HCN4

HCN4
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2MNG, 3OTF, 3U11, 4HBN, 4KL1, 4NVP
Identifiers
Aliases	HCN4, SSS2, hyperpolarization activated cyclic nucleotide gated potassium channel 4, BRGDA8, EIG18
External IDs	OMIM: 605206; MGI: 1298209; HomoloGene: 3997; GeneCards: HCN4; OMA:HCN4 - orthologs
Gene location (Human)
Chr.	Chromosome 15 (human)
End	73,368,958 bp
Gene location (Mouse)
Chr.	Chromosome 9 (mouse)
End	58,770,458 bp
RNA expression pattern
	Top expressed in
	tibialis anterior muscle; ; right atrium; ; right auricle; ; apex of heart; ; testicle; ; left ventricle; ; secondary oocyte; ; right ventricle; ; gonad; ; mucosa of ileum;
	Top expressed in
	myocardium; ; cardiac muscles; ; Cardiac muscle tissue of myocardium; ; electrical conduction system of the heart; ; sinus venosus; ; right atrium; ; sinoatrial node; ; septum transversum; ; vein; ; left horn of sinus venosus;
	More reference expression data
	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; voltage-gated potassium channel activity involved in SA node cell action potential depolarization;
Cellular component	integral component of membrane; membrane; intrinsic component of plasma membrane; plasma membrane; perinuclear region of cytoplasm; HCN channel complex;
Biological process	cellular response to cGMP; muscle contraction; sodium ion transmembrane transport; sodium ion transport; SA node cell action potential; regulation of membrane potential; regulation of ion transmembrane transport; cation transport; ion transport; blood circulation; regulation of membrane depolarization; regulation of heart rate; potassium ion transport; transmembrane transport; potassium ion transmembrane transport; regulation of cardiac muscle contraction; regulation of heart rate by cardiac conduction; cellular response to cAMP; membrane depolarization during cardiac muscle cell action potential; membrane depolarization during SA node cell action potential; sodium ion import across plasma membrane; regulation of cardiac muscle cell action potential involved in regulation of contraction; potassium ion import across plasma membrane;
	Sources:Amigo / QuickGO
Orthologs
	10021
	330953
	ENSG00000138622
	ENSMUSG00000032338
	Q9Y3Q4
	O70507
	NM_005477
	NM_001081192
	NP_005468
	NP_001074661
	Wikidata
View/Edit Human	View/Edit Mouse

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 is a protein that in humans is encoded by the HCN4 gene.^[5]^[6]^[7]^[8]

There are four HCN channels. HCN4 is prominently expressed in the pace maker region of the mammalian heart.^[9] Some humans with bradycardia and Sick sinus syndrome have been shown to have mutations in their HCN4 gene.^[10]^[11]^[12] The role of HCN channels in autonomic control of heart rate is currently a matter of ongoing investigation.^[13]^[14]^[15]^[16]

