D
IPR010599

Connector enhancer of kinase suppressor of ras 2/3 domain

InterPro entry
Short nameCNK2/3_dom

Description

This region is found in Connector enhancer of kinase suppressor of ras 2 (CNK2), Connector enhancer of kinase suppressor of ras 3 (CNK3) and CNK3/IPCEF1 fusion protein. This domain of unknown function is situated between the PDZ
IPR001478
and PH
IPR001849
domains in CNK2 and CNK3/IPCEF1 proteins and after the PDZ domain in CNK3 (which does not have a PH 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 by binding to the Ras effector RAF 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
[1, 3]
. 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)
[2]
. CNK3/IPCEF1 is required for hepatocyte growth factor (HGF)-dependent activation of Arf6 and HGF-stimulated cell migration
[4]
.

References

1.Human homologue of Drosophila CNK interacts with Ras effector proteins Raf and Rlf. Lanigan TM, Liu A, Huang YZ, Mei L, Margolis B, Guan KL. FASEB J. 17, 2048-60, (2003). View articlePMID: 14597674

2.Scaffold protein connector enhancer of kinase suppressor of Ras isoform 3 (CNK3) coordinates assembly of a multiprotein epithelial sodium channel (ENaC)-regulatory complex. Soundararajan R, Ziera T, Koo E, Ling K, Wang J, Borden SA, Pearce D. J Biol Chem 287, 33014-25, (2012). PMID: 22851176

3.Disease-associated synaptic scaffold protein CNK2 modulates PSD size and influences localisation of the regulatory kinase TNIK. Zieger HL, Kunde SA, Rademacher N, Schmerl B, Shoichet SA. Sci Rep 10, 5709, (2020). PMID: 32235845

4.CNK3 and IPCEF1 produce a single protein that is required for HGF dependent Arf6 activation and migration. Attar MA, Salem JC, Pursel HS, Santy LC. Exp Cell Res 318, 228-37, (2012). PMID: 22085542

GO terms

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