InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Krit1

Summary

InnateDB Protein

IDBP-131995.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Krit1

Protein Name

KRIT1, ankyrin repeat containing

Synonyms

2010007K12Rik; A630036P20Rik; AA432855; AI450393; AI643869; BB155247; BB235701; Ccm1;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000078985

InnateDB Gene

IDBG-131993 (Krit1)

Protein Structure

UniProt Annotation

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. 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 (By similarity). 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:20332120, ECO:0000269PubMed:20616044, ECO:0000269PubMed:20668652}.

Subcellular Localization

Cytoplasm, cytoskeleton {ECO:0000250}. Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Cell junction {ECO:0000250}. 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 an ITGB1BP1-dependent manner (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

Expressed in heart, brain, spleen, lung, thymus, kidney and testis. Isoform 2 was more frequently expressed in the thymus than isoform 1. {ECO:0000269PubMed:12172908, ECO:0000269PubMed:14697511}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 3 experimentally validated interaction(s) in this database.
They are also associated with 15 interaction(s) predicted by orthology.

Experimentally validated
Total	3 [view]
Protein-Protein	2 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	15 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005083	small GTPase regulator activity
GO:0005515	protein binding
GO:0005546	phosphatidylinositol-4,5-bisphosphate binding
GO:0008017	microtubule binding
GO:0032403	protein complex binding

Biological Process

GO:0001525	angiogenesis
GO:0001937	negative regulation of endothelial cell proliferation
GO:0010596	negative regulation of endothelial cell migration
GO:0016525	negative regulation of angiogenesis
GO:0032092	positive regulation of protein binding
GO:0045454	cell redox homeostasis
GO:0050790	regulation of catalytic activity
GO:2000114	regulation of establishment of cell polarity
GO:2000352	negative regulation of endothelial cell apoptotic process

Cellular Component

GO:0005615	extracellular space
GO:0005737	cytoplasm
GO:0005856	cytoskeleton
GO:0005874	microtubule
GO:0005886	plasma membrane
GO:0005911	cell-cell junction
GO:0043234	protein complex

Protein Structure and Domains

PDB ID

MGI:1930618

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