HCN2

Protein-coding gene in the species Homo sapiens

HCN2

Available structures

PDB

Ortholog search: PDBe RCSB

List of PDB id codes
2MPF, 3U10

Identifiers

Aliases

HCN2, BCNG-2, BCNG2, HAC-1, hyperpolarization activated cyclic nucleotide gated potassium channel 2, hyperpolarization activated cyclic nucleotide gated potassium and sodium channel 2, EIG17, FEB2, GEFSP11

External IDs

OMIM: 602781 MGI: 1298210 HomoloGene: 31022 GeneCards: HCN2

Gene location (Human)

Chr.	Chromosome 19 (human)^[1]

Band	19p13.3	Start	589,881 bp^[1]
Band	19p13.3	End	617,159 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 10 (mouse)^[2]

Band	10\|10 C1	Start	79,552,468 bp^[2]
Band	10\|10 C1	End	79,571,942 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

putamen

nucleus accumbens

caudate nucleus

Brodmann area 10

Brodmann area 9

amygdala

hypothalamus

substantia nigra

hippocampus proper

middle frontal gyrus

Top expressed in

entorhinal cortex

superior frontal gyrus

cerebellar cortex

medulla oblongata

inferior colliculus

medial vestibular nucleus

hippocampus proper

superior colliculus

pontine nuclei

lateral geniculate nucleus

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	nucleotide binding potassium channel activity cAMP binding sodium channel activity voltage-gated ion channel activity ion channel activity intracellular cAMP-activated cation channel activity identical protein binding voltage-gated potassium channel activity voltage-gated sodium channel activity protein binding
Cellular component	integral component of membrane membrane voltage-gated potassium channel complex plasma membrane integral component of plasma membrane HCN channel complex
Biological process	cellular response to cGMP sodium ion transmembrane transport sodium ion transport cell-cell signaling regulation of membrane potential regulation of ion transmembrane transport ion transport potassium ion transport transmembrane transport potassium ion transmembrane transport cellular response to cAMP membrane depolarization during cardiac muscle cell action potential sodium ion import across plasma membrane potassium ion import across plasma membrane
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


610


15166

Ensembl


ENSG00000099822


ENSMUSG00000020331

UniProt


Q9UL51


O88703

RefSeq (mRNA)


NM_001194


NM_008226

RefSeq (protein)


NP_001185


NP_032252

Location (UCSC)

Chr 19: 0.59 – 0.62 Mb

Chr 10: 79.55 – 79.57 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated ion channel 2 is a protein that in humans is encoded by the HCN2 gene.^[5]^[6]^[7]^[8]

Interactions

HCN2 has been shown to interact with HCN1^[9]^[10] and HCN4.^[9]

Function

The function of the channel is not known although its activation by hyperpolarization alludes to the funny channels in the sinoatrial node of the heart (which form the basis of spontaneous generation of electrical rhythm). These channels have recently been associated with chronic pain and blocking the gene is associated with resolution of neuropathic episodes of pain.^[11]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000099822 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000020331 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Santoro B, Grant SG, Bartsch D, Kandel ER (Dec 1997). "Interactive cloning with the SH3 domain of N-src identifies a new brain specific ion channel protein, with homology to eag and cyclic nucleotide-gated channels". Proceedings of the National Academy of Sciences of the United States of America. 94 (26): 14815–20. Bibcode:1997PNAS...9414815S. doi:10.1073/pnas.94.26.14815. PMC 25120. PMID 9405696.
^ Santoro B, Liu DT, Yao H, Bartsch D, Kandel ER, Siegelbaum SA, Tibbs GR (May 1998). "Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain". Cell. 93 (5): 717–29. doi:10.1016/S0092-8674(00)81434-8. PMID 9630217. S2CID 10265917.
^ Hofmann F, Biel M, Kaupp UB (Dec 2005). "International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels". Pharmacological Reviews. 57 (4): 455–62. doi:10.1124/pr.57.4.8. PMID 16382102. S2CID 45853869.
^ "Entrez Gene: HCN2 hyperpolarization activated cyclic nucleotide-gated potassium channel 2".
^ ^a ^b Much B, Wahl-Schott C, Zong X, Schneider A, Baumann L, Moosmang S, Ludwig A, Biel M (Oct 2003). "Role of subunit heteromerization and N-linked glycosylation in the formation of functional hyperpolarization-activated cyclic nucleotide-gated channels". The Journal of Biological Chemistry. 278 (44): 43781–6. doi:10.1074/jbc.M306958200. PMID 12928435.
^ Proenza C, Tran N, Angoli D, Zahynacz K, Balcar P, Accili EA (Aug 2002). "Different roles for the cyclic nucleotide binding domain and amino terminus in assembly and expression of hyperpolarization-activated, cyclic nucleotide-gated channels". The Journal of Biological Chemistry. 277 (33): 29634–42. doi:10.1074/jbc.M200504200. PMID 12034718.
^ "Gene find may lead to pills that kill chronic pain". The Times of India. 10 September 2011. Archived from the original on 6 November 2012.

