HCN1

Protein-coding gene in the species Homo sapiens

HCN1

Available structures

PDB

Ortholog search: PDBe RCSB

List of PDB id codes
3U0Z

Identifiers

Aliases

HCN1, BCNG-1, BCNG1, EIEE24, HAC-2, hyperpolarization activated cyclic nucleotide gated potassium channel 1, GEFSP10, DEE24

External IDs

OMIM: 602780; MGI: 1096392; HomoloGene: 32093; GeneCards: HCN1; OMA:HCN1 - orthologs

Gene location (Human)

Chr.	Chromosome 5 (human)^[1]

Band	5p12	Start	45,254,948 bp^[1]
Band	5p12	End	45,696,498 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 13 (mouse)^[2]

Band	13 D2.3\|13 66.34 cM	Start	117,738,856 bp^[2]
Band	13 D2.3\|13 66.34 cM	End	118,123,954 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

endothelial cell

Brodmann area 23

trigeminal ganglion

Brodmann area 46

spinal ganglia

prefrontal cortex

superior frontal gyrus

middle temporal gyrus

parietal lobe

dorsolateral prefrontal cortex

Top expressed in

subiculum

medial vestibular nucleus

pontine nuclei

cerebellar vermis

facial motor nucleus

anterior horn of spinal cord

inferior colliculus

retinal pigment epithelium

Region I of hippocampus proper

ventromedial nucleus

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	nucleotide binding intracellular cAMP-activated cation channel activity identical protein binding voltage-gated sodium channel activity ion channel activity potassium channel activity sodium channel activity voltage-gated ion channel activity voltage-gated potassium channel activity voltage-gated cation channel activity cAMP binding protein binding
Cellular component	axon membrane dendrite plasma membrane integral component of membrane HCN channel complex integral component of plasma membrane
Biological process	transmembrane transport retinal cone cell development regulation of ion transmembrane transport apical protein localization ion transport sodium ion transport regulation of membrane potential sodium ion transmembrane transport potassium ion transmembrane transport potassium ion transport protein homotetramerization cellular response to cAMP
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


348980


15165

Ensembl


ENSG00000164588


ENSMUSG00000021730

UniProt


O60741


O88704

RefSeq (mRNA)


NM_021072


NM_010408

RefSeq (protein)


NP_066550


NP_034538

Location (UCSC)

Chr 5: 45.25 – 45.7 Mb

Chr 13: 117.74 – 118.12 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 is a protein that in humans is encoded by the HCN1 gene.^[5]^[6]^[7]^[8]

Function

Hyperpolarization-activated cation channels of the HCN gene family, such as HCN1, contribute to spontaneous rhythmic activity in both heart and brain.^[8]

Tissue distribution

HCN1 channel expression is found in the sinoatrial node,^[9]^[10] the neocortex, hippocampus, cerebellar cortex, dorsal root ganglion, trigeminal ganglion and brainstem.^[11]^[12]^[13]^[14]^[15]

Ligands

Ketamine is an inhibitor of HCN1 in addition to its other targets.^[16]^[17]

Propofol also inhibits HCN1.^[18]

Isoflurane and Sevoflurane inhibit HCN1.^[19]

Interactions

HCN1 has been shown to interact with HCN2.^[20]^[21]

