Kcnh2 potassium voltage-gated channel, subfamily H (eag-related), member 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Kcnh2provided by MGI
Official Full Name: potassium voltage-gated channel, subfamily H (eag-related), member 2provided by MGI
Primary source: MGI:MGI:1341722
See related: Ensembl:ENSMUSG00000038319 AllianceGenome:MGI:1341722
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: LQT; ERG1; Lqt2; M-erg; Merg1; merg1a; merg1b
Summary: Enables inward rectifier potassium channel activity. Acts upstream of or within potassium ion transmembrane transport; regulation of heart rate by cardiac conduction; and regulation of ventricular cardiac muscle cell membrane repolarization. Predicted to be located in cell surface and perinuclear region of cytoplasm. Predicted to be part of inward rectifier potassium channel complex. Predicted to be active in plasma membrane. Is expressed in several structures, including brain; early conceptus; gonad; heart; and retina. Used to study short QT syndrome. Human ortholog(s) of this gene implicated in long QT syndrome; long QT syndrome 2; and short QT syndrome. Orthologous to human KCNH2 (potassium voltage-gated channel subfamily H member 2). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Broad expression in ovary adult (RPKM 33.4), thymus adult (RPKM 29.0) and 22 other tissues See more
Orthologs: human all
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Genomic context

Location:: 5 A3; 5 10.94 cM

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	5	NC_000071.7 (24524583..24556671, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	5	NC_000071.6 (24319589..24351684, complement)

Chromosome 5 - NC_000071.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

MERG1A Protein Abundance Increases in the Atrophied Skeletal Muscle of Denervated Mice, But Does Not Affect NFkappaB Activity.
Title: MERG1A Protein Abundance Increases in the Atrophied Skeletal Muscle of Denervated Mice, But Does Not Affect NFκB Activity.
Identification and Characterization of a Transcribed Distal Enhancer Involved in Cardiac Kcnh2 Regulation.
Title: Identification and Characterization of a Transcribed Distal Enhancer Involved in Cardiac Kcnh2 Regulation.
These results indicate that hERG is a substrate of HDAC6.
Title: Restoration of mutant hERG stability by inhibition of HDAC6.
PKD1 mediates the PKC effects on KV11.1 and we found that PKD targets S284 in the N-terminus of the channel.
Title: PKD Phosphorylation as Novel Pathway of KV11.1 Regulation.
histone H4 hyperacetylation induced by Class I HDACs inhibitors promoted the expression profiles of potassium channels (Kcnj2, Kcnj3, Kcnj5, Kcnj11, and Kcnh2)
Title: Regulation of Histone Acetylation on Expression Profiles of Potassium Channels During Cardiomyocyte Differentiation From Mouse Embryonic Stem Cells.
Using a combination of mouse genetics, biochemistry, molecular and cell biology, we demonstrate that Nkx2-5 regulates the gene encoding Kcnh2 channel and others, shedding light on potential mechanisms generating electrical abnormalities observed in patients bearing NKX2-5 dysfunction and opening opportunities to the study of novel therapeutic targets for anti-arrhythmogenic therapies
Title: A novel conditional mouse model for Nkx2-5 reveals transcriptional regulation of cardiac ion channels.
Report altered protein trafficking/function of mouse ERG K(+) channel clones.
Title: Mouse ERG K(+) channel clones reveal differences in protein trafficking and function.
Enhancement of HERG protein expression through Hsp90 inhibition of CHIP binding might be a novel therapeutic strategy for long QT syndrome 2 caused by trafficking abnormalities of HERG proteins.
Title: Hsp90 prevents interaction between CHIP and HERG proteins to facilitate maturation of wild-type and mutant HERG proteins.
The findings of this study suggested that MERG1a may not modulate Murf1 expression through the AKT/FOXO pathway.
Title: The mERG1a channel modulates skeletal muscle MuRF1, but not MAFbx, expression.
Data indicate presence of KCNH2 in left/right atria & indicate functional interaction between KCNH2 & KCNA5. Kinetic analyses confirm KCNH2 as "rapid" and KCNA5 as "ultra rapid" potassium channels.
Title: Presence and functional role of the rapidly activating delayed rectifier K(+) current in left and right atria of adult mice.

