KRIT1

Existing Annotations Review

GO Term	Evidence	Action	Reason
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	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:0051093 negative regulation of developmental process	IEA GO_REF:0000117	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: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:2000026 regulation of multicellular organismal development	IEA GO_REF:0000117	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.