Epilepsy

De novo mutations in HCN1 cause epilepsy.^[22]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000164588 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000021730 – 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 (December 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): 14815–14820. 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): 717–729. doi:10.1016/S0092-8674(00)81434-8. PMID 9630217.
^ Hofmann F, Biel M, Kaupp UB (December 2005). "International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels". Pharmacological Reviews. 57 (4): 455–462. doi:10.1124/pr.57.4.8. PMID 16382102. S2CID 45853869.
^ ^a ^b "Entrez Gene: HCN1 hyperpolarization activated cyclic nucleotide-gated potassium channel 1".
^ Marionneau C, Couette B, Liu J, Li H, Mangoni ME, Nargeot J, et al. (January 2005). "Specific pattern of ionic channel gene expression associated with pacemaker activity in the mouse heart". The Journal of Physiology. 562 (Pt 1): 223–234. doi:10.1113/jphysiol.2004.074047. PMC 1665484. PMID 15498808.
^ Shi W, Wymore R, Yu H, Wu J, Wymore RT, Pan Z, et al. (July 1999). "Distribution and prevalence of hyperpolarization-activated cation channel (HCN) mRNA expression in cardiac tissues". Circulation Research. 85 (1): e1–e6. doi:10.1161/01.RES.85.1.e1. PMID 10400919.
^ Lörincz A, Notomi T, Tamás G, Shigemoto R, Nusser Z (November 2002). "Polarized and compartment-dependent distribution of HCN1 in pyramidal cell dendrites". Nature Neuroscience. 5 (11): 1185–1193. doi:10.1038/nn962. PMID 12389030. S2CID 18132966.
^ Milligan CJ, Edwards IJ, Deuchars J (April 2006). "HCN1 ion channel immunoreactivity in spinal cord and medulla oblongata". Brain Research. 1081 (1): 79–91. doi:10.1016/j.brainres.2006.01.019. PMID 16503331. S2CID 30929772.
^ Moosmang S, Biel M, Hofmann F, Ludwig A (1999). "Differential distribution of four hyperpolarization-activated cation channels in mouse brain". Biological Chemistry. 380 (7–8): 975–980. doi:10.1515/BC.1999.121. PMID 10494850. S2CID 22722872.
^ Wells JE, Rowland KC, Proctor EK (September 2007). "Hyperpolarization-activated channels in trigeminal ganglia innervating healthy and pulp-exposed teeth". International Endodontic Journal. 40 (9): 715–721. doi:10.1111/j.1365-2591.2007.01297.x. PMID 17645513.
^ Santoro B, Grant SG, Bartsch D, Kandel ER (December 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): 14815–14820. Bibcode:1997PNAS...9414815S. doi:10.1073/pnas.94.26.14815. PMC 25120. PMID 9405696.
^ Chen X, Shu S, Bayliss DA (January 2009). "HCN1 channel subunits are a molecular substrate for hypnotic actions of ketamine". The Journal of Neuroscience. 29 (3): 600–609. doi:10.1523/JNEUROSCI.3481-08.2009. PMC 2744993. PMID 19158287.
^ Zhou C, Douglas JE, Kumar NN, Shu S, Bayliss DA, Chen X (April 2013). "Forebrain HCN1 channels contribute to hypnotic actions of ketamine". Anesthesiology. 118 (4): 785–795. doi:10.1097/ALN.0b013e318287b7c8. PMC 3605219. PMID 23377220.
^ Bojak I, Day HC, Liley DT (2013). "Ketamine, Propofol, and the EEG: A Neural Field Analysis of HCN1-Mediated Interactions". Frontiers in Computational Neuroscience. 7: 22. doi:10.3389/fncom.2013.00022. PMC 3617565. PMID 23576979.
^ Zhou C, Liang P, Liu J, Ke B, Wang X, Li F, et al. (September 2015). "HCN1 Channels Contribute to the Effects of Amnesia and Hypnosis but not Immobility of Volatile Anesthetics". Anesthesia and Analgesia. 121 (3): 661–666. doi:10.1213/ANE.0000000000000830. PMC 4544830. PMID 26287296.
^ Much B, Wahl-Schott C, Zong X, Schneider A, Baumann L, Moosmang S, et al. (October 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): 43781–43786. doi:10.1074/jbc.M306958200. PMID 12928435.
^ Proenza C, Tran N, Angoli D, Zahynacz K, Balcar P, Accili EA (August 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): 29634–29642. doi:10.1074/jbc.M200504200. PMID 12034718.
^ Nava C, Dalle C, Rastetter A, Striano P, de Kovel CG, Nabbout R, et al. (June 2014). "De novo mutations in HCN1 cause early infantile epileptic encephalopathy" (PDF). Nature Genetics. 46 (6): 640–645. doi:10.1038/ng.2952. PMID 24747641. S2CID 861414.

External links

HCN1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
Overview of all the structural information available in the PDB for UniProt: O60741 (Human Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1) at the PDBe-KB.
Overview of all the structural information available in the PDB for UniProt: O88704 (Mouse Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1) at the PDBe-KB.

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