KRIT1

UniProt ID: O00522
Organism: Homo sapiens
Review Status: IN PROGRESS
πŸ“ Provide Detailed Feedback

Gene Description

KRIT1/CCM1 is a multidomain scaffold and Rap1 effector that organizes endothelial cell junctions and vascular signaling. Its N-terminal interaction motifs, ankyrin repeats and C-terminal FERM domain couple CCM-complex partners, integrin regulation, microtubule association and membrane recruitment. It supports vascular barrier integrity and endothelial polarity and restrains excessive angiogenic signaling. Human loss-of-function variants cause cerebral cavernous malformations.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0001937 negative regulation of endothelial cell proliferation
IMP
PMID:20616044
Cerebral cavernous malformation protein CCM1 inhibits sprout...
KEEP AS NON CORE
Summary: Human endothelial perturbation supports this antiangiogenic/developmental regulatory effect.
Reason: CCM1 perturbation directly changes endothelial proliferation, migration, apoptosis and sprouting in primary human endothelial cells. These are documented consequences of the junctional signaling regulator. Broad developmental-process annotations are retained as non-core; they do not identify a distinct enzyme function or germline piRNA mechanism.
Supporting Evidence:
PMID:20616044
CCM1 inhibits endothelial proliferation, apoptosis, migration, lumen formation, and sprouting angiogenesis in primary human endothelial cells.
GO:0003158 endothelium development
NAS
PMID:17657516
CCM3 interacts with CCM2 indicating common pathogenesis for ...
KEEP AS NON CORE
Summary: Vascular developmental regulation is supported by the CCM1 scaffold mechanism.
Reason: KRIT1 regulates endothelial organization and quiescence, with experimental vascular-development phenotypes. The generic developmental/regulatory term is compatible but less informative than the endothelial-junction and angiogenesis mechanisms.
Supporting Evidence:
PMID:20616044
CCM1 inhibits endothelial proliferation, apoptosis, migration, lumen formation, and sprouting angiogenesis in primary human endothelial cells.
GO:0005515 protein binding
IPI
PMID:16037064
CCM1 and CCM2 protein interactions in cell signaling: implic...
KEEP AS NON CORE
Summary: Retain the curated interaction as a non-core observation rather than generic core binding.
Reason: The IPI row from PMID:16037064 records a physical interaction. KRIT1 has a defined scaffold/Rap1-effector role, but generic protein binding does not establish the function of every partner. No interaction is rejected because a title foregrounds another protein.
GO:0005515 protein binding
IPI
PMID:17657516
CCM3 interacts with CCM2 indicating common pathogenesis for ...
KEEP AS NON CORE
Summary: Retain the curated interaction as a non-core observation rather than generic core binding.
Reason: The IPI row from PMID:17657516 records a physical interaction. KRIT1 has a defined scaffold/Rap1-effector role, but generic protein binding does not establish the function of every partner. No interaction is rejected because a title foregrounds another protein.
GO:0005515 protein binding
IPI
PMID:17916086
Krit 1 interactions with microtubules and membranes are regu...
KEEP AS NON CORE
Summary: Retain the curated interaction as a non-core observation rather than generic core binding.
Reason: The IPI row from PMID:17916086 records a physical interaction. KRIT1 has a defined scaffold/Rap1-effector role, but generic protein binding does not establish the function of every partner. No interaction is rejected because a title foregrounds another protein.
GO:0005515 protein binding
IPI
PMID:17916086
Krit 1 interactions with microtubules and membranes are regu...
KEEP AS NON CORE
Summary: Retain the curated interaction as a non-core observation rather than generic core binding.
Reason: The IPI row from PMID:17916086 records a physical interaction. KRIT1 has a defined scaffold/Rap1-effector role, but generic protein binding does not establish the function of every partner. No interaction is rejected because a title foregrounds another protein.
GO:0005515 protein binding
IPI
PMID:20332120
CCM1 regulates vascular-lumen organization by inducing endot...
KEEP AS NON CORE
