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K+ voltage-gated channel subfamily H member 2; voltage-gated K+ channel subunit Kv11.1; ether-a-go-go-related gene K+ channel 1; ether-a-go-go-related protein 1; Eag-related protein 1; ERG-1; hERG-1; hERG1; H-ERG; Eag homolog (KCNH2, ERG, ERG1, HERG)
Function:
- pore-forming (alpha) subunit of the voltage-gated inwardly rectifying K+ channel
- channel properties are modulated by cAMP & subunit assembly
- mediates the rapidly activating component of the delayed rectifying K+ current in heart (IKr)
- isoform 3 has no channel activity by itself, but modulates channel characteristics when associated with isoform 1
- phosphorylated on Ser & Thr
- phosphorylation by PKA inhibits ion conduction
- the K+ channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits
- heteromultimer with KCNH6/ERG2 & KCNH7/ERG3
- interacts with ALG10B (putative)
- heteromultimer with KCNE1 & KCNE2
Structure:
- the segment S4 is probably the voltage-sensor
- contains series of positively charged amino acids at every 3rd position
- belongs to the K+ channel family, H (Eag) subfamily
- contains 1 cyclic nucleotide-binding domain
- contains 1 PAC (PAS-associated C-terminal) domain
- contains 1 PAS (PER-ARNT-SIM) domain
Compartment:
- membrane
Alternative splicing:
- named isoforms=4
Expression:
- highly expressed in heart & brain
Pathology:
- defects in KCNH2 are the cause of:
a) short QT syndrome type 1
b) long QT syndrome type 2
Notes:
- how is this different from the Cardiac Inward Rectifier (CIR)?
Related
cardiac inward rectifier (CIR)
General
glycoprotein
inwardly-rectifying K+ channel
phosphoprotein
transmembrane 6 protein
Properties
SIZE: entity length = 1159 aa
MW = 127 kD
COMPARTMENT: plasma membrane
MOTIF: cytoplasmic domain {1-403}
MOTIF: PAS domain {41-70}
PAC domain {92-144}
proline-rich region
SITE: 297-300
MOTIF: proline residue (SEVERAL)
Ser phosphorylation site {S320}
transmembrane domain {404-424}
exoplasmic loop {425-450}
transmembrane domain {451-471}
cytoplasmic loop {472-495}
transmembrane domain {496-516}
exoplasmic loop {517-520}
transmembrane domain {521-541}
cytoplasmic loop {542-547}
transmembrane domain {548-568}
exoplasmic loop {569-638}
MOTIF: N-glycosylation site {N598}
H5 {612-632}
Selectivity filter {624-629}
transmembrane domain {639-659}
cytoplasmic domain {660-1159}
MOTIF: cyclic nucleotide-binding site
SITE: 742-842
ION-PERMEABILITY: K+
Database Correlations
OMIM correlations
MORBIDMAP 152427
UniProt Q12809
PFAM correlations
Entrez Gene 3757
Kegg hsa:3757
References
- UniProt :accession Q12809
- LQTSdb; Note: KCNH2 mutations page
http://www.ssi.dk/graphics/html/lqtsdb/herg.htm
- GeneReviews
http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/KCNH2
- Wikipedia; Note: ether-a-go-go K+ channels entry
http://en.wikipedia.org/wiki/ether-a-go-go_K+_channels
- Medical Knowledge Self Assessment Program (MKSAP) 11, American
College of Physicians, Philadelphia 1998