Submit: New GeneRIF Correction See all GeneRIFs (22)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (2)
Targeted (4) 1 citation

General gene information

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Markers

Kcnh2 (e-PCR), detects polymorphism
- UniSTS:166225

AF012871 (e-PCR)
- UniSTS:159345

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables C3HC4-type RING finger domain binding	ISO Inferred from Sequence Orthology more info
enables delayed rectifier potassium channel activity	ISO Inferred from Sequence Orthology more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables inward rectifier potassium channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables inward rectifier potassium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables inward rectifier potassium channel activity	ISO Inferred from Sequence Orthology more info
enables monoatomic ion channel activity	ISO Inferred from Sequence Orthology more info
enables potassium channel activity	ISO Inferred from Sequence Orthology more info
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein-containing complex binding	ISO Inferred from Sequence Orthology more info
enables scaffold protein binding	ISO Inferred from Sequence Orthology more info
enables transcription cis-regulatory region binding	ISO Inferred from Sequence Orthology more info
enables ubiquitin protein ligase binding	ISO Inferred from Sequence Orthology more info
enables voltage-gated potassium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables voltage-gated potassium channel activity	ISO Inferred from Sequence Orthology more info
enables voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in cardiac muscle contraction	ISO Inferred from Sequence Orthology more info
involved_in cellular response to xenobiotic stimulus	ISO Inferred from Sequence Orthology more info
involved_in membrane depolarization during action potential	ISO Inferred from Sequence Orthology more info
involved_in membrane repolarization	ISO Inferred from Sequence Orthology more info
involved_in membrane repolarization during action potential	ISO Inferred from Sequence Orthology more info
involved_in membrane repolarization during cardiac muscle cell action potential	IBA Inferred from Biological aspect of Ancestor more info
involved_in membrane repolarization during cardiac muscle cell action potential	ISO Inferred from Sequence Orthology more info
involved_in membrane repolarization during ventricular cardiac muscle cell action potential	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of potassium ion export across plasma membrane	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of potassium ion transmembrane transport	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of potassium ion transmembrane transport	ISO Inferred from Sequence Orthology more info
involved_in potassium ion export across plasma membrane	ISO Inferred from Sequence Orthology more info
involved_in potassium ion homeostasis	ISO Inferred from Sequence Orthology more info
involved_in potassium ion import across plasma membrane	ISO Inferred from Sequence Orthology more info
involved_in potassium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within potassium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in potassium ion transmembrane transport	ISO Inferred from Sequence Orthology more info
involved_in potassium ion transport	ISO Inferred from Sequence Orthology more info
involved_in regulation of heart rate by cardiac conduction	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within regulation of heart rate by cardiac conduction	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within regulation of heart rate by cardiac conduction	ISO Inferred from Sequence Orthology more info
involved_in regulation of heart rate by cardiac conduction	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of membrane potential	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of membrane potential	ISO Inferred from Sequence Orthology more info
involved_in regulation of membrane repolarization	ISO Inferred from Sequence Orthology more info
involved_in regulation of potassium ion transmembrane transport	ISO Inferred from Sequence Orthology more info
involved_in regulation of ventricular cardiac muscle cell membrane repolarization	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within regulation of ventricular cardiac muscle cell membrane repolarization	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of ventricular cardiac muscle cell membrane repolarization	ISO Inferred from Sequence Orthology more info
involved_in ventricular cardiac muscle cell action potential	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in cell surface	ISO Inferred from Sequence Orthology more info
part_of inward rectifier potassium channel complex	ISO Inferred from Sequence Orthology more info
part_of monoatomic ion channel complex	IEA Inferred from Electronic Annotation more info
located_in perinuclear region of cytoplasm	ISO Inferred from Sequence Orthology more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
part_of voltage-gated potassium channel complex	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: voltage-gated inwardly rectifying potassium channel KCNH2; potassium voltage-gated channel subfamily H member 2

Names: eag-related protein 1; ether-a-go-go-related gene potassium channel 1; ether-a-go-go-related protein 1; voltage-gated potassium channel subunit Kv11.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001294162.1 → NP_001281091.1 voltage-gated inwardly rectifying potassium channel KCNH2 isoform 2

See identical proteins and their annotated locations for NP_001281091.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks several exons in the 5' coding region and contains an alternate 5' terminal exon, compared to variant 1. It encodes isoform 2 (also known as Merg1b), which is shorter and has a distinct N-terminus, compared to isoform 1.

