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 Rohatgi, R, Hughes, CE, Dorn, KV	Dev. Cell	2012
24582806	EFCAB7 and IQCE regulate hedgehog signaling by tethering the EVC-EVC2 complex to the base of primary cilia Aravind, L, Rohatgi, R, Sugianto, P, Zhang, D, Hughes, CE, Dorn, KV, Pusapati, GV	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 Campbell, J, Blair, HJ, Ruiz-Perez, VL, Goodship, JA, MacArthur, K, Tompson, S, Liu, YN, Ponting, CP	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 Ruiz-Perez, VL, Gean, E, Fernandez, M, Goodship, JA, Valencia, M, Pacheco, M, Lapunzina, P, Perez-Aytes, A, Reytor, E, Caparrós-Martín, JA, Peters, H	Hum. Mol. Genet.	2013