PubMed 25413349

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPV , TRPV3

Title: Oxygen-dependent hydroxylation by FIH regulates the TRPV3 ion channel.

Authors: Sarah Karttunen, Michael Duffield, Nathan R Scrimgeour, Lauren Squires, Wai Li Lim, Mark L Dallas, Jason L Scragg, Johana Chicher, Keyur A Dave, Murray L Whitelaw, Chris Peers, Jeffrey J Gorman, Jonathan M Gleadle, Grigori Y Rychkov, Daniel J Peet

Journal, date & volume: J. Cell. Sci., 2015 Jan 15 , 128, 225-31

PubMed link:

Factor inhibiting HIF (FIH, also known as HIF1AN) is an oxygen-dependent asparaginyl hydroxylase that regulates the hypoxia-inducible factors (HIFs). Several proteins containing ankyrin repeat domains (ARDs) have been characterised as substrates of FIH, although there is little evidence for a functional consequence of hydroxylation on these substrates. This study demonstrates that the transient receptor potential vanilloid 3 (TRPV3) channel is hydroxylated by FIH on asparagine 242 within the cytoplasmic ARD. Hypoxia, FIH inhibitors and mutation of asparagine 242 all potentiated TRPV3-mediated current, without altering TRPV3 protein levels, indicating that oxygen-dependent hydroxylation inhibits TRPV3 activity. This novel mechanism of channel regulation by oxygen-dependent asparaginyl hydroxylation is likely to extend to other ion channels.