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Connector enhancer of kinase suppressor of ras 2/3 domain This family represents a conserved region of unknown function within Connector enhancer of kinase suppressor of ras 2 (CNK2, also known MAGUIN), Connector enhancer of kinase suppressor of ras 3 (CNK3) and CNK3/IPCEF1 fusion protein. This region is situated between the PDZ pfam00595 and PH pfam00169 domains in CNK2 and CNK3/IPCEF1, and after the PDZ domain in CNK3. All family members also contain an N-terminal pfam00536 domain. CNK2 is predominantly expressed in neural tissues, being critical for postsynaptic density morphology, implicated in X-linked intellectual disability (ID). CNK2 was first described as a regulator of Ras/MAPK signalling that lead to further studies concluding that it act as a scaffold for multiple signal cascades. It is able to direct the localization of regulatory proteins within the cell and influences the behaviour of important regulatory molecules. CNK3 regulates aldosterone-induced and epithelial sodium channel (ENaC)-mediated sodium transport through regulation of ENaC cell surface expression, acting as a scaffold protein that coordinates the assembly of an ENaC-regulatory complex (ERC). CNK3/IPCEF1 is required for hepatocyte growth factor (HGF)-dependent activation of Arf6 and HGF-stimulated cell migration. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",