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HCN4 - Wikipedia

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HCN4
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

2MNG, 3OTF, 3U11, 4HBN, 4KL1, 4NVP

Identifiers
AliasesHCN4, SSS2, hyperpolarization activated cyclic nucleotide gated potassium channel 4, BRGDA8, EIG18
External IDsOMIM: 605206; MGI: 1298209; HomoloGene: 3997; GeneCards: HCN4; OMA:HCN4 - orthologs
Gene location (Human)
Chromosome 15 (human)
Chr.Chromosome 15 (human)[1]

Chromosome 15 (human)

Genomic location for HCN4

Genomic location for HCN4

Band15q24.1Start73,319,859 bp[1]
End73,368,958 bp[1]
Gene location (Mouse)
Chromosome 9 (mouse)
Chr.Chromosome 9 (mouse)[2]

Chromosome 9 (mouse)

Genomic location for HCN4

Genomic location for HCN4

Band9|9 BStart58,730,695 bp[2]
End58,770,458 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
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
BioGPS
More reference expression data
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

10021

330953

Ensembl

ENSG00000138622

ENSMUSG00000032338

UniProt

Q9Y3Q4

O70507

RefSeq (mRNA)

NM_005477

NM_001081192

RefSeq (protein)

NP_005468

NP_001074661

Location (UCSC)Chr 15: 73.32 – 73.37 MbChr 9: 58.73 – 58.77 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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]

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

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000138622Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032338Ensembl, 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.
  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.
  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.
  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.
  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.
  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. ^
  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.
  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.

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