. Author manuscript; available in PMC: 2019 Nov 1.

Published in final edited form as: Biochim Biophys Acta Mol Cell Res. 2018 Jul 17;1865(11 Pt B):1698–1706. doi: 10.1016/j.bbamcr.2018.07.004

Table 1:

Summary of the proteolytic regulation of ion channels

Protein	Protease(s)	Cleavage site(s)	Functional outcome of proteolysis
hERG [16]	calpain, proteinase K, proteinase XIV and XXIV	In the S5-pore linerGly- 603 for calpain	Disable channel activity
NMDA receptor: NR2A subunit [20]	calpain	After the amino acid 1051 in the C-terminal region	Disable channel activity
STIM1 [21, 22, 26]	calpain, γ-secretase and casepase-3		Disable channel activity
CFTR [23]	calpain	Between the first nucleotide-binding site and the regulatory domain	Disable channel activity
Voltage gated sodium channel: b2 subunit [89]	BACE1 and γ secretase		Disable channel activity
ENaC [90]	furin	Arginine 205 and arginine 231 on the a subunit; arginine 143 on the γ subunit for furin	Activate the channel
TRPC5 [31]	calpain	Threonine 857	Activate the channel
Nav. 1.6 [11]	calpain		Decrease the activation threshold of I_NaP and increase its amplitude
ASIC-1a [12, 91]	trypsin, chymotrypsin and proteinase K	Arginine 145 for trypsin	Shift both the pH dependence of channel activation and the steady- state channel inactivation to lower pH values; be resistant to the inhibition of venom of P. cambridgei and display faster recovery from inactivation than wild type channels
EAG2 [14]	calpain		Decrease current density; a positive shift in voltage dependence of channel activation; a lack of EAG2 signature fast activation
Cav 1.2 [32, 34]	calpain, proteasome		Alter channel voltage-current relationship and voltage-dependent channel inactivation
TRPM7 [13]	caspase	Aspartic acid 1510	Potentiate TRPM7 channel activity
NMDA receptors: NR1 and NR2B subunits [39, 40]	tissue plasminogen activator	Arginine 260 in NR1 Arginine 67 in NR2B	Enhance NMDA-mediated C^a2+ influx for NR1; reduce ifenprodil inhibition and increase glycine EC50 for NR2B
CNG channel [36]	metalloproteinase 2 and 9		Increase the apparent affinity for cGMP and the efficacy of cAMP to regulate CNG channel activity
R1 [15]	caspase and calpain	Aspartic acid 1891 for caspase; Glutamic acid 1917 for calpain	Increase the frequency of Ca²⁺ oscillations and augment single channel open probability; abolish the PKA regulation of R1
R2 and R3 [65]	Digestive enzymes	Third and fourth solvent exposed regions	Decrease the frequency of Ca²⁺ oscillations; decrease the single channel open probability.