Hcn2 hyperpolarization-activated, cyclic nucleotide-gated K+ 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Hcn2provided by MGI
Official Full Name: hyperpolarization-activated, cyclic nucleotide-gated K+ 2provided by MGI
Primary source: MGI:MGI:1298210
See related: Ensembl:ENSMUSG00000020331 AllianceGenome:MGI:1298210
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: HAC1; trls; BCNG2
Summary: Predicted to enable several functions, including PDZ domain binding activity; cation channel activity; and identical protein binding activity. Acts upstream of or within regulation of membrane potential. Predicted to be located in several cellular components, including axon; dendrite; and neuronal cell body. Predicted to be integral component of plasma membrane. Predicted to be part of HCN channel complex. Is expressed in heart; heart ventricle; spinal cord; and ventral grey horn. Human ortholog(s) of this gene implicated in familial febrile seizures 2. Orthologous to human HCN2 (hyperpolarization activated cyclic nucleotide gated potassium and sodium channel 2). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in cerebellum adult (RPKM 65.1), frontal lobe adult (RPKM 31.4) and 10 other tissues See more
Orthologs: human all
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Genomic context

Location:: 10 C1; 10 39.72 cM

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	10	NC_000076.7 (79552468..79571942)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	10	NC_000076.6 (79716634..79736108)

Chromosome 10 - NC_000076.7 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?

HCN2 Channels in the Ventral Hippocampal CA1 Regulate Nociceptive Hypersensitivity in Mice.
Title: HCN2 Channels in the Ventral Hippocampal CA1 Regulate Nociceptive Hypersensitivity in Mice.
Thalamocortical Circuit Controls Neuropathic Pain via Up-regulation of HCN2 in the Ventral Posterolateral Thalamus.
Title: Thalamocortical Circuit Controls Neuropathic Pain via Up-regulation of HCN2 in the Ventral Posterolateral Thalamus.
The Role of Prostaglandin E1 as a Pain Mediator through Facilitation of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 via the EP2 Receptor in Trigeminal Ganglion Neurons of Mice.
Title: The Role of Prostaglandin E1 as a Pain Mediator through Facilitation of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 via the EP2 Receptor in Trigeminal Ganglion Neurons of Mice.
HCN channels in the mammalian cochlea: Expression pattern, subcellular location, and age-dependent changes.
Title: HCN channels in the mammalian cochlea: Expression pattern, subcellular location, and age-dependent changes.
Incorporation of one N-glycosylation-deficient subunit within a tetramer of HCN2 channel is tolerated.
Title: Incorporation of one N-glycosylation-deficient subunit within a tetramer of HCN2 channel is tolerated.
Loss of HCN2 in Dorsal Hippocampus of Young Adult Mice Induces Specific Apoptosis of the CA1 Pyramidal Neuron Layer.
Title: Loss of HCN2 in Dorsal Hippocampus of Young Adult Mice Induces Specific Apoptosis of the CA1 Pyramidal Neuron Layer.
The HCN domain is required for HCN channel cell-surface expression and couples voltage- and cAMP-dependent gating mechanisms.
Title: The HCN domain is required for HCN channel cell-surface expression and couples voltage- and cAMP-dependent gating mechanisms.
Abolishing cAMP sensitivity in HCN2 pacemaker channels induces generalized seizures.
Title: Abolishing cAMP sensitivity in HCN2 pacemaker channels induces generalized seizures.
Results establish that thalamic HCN4 channels are essential for the production of rhythmic intrathalamic oscillations and determine regular thalamocortical oscillatory activity during alert states.
Title: The Hyperpolarization-Activated HCN4 Channel is Important for Proper Maintenance of Oscillatory Activity in the Thalamocortical System.
Docking experiments suggested a pivotal role of Arg-635 at the entrance of the binding pocket in HCN2, either causing stabilizing cation-pi interactions with the aromatic ring in N (6)-Phe-cAMP or N (6)-Bn-cAMP or a steric clash with the aromatic ring in N (6)-Bnz-cAMP.
Title: N(6)-modified cAMP derivatives that activate protein kinase A also act as full agonists of murine HCN2 channels.

Submit: New GeneRIF Correction See all GeneRIFs (74)

Variation

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Alleles

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

Spontaneous (3) 1 citation
Targeted (6) 1 citation
Chemically induced (ENU) (4)
Endonuclease-mediated (4)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables PDZ domain binding	ISO Inferred from Sequence Orthology more info
enables cAMP binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables intracellularly cAMP-activated cation channel activity	ISO Inferred from Sequence Orthology more info
enables molecular adaptor activity	ISO Inferred from Sequence Orthology more info
enables monoatomic ion channel activity	IEA Inferred from Electronic Annotation more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables potassium channel activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	ISO Inferred from Sequence Orthology more info
enables sodium channel activity	IEA Inferred from Electronic Annotation more info
enables voltage-gated potassium channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables voltage-gated potassium channel activity	ISO Inferred from Sequence Orthology more info
enables voltage-gated sodium channel activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in cellular response to cAMP	ISO Inferred from Sequence Orthology more info
involved_in cellular response to cGMP	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within monoatomic ion transmembrane transport	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within monoatomic ion transport	IEA Inferred from Electronic Annotation more info
involved_in monoatomic ion transport	IEA Inferred from Electronic Annotation 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
involved_in potassium ion transmembrane transport	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within potassium ion transport	IEA Inferred from Electronic Annotation more info
involved_in potassium ion transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of membrane depolarization	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within regulation of membrane potential	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within regulation of membrane potential	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of membrane potential	ISO Inferred from Sequence Orthology more info
involved_in sodium ion import across plasma membrane	ISO Inferred from Sequence Orthology more info
involved_in sodium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in sodium ion transmembrane transport	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within sodium ion transport	IEA Inferred from Electronic Annotation more info
involved_in transmembrane transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of HCN channel complex	IBA Inferred from Biological aspect of Ancestor more info
part_of HCN channel complex	ISO Inferred from Sequence Orthology more info
is_active_in axon	IBA Inferred from Biological aspect of Ancestor more info
located_in axon	ISO Inferred from Sequence Orthology more info
is_active_in dendrite	IBA Inferred from Biological aspect of Ancestor more info
located_in dendrite membrane	ISO Inferred from Sequence Orthology more info
located_in dendritic shaft	ISO Inferred from Sequence Orthology more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
part_of monoatomic ion channel complex	IEA Inferred from Electronic Annotation more info
located_in neuronal cell body	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in somatodendritic compartment	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2

Names: BCNG-2; HAC-1; brain cyclic nucleotide-gated channel 2; hyperpolarization-activated cation channel 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_008226.2 → NP_032252.1 potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2

See identical proteins and their annotated locations for NP_032252.1

Status: PROVISIONAL

Source sequence(s)

AC151828, AF064873, CX242892

Consensus CDS

CCDS23986.1

UniProtKB/Swiss-Prot

O70506, O88703

UniProtKB/TrEMBL

C9K0Z8

Related

ENSMUSP00000097113.2, ENSMUST00000099513.8

Conserved Domains (4) summary

COG0664
Location:511 → 646

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

cd00038
Location:517 → 625

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:202 → 447

Ion_trans; Ion transport protein

pfam08412
Location:140 → 182

Ion_trans_N; Ion transport protein N-terminal