Summary: Retain the curated interaction as a non-core observation rather than generic core binding.
Reason: The IPI row from PMID:20332120 records a physical interaction. KRIT1 has a defined scaffold/Rap1-effector role, but generic protein binding does not establish the function of every partner. No interaction is rejected because a title foregrounds another protein.
GO:0005515 protein binding
IPI
PMID:23007647
Structural basis of the junctional anchorage of the cerebral...
KEEP AS NON CORE
Summary: Retain the curated interaction as a non-core observation rather than generic core binding.
Reason: The IPI row from PMID:23007647 records a physical interaction. KRIT1 has a defined scaffold/Rap1-effector role, but generic protein binding does not establish the function of every partner. No interaction is rejected because a title foregrounds another protein.
GO:0005515 protein binding
IPI
PMID:23007647
Structural basis of the junctional anchorage of the cerebral...
KEEP AS NON CORE
Summary: Retain the curated interaction as a non-core observation rather than generic core binding.
Reason: The IPI row from PMID:23007647 records a physical interaction. KRIT1 has a defined scaffold/Rap1-effector role, but generic protein binding does not establish the function of every partner. No interaction is rejected because a title foregrounds another protein.
GO:0005515 protein binding
IPI
PMID:25525273
Structural basis for the disruption of the cerebral cavernou...
KEEP AS NON CORE
Summary: Retain the curated interaction as a non-core observation rather than generic core binding.
Reason: The IPI row from PMID:25525273 records a physical interaction. KRIT1 has a defined scaffold/Rap1-effector role, but generic protein binding does not establish the function of every partner. No interaction is rejected because a title foregrounds another protein.
GO:0005515 protein binding
IPI
PMID:25814554
Phospho-tyrosine dependent protein-protein interaction netwo...
KEEP AS NON CORE
Summary: Retain the curated interaction as a non-core observation rather than generic core binding.
Reason: The IPI row from PMID:25814554 records a physical interaction. KRIT1 has a defined scaffold/Rap1-effector role, but generic protein binding does not establish the function of every partner. No interaction is rejected because a title foregrounds another protein.
GO:0005515 protein binding
IPI
PMID:25814554
Phospho-tyrosine dependent protein-protein interaction netwo...
KEEP AS NON CORE
Summary: Retain the curated interaction as a non-core observation rather than generic core binding.
Reason: The IPI row from PMID:25814554 records a physical interaction. KRIT1 has a defined scaffold/Rap1-effector role, but generic protein binding does not establish the function of every partner. No interaction is rejected because a title foregrounds another protein.
GO:0005515 protein binding
IPI
PMID:25910212
Widespread macromolecular interaction perturbations in human...
KEEP AS NON CORE
Summary: Retain the curated interaction as a non-core observation rather than generic core binding.
Reason: The IPI row from PMID:25910212 records a physical interaction. KRIT1 has a defined scaffold/Rap1-effector role, but generic protein binding does not establish the function of every partner. No interaction is rejected because a title foregrounds another protein.
GO:0005515 protein binding
IPI
PMID:25910212
Widespread macromolecular interaction perturbations in human...
KEEP AS NON CORE
Summary: Retain the curated interaction as a non-core observation rather than generic core binding.
Reason: The IPI row from PMID:25910212 records a physical interaction. KRIT1 has a defined scaffold/Rap1-effector role, but generic protein binding does not establish the function of every partner. No interaction is rejected because a title foregrounds another protein.
GO:0005515 protein binding
IPI
PMID:26780829
Heart of glass anchors Rasip1 at endothelial cell-cell junct...
KEEP AS NON CORE
Summary: Retain the curated interaction as a non-core observation rather than generic core binding.
Reason: The IPI row from PMID:26780829 records a physical interaction. KRIT1 has a defined scaffold/Rap1-effector role, but generic protein binding does not establish the function of every partner. No interaction is rejected because a title foregrounds another protein.
