Identification |
HMDB Protein ID
| HMDBP08131 |
Secondary Accession Numbers
| |
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
|
- Membrane
- 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
|
|
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
|
External Links |
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
| - 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
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