{"metadata":{"accession":"PF06663","entry_id":null,"type":"domain","go_terms":null,"source_database":"pfam","member_databases":null,"integrated":"IPR010599","hierarchy":null,"name":{"name":"Connector enhancer of kinase suppressor of ras 2/3 domain","short":"CNK2_3_dom"},"description":[{"text":"<p>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]].</p>","llm":false,"checked":false,"updated":false}],"wikipedia":null,"literature":{"PUB00097809":{"PMID":22851176,"ISBN":null,"volume":"287","issue":"39","year":2012,"title":"Scaffold protein connector enhancer of kinase suppressor of Ras isoform 3 (CNK3) coordinates assembly of a multiprotein epithelial sodium channel (ENaC)-regulatory complex.","URL":null,"raw_pages":"33014-25","medline_journal":"J Biol Chem","ISO_journal":"J Biol Chem","authors":["Soundararajan R","Ziera T","Koo E","Ling K","Wang J","Borden SA","Pearce D."],"DOI_URL":null},"PUB00016229":{"PMID":14597674,"ISBN":null,"volume":"17","issue":"14","year":2003,"title":"Human homologue of Drosophila CNK interacts with Ras effector proteins Raf and Rlf.","URL":null,"raw_pages":"2048-60","medline_journal":"FASEB J","ISO_journal":"FASEB J.","authors":["Lanigan TM","Liu A","Huang YZ","Mei L","Margolis B","Guan KL."],"DOI_URL":"http://www.fasebj.org/cgi/content/abstract/17/14/2048"},"PUB00097808":{"PMID":32235845,"ISBN":null,"volume":"10","issue":"1","year":2020,"title":"Disease-associated synaptic scaffold protein CNK2 modulates PSD size and influences localisation of the regulatory kinase TNIK.","URL":null,"raw_pages":"5709","medline_journal":"Sci Rep","ISO_journal":"Sci Rep","authors":["Zieger HL","Kunde SA","Rademacher N","Schmerl B","Shoichet SA."],"DOI_URL":null},"PUB00097810":{"PMID":22085542,"ISBN":null,"volume":"318","issue":"3","year":2012,"title":"CNK3 and IPCEF1 produce a single protein that is required for HGF dependent Arf6 activation and migration.","URL":null,"raw_pages":"228-37","medline_journal":"Exp Cell Res","ISO_journal":"Exp Cell Res","authors":["Attar MA","Salem JC","Pursel HS","Santy LC."],"DOI_URL":null},"PUB00012782":{"PMID":10207009,"ISBN":null,"volume":"274","issue":"17","year":1999,"title":"MAGUIN, a novel neuronal membrane-associated guanylate kinase-interacting protein.","URL":null,"raw_pages":"11889-96","medline_journal":"J Biol Chem","ISO_journal":"J. Biol. Chem.","authors":["Yao I","Hata Y","Ide N","Hirao K","Deguchi M","Nishioka H","Mizoguchi A","Takai Y."],"DOI_URL":"http://dx.doi.org/10.1074/jbc.274.17.11889"}},"set_info":null,"overlaps_with":null,"counters":{"subfamilies":0,"domain_architectures":52,"interactions":0,"matches":3637,"pathways":0,"proteins":3585,"proteomes":735,"sets":0,"structural_models":{"alphafold":3207},"structures":0,"taxa":2235},"entry_annotations":{"hmm":0,"logo":0,"alignment:seed":16,"alignment:full":2929},"cross_references":{},"is_llm":false,"is_reviewed_llm":false,"is_updated_llm":false,"representative_structure":null}}