KCNH2
Domain
The S4-S5 linker acts as a signal integrator where it both couples voltage-sensor domain (VSD) movement to pore opening and closure, as well as providing a binding site for other domains that regulate activation and/or deactivation of the channel.
Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:18559421, PubMed:22314138, PubMed:22359612, PubMed:26363003, PubMed:27916661, PubMed:9230439, PubMed:9351446, PubMed:9765245). Channel properties are modulated by cAMP and subunit assembly (PubMed:10837251). Characterized by unusual gating kinetics by producing relatively small outward currents during membrane depolarization and large inward currents during subsequent repolarization which reflect a rapid inactivation during depolarization and quick recovery from inactivation but slow deactivation (closing) during repolarization (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:18559421, PubMed:22314138, PubMed:22359612, PubMed:26363003, PubMed:27916661, PubMed:9230439, PubMed:9351446, PubMed:9765245). Channel properties are modulated by cAMP and subunit assembly (PubMed:10837251). Forms a stable complex with KCNE1 or KCNE2, and that this heteromultimerization regulates inward rectifier potassium channel activity (PubMed:10219239, PubMed:9230439).
Isoform A-USO
Has no inward rectifier potassium channel activity by itself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
Isoform B-USO
Has no inward rectifier potassium channel activity by itself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
Involvement in disease
Long QT syndrome 2
LQT2
A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. Deafness is often associated with long QT syndrome type 2.
None
The disease is caused by variants affecting the gene represented in this entry.
Short QT syndrome 1
SQT1
A form of short QT syndrome, a heart disorder characterized by idiopathic persistently and uniformly short QT interval on ECG in the absence of structural heart disease in affected individuals. It can cause syncope and sudden death.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated on serine and threonine residues. Phosphorylation by PKA inhibits ion conduction.
Sequence Similarities
Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv11.1/KCNH2 sub-subfamily.
Tissue Specificity
Highly expressed in heart and brain. Isoforms USO are frequently overexpressed in cancer cells.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
Alternative names
ERG, ERG1, HERG, KCNH2, Voltage-gated inwardly rectifying potassium channel KCNH2, Eag homolog, Ether-a-go-go-related gene potassium channel 1, Potassium voltage-gated channel subfamily H member 2, Voltage-gated potassium channel subunit Kv11.1, ERG-1, Eag-related protein 1, Ether-a-go-go-related protein 1, H-ERG, hERG-1, hERG1