Homo sapiens Protein: KRIT1 | |||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Summary | |||||||||||||||||||||||
InnateDB Protein | IDBP-241413.7 | ||||||||||||||||||||||
Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||
Gene Symbol | KRIT1 | ||||||||||||||||||||||
Protein Name | KRIT1, ankyrin repeat containing | ||||||||||||||||||||||
Synonyms | CAM; CCM1; | ||||||||||||||||||||||
Species | Homo sapiens | ||||||||||||||||||||||
Ensembl Protein | ENSP00000378011 | ||||||||||||||||||||||
InnateDB Gene | IDBG-26317 (KRIT1) | ||||||||||||||||||||||
Protein Structure | |||||||||||||||||||||||
UniProt Annotation | |||||||||||||||||||||||
Function | 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 indirectly 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. {ECO:0000250, ECO:0000269PubMed:11741838, ECO:0000269PubMed:17916086, ECO:0000269PubMed:20332120, ECO:0000269PubMed:20616044, ECO:0000269PubMed:20668652, ECO:0000269PubMed:21633110, ECO:0000269Ref.20}. | ||||||||||||||||||||||
Subcellular Localization | Cytoplasm, cytoskeleton. Cell membrane; Peripheral membrane protein. Cell junction. Note=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. | ||||||||||||||||||||||
Disease Associations | Cerebral cavernous malformations 1 (CCM1) [MIM:116860]: A congenital vascular anomaly of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. The lesions are characterized by grossly enlarged blood vessels consisting of a single layer of endothelium and without any intervening neural tissue, ranging in diameter from a few millimeters to several centimeters. {ECO:0000269PubMed:12172908}. Note=The disease is caused by mutations affecting the gene represented in this entry. | ||||||||||||||||||||||
Tissue Specificity | Low levels in brain. Very weak expression found in heart and muscle. {ECO:0000269PubMed:9285558}. | ||||||||||||||||||||||
Comments | |||||||||||||||||||||||
Interactions | |||||||||||||||||||||||
Number of Interactions |
This gene and/or its encoded proteins are associated with 19 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.
|
||||||||||||||||||||||
Gene Ontology | |||||||||||||||||||||||
Molecular Function |
|
||||||||||||||||||||||
Biological Process |
|
||||||||||||||||||||||
Cellular Component |
|
||||||||||||||||||||||
Protein Structure and Domains | |||||||||||||||||||||||
PDB ID | |||||||||||||||||||||||
InterPro |
IPR000299
FERM domain IPR002110 Ankyrin repeat IPR019748 FERM central domain IPR019749 Band 4.1 domain IPR020683 Ankyrin repeat-containing domain IPR029071 Ubiquitin-related domain |
||||||||||||||||||||||
PFAM |
PF00023
PF13606 PF00373 PF11929 PF12796 |
||||||||||||||||||||||
PRINTS |
PR01415
|
||||||||||||||||||||||
PIRSF | |||||||||||||||||||||||
SMART |
SM00248
SM00295 |
||||||||||||||||||||||
TIGRFAMs | |||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||
Modification | |||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||
SwissProt | O00522 | ||||||||||||||||||||||
PhosphoSite | PhosphoSite-O00522 | ||||||||||||||||||||||
TrEMBL | C9JXI9 | ||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||
Entrez Gene | 889 | ||||||||||||||||||||||
UniGene | Hs.531987 | ||||||||||||||||||||||
RefSeq | NP_001013424 | ||||||||||||||||||||||
HUGO | HGNC:1573 | ||||||||||||||||||||||
OMIM | 604214 | ||||||||||||||||||||||
CCDS | CCDS34679 | ||||||||||||||||||||||
HPRD | 05020 | ||||||||||||||||||||||
IMGT | |||||||||||||||||||||||
EMBL | AC000120 AF296765 AF310133 AF388384 AJ294850 AK055305 AY380057 AY993945 BC094684 BC098442 U90268 U90269 | ||||||||||||||||||||||
GenPept | AAB58582 AAC01535 AAG10220 AAG47774 AAH94684 AAH98442 AAM19465 AAQ94072 AAS07420 AAY25568 BAG51497 CAC17608 | ||||||||||||||||||||||