQLPGHLTQEHDAVLSLSAYNV
  KLAWRDGEDIILRVPIHDIAAVSYVRDDAAHLVVLKTAQDPGISPSQSLCAESSRGLSAG
  SLSESAVGPVEACCLVILAAESKVAAEELCCLLGQVFQVVYTESTIDFLDRAIFDGASTP
  THHLSLHSDDSSTKVDIKETYEVEASTFCFPESVDVGGASPHSKTISESELSASATELLQ
  DYMLTLRTKLSSQEIQQFAALLHEYRNGASIHEFCINLRQLYGDSRKFLLLGLRPFIPEK
  DSQHFENFLETIGVKDGRGIITDSFGRHRRALSTTSSSTTNGNRATGSSDDRSAPSEGDE
  WDRMISDISSDIEALGCSMDQDSA

• Sequence length: 444