GO:0005515 protein binding
IPI
PMID:27027284
Cerebral cavernous malformations arise from endothelial gain...
KEEP AS NON CORE
Summary: Retain the curated interaction as a non-core observation rather than generic core binding.
Reason: The IPI row from PMID:27027284 records a physical interaction. KRIT1 has a defined scaffold/Rap1-effector role, but generic protein binding does not establish the function of every partner. No interaction is rejected because a title foregrounds another protein.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: Retain the curated interaction as a non-core observation rather than generic core binding.
Reason: The IPI row from PMID:32296183 records a physical interaction. KRIT1 has a defined scaffold/Rap1-effector role, but generic protein binding does not establish the function of every partner. No interaction is rejected because a title foregrounds another protein.
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling...
KEEP AS NON CORE
Summary: Retain the curated interaction as a non-core observation rather than generic core binding.
Reason: The IPI row from PMID:33961781 records a physical interaction. KRIT1 has a defined scaffold/Rap1-effector role, but generic protein binding does not establish the function of every partner. No interaction is rejected because a title foregrounds another protein.
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling...
KEEP AS NON CORE
Summary: Retain the curated interaction as a non-core observation rather than generic core binding.
Reason: The IPI row from PMID:33961781 records a physical interaction. KRIT1 has a defined scaffold/Rap1-effector role, but generic protein binding does not establish the function of every partner. No interaction is rejected because a title foregrounds another protein.
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling...
KEEP AS NON CORE
Summary: Retain the curated interaction as a non-core observation rather than generic core binding.
Reason: The IPI row from PMID:33961781 records a physical interaction. KRIT1 has a defined scaffold/Rap1-effector role, but generic protein binding does not establish the function of every partner. No interaction is rejected because a title foregrounds another protein.
GO:0005515 protein binding
IPI
PMID:40205054
Multimodal cell maps as a foundation for structural and func...
KEEP AS NON CORE
Summary: Retain the curated interaction as a non-core observation rather than generic core binding.
Reason: The IPI row from PMID:40205054 records a physical interaction. KRIT1 has a defined scaffold/Rap1-effector role, but generic protein binding does not establish the function of every partner. No interaction is rejected because a title foregrounds another protein.
GO:0005546 phosphatidylinositol-4,5-bisphosphate binding
IDA
PMID:17916086
Krit 1 interactions with microtubules and membranes are regu...
ACCEPT
Summary: KRIT1 binds PIP2-containing membranes.
Reason: The primary sedimentation/liposome study demonstrates PIP2-liposome association enhanced by Rap1. This directly supports the lipid-binding activity within its membrane-recruitment mechanism.
Supporting Evidence:
PMID:17916086
Krit1 binds to phosphatidylinositol 4,5-P(2)-containing liposomes
GO:0005576 extracellular region
HDA
PMID:22664934
Comparison of tear protein levels in breast cancer patients ...
KEEP AS NON CORE
Summary: Retain extracellular proteomics detection as a non-core observation.
Reason: The HDA source records detection outside cells. KRIT1 is principally an intracellular scaffold; this observation alone does not establish a secreted physiological function. Detection is retained without inferring a secretion mechanism.
GO:0005737 cytoplasm
IEA
GO_REF:0000107
ACCEPT
Summary: Membrane/junctional and cytoplasmic pools are supported by KRIT1 recruitment experiments.
Reason: Rap1-dependent release from microtubules permits junctional recruitment, while CCM1 participates in the VE-cadherin polarity complex. The selected horse sequence retains the corresponding scaffold architecture and extensive sequence conservation, supporting transfer of these broad compartments.
