Voltage-gated delayed rectifier potassium channel KCNH1

UniProt O95259 Organism Homo sapiens Gene EAG, EAG1, KCNH1

Also known as: EAG, EAG1, KCNH1

Function

Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel that mediates outward-rectifying potassium currents which, on depolarization, reaches a steady-state level and do not inactivate. The activation kinetics depend on the prepulse potential and external divalent cation concentration. With negative prepulses, the current activation is delayed and slowed down several fold, whereas more positive prepulses speed up activation. The time course of activation is biphasic with a fast and a slowly activating current component. Activates at more positive membrane potentials and exhibit a steeper activation curve. Channel properties are modulated by subunit assembly. Mediates IK(NI) current in myoblasts. Involved in the regulation of cell proliferation and differentiation, in particular adipogenic and osteogenic differentiation in bone marrow-derived mesenchymal stem cells (MSCs).

Classification

Family (Pfam): PF00027 cNMP_binding, PF00520 Ion_trans, PF13426 PAS_9
InterPro: cNMP-bd_dom, cNMP-bd_dom_sf, Ion_trans_dom, K_chnl_volt-dep_EAG, K_chnl_volt-dep_EAG/ELK/ERG, KCNH_animal-type, PAC, PAS, PAS-assoc_C, PAS-like_dom_sf, RmlC-like_jellyroll
Functional cluster: Protein Serine/Threonine Kinases

Experimental structures · PDB · 1

5J7E X-ray 1.90A

A predicted model is available from AlphaFold.

Gene Ontology · 19

Disease associations

Zimmermann-Laband syndrome 1 MONDO:0024526
Temple-Baraitser syndrome MONDO:0012735

Drugs targeting this protein · 6

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Voltage-gated delayed rectifier potassium channel KCNH1 4 shared papers
Voltage-gated delayed rectifier potassium channel KCNH5 1 shared papers
Kappa-theraphotoxin-Aa1a 1 shared papers
Mu/kappa-theraphotoxin-Ap1a 1 shared papers
Voltage-gated delayed rectifier potassium channel KCNH1 3 shared papers
V-type proton ATPase subunit B, brain isoform 1 shared papers
Rab GTPase-binding effector protein 1 1 shared papers
Src substrate cortactin 1 shared papers
Rab GTPase-binding effector protein 1 1 shared papers
Src substrate cortactin 1 shared papers
Rab GTPase-binding effector protein 1 1 shared papers

Literature · 20 cited papers

Novel venom-derived inhibitors of the human EAG channel, a putative antiepileptic drug target. Biochem. Pharmacol. · 2018
Molecular insights into the mechanism of calmodulin inhibition of the EAG1 potassium channel. Structure · 2016
Crystal structure of the PAS domain of the hEAG potassium channel. Acta Crystallogr. F Struct. Biol. Commun. · 2016
Calmodulin regulates human ether a go-go 1 (hEAG1) potassium channels through interactions of the Eag domain with the cyclic nucleotide binding homology domain. J. Biol. Chem. · 2016
Human EAG channels are directly modulated by PIP2 as revealed by electrophysiological and optical interference investigations. Sci. Rep. · 2016
Mutations in KCNH1 and ATP6V1B2 cause Zimmermann-Laband syndrome. Nat. Genet. · 2015
KV 10.1 opposes activity-dependent increase in Ca2+ influx into the presynaptic terminal of the parallel fibre-Purkinje cell synapse. J. Physiol. (Lond.) · 2015
Mutations in the voltage-gated potassium channel gene KCNH1 cause Temple-Baraitser syndrome and epilepsy. Nat. Genet. · 2015
Regulation of hERG and hEAG channels by Src and by SHP-1 tyrosine phosphatase via an ITIM region in the cyclic nucleotide binding domain. PLoS ONE · 2014
BKCa and hEag1 channels regulate cell proliferation and differentiation in human bone marrow-derived mesenchymal stem cells. J. Cell. Physiol. · 2014
Cortactin controls surface expression of the voltage-gated potassium channel K(V)10.1. J. Biol. Chem. · 2012
Physical and functional interaction of KV10.1 with Rabaptin-5 impacts ion channel trafficking. FEBS Lett. · 2012
… and 8 more in the literature graph

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