Hmdb loader
Identification
HMDB Protein ID HMDBP08131
Secondary Accession Numbers
  • 13842
Name Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4
Synonyms Not Available
Gene Name HCN4
Protein Type Unknown
Biological Properties
General Function Involved in ion channel activity
Specific Function Hyperpolarization-activated ion channel with very slow activation and inactivation exhibiting weak selectivity for potassium over sodium ions. May contribute to the native pacemaker currents in heart (If) and in neurons (Ih). Activated by cAMP. May mediate responses to sour stimuli
Pathways
  • Acebutolol Action Pathway
  • Alprenolol Action Pathway
  • Amiodarone Action Pathway
  • Amlodipine Action Pathway
  • Arbutamine Action Pathway
  • Atenolol Action Pathway
  • Betaxolol Action Pathway
  • Bevantolol Action Pathway
  • Bisoprolol Action Pathway
  • Bopindolol Action Pathway
  • Bupranolol Action Pathway
  • Carteolol Action Pathway
  • Carvedilol Action Pathway
  • Diltiazem Action Pathway
  • Disopyramide Action Pathway
  • Dobutamine Action Pathway
  • Epinephrine Action Pathway
  • Esmolol Action Pathway
  • Felodipine Action Pathway
  • Flecainide Action Pathway
  • Fosphenytoin (Antiarrhythmic) Action Pathway
  • Ibutilide Action Pathway
  • Isoprenaline Action Pathway
  • Isradipine Action Pathway
  • Labetalol Action Pathway
  • Levobunolol Action Pathway
  • Lidocaine (Antiarrhythmic) Action Pathway
  • Metipranolol Action Pathway
  • Metoprolol Action Pathway
  • Mexiletine Action Pathway
  • Muscle/Heart Contraction
  • Nadolol Action Pathway
  • Nebivolol Action Pathway
  • Nifedipine Action Pathway
  • Nimodipine Action Pathway
  • Nisoldipine Action Pathway
  • Nitrendipine Action Pathway
  • Oxprenolol Action Pathway
  • Penbutolol Action Pathway
  • Phenytoin (Antiarrhythmic) Action Pathway
  • Pindolol Action Pathway
  • Practolol Action Pathway
  • Procainamide (Antiarrhythmic) Action Pathway
  • Propranolol Action Pathway
  • Quinidine Action Pathway
  • Sotalol Action Pathway
  • Timolol Action Pathway
  • Tocainide Action Pathway
  • Verapamil Action Pathway
Reactions Not Available
GO Classification
Component
membrane
cell part
Function
transmembrane transporter activity
substrate-specific transmembrane transporter activity
ion transmembrane transporter activity
transporter activity
ion channel activity
