EVC2:EVC binds p-SMO

Stable Identifier
Reaction [binding]
Homo sapiens
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EVC2 and EVC are components of a complex that localizes to the base of the cilium in a so-called EvC zone just distal to the transition zone. Mutations in the genes for EVC2 and EVC are associated with the ciliopathy Ellis van Creveld syndrome and result in an abrogated response to stimulation by Hh, making EVC2 and EVC positive regulators of Hh signaling (Blair et al, 2011; Dorn et al, 2012; Caparros-Martin et al, 2013). The EVC2:EVC complex interacts with SMO in the cilium after Hh stimulation and restricts SMO localization to the EvC zone (Dorn et al, 2012; Yang et al, 2012; Caparros-Martin et al, 2013). Disruption of the EVC2:EVC complex does not interfere with SMO ciliary localization or its activation by CSNK1A1 and ADRBK1, but prevents the Hh-dependent localization of the GLI transcription factors to the tip of the cilium and abrogates the dissociation of the GLI:SUFU complex (Dorn et al, 2012; Yang et al, 2012; Caparros-Martin et al, 2013). These events are required for the activation of the GLI transcription factors in response to ligand stimulation. Localization of the EVC2:EVC complex to the EVC zone depends on an interaction between the EVC2 W peptide (a stretch of 43 amino-acids in the C-terminal tail that is missing in a disease associated EVC2-variant), and the IQCE:EFCAB7 complex. Abrogation of this interaction causes the EVC2:EVC complex to localize along the length of the cilium and disrupts production and nuclear translocation of the full length GLI2 transcriptional activator (Pusapati et al, 2014). How the Hh signal is transmitted from the SMO:EVC2:EVC complex to downstream components is not known.
Literature References
PubMed ID Title Journal Year
22986504 Smoothened transduces Hedgehog signal by forming a complex with Evc/Evc2

Yang, C, Chen, W, Jiang, J, Chen, Y

Cell Res. 2012
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
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
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
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