Anti-KRIT1 Antibody Picoband® Fluoro647 Conjugated

Krev interaction trapped protein 1 (KRIT1) is a protein that in humans is encoded by the CCM1 gene. This gene encodes a protein containing four ankyrin repeats, a band 4.1/ezrin/radixin/moesin (FERM) domain, and multiple NPXY sequences. The encoded protein is localized in the nucleus and cytoplasm. It binds to integrin cytoplasmic domain-associated protein-1 alpha (ICAP1alpha), and plays a critical role in beta1-integrin-mediated cell proliferation. It associates with junction proteins and RAS-related protein 1A (Rap1A), which requires the encoded protein for maintaining the integrity of endothelial junctions. It is also a microtubule-associated protein and may play a role in microtubule targeting. Mutations in this gene result in cerebral cavernous malformations. Multiple alternatively spliced transcript variants have been found for this gene.

Cardiovascular, G Protein Signaling, Neurogenesis, Neurology Process, Neuroscience, Regulators, Signal Transduction, Signaling Pathway, Small G Proteins, Vasculature

Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity (By similarity) . Negative regulator of angiogenesis. Inhibits endothelial proliferation, apoptosis, migration, lumen formation and sprouting angiogenesis in primary endothelial cells. Promotes AKT phosphorylation in a NOTCH-dependent and independent manner, and inhibits ERK1/2 phosphorylation inly through activation of the DELTA-NOTCH cascade. Acts in concert with CDH5 to establish and maintain correct endothelial cell polarity and vascular lumen and these effects are mediated by recruitment and activation of the Par polarity complex and RAP1B. Required for the localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction, and cell junction stabilization. Plays a role in integrin signaling via its interaction with ITGB1BP1; this prevents the interaction between ITGB1 and ITGB1BP1. Microtubule- associated protein that binds to phosphatidylinositol 4,5- bisphosphate (PIP2) -containing membranes in a GTP-bound RAP1- dependent manner. Plays an important role in the maintenance of the intracellular reactive oxygen species (ROS) homeostasis to prevent oxidative cellular damage. Regulates the homeostasis of intracellular ROS through an antioxidant pathway involving FOXO1 and SOD2. 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 through the modulation of FOXO1 and SOD2 levels. .

1. Eerola I, McIntyre B, Vikkula M (Feb 2001) . Identification of eight novel 5'-exons in cerebral capillary malformation gene-1 (CCM1) encoding KRIT1.Biochimica et Biophysica Acta 1517 (3) : 464–7. 2. Pagenstecher A, Stahl S, Sure U, Felbor U (Mar 2009) .A two-hit mechanism causes cerebral cavernous malformations: complete inactivation of CCM1, CCM2 or CCM3 in affected endothelial cells. Human Molecular Genetics 18 (5) : 911–8.

Cytoplasm, cytoskeleton. Cell membrane; Peripheral membrane protein. Cell junction. KRIT1 and CDH5 reciprocally regulate their localization to endothelial cell-cell junctions. Association with RAP1 relocalizes KRIT1 from microtubules to cell junction membranes. Translocates from the cytoplasm along microtubules to the cell membrane in a ITGB1BP1- dependent manner.