cation channel activity
potassium channel activity
voltage-gated potassium channel activity
Process
establishment of localization
transport
transmembrane transport
monovalent inorganic cation transport
potassium ion transport
ion transport
cation transport
Cellular Location
  1. Membrane
  2. Multi-pass membrane protein
Gene Properties
Chromosome Location Chromosome:1
Locus 15q24.1
SNPs HCN4
Gene Sequence
>3612 bp
ATGGACAAGCTGCCGCCGTCCATGCGCAAGCGGCTCTACAGCCTCCCGCAGCAGGTGGGG
GCCAAGGCGTGGATCATGGACGAGGAAGAGGACGCCGAGGAGGAGGGGGCCGGGGGCCGC
CAAGACCCCAGCCGCAGGAGCATCCGGCTGCGGCCACTGCCCTCGCCCTCCCCCTCGGCG
GCCGCGGGTGGCACGGAGTCCCGGAGCTCGGCCCTCGGGGCAGCGGACAGCGAAGGGCCG
GCCCGCGGCGCGGGCAAGTCCAGCACGAACGGCGACTGCAGGCGCTTCCGCGGGAGCCTG
GCCTCGCTGGGCAGCCGGGGCGGCGGCAGCGGCGGCACGGGGAGCGGCAGCAGTCACGGA
CACCTGCATGACTCCGCGGAGGAGCGGCGGCTCATCGCCGAGGGCGACGCGTCCCCCGGC
GAGGACAGGACGCCCCCAGGCCTGGCGGCCGAGCCCGAGCGCCCCGGCGCCTCGGCGCAG
CCCGCAGCCTCGCCGCCGCCGCCCCAGCAGCCACCGCAGCCGGCCTCCGCCTCCTGCGAG
CAGCCCTCGGTGGACACCGCTATCAAAGTGGAGGGAGGCGCGGCTGCCGGCGACCAGATC
CTCCCGGAGGCCGAGGTGCGCCTGGGCCAGGCCGGCTTCATGCAGCGCCAGTTCGGGGCC
ATGCTCCAACCCGGGGTCAACAAATTCTCCCTAAGGATGTTCGGCAGCCAGAAAGCCGTG
GAGCGCGAACAGGAGAGGGTCAAGTCGGCCGGATTTTGGATTATCCACCCCTACAGTGAC
TTCAGATTTTACTGGGACCTGACCATGCTGCTGCTGATGGTGGGAAACCTGATTATCATT
CCTGTGGGCATCACCTTCTTCAAGGATGAGAACACCACACCCTGGATTGTCTTCAATGTG
GTGTCAGACACATTCTTCCTCATCGACTTGGTCCTCAACTTCCGCACAGGGATCGTGGTG
GAGGACAACACAGAGATCATCCTGGACCCGCAGCGGATTAAAATGAAGTACCTGAAAAGC
TGGTTCATGGTAGATTTCATTTCCTCCATCCCCGTGGACTACATCTTCCTCATTGTGGAG
ACACGCATCGACTCGGAGGTCTACAAGACTGCCCGGGCCCTGCGCATTGTCCGCTTCACG
AAGATCCTCAGCCTCTTACGCCTGTTACGCCTCTCCCGCCTCATTCGATATATTCACCAG
TGGGAAGAGATCTTCCACATGACCTACGACCTGGCCAGCGCCGTGGTGCGCATCGTGAAC
CTCATCGGCATGATGCTCCTGCTCTGCCACTGGGACGGCTGCCTGCAGTTCCTGGTACCC
ATGCTACAGGACTTCCCTGACGACTGCTGGGTGTCCATCAACAACATGGTGAACAACTCC
TGGGGGAAGCAGTACTCCTACGCGCTCTTCAAGGCCATGAGCCACATGCTGTGCATCGGC
TACGGGCGGCAGGCGCCCGTGGGCATGTCCGACGTCTGGCTCACCATGCTCAGCATGATC
GTGGGTGCCACCTGCTACGCCATGTTCATTGGCCACGCCACTGCCCTCATCCAGTCCCTG
GACTCCTCCCGGCGCCAGTACCAGGAAAAGTACAAGCAGGTGGAGCAGTACATGTCCTTT
CACAAGCTCCCGCCCGACACCCGGCAGCGCATCCACGACTACTACGAGCACCGCTACCAG
GGCAAGATGTTCGACGAGGAGAGCATCCTGGGCGAGCTAAGCGAGCCCCTGCGGGAGGAG
ATCATCAACTTTAACTGTCGGAAGCTGGTGGCCTCCATGCCACTGTTTGCCAATGCGGAC
CCCAACTTCGTGACGTCCATGCTGACCAAGCTGCGTTTCGAGGTCTTCCAGCCTGGGGAC
TACATCATCCGGGAAGGCACCATTGGCAAGAAGATGTACTTCATCCAGCATGGCGTGGTC
