T3DB: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4

Name	Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4
Synonyms	Not Available
Gene Name	HCN4
Organism	Human
Amino acid sequence	>lcl\|BSEQ0020824\|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
Number of residues	1203
Molecular Weight	129040.65
Theoretical pI	Not Available
GO Classification	Functions cAMP binding identical protein binding intracellular cAMP activated cation channel activity voltage-gated potassium channel activity voltage-gated sodium channel activity Processes sodium ion transmembrane transport regulation of membrane depolarization cellular response to steroid hormone stimulus blood circulation cellular response to cGMP response to cisplatin potassium ion transmembrane transport regulation of heart rate regulation of heart rate by cardiac conduction SA node cell action potential cation transport regulation of membrane potential muscle contraction synaptic transmission cellular response to cAMP regulation of cardiac muscle contraction Components integral component of plasma membrane basolateral plasma membrane intrinsic component of plasma membrane neuronal cell body plasma membrane terminal bouton perinuclear region of cytoplasm
General Function	Voltage-gated sodium channel activity
Specific Function	Hyperpolarization-activated ion channel with very slow activation and inactivation exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) that regulate the rhythm of heart beat. May contribute to the native pacemaker currents in neurons (Ih). May mediate responses to sour stimuli.
Pfam Domain Function	Ion_trans (PF00520 ) cNMP_binding (PF00027 ) Ion_trans_N (PF08412 )
Transmembrane Regions	267-287 294-314 341-361 369-389 421-441 497-517
GenBank Protein ID	Not Available
UniProtKB ID	Q9Y3Q4
UniProtKB Entry Name	HCN4_HUMAN
Cellular Location	Cell membrane
Gene sequence	>lcl\|BSEQ0020825\|Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) 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
GenBank Gene ID	Not Available
GeneCard ID	Not Available
GenAtlas ID	Not Available
HGNC ID	HGNC:16882
Chromosome Location	15
Locus	Not Available
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. 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. 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. 19165230 Xu X, Vysotskaya ZV, Liu Q, Zhou L: Structural basis for the cAMP-dependent gating in the human HCN4 channel. J Biol Chem. 2010 Nov 19;285(47):37082-91. doi: 10.1074/jbc.M110.152033. Epub 2010 Sep 9. 20829353 Lolicato M, Nardini M, Gazzarrini S, Moller S, Bertinetti D, Herberg FW, Bolognesi M, Martin H, Fasolini M, Bertrand JA, Arrigoni C, Thiel G, Moroni A: Tetramerization dynamics of C-terminal domain underlies isoform-specific cAMP gating in hyperpolarization-activated cyclic nucleotide-gated channels. J Biol Chem. 2011 Dec 30;286(52):44811-20. doi: 10.1074/jbc.M111.297606. Epub 2011 Oct 17. 22006928 Xu X, Marni F, Wu S, Su Z, Musayev F, Shrestha S, Xie C, Gao W, Liu Q, Zhou L: Local and global interpretations of a disease-causing mutation near the ligand entry path in hyperpolarization-activated cAMP-gated channel. Structure. 2012 Dec 5;20(12):2116-23. doi: 10.1016/j.str.2012.09.017. Epub 2012 Oct 25. 23103389 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. 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. 16407510 Laish-Farkash A, Glikson M, Brass D, Marek-Yagel D, Pras E, Dascal N, Antzelevitch C, Nof E, Reznik H, Eldar M, Luria D: A novel mutation in the HCN4 gene causes symptomatic sinus bradycardia in Moroccan Jews. J Cardiovasc Electrophysiol. 2010 Dec;21(12):1365-72. doi: 10.1111/j.1540-8167.2010.01844.x. 20662977