CCDC88C
Domain
The GBA (G-alpha binding and activating) motif mediates binding to the alpha subunits of guanine nucleotide-binding proteins (G proteins).
The PDZ domain is required for localization to apical junctions.
Function
Required for activation of guanine nucleotide-binding proteins (G-proteins) during non-canonical Wnt signaling (PubMed:26126266). Binds to ligand-activated Wnt receptor FZD7, displacing DVL1 from the FZD7 receptor and leading to inhibition of canonical Wnt signaling (PubMed:26126266). Acts as a non-receptor guanine nucleotide exchange factor by also binding to guanine nucleotide-binding protein G(i) alpha (Gi-alpha) subunits, leading to their activation (PubMed:26126266). Binding to Gi-alpha subunits displaces the beta and gamma subunits from the heterotrimeric G-protein complex, triggering non-canonical Wnt responses such as activation of RAC1 and PI3K-AKT signaling (PubMed:26126266). Promotes apical constriction of cells via ARHGEF18 (PubMed:30948426).
Involvement in disease
Hydrocephalus, congenital, 1
HYC1
A form of congenital hydrocephalus, a disease characterized by onset in utero of enlarged ventricles due to accumulation of ventricular cerebrospinal fluid. Affected individuals may have neurologic impairment. HYC1 inheritance is autosomal recessive.
None
The disease is caused by variants affecting the gene represented in this entry.
Spinocerebellar ataxia 40
SCA40
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA40 is an autosomal dominant, slowly progressive form. Brain MRI shows pontocerebellar atrophy along with a global reduction in brain volume.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the CCDC88 family.
Cellular localization
- Cytoplasm
- Cell junction
- Enriched at apical cell junctions.
Alternative names
DAPLE, KIAA1509, CCDC88C, Protein Daple, Coiled-coil domain-containing protein 88C, Dvl-associating protein with a high frequency of leucine residues, Hook-related protein 2, hDaple, HkRP2