Supporting Evidence:
PMID:20332120
Both VEC and CCM1 control Rap1 concentration at cell-cell junctions.
PMID:21633110
Rap1 binding released KRIT1 from microtubules
GO:0005856 cytoskeleton
IEA
GO_REF:0000044
ACCEPT
Summary: Microtubule association contributes to KRIT1 spatial regulation.
Reason: In vitro binding and cellular localization demonstrate microtubule association, and Rap1/ICAP1 alter that association. This is a mechanistic localization/binding property of the scaffold rather than evidence of a microtubule motor.
Supporting Evidence:
PMID:17916086
Krit1 binds in vitro to microtubules through its N- and C-termini
GO:0005886 plasma membrane
IBA
GO_REF:0000033
ACCEPT
Summary: Membrane/junctional and cytoplasmic pools are supported by KRIT1 recruitment experiments.
Reason: Rap1-dependent release from microtubules permits junctional recruitment, while CCM1 participates in the VE-cadherin polarity complex. The selected horse sequence retains the corresponding scaffold architecture and extensive sequence conservation, supporting transfer of these broad compartments.
Supporting Evidence:
PMID:20332120
Both VEC and CCM1 control Rap1 concentration at cell-cell junctions.
PMID:21633110
Rap1 binding released KRIT1 from microtubules
GO:0005886 plasma membrane
IDA
PMID:17916086
Krit 1 interactions with microtubules and membranes are regu...
ACCEPT
Summary: Membrane/junctional and cytoplasmic pools are supported by KRIT1 recruitment experiments.
Reason: Rap1-dependent release from microtubules permits junctional recruitment, while CCM1 participates in the VE-cadherin polarity complex. The selected horse sequence retains the corresponding scaffold architecture and extensive sequence conservation, supporting transfer of these broad compartments.
Supporting Evidence:
PMID:20332120
Both VEC and CCM1 control Rap1 concentration at cell-cell junctions.
PMID:21633110
Rap1 binding released KRIT1 from microtubules
GO:0005886 plasma membrane
IEA
GO_REF:0000044
ACCEPT
Summary: Membrane/junctional and cytoplasmic pools are supported by KRIT1 recruitment experiments.
Reason: Rap1-dependent release from microtubules permits junctional recruitment, while CCM1 participates in the VE-cadherin polarity complex. The selected horse sequence retains the corresponding scaffold architecture and extensive sequence conservation, supporting transfer of these broad compartments.
Supporting Evidence:
PMID:20332120
Both VEC and CCM1 control Rap1 concentration at cell-cell junctions.
PMID:21633110
Rap1 binding released KRIT1 from microtubules
GO:0005911 cell-cell junction
IDA
PMID:20332120
CCM1 regulates vascular-lumen organization by inducing endot...
ACCEPT
Summary: Membrane/junctional and cytoplasmic pools are supported by KRIT1 recruitment experiments.
Reason: Rap1-dependent release from microtubules permits junctional recruitment, while CCM1 participates in the VE-cadherin polarity complex. The selected horse sequence retains the corresponding scaffold architecture and extensive sequence conservation, supporting transfer of these broad compartments.
Supporting Evidence:
PMID:20332120
Both VEC and CCM1 control Rap1 concentration at cell-cell junctions.
PMID:21633110
Rap1 binding released KRIT1 from microtubules
GO:0005911 cell-cell junction
IDA
PMID:23007647
Structural basis of the junctional anchorage of the cerebral...
ACCEPT
Summary: Membrane/junctional and cytoplasmic pools are supported by KRIT1 recruitment experiments.
Reason: Rap1-dependent release from microtubules permits junctional recruitment, while CCM1 participates in the VE-cadherin polarity complex. The selected horse sequence retains the corresponding scaffold architecture and extensive sequence conservation, supporting transfer of these broad compartments.
Supporting Evidence:
PMID:20332120
Both VEC and CCM1 control Rap1 concentration at cell-cell junctions.
PMID:21633110
Rap1 binding released KRIT1 from microtubules
GO:0007264 small GTPase-mediated signal transduction
TAS
PMID:9285558
Association of Krev-1/rap1a with Krit1, a novel ankyrin repe...
ACCEPT
Summary: KRIT1 is a direct Rap1 effector in small-GTPase signaling.
