Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

KCNH2 (Q12809) - Overview - Molecular Target Synopsis

Protein


KCNH2, Potassium voltage-gated channel subfamily H member 2
UniProt Q12809

Also Known as KCNH2_HUMAN, KCNH2, ERG, ERG1, HERG

Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr) (PubMed:18559421, PubMed:26363003, PubMed:27916661)., Isoform A-USO: Has no 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 channel activity by itself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation. The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits (PubMed:27916661). Interacts with DNAJB12 and DNAJB14; chaperones DNAJB12 and DNAJB14 promote tetramerization (PubMed:27916661). Heteromultimer with KCNH6/ERG2 and KCNH7/ERG3 (By similarity). Interacts with ALG10B (By similarity). Heteromultimer with KCNE1 and KCNE2 (PubMed:9230439, PubMed:10219239). Interacts with CANX (PubMed:16361248). The core-glycosylated, but not the fully glycosylated form interacts with RNF207 (PubMed:25281747). Interacts with NDFIP1 and NDFIP2 (PubMed:26363003).

5VA2
CRYO-EM STRUCTURE OF THE HUMAN ETHER-A-GO-GO RELATED K+ CHANNEL
RCSB/PDB
Inspect Structure
See all 3D Structures for KCNH2

Isoforms / Transcripts (Protein Coding)


Drugs


KCNH2 is targeted by Approved Drugs Ibutilide, Amiodarone, Dofetilide, Dalfampridine, Guanidine. (see details)
Ibutilide
Amiodarone
Dofetilide
Dalfampridine
Guanidine

Sub-cellular localization


UniProt: KCNH2 is active in the following subcellular-locations: cell membrane.
GO terms: KCNH2 is active in the following subcellular-locations: cell surface, integral component of plasma membrane, inward rectifier potassium channel complex, perinuclear region of cytoplasm, plasma membrane, voltage-gated potassium channel complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project KCNH2 has gain in 4 cell-lines, loss in 5 cell-lines and no signal in 996 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: K_562, SW_620, RXF_393

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: OCI-M2, KU812, K-562

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: K562, SK-N-SH, NHLF

(see details)

RNA Interference


KCNH2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: CAMA1, PCI30. (see details)

3D Structures


For KCNH2 there are:
12 structures (12 chains) solved
0 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


KCNH2 has been screened with 15194 compounds (20147 bioactivities), 1234 compounds have bioactivities that show binding affinity of <= 500nM (1695 bioactivities). (see details)