Hcn2 hyperpolarization activated cyclic nucleotide gated potassium and sodium channel 2 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Hcn2provided by RGD
Official Full Name: hyperpolarization activated cyclic nucleotide gated potassium and sodium channel 2provided by RGD
Primary source: RGD:620689
See related: Ensembl:ENSRNOG00000008831 AllianceGenome:RGD:620689
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Summary: Enables PDZ domain binding activity and molecular adaptor activity. Involved in several processes, including aging; cellular response to aldosterone; and response to cisplatin. Located in several cellular components, including axon; dendrite; and neuronal cell body. Biomarker of dermatitis; meningitis; and visual epilepsy. 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 Heart (RPKM 117.3), Brain (RPKM 113.8) and 4 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 7q11

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	7	NC_086025.1 (10620422..10639457, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	7	NC_051342.1 (9969801..9988839, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	7	NC_005106.4 (12851730..12870087, complement)

Chromosome 7 - NC_086025.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Activation of CB1R alleviates central sensitization by regulating HCN2-pNR2B signaling in a chronic migraine rat model.
Title: Activation of CB1R alleviates central sensitization by regulating HCN2-pNR2B signaling in a chronic migraine rat model.
Activation of HCN channels caused by elevated cAMP levels in periaqueductal gray promotes bone cancer pain.
Title: Activation of HCN channels caused by elevated cAMP levels in periaqueductal gray promotes bone cancer pain.
Decreased Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 Activity in a Rat Model of Absence Epilepsy and the Effect of ZD7288, an Ih Inhibitor, on the Spike-and-Wave Discharges.
Title: Decreased Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 Activity in a Rat Model of Absence Epilepsy and the Effect of ZD7288, an Ih Inhibitor, on the Spike-and-Wave Discharges.
Role of hyperpolarization-activated cyclic nucleotide-gated channels in aging bladder phenotype.
Title: Role of hyperpolarization-activated cyclic nucleotide-gated channels in aging bladder phenotype.
Isolated downregulation of HCN2 in ventricles of rats with streptozotocin-induced diabetic cardiomyopathy.
Title: Isolated downregulation of HCN2 in ventricles of rats with streptozotocin-induced diabetic cardiomyopathy.
HCN2 contributes to oxaliplatin-induced neuropathic pain by inducing spinal long-term potentiation via activation of NMDA receptor-mediated CaMKII signaling.
Title: HCN2 contributes to oxaliplatin-induced neuropathic pain by inducing spinal long-term potentiation via activation of NMDA receptor-mediated CaMKII signaling.
Shank3 contributes to neuropathic pain by facilitating the SNI-dependent increase of HCN2 and the expression of PSD95.
Title: Shank3 contributes to neuropathic pain by facilitating the SNI-dependent increase of HCN2 and the expression of PSD95.
The present study provided evidence that SK4 and HCN2 combined could construct an ectopic pacemaker, laying the groundwork for the development of improved biological pacing mechanisms in the future.
Title: Overexpression of the medium‑conductance calcium‑activated potassium channel (SK4) and the HCN2 channel to generate a biological pacemaker.
HCN2 is conducive to oxaliplatin-induced neuropathic pain by activating the neuronal CaMKII/CREB cascade.
Title: HCN2 contributes to oxaliplatin-induced neuropathic pain through activation of the CaMKII/CREB cascade in spinal neurons.
Hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 protein expression levels were increased in the thalamus under chronic pain condition. Results suggest, increased HCN channel activity in the thalamus of the ascending nociceptive pathway contributes to both chronic neuropathic and inflammatory pain conditions.
Title: Inhibition of HCN channel activity in the thalamus attenuates chronic pain in rats.

Submit: New GeneRIF Correction See all GeneRIFs (56)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by RGD

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

Process	Evidence Code	Pubs
involved_in cellular response to aldosterone	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to cAMP	IEA Inferred from Electronic Annotation more info
involved_in cellular response to cAMP	ISO Inferred from Sequence Orthology more info
involved_in cellular response to cAMP	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to cGMP	IEA Inferred from Electronic Annotation more info
involved_in cellular response to cGMP	ISO Inferred from Sequence Orthology more info
involved_in potassium ion import across plasma membrane	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
involved_in potassium ion transmembrane transport	ISS Inferred from Sequence or Structural Similarity 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	ISO Inferred from Sequence Orthology more info
involved_in regulation of membrane potential	ISO Inferred from Sequence Orthology more info
involved_in response to hormone	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to xenobiotic stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in sodium ion import across plasma membrane	IEA Inferred from Electronic Annotation 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

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

General protein information

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

Names: hyperpolarization activated cyclic nucleotide-gated potassium channel 2

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_053684.2 → NP_446136.1 potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2

See identical proteins and their annotated locations for NP_446136.1

Status: VALIDATED

Source sequence(s)

JAXUCZ010000007

UniProtKB/Swiss-Prot

Q6BCT5, Q9JKA9, Q9QZW6

UniProtKB/TrEMBL

F1LRY7

Related

ENSRNOP00000011837.7, ENSRNOT00000011837.7

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

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

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

Reference GRCr8

Genomic

NC_086025.1 Reference GRCr8

Range

10620422..10639457 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_039078239.2 → XP_038934167.1 potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 isoform X1

Conserved Domains (3) summary

PLN03192
Location:51 → 325

PLN03192; Voltage-dependent potassium channel; Provisional

PRK07003
Location:433 → 526

PRK07003; DNA polymerase III subunit gamma/tau

cd00038
Location:181 → 289

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 ...