Stable Identifier
Reaction [binding]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
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
Orthologous Events
Cite Us!