Source sequence(s)

AA145089, AC113055, AI326795, BM936394, BQ745654, BU707188, CK619061, CX565252

Consensus CDS

CCDS80224.1

UniProtKB/TrEMBL

A0A0R4J1K0

Related

ENSMUSP00000110750.3, ENSMUST00000115098.7

Conserved Domains (5) summary

COG0664
Location:396 → 516

Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]

cd00038
Location:402 → 513

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

pfam00520
Location:109 → 328

Ion_trans; Ion transport protein

pfam07885
Location:271 → 325

Ion_trans_2; Ion channel

pfam15836
Location:673 → 774

SSTK-IP; SSTK-interacting protein, TSSK6-activating co-chaperone protein
NM_013569.2 → NP_038597.2 voltage-gated inwardly rectifying potassium channel KCNH2 isoform 1

See identical proteins and their annotated locations for NP_038597.2

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1, also known as Merg1a).

Source sequence(s)

AC113055

Consensus CDS

CCDS19116.1

UniProtKB/Swiss-Prot

O35219, O35220, O35221, O35989

UniProtKB/TrEMBL

Q53Z09

Related

ENSMUSP00000047705.8, ENSMUST00000036092.10

Conserved Domains (7) summary

COG0664
Location:738 → 858

Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]

cd00038
Location:744 → 855

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

cd00130
Location:41 → 132

PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...

pfam00520
Location:451 → 670

Ion_trans; Ion transport protein

pfam07885
Location:613 → 667

Ion_trans_2; Ion channel

pfam13426
Location:29 → 130

PAS_9; PAS domain

pfam15836
Location:1015 → 1116

SSTK-IP; SSTK-interacting protein, TSSK6-activating co-chaperone protein

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000071.7 Reference GRCm39 C57BL/6J

Range

24524583..24556671 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006535634.5 → XP_006535697.1 potassium voltage-gated channel subfamily H member 2 isoform X3

See identical proteins and their annotated locations for XP_006535697.1

UniProtKB/Swiss-Prot

O35219, O35220, O35221, O35989

Conserved Domains (5) summary

PRK13559
Location:7 → 269

PRK13559; hypothetical protein; Provisional

cd00038
Location:685 → 796

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

pfam00520
Location:352 → 611

Ion_trans; Ion transport protein

pfam15836
Location:956 → 1057

SSTK-IP; SSTK-interacting protein, TSSK6-activating co-chaperone protein

pfam13426
Location:1 → 71

PAS_9; PAS domain
XM_006535635.5 → XP_006535698.1 potassium voltage-gated channel subfamily H member 2 isoform X3

See identical proteins and their annotated locations for XP_006535698.1

UniProtKB/Swiss-Prot

O35219, O35220, O35221, O35989

Conserved Domains (5) summary

PRK13559
Location:7 → 269

PRK13559; hypothetical protein; Provisional

cd00038
Location:685 → 796

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

pfam00520
Location:352 → 611

Ion_trans; Ion transport protein

pfam15836
Location:956 → 1057

SSTK-IP; SSTK-interacting protein, TSSK6-activating co-chaperone protein

pfam13426
Location:1 → 71

PAS_9; PAS domain
XM_006535632.5 → XP_006535695.1 potassium voltage-gated channel subfamily H member 2 isoform X1

UniProtKB/Swiss-Prot

O35219, O35220, O35221, O35989

Conserved Domains (3) summary

cd00038
Location:691 → 802

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

pfam00520
Location:358 → 617

Ion_trans; Ion transport protein

pfam15836
Location:962 → 1063

SSTK-IP; SSTK-interacting protein, TSSK6-activating co-chaperone protein
XM_006535633.4 → XP_006535696.1 potassium voltage-gated channel subfamily H member 2 isoform X2

UniProtKB/Swiss-Prot

O35219, O35220, O35221, O35989

Conserved Domains (4) summary

cd00038
Location:687 → 798

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...

pfam00520
Location:354 → 613

Ion_trans; Ion transport protein

pfam15836
Location:958 → 1059

SSTK-IP; SSTK-interacting protein, TSSK6-activating co-chaperone protein

pfam13426
Location:29 → 130

PAS_9; PAS domain