AGCGTGCTCACCAAGGGCAACAAGGAGACCAAGCTGGCCGACGGCTCCTACTTTGGAGAG
ATCTGCCTGCTGACCCGGGGCCGGCGCACAGCCAGCGTGAGGGCCGACACCTACTGCCGC
CTCTACTCGCTGAGCGTGGACAACTTCAATGAGGTGCTGGAGGAGTACCCCATGATGCGA
AGGGCCTTCGAGACCGTGGCGCTGGACCGCCTGGACCGCATTGGCAAGAAGAACTCCATC
CTCCTCCACAAAGTCCAGCACGACCTCAACTCCGGCGTCTTCAACTACCAGGAGAATGAG
ATCATCCAGCAGATTGTGCAGCATGACCGGGAGATGGCCCACTGCGCGCACCGCGTCCAG
GCTGCTGCCTCTGCCACCCCAACCCCCACGCCCGTCATCTGGACCCCGCTGATCCAGGCA
CCACTGCAGGCTGCCGCTGCCACCACTTCTGTGGCCATAGCCCTCACCCACCACCCTCGC
CTGCCTGCTGCCATCTTCCGCCCTCCCCCAGGATCTGGGCTGGGCAACCTCGGTGCCGGG
CAGACGCCAAGGCACCTGAAACGGCTGCAGTCCCTGATCCCTTCTGCGCTGGGCTCCGCC
TCGCCCGCCAGCAGCCCGTCCCAGGTGGACACACCGTCTTCATCCTCCTTCCACATCCAA
CAGCTGGCTGGATTCTCTGCCCCCGCTGGACTGAGCCCACTCCTGCCCTCATCCAGCTCC
TCCCCACCCCCCGGGGCCTGTGGCTCCCCCTCGGCTCCCACACCATCAGCTGGCGTAGCC
GCCACCACCATAGCCGGGTTTGGCCACTTCCACAAGGCGCTGGGTGGCTCCCTGTCCTCC
TCCGACTCTCCCCTGCTCACCCCGCTGCAGCCAGGCGCCCGCTCCCCGCAGGCTGCCCAG
CCATCTCCCGCGCCACCCGGGGCCCGGGGAGGCCTGGGACTCCCGGAGCACTTCCTGCCA
CCCCCACCCTCATCCAGATCCCCGTCATCTAGCCCCGGGCAGCTGGGCCAGCCTCCCGGG
GAGTTGTCCCTAGGTCTGGCCACTGGCCCACTGAGCACGCCAGAGACACCCCCACGGCAG
CCTGAGCCGCCGTCCCTTGTGGCAGGGGCCTCTGGGGGGGCTTCCCCTGTAGGCTTTACT
CCCCGAGGAGGTCTCAGCCCCCCTGGCCACAGCCCAGGCCCCCCAAGAACCTTCCCGAGT
GCCCCGCCCCGGGCCTCTGGCTCCCACGGATCCTTGCTCCTGCCACCTGCATCCAGCCCC
CCACCACCCCAGGTCCCCCAGCGCCGGGGCACACCCCCGCTCACCCCCGGCCGCCTCACC
CAGGACCTCAAGCTCATCTCCGCGTCTCAGCCAGCCCTGCCTCAGGACGGGGCGCAGACT
CTCCGCAGAGCCTCCCCGCACTCCTCAGGGGAGTCCATGGCTGCCTTCCCGCTCTTCCCC
AGGGCTGGGGGTGGCAGCGGGGGCAGTGGGAGCAGCGGGGGCCTCGGTCCCCCTGGGAGG
CCCTATGGTGCCATCCCCGGCCAGCACGTCACTCTGCCTCGGAAGACATCCTCAGGTTCT
TTGCCACCCCCTCTGTCTTTGTTTGGGGCAAGAGCCACCTCTTCTGGGGGGCCCCCTCTG
ACTGCTGGACCCCAGAGGGAACCTGGGGCCAGGCCTGAGCCAGTGCGCTCCAAACTGCCA
TCCAATCTATGA
Protein Properties
Number of Residues 1203
Molecular Weight 129040.7
Theoretical pI 9.15
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • 267-287
  • 294-314
  • 341-361
  • 369-389
  • 421-441
  • 497-517
Protein Sequence
>Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4
MDKLPPSMRKRLYSLPQQVGAKAWIMDEEEDAEEEGAGGRQDPSRRSIRLRPLPSPSPSA
AAGGTESRSSALGAADSEGPARGAGKSSTNGDCRRFRGSLASLGSRGGGSGGTGSGSSHG
HLHDSAEERRLIAEGDASPGEDRTPPGLAAEPERPGASAQPAASPPPPQQPPQPASASCE
QPSVDTAIKVEGGAAAGDQILPEAEVRLGQAGFMQRQFGAMLQPGVNKFSLRMFGSQKAV
EREQERVKSAGFWIIHPYSDFRFYWDLTMLLLMVGNLIIIPVGITFFKDENTTPWIVFNV
VSDTFFLIDLVLNFRTGIVVEDNTEIILDPQRIKMKYLKSWFMVDFISSIPVDYIFLIVE