Interactions

HCN4 has been shown to interact with HCN2.^[17]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000138622 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000032338 – 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.
^ Ludwig A, Zong X, Stieber J, Hullin R, Hofmann F, Biel M (May 1999). "Two pacemaker channels from human heart with profoundly different activation kinetics". The EMBO Journal. 18 (9): 2323–9. doi:10.1093/emboj/18.9.2323. PMC 1171315. PMID 10228147.
^ Seifert R, Scholten A, Gauss R, Mincheva A, Lichter P, Kaupp UB (Aug 1999). "Molecular characterization of a slowly gating human hyperpolarization-activated channel predominantly expressed in thalamus, heart, and testis". Proceedings of the National Academy of Sciences of the United States of America. 96 (16): 9391–6. Bibcode:1999PNAS...96.9391S. doi:10.1073/pnas.96.16.9391. PMC 17793. PMID 10430953.
^ 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: HCN4 hyperpolarization activated cyclic nucleotide-gated potassium channel 4".
^ Baruscotti M, Bucchi A, Viscomi C, Mandelli G, Consalez G, Gnecchi-Rusconi T, Montano N, Casali KR, Micheloni S, Barbuti A, DiFrancesco D (Jan 2011). "Deep bradycardia and heart block caused by inducible cardiac-specific knockout of the pacemaker channel gene Hcn4". Proceedings of the National Academy of Sciences of the United States of America. 108 (4): 1705–10. Bibcode:2011PNAS..108.1705B. doi:10.1073/pnas.1010122108. PMC 3029742. PMID 21220308.
^ Jou, Chuanchau J.; Arrington, Cammon B.; Barnett, Spencer M; Shen, Jiaxiang; Cho, Scott; Sheng, Xiaoming; McCullagh, Patrick C.; Bowles, Neil E.; Pribble, Chase M.; Saarel, Elizabeth V.; Pilcher, Thomas A.; Etheridge, Susan P.; Tristani-Firouzi, Martin (2017). "A Functional Assay for Sick Sinus Syndrome Genetic Variants". Cellular Physiology and Biochemistry. 42 (5): 2021–2029. doi:10.1159/000479897. ISSN 1015-8987. PMID 28803248.
^ Schulze-Bahr E, Neu A, Friederich P, Kaupp UB, Breithardt G, Pongs O, Isbrandt D (May 2003). "Pacemaker channel dysfunction in a patient with sinus node disease". The Journal of Clinical Investigation. 111 (10): 1537–45. doi:10.1172/JCI16387. PMC 155041. PMID 12750403.
^ Laish-Farkash A, Glikson M, Brass D, Marek-Yagel D, Pras E, Dascal N, Antzelevitch C, Nof E, Reznik H, Eldar M, Luria D (Dec 2010). "A novel mutation in the HCN4 gene causes symptomatic sinus bradycardia in Moroccan Jews". Journal of Cardiovascular Electrophysiology. 21 (12): 1365–72. doi:10.1111/j.1540-8167.2010.01844.x. PMC 3005590. PMID 20662977.
^ Larsson HP (Sep 2010). "How is the heart rate regulated in the sinoatrial node? Another piece to the puzzle". The Journal of General Physiology. 136 (3): 237–41. doi:10.1085/jgp.201010506. PMC 2931147. PMID 20713549.
^ Schweizer PA, Duhme N, Thomas D, Becker R, Zehelein J, Draguhn A, Bruehl C, Katus HA, Koenen M (Oct 2010). "cAMP sensitivity of HCN pacemaker channels determines basal heart rate but is not critical for autonomic rate control". Circulation: Arrhythmia and Electrophysiology. 3 (5): 542–52. doi:10.1161/CIRCEP.110.949768. hdl:11858/00-001M-0000-002C-5DAB-C. PMID 20693575.
^ Liao Z, Lockhead D, Larson ED, Proenza C (Sep 2010). "Phosphorylation and modulation of hyperpolarization-activated HCN4 channels by protein kinase A in the mouse sinoatrial node". The Journal of General Physiology. 136 (3): 247–58. doi:10.1085/jgp.201010488. PMC 2931151. PMID 20713547.
^ Nof E, Antzelevitch C, Glikson M (Jan 2010). "The Contribution of HCN4 to normal sinus node function in humans and animal models". Pacing and Clinical Electrophysiology. 33 (1): 100–6. doi:10.1111/j.1540-8159.2009.02563.x. PMC 2865562. PMID 19796353.
^ 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.

External links

GeneReviews/NIH/NCBI/UW entry on Brugada syndrome
HCN4+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
HCN4 human gene location in the UCSC Genome Browser.
HCN4 human gene details in the UCSC Genome Browser.

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

This membrane protein–related article is a stub. You can help Wikipedia by expanding it.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000138622 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000032338 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid10228147-5] Ludwig A, Zong X, Stieber J, Hullin R, Hofmann F, Biel M (May 1999). "Two pacemaker channels from human heart with profoundly different activation kinetics". The EMBO Journal. 18 (9): 2323–9. doi:10.1093/emboj/18.9.2323. PMC 1171315. PMID 10228147.

