UniProt ID: F1REV3 |
FUNCTION: Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity. Negative regulator of angiogenesis. Inhibits endothelial proliferation, apoptosis, migration, lumen formation and sprouting angiogenesis in primary endothelial cells. Plays a role in integrin signaling. Plays an important role in the maintenance of the intracellular reactive oxygen species (ROS) homeostasis to prevent oxidative cellular damage. Facilitates the down-regulation of cyclin-D1 (CCND1) levels required for cell transition from proliferative growth to quiescence by preventing the accumulation of intracellular ROS. Probable microtubule- associated protein that may bind to phosphatidylinositol 4,5- bisphosphate (PIP2)-containing membranes (By similarity). Required for correct endothelial cell polarity and cell junction stabilization in cardiovascular development. May play a role in the regulation of macroautophagy through the down-regulation of the mTOR pathway (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:O00522, ECO:0000269|PubMed:21633110, ECO:0000269|PubMed:23007647}. SUBUNIT: Interacts with heg1 and ccm2; greatly facilitates ccm2-binding to heg1. Interacts with rap1. {ECO:0000269|PubMed:19151727, ECO:0000269|PubMed:21633110}. SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cell membrane; Peripheral membrane protein. Cell junction. Note=KRIT1 and CDH5 reciprocally regulate their localization to endothelial cell-cell junctions (By similarity). Association with RAP1 relocalizes KRIT1 from microtubules to cell junction membranes. {ECO:0000250}. DEVELOPMENTAL STAGE: Expressed in the ventricular zone of the brain at 28 hours post fertilization (hpf) and at lower levels, throughout the entire brain and in the posterior cardinal vein. Venous expression is maintained at 48 hpf. At the same time, there is also prominent notochord expression. {ECO:0000269|PubMed:16873582}. DOMAIN: The FERM domain mediates binding to rap1. DOMAIN: The N-terminal domain has structural similarity to the nudix hydrolase domain, despite the absence of a nudix box and low sequence similarity with nudix hydrolase domains. {ECO:0000250|UniProtKB:O00522}. DOMAIN: Contains 4 ANK repeats that precede the FERM domain. {ECO:0000250|UniProtKB:O00522}. DISRUPTION PHENOTYPE: The heart chambers in mutant animals are huge, constituted of a monolayered myocardium lined by endocardium. {ECO:0000269|PubMed:16873582}. SEQUENCE CAUTION: Sequence=CAX12105.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; |
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