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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 localisation of regulatory proteins within the cell and influences the behaviour of important regulatory molecules [[cite:PUB00016229],[cite:PUB00097808]]. 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) [[cite:PUB00097809]]. CNK3/IPCEF1 is required for hepatocyte growth factor (HGF)-dependent activation of Arf6 and HGF-stimulated cell migration [[cite:PUB00097810]].","domain_architectures":52,"interpro_id":"IPR010599","known_evidence_count":null,"matches":3637,"name":"Connector enhancer of kinase suppressor of ras 2/3 domain","partial_evidence_count":null,"pfam_id":"PF06663","proteins":3585,"proteomes":735,"short_name":"CNK2_3_dom","source_url":"https://www.ebi.ac.uk/interpro/api/entry/pfam/PF06663","structures":0,"taxa":2235,"unknown_status":"EX_DUF"},"inputs":{"cross_mech":"cross-mech-duf-examples-2026-10-10","members":"pfam-uniprot-uniref90-2026-10-07","protein_examples":"duf-protein-examples-2026-10-13","worklist":"interpro-pfam-duf-2026-10-10"},"members":[],"metadata":{"curation_status":"SEEDED","local_source":"source/data/families/PF06663.yaml","record":{"characterization_status":"UNSCORED","counters":{"alphafold_models":3207,"domain_architectures":52,"matches":3637,"proteins":3585,"proteomes":735,"structures":0,"taxa":2235},"curation_status":"SEEDED","description":"This family represents a conserved region of unknown function within Connector enhancer of kinase suppressor of ras 2 (CNK2, also known MAGUIN) [[cite:PUB00012782],[cite:PUB00016229]], Connector enhancer of kinase suppressor of ras 3 (CNK3) and CNK3/IPCEF1 fusion protein. This region is situated between the PDZ [pfam:PF00595] and PH [pfam:PF00169] domains in CNK2 and CNK3/IPCEF1, and after the PDZ domain in CNK3. All family members also contain an N-terminal [pfam:PF00536] 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 localisation of regulatory proteins within the cell and influences the behaviour of important regulatory molecules [[cite:PUB00016229],[cite:PUB00097808]]. 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) [[cite:PUB00097809]]. CNK3/IPCEF1 is required for hepatocyte growth factor (HGF)-dependent activation of Arf6 and HGF-stimulated cell migration [[cite:PUB00097810]].","id":"Pfam:PF06663","interpro_id":"InterPro:IPR010599","name":"Connector enhancer of kinase suppressor of ras 2/3 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