[pmid10430953-6] Seifert R, Scholten A, Gauss R, Mincheva A, Lichter P, Kaupp UB (Aug 1999). "Molecular characterization of a slowly gating human hyperpolarization-activated channel predominantly expressed in thalamus, heart, and testis". Proceedings of the National Academy of Sciences of the United States of America. 96 (16): 9391–6. Bibcode:1999PNAS...96.9391S. doi:10.1073/pnas.96.16.9391. PMC 17793. PMID 10430953.

[pmid16382102-7] 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-8] "Entrez Gene: HCN4 hyperpolarization activated cyclic nucleotide-gated potassium channel 4".

[9] Baruscotti M, Bucchi A, Viscomi C, Mandelli G, Consalez G, Gnecchi-Rusconi T, Montano N, Casali KR, Micheloni S, Barbuti A, DiFrancesco D (Jan 2011). "Deep bradycardia and heart block caused by inducible cardiac-specific knockout of the pacemaker channel gene Hcn4". Proceedings of the National Academy of Sciences of the United States of America. 108 (4): 1705–10. Bibcode:2011PNAS..108.1705B. doi:10.1073/pnas.1010122108. PMC 3029742. PMID 21220308.

[Jou,_et_al-10] Jou, Chuanchau J.; Arrington, Cammon B.; Barnett, Spencer M; Shen, Jiaxiang; Cho, Scott; Sheng, Xiaoming; McCullagh, Patrick C.; Bowles, Neil E.; Pribble, Chase M.; Saarel, Elizabeth V.; Pilcher, Thomas A.; Etheridge, Susan P.; Tristani-Firouzi, Martin (2017). "A Functional Assay for Sick Sinus Syndrome Genetic Variants". Cellular Physiology and Biochemistry. 42 (5): 2021–2029. doi:10.1159/000479897. ISSN 1015-8987. PMID 28803248.

[11] Schulze-Bahr E, Neu A, Friederich P, Kaupp UB, Breithardt G, Pongs O, Isbrandt D (May 2003). "Pacemaker channel dysfunction in a patient with sinus node disease". The Journal of Clinical Investigation. 111 (10): 1537–45. doi:10.1172/JCI16387. PMC 155041. PMID 12750403.

[12] Laish-Farkash A, Glikson M, Brass D, Marek-Yagel D, Pras E, Dascal N, Antzelevitch C, Nof E, Reznik H, Eldar M, Luria D (Dec 2010). "A novel mutation in the HCN4 gene causes symptomatic sinus bradycardia in Moroccan Jews". Journal of Cardiovascular Electrophysiology. 21 (12): 1365–72. doi:10.1111/j.1540-8167.2010.01844.x. PMC 3005590. PMID 20662977.

[13] Larsson HP (Sep 2010). "How is the heart rate regulated in the sinoatrial node? Another piece to the puzzle". The Journal of General Physiology. 136 (3): 237–41. doi:10.1085/jgp.201010506. PMC 2931147. PMID 20713549.

[14] Schweizer PA, Duhme N, Thomas D, Becker R, Zehelein J, Draguhn A, Bruehl C, Katus HA, Koenen M (Oct 2010). "cAMP sensitivity of HCN pacemaker channels determines basal heart rate but is not critical for autonomic rate control". Circulation: Arrhythmia and Electrophysiology. 3 (5): 542–52. doi:10.1161/CIRCEP.110.949768. hdl:11858/00-001M-0000-002C-5DAB-C. PMID 20693575.

[15] Liao Z, Lockhead D, Larson ED, Proenza C (Sep 2010). "Phosphorylation and modulation of hyperpolarization-activated HCN4 channels by protein kinase A in the mouse sinoatrial node". The Journal of General Physiology. 136 (3): 247–58. doi:10.1085/jgp.201010488. PMC 2931151. PMID 20713547.

[16] Nof E, Antzelevitch C, Glikson M (Jan 2010). "The Contribution of HCN4 to normal sinus node function in humans and animal models". Pacing and Clinical Electrophysiology. 33 (1): 100–6. doi:10.1111/j.1540-8159.2009.02563.x. PMC 2865562. PMID 19796353.

[pmid12928435-17] 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.

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HCN4

Interactions

See also

References

Further reading

External links