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1.A.1.5.2
Hyperpolarization-activated and cyclic nucleotide-gated K+ channel, HCN (bCNG-1) (PNa+/PK+ ≈ 0.3). The human orthologue (O88703) is 863 aas in length and also catalyzes mixed monovalent cation currents K+:Na+= 4:1 (Lyashchenko and Tibbs et al., 2008). Biel et al. (2009) presented a detailed review of hyperpolarization-activated cation-channels. They are inhibited by nicotine and epibatidine which bind to the inner pore (Griguoli et al., 2010). They control cardiac and neuronal rhythmicity. HCN channels contain cyclic nucleotide-binding domains (CNBDs) in their C-terminal regions, linked to the pore-forming transmembrane segment with a C-linker. The C-linker couples the conformational changes caused by the direct binding of cyclic nucleotides to the HCN pore opening. Cyclic dinucleotides antagonize the effect of cyclic nucleotides in HCN4 but not in HCN2 channels. Interaction of the C-linker/CNBD with other parts of the channel appears to be necessary for cyclic-dinucleotide binding in HCN4 channels (Hayoz et al. 2017).

Accession Number:O88704
Protein Name:Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
Length:910
Molecular Weight:102432.00
Species: [10090]
Number of TMSs:3
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate K+

Cross database links:

Genevestigator: O88704
eggNOG: roNOG13745
HEGENOM: HBG447083
RefSeq: NP_034538.2   
Entrez Gene ID: 15165   
Pfam: PF00027    PF00520    PF08412   
KEGG: mmu:15165   

Gene Ontology

GO:0030424 C:axon
GO:0030425 C:dendrite
GO:0016021 C:integral to membrane
GO:0030552 F:cAMP binding
GO:0005515 F:protein binding
GO:0005272 F:sodium channel activity
GO:0005249 F:voltage-gated potassium channel activity
GO:0045176 P:apical protein localization
GO:0006813 P:potassium ion transport
GO:0006814 P:sodium ion transport
GO:0055085 P:transmembrane transport

References (11)

[1] “Interactive cloning with the SH3 domain of N-src identifies a new brain specific ion channel protein, with homology to eag and cyclic nucleotide-gated channels.”  Santoro B.et.al.   9405696
[2] “A family of hyperpolarization-activated cation channels.”  Ludwig A.et.al.   9634236
[3] “The transcriptional landscape of the mammalian genome.”  Carninci P.et.al.   16141072
[4] “Identification of a gene encoding a hyperpolarization-activated 'pacemaker' channel of brain.”  Santoro B.et.al.   9630217
[5] “MinK-related peptide 1: a beta subunit for the HCN ion channel subunit family enhances expression and speeds activation.”  Yu H.et.al.   11420311
[6] “Molecular mechanism of cAMP modulation of HCN pacemaker channels.”  Wainger B.J.et.al.   11459060
[7] “Hyperpolarization-activated channels HCN1 and HCN4 mediate responses to sour stimuli.”  Stevens D.R.et.al.   11675786
[8] “Dominant-negative suppression of HCN1- and HCN2-encoded pacemaker currents by an engineered HCN1 construct: insights into structure-function relationships and multimerization.”  Xue T.et.al.   12089064
[9] “Different roles for the cyclic nucleotide binding domain and amino terminus in assembly and expression of hyperpolarization-activated, cyclic nucleotide-gated channels.”  Proenza C.et.al.   12034718
[10] “An external determinant in the S5-P linker of the pacemaker (HCN) channel identified by sulfhydryl modification.”  Xue T.et.al.   12351622
[11] “Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations.”  Munton R.P.et.al.   17114649
Structure:
3U0Z     

External Searches:

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  • 2° Structure (Network Protein Sequence Analysis)

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MEGGGKPNSA SNSRDDGNSV FPSKAPATGP VAADKRLGTP PGGGAAGKEH GNSVCFKVDG 
61:	GGGEEPAGSF EDAEGPRRQY GFMQRQFTSM LQPGVNKFSL RMFGSQKAVE KEQERVKTAG 
121:	FWIIHPYSDF RFYWDLIMLI MMVGNLVIIP VGITFFTEQT TTPWIIFNVA SDTVFLLDLI 
181:	MNFRTGTVNE DSSEIILDPK VIKMNYLKSW FVVDFISSIP VDYIFLIVEK GMDSEVYKTA 
241:	RALRIVRFTK ILSLLRLLRL SRLIRYIHQW EEIFHMTYDL ASAVVRIFNL IGMMLLLCHW 
301:	DGCLQFLVPL LQDFPPDCWV SLNEMVNDSW GKQYSYALFK AMSHMLCIGY GAQAPVSMSD 
361:	LWITMLSMIV GATCYAMFVG HATALIQSLD SSRRQYQEKY KQVEQYMSFH KLPADMRQKI 
421:	HDYYEHRYQG KIFDEENILS ELNDPLREEI VNFNCRKLVA TMPLFANADP NFVTAMLSKL 
481:	RFEVFQPGDY IIREGAVGKK MYFIQHGVAG VITKSSKEMK LTDGSYFGEI CLLTKGRRTA 
541:	SVRADTYCRL YSLSVDNFNE VLEEYPMMRR AFETVAIDRL DRIGKKNSIL LQKFQKDLNT 
601:	GVFNNQENEI LKQIVKHDRE MVQAIPPINY PQMTALNCTS STTTPTSRMR TQSPPVYTAT 
661:	SLSHSNLHSP SPSTQTPQPS AILSPCSYTT AVCSPPIQSP LATRTFHYAS PTASQLSLMQ 
721:	QPQQQLPQSQ VQQTQTQTQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQPQTPG 
781:	SSTPKNEVHK STQALHNTNL TKEVRPLSAS QPSLPHEVST LISRPHPTVG ESLASIPQPV 
841:	AAVHSTGLQA GSRSTVPQRV TLFRQMSSGA IPPNRGVPPA PPPPAAVQRE SPSVLNTDPD 
901:	AEKPRFASNL