Reason: The GTP-dependent Rap1 interaction and structure-guided mutagenesis establish direct participation in the signaling mechanism, without implying intrinsic GTPase catalytic activity.
Supporting Evidence:
PMID:21633110
native KRIT1 protein binds the effector loop of Rap1A but not H-Ras in a GTP-dependent manner
GO:0008017 microtubule binding
IBA
GO_REF:0000033
ACCEPT
Summary: Microtubule association contributes to KRIT1 spatial regulation.
Reason: In vitro binding and cellular localization demonstrate microtubule association, and Rap1/ICAP1 alter that association. This is a mechanistic localization/binding property of the scaffold rather than evidence of a microtubule motor.
Supporting Evidence:
PMID:17916086
Krit1 binds in vitro to microtubules through its N- and C-termini
GO:0008017 microtubule binding
IDA
PMID:17916086
Krit 1 interactions with microtubules and membranes are regu...
ACCEPT
Summary: Microtubule association contributes to KRIT1 spatial regulation.
Reason: In vitro binding and cellular localization demonstrate microtubule association, and Rap1/ICAP1 alter that association. This is a mechanistic localization/binding property of the scaffold rather than evidence of a microtubule motor.
Supporting Evidence:
PMID:17916086
Krit1 binds in vitro to microtubules through its N- and C-termini
GO:0009948 anterior/posterior axis specification
IBA
GO_REF:0000033
UNDECIDED
Summary: The anterior/posterior-axis IBA requires direct assessment of the ancestral developmental evidence.
Reason: Vascular morphogenesis and polarity evidence do not by themselves establish anterior/posterior axis specification. The PAINT assertion is a curated phylogenetic judgment and is not rejected, but the pertinent developmental evidence has not been resolved in this review.
GO:0010596 negative regulation of endothelial cell migration
IMP
PMID:20616044
Cerebral cavernous malformation protein CCM1 inhibits sprout...
KEEP AS NON CORE
Summary: Human endothelial perturbation supports this antiangiogenic/developmental regulatory effect.
Reason: CCM1 perturbation directly changes endothelial proliferation, migration, apoptosis and sprouting in primary human endothelial cells. These are documented consequences of the junctional signaling regulator. Broad developmental-process annotations are retained as non-core; they do not identify a distinct enzyme function or germline piRNA mechanism.
Supporting Evidence:
PMID:20616044
CCM1 inhibits endothelial proliferation, apoptosis, migration, lumen formation, and sprouting angiogenesis in primary human endothelial cells.
GO:0016525 negative regulation of angiogenesis
IBA
GO_REF:0000033
ACCEPT
Summary: Human endothelial perturbation supports this antiangiogenic/developmental regulatory effect.
Reason: CCM1 perturbation directly changes endothelial proliferation, migration, apoptosis and sprouting in primary human endothelial cells. These are documented consequences of the junctional signaling regulator. Broad developmental-process annotations are retained as non-core; they do not identify a distinct enzyme function or germline piRNA mechanism.
Supporting Evidence:
PMID:20616044
CCM1 inhibits endothelial proliferation, apoptosis, migration, lumen formation, and sprouting angiogenesis in primary human endothelial cells.
GO:0016525 negative regulation of angiogenesis
IEA
GO_REF:0000120
ACCEPT
Summary: Human endothelial perturbation supports this antiangiogenic/developmental regulatory effect.
Reason: CCM1 perturbation directly changes endothelial proliferation, migration, apoptosis and sprouting in primary human endothelial cells. These are documented consequences of the junctional signaling regulator. Broad developmental-process annotations are retained as non-core; they do not identify a distinct enzyme function or germline piRNA mechanism.
Supporting Evidence:
PMID:20616044
CCM1 inhibits endothelial proliferation, apoptosis, migration, lumen formation, and sprouting angiogenesis in primary human endothelial cells.
GO:0016525 negative regulation of angiogenesis
IMP
PMID:20616044
Cerebral cavernous malformation protein CCM1 inhibits sprout...
ACCEPT
Summary: Human endothelial perturbation supports this antiangiogenic/developmental regulatory effect.