TRIDSEVYKTARALRIVRFTKILSLLRLLRLSRLIRYIHQWEEIFHMTYDLASAVVRIVN
LIGMMLLLCHWDGCLQFLVPMLQDFPDDCWVSINNMVNNSWGKQYSYALFKAMSHMLCIG
YGRQAPVGMSDVWLTMLSMIVGATCYAMFIGHATALIQSLDSSRRQYQEKYKQVEQYMSF
HKLPPDTRQRIHDYYEHRYQGKMFDEESILGELSEPLREEIINFNCRKLVASMPLFANAD
PNFVTSMLTKLRFEVFQPGDYIIREGTIGKKMYFIQHGVVSVLTKGNKETKLADGSYFGE
ICLLTRGRRTASVRADTYCRLYSLSVDNFNEVLEEYPMMRRAFETVALDRLDRIGKKNSI
LLHKVQHDLNSGVFNYQENEIIQQIVQHDREMAHCAHRVQAAASATPTPTPVIWTPLIQA
PLQAAAATTSVAIALTHHPRLPAAIFRPPPGSGLGNLGAGQTPRHLKRLQSLIPSALGSA
SPASSPSQVDTPSSSSFHIQQLAGFSAPAGLSPLLPSSSSSPPPGACGSPSAPTPSAGVA
ATTIAGFGHFHKALGGSLSSSDSPLLTPLQPGARSPQAAQPSPAPPGARGGLGLPEHFLP
PPPSSRSPSSSPGQLGQPPGELSLGLATGPLSTPETPPRQPEPPSLVAGASGGASPVGFT
PRGGLSPPGHSPGPPRTFPSAPPRASGSHGSLLLPPASSPPPPQVPQRRGTPPLTPGRLT
QDLKLISASQPALPQDGAQTLRRASPHSSGESMAAFPLFPRAGGGSGGSGSSGGLGPPGR
PYGAIPGQHVTLPRKTSSGSLPPPLSLFGARATSSGGPPLTAGPQREPGARPEPVRSKLP
SNL
GenBank ID Protein 4775353
UniProtKB/Swiss-Prot ID Q9Y3Q4
UniProtKB/Swiss-Prot Entry Name HCN4_HUMAN
PDB IDs
GenBank Gene ID AJ132429
GeneCard ID HCN4
GenAtlas ID HCN4
HGNC ID HGNC:16882
References
General References
  1. Ludwig A, Zong X, Stieber J, Hullin R, Hofmann F, Biel M: Two pacemaker channels from human heart with profoundly different activation kinetics. EMBO J. 1999 May 4;18(9):2323-9. [PubMed:10228147 ]
  2. Seifert R, Scholten A, Gauss R, Mincheva A, Lichter P, Kaupp UB: Molecular characterization of a slowly gating human hyperpolarization-activated channel predominantly expressed in thalamus, heart, and testis. Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9391-6. [PubMed:10430953 ]
  3. Ueda K, Hirano Y, Higashiuesato Y, Aizawa Y, Hayashi T, Inagaki N, Tana T, Ohya Y, Takishita S, Muratani H, Hiraoka M, Kimura A: Role of HCN4 channel in preventing ventricular arrhythmia. J Hum Genet. 2009 Feb;54(2):115-21. doi: 10.1038/jhg.2008.16. Epub 2009 Jan 23. [PubMed:19165230 ]
  4. Ueda K, Nakamura K, Hayashi T, Inagaki N, Takahashi M, Arimura T, Morita H, Higashiuesato Y, Hirano Y, Yasunami M, Takishita S, Yamashina A, Ohe T, Sunamori M, Hiraoka M, Kimura A: Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia. J Biol Chem. 2004 Jun 25;279(26):27194-8. Epub 2004 Apr 30. [PubMed:15123648 ]
  5. Milanesi R, Baruscotti M, Gnecchi-Ruscone T, DiFrancesco D: Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel. N Engl J Med. 2006 Jan 12;354(2):151-7. [PubMed:16407510 ]