External links

HCN2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

PDB gallery

1q3e: HCN2J 443-645 in the presence of cGMP
1q43: HCN2I 443-640 in the presence of cAMP, selenomethionine derivative
1q5o: HCN2J 443-645 in the presence of cAMP, selenomethionine derivative

Membrane transport protein: ion channels (TC 1A)

Ca²⁺: Calcium channel

Ligand-gated	Inositol trisphosphate receptor 1 2 3 Ryanodine receptor 1 2 3
Voltage-gated	L-type/Ca_vα 1.1 1.2 1.3 1.4 N-type/Ca_vα2.2 P-type/Ca_vα 2.1 Q-type/Ca_vα2.1 R-type/Ca_vα2.3 T-type/Ca_vα 3.1 3.2 3.3 α₂δ-subunits 1 2 β-subunits β1 β2 β3 β4 γ-subunits γ1 γ2 γ3 γ4 Cation channels of sperm 1 2 3 4 Two-pore channel 1 2

Na⁺: Sodium channel

Constitutively active	Epithelial sodium channel α β γ δ
Proton-gated	Amiloride-sensitive cation channel 1 2 3 4
Voltage-gated	Na_vα 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 7A Na_vβ 1 2 3 4

K⁺: Potassium channel

Calcium-activated	BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 K_Ca 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1
Inward-rectifier	K_ATP K_ir 1.1 2.1 2.2 2.3 2.4 2.6 GIRK/K_ir 3.1 3.2 3.3 3.4 K_ir 4.1 4.2 5.1 6.1 6.2 7.1
Tandem pore domain	K2P 1 2 3 4 5 6 7 9 10 12 13 15 16 17 18
Voltage-gated	K_vα1-6 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2.1 2.2 3.1 3.2 3.3 3.4 4.1 4.2 4.3 5.1 6.1 6.2 6.3 6.4 K_vα7-12 7.1 7.2 7.3 7.4 7.5 8.1 8.2 9.1 9.2 9.3 10.1 10.2 11.1/hERG 11.2 11.3 12.1 12.2 12.3 K_vβ 1 2 3 KCNIP 1 2 3 4 minK/ISK minK/ISK-like MiRP 1 2 3 Shaker (gene)

Miscellaneous

Cl⁻: Chloride channel	Calcium-activated chloride channels Anoctamin ANO1 Bestrophin 1 2 Chloride Channel Accessory 1 2 3 4 CFTR CLCN 1 2 3 4 5 6 7 KA KB CLIC 1 2 3 4 5 6 L1 CLNS 1A 1B
H⁺: Proton channel	HVCN1
M⁺: CNG cation channel	α 1 2 3 4 β 1 2 3 HCN FC 1 2 3 4
M⁺: TRP cation channel	TRPA (1) TRPC 1 2 3 4 4AP 5 6 7 TRPM 1 2 3 4 5 6 7 8 TRPML 1 2 3 TRPN TRPP 1 2 TRPV 1 2 3 4 5 6
H₂O (+ solutes): Porin	Aquaporin 0 1 2 3 4 5 6 7 8 9 Voltage-dependent anion channel 1 2 3 General bacterial porin family
Cytoplasm: Gap junction	Connexin A GJA1 GJA3 GJA4 GJA5 GJA8 GJA9 GJA10 B GJB1 GJB2 GJB3 GJB4 GJB5 GJB6 GJB7 C GJC1 GJC2 GJC3 D GJD2 GJD3 GJD4 Innexin