Reason: CCM1 perturbation directly changes endothelial proliferation, migration, apoptosis and sprouting in primary human endothelial cells. These are documented consequences of the junctional signaling regulator. Broad developmental-process annotations are retained as non-core; they do not identify a distinct enzyme function or germline piRNA mechanism.
Supporting Evidence:
PMID:20616044
CCM1 inhibits endothelial proliferation, apoptosis, migration, lumen formation, and sprouting angiogenesis in primary human endothelial cells.
GO:0030695 GTPase regulator activity
IEA
GO_REF:0000117
MODIFY
Summary: Direct Rap1 binding is established; intrinsic GTPase regulation is not the demonstrated mechanism.
Reason: The early two-hybrid paper suggested KRIT1 might regulate Krev-1, but later direct binding and mutagenesis establish a GTP-dependent Rap1 effector. These experiments do not show nucleotide exchange or GTPase activation. Use small GTPase binding to express the demonstrated molecular interaction.
Proposed replacements: small GTPase binding
Supporting Evidence:
PMID:21633110
native KRIT1 protein binds the effector loop of Rap1A but not H-Ras in a GTP-dependent manner
GO:0030695 GTPase regulator activity
TAS
PMID:9285558
Association of Krev-1/rap1a with Krit1, a novel ankyrin repe...
MODIFY
Summary: Direct Rap1 binding is established; intrinsic GTPase regulation is not the demonstrated mechanism.
Reason: The early two-hybrid paper suggested KRIT1 might regulate Krev-1, but later direct binding and mutagenesis establish a GTP-dependent Rap1 effector. These experiments do not show nucleotide exchange or GTPase activation. Use small GTPase binding to express the demonstrated molecular interaction.
Proposed replacements: small GTPase binding
Supporting Evidence:
PMID:21633110
native KRIT1 protein binds the effector loop of Rap1A but not H-Ras in a GTP-dependent manner
GO:0032991 protein-containing complex
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Generic complex membership is compatible with the CCM scaffold.
Reason: KRIT1 forms defined partner assemblies, but the generic protein-containing-complex term does not specify which functional assembly. It is a compatible non-core annotation.
Supporting Evidence:
PMID:20332120
We propose that VEC, CCM1 and Rap1 form a signaling complex.
GO:0033622 integrin activation
IDA
PMID:23317506
Mechanism for KRIT1 release of ICAP1-mediated suppression of...
ACCEPT
Summary: KRIT1 promotes integrin activation by competing for ICAP1.
Reason: The cocrystal/competition study demonstrates a bidentate KRIT1–ICAP1 interface and antagonism of ICAP1-mediated integrin inhibition. This is direct scaffold regulation of integrin activation.
Supporting Evidence:
PMID:23317506
KRIT1 directly competes with integrin Ξ²1 to bind ICAP1
GO:0045454 cell redox homeostasis
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: KRIT1 affects cellular redox homeostasis through signaling regulation.
Reason: Loss and restoration of KRIT1 modulate ROS and FOXO1/SOD2 levels. The phenotype supports redox homeostasis but does not imply intrinsic antioxidant enzyme activity.
Supporting Evidence:
PMID:20668652
KRIT1 loss/down-regulation is associated with a significant increase in intracellular ROS levels.
GO:0045454 cell redox homeostasis
IEA
GO_REF:0000120
KEEP AS NON CORE
Summary: KRIT1 affects cellular redox homeostasis through signaling regulation.
Reason: Loss and restoration of KRIT1 modulate ROS and FOXO1/SOD2 levels. The phenotype supports redox homeostasis but does not imply intrinsic antioxidant enzyme activity.
Supporting Evidence:
PMID:20668652
KRIT1 loss/down-regulation is associated with a significant increase in intracellular ROS levels.
GO:0045454 cell redox homeostasis
IMP
PMID:20668652
KRIT1 regulates the homeostasis of intracellular reactive ox...
KEEP AS NON CORE
Summary: KRIT1 affects cellular redox homeostasis through signaling regulation.
Reason: Loss and restoration of KRIT1 modulate ROS and FOXO1/SOD2 levels. The phenotype supports redox homeostasis but does not imply intrinsic antioxidant enzyme activity.
Supporting Evidence:
PMID:20668652
KRIT1 loss/down-regulation is associated with a significant increase in intracellular ROS levels.
GO:0045765 regulation of angiogenesis
NAS
PMID:17657516
