CCM-1

• Description:

  Cerebral cavernous malformations (CCM) are frequent vascular abnormalities caused by mutations in one of the CCM genes. CCM-1 (also known as KRIT1) stabilizes endothelial junctions and is essential for vascular morphogenesis in mouse embryos. However, cellular functions of CCM-1 during the early steps of the CCM pathogenesis remain unknown. It was shown that CCM-1 represents an antiangiogenic protein to keep the human endothelium quiescent. CCM-1 inhibits endothelial proliferation, apoptosis, migration, lumen formation, and sprouting angiogenesis in primary human endothelial cells. CCM-1 strongly induces DLL4-NOTCH signaling, which promotes AKT phosphorylation but reduces phosphorylation of the mitogen-activated protein kinase ERK. Consistently, blocking of NOTCH activity alleviates CCM-1 effects. ERK phosphorylation is increased in human CCM lesions. Transplantation of CCM-1-silenced human endothelial cells into SCID mice recapitulates hallmarks of the CCM pathology and serves as a unique CCM model system.

• Synonyms:

  CCM-1; Cerebral cavernous malformations protein 1; KRIT1; KRIT1, ankyrin repeat containing; CAM

• NCBI Gene ID:

  889

• UniProt:

  O00522

• Accession Number:

  NP_004903.2

• Accession Number mRNA:

  NM_004912.3

• Chromosomal Location:

  7q21.2

• Reactivity:

  Human

• Cross Reactivity:

  Human

• Label:

  His-Tag

• Sequence:

  MLLKEAINKPYEKVRIYRMDGSYRSVELKHGNNTTVQQIMEGMRLSQETQQYFTIWICSENLSLQLKPYHKPLQHVRDWPEILAELTNLDPQRETPQLFLRRDVRLPLEVEKQIEDPLAILILFDEARYNLLKGFYTAPDAKLITLASLLLQIVYGNYESKKHKQGFLNEENLKSIVPVTKLKSKAPHWTNRILHEYKNLSTSEGVSKEMHHLQRMFLQNCWEIPTYGAAFFTGQIFTKASPSNHKVIPVYVGVNIKGLHLLNMETKALLISLKYGCFMWQLGDTDTCFQIHSMENKMSFIVHTKQAGLVVKLLMKLNGQLMPTERNSLEHHHHH

• Assay Protocol:

  Human CCM1 should be reconstituted in water or other buffer solutions and stored at -20°C.

• Purity:

  > 90% by SDS-PAGE

• Bioactivity:

  Data not available.

• Length:

  335

• Form:

  Lyophilized

• Buffer:

  30mM NaCl. 50 mM NaP, pH 7.4

• Reconstitution:

  Water

• Molecular Weight:

  39 kDa

• Storage Conditions:

  The lyophilized human CCM1, though stable at room temperature, is best stored desiccated below 0°C.

• Host or Source:

  E. coli