Reactome | EFCAB7:IQCE binds EVC2:EVC

EFCAB7:IQCE binds EVC2:EVC

Stable Identifier

R-HSA-5633051

Type

Reaction [binding]

Species

Homo sapiens

Compartment

ciliary membrane

ReviewStatus

5/5

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IQCE and EFCAB7 are ciliary proteins that are required to restrict the EVC2:EVC complex to the 'EVC region' at the base of the cilium, just distal to the transition zone (Pusapati et al, 2014). EVC2 and EVC are transmembrane proteins that form a ciliary-localized complex that is a positive regulator of Hh signal transduction. The EVC2:EVC complex appears to act downstream of both SMO ciliary localization and its activation by CSNK1A1 and ADRBK1, and is required for the dissociation of the GLI:SUFU complex at the ciliary tip, although the mechanism for this is not known (Blair et al, 2011; Dorn et al, 2012; Capparos-Martin et al, 2013; Pusapati et al, 2014). EVC2 interacts with the IQCE:EFCAB7 subcomplex through the so called 'W-peptide', a stretch of amino acids in the intracellular tail that is deleted in the ciliopathy Weyers Acrofacial Dysostosis. Deletion of the W-peptide results in mislocalization of EVC2 throughout the length of the cilium, rather than being concentrated in the 'EVC zone' (Pusapati et al, 2014; Dorn et al, 2012; Capparos-Martin et al, 2011). EVC2:EVC localization to the EVC region, mediated by the IQCE:EFCAB7 complex and the W-peptide, is required for the Hh-dependent activation of full-length GLI2, but does not appear to critical for the regulation of GLI3R levels, suggesting a bifurcation of the pathway (Pusapati et al, 2014).

Literature References

PubMed ID	Title	Journal	Year
22981989	A Smoothened-Evc2 complex transduces the Hedgehog signal at primary cilia Dorn, KV, Hughes, CE, Rohatgi, R	Dev. Cell	2012
24582806	EFCAB7 and IQCE regulate hedgehog signaling by tethering the EVC-EVC2 complex to the base of primary cilia Pusapati, GV, Hughes, CE, Dorn, KV, Zhang, D, Sugianto, P, Aravind, L, Rohatgi, R	Dev. Cell	2014
21356043	Evc2 is a positive modulator of Hedgehog signalling that interacts with Evc at the cilia membrane and is also found in the nucleus Blair, HJ, Tompson, S, Liu, YN, Campbell, J, MacArthur, K, Ponting, CP, Ruiz-Perez, VL, Goodship, JA	BMC Biol.	2011
23026747	The ciliary Evc/Evc2 complex interacts with Smo and controls Hedgehog pathway activity in chondrocytes by regulating Sufu/Gli3 dissociation and Gli3 trafficking in primary cilia Caparrós-Martín, JA, Valencia, M, Reytor, E, Pacheco, M, Fernandez, M, Perez-Aytes, A, Gean, E, Lapunzina, P, Peters, H, Goodship, JA, Ruiz-Perez, VL	Hum. Mol. Genet.	2013