CCM3 interacts with CCM2 indicating common pathogenesis for ...
KEEP AS NON CORE
Summary: Vascular developmental regulation is supported by the CCM1 scaffold mechanism.
Reason: KRIT1 regulates endothelial organization and quiescence, with experimental vascular-development phenotypes. The generic developmental/regulatory term is compatible but less informative than the endothelial-junction and angiogenesis mechanisms.
Supporting Evidence:
PMID:20616044
CCM1 inhibits endothelial proliferation, apoptosis, migration, lumen formation, and sprouting angiogenesis in primary human endothelial cells.
GO:0070161 anchoring junction
IEA
GO_REF:0000044
ACCEPT
Summary: Membrane/junctional and cytoplasmic pools are supported by KRIT1 recruitment experiments.
Reason: Rap1-dependent release from microtubules permits junctional recruitment, while CCM1 participates in the VE-cadherin polarity complex. The selected horse sequence retains the corresponding scaffold architecture and extensive sequence conservation, supporting transfer of these broad compartments.
Supporting Evidence:
PMID:20332120
Both VEC and CCM1 control Rap1 concentration at cell-cell junctions.
PMID:21633110
Rap1 binding released KRIT1 from microtubules
GO:2000114 regulation of establishment of cell polarity
IBA
GO_REF:0000033
ACCEPT
Summary: KRIT1 directly supports endothelial polarity-complex organization.
Reason: CCM1 interacts with VE-cadherin and organizes adherens-junction association with the Par polarity complex; loss disrupts cell polarity. This is a specific regulatory role of the scaffold.
Supporting Evidence:
PMID:20332120
In the absence of any of these proteins, AJs are dismantled, cell polarity is lost
GO:2000114 regulation of establishment of cell polarity
IEA
GO_REF:0000120
ACCEPT
Summary: KRIT1 directly supports endothelial polarity-complex organization.
Reason: CCM1 interacts with VE-cadherin and organizes adherens-junction association with the Par polarity complex; loss disrupts cell polarity. This is a specific regulatory role of the scaffold.
Supporting Evidence:
PMID:20332120
In the absence of any of these proteins, AJs are dismantled, cell polarity is lost
GO:2000114 regulation of establishment of cell polarity
IMP
PMID:20332120
CCM1 regulates vascular-lumen organization by inducing endot...
ACCEPT
Summary: KRIT1 directly supports endothelial polarity-complex organization.
Reason: CCM1 interacts with VE-cadherin and organizes adherens-junction association with the Par polarity complex; loss disrupts cell polarity. This is a specific regulatory role of the scaffold.
Supporting Evidence:
PMID:20332120
In the absence of any of these proteins, AJs are dismantled, cell polarity is lost
GO:2000352 negative regulation of endothelial cell apoptotic process
IMP
PMID:20616044
Cerebral cavernous malformation protein CCM1 inhibits sprout...
KEEP AS NON CORE
Summary: Human endothelial perturbation supports this antiangiogenic/developmental regulatory effect.
Reason: CCM1 perturbation directly changes endothelial proliferation, migration, apoptosis and sprouting in primary human endothelial cells. These are documented consequences of the junctional signaling regulator. Broad developmental-process annotations are retained as non-core; they do not identify a distinct enzyme function or germline piRNA mechanism.
Supporting Evidence:
PMID:20616044
CCM1 inhibits endothelial proliferation, apoptosis, migration, lumen formation, and sprouting angiogenesis in primary human endothelial cells.

Core Functions

Rap1-effector binding coupled to recruitment of the KRIT1 junctional scaffold.

Molecular Function:
small GTPase binding
Cellular Locations:
Supporting Evidence:
  • PMID:21633110
    native KRIT1 protein binds the effector loop of Rap1A but not H-Ras in a GTP-dependent manner

References

Loading supporting content…

Download this section (compressed HTML)

Deep Research

Falcon

(KRIT1-deep-research-falcon.md)

Loading supporting content…

Download this section (compressed HTML)

πŸ“š Additional Documentation

Notes

(KRIT1-notes.md)

Loading supporting content…

Download this section (compressed HTML)

πŸ“„ View Raw YAML

Loading supporting content…

Download this section (compressed HTML)