CCDC88A
Description
The CCDC88A (coiled-coil domain containing 88A) is a protein-coding gene located on chromosome 2.
Girdin is a protein encoded by the CCDC88A gene in humans. While its cellular function is not fully understood, it has been linked to glioma.
CCDC88A (Girdin) is a bifunctional modulator of G proteins. It acts as a non-receptor guanine nucleotide exchange factor that binds and activates G(i) alpha subunits, and also functions as a guanine nucleotide dissociation inhibitor for G(s) subunit alpha GNAS. This protein is essential for cell migration and interacts with G(i) alpha subunits and the EGFR receptor, promoting EGFR signaling and retaining EGFR at the cell membrane following ligand stimulation. CCDC88A binding to Gi-alpha subunits displaces the beta and gamma subunits from the heterotrimeric G-protein complex, enhancing AKT1/PKB phosphorylation and kinase activity. AKT1/PKB phosphorylation leads to phosphorylation of downstream effectors GSK3 and FOXO1/FKHR, regulating DNA replication and cell proliferation. CCDC88A in its tyrosine-phosphorylated form binds to the PI3K regulatory subunit PIK3R1, enabling PIK3R1 recruitment to the EGFR receptor and enhancing PI3K activity and cell migration. It is also a key modulator of the AKT-mTOR signaling pathway, controlling newborn neuron integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Inhibition of G(s) subunit alpha GNAS reduces cellular cAMP levels and suppresses cell proliferation. CCDC88A is crucial for maintaining the integrity of the actin cytoskeleton, playing a role in the formation of actin stress fibers and lamellipodia. It may be involved in membrane sorting within the early endosome and contributes to ciliogenesis, cilium morphology, and positioning, potentially through regulation of the localization of the scaffolding protein CROCC/Rootletin.
CCDC88A is also known as APE, GIRDIN, GIV, GRDN, HkRP1, KIAA1212, PEHO, PEHOL.
