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Protein

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1

Gene

Hcn1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). May mediate responses to sour stimuli.5 Publications

Enzyme regulationi

Activated by cAMP, and at 10-100 times higher concentrations, also by cGMP. cAMP binding causes a conformation change that leads to the assembly of an active tetramer and channel opening. Compared to other family members, cAMP has less stimulatory effect on HCN1 because part of the molecules already contain bound cAMP and form homotetramers when cAMP levels are low.3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi528 – 531cAMP1 Publication4
Nucleotide bindingi538 – 539cAMP1 Publication2
Nucleotide bindingi579 – 582cAMP1 Publication4

GO - Molecular functioni

  • cAMP binding Source: UniProtKB
  • intracellular cAMP activated cation channel activity Source: UniProtKB
  • voltage-gated potassium channel activity Source: UniProtKB
  • voltage-gated sodium channel activity Source: MGI

GO - Biological processi

  • apical protein localization Source: MGI
  • cellular response to cAMP Source: UniProtKB
  • potassium ion transmembrane transport Source: UniProtKB
  • regulation of membrane potential Source: MGI
  • retinal cone cell development Source: MGI
  • sodium ion transmembrane transport Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Ligand-gated ion channel, Potassium channel, Sodium channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Potassium transport, Sodium transport, Transport

Keywords - Ligandi

cAMP, cAMP-binding, Nucleotide-binding, Potassium, Sodium

Enzyme and pathway databases

ReactomeiR-MMU-1296061. HCN channels.

Protein family/group databases

TCDBi1.A.1.5.2. the voltage-gated ion channel (vic) superfamily.

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
Alternative name(s):
Brain cyclic nucleotide-gated channel 1
Short name:
BCNG-1
Hyperpolarization-activated cation channel 2
Short name:
HAC-2
Gene namesi
Name:Hcn1
Synonyms:Bcng1, Hac2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:1096392. Hcn1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 135CytoplasmicSequence analysisAdd BLAST135
Transmembranei136 – 156Helical; Name=Segment S1Sequence analysisAdd BLAST21
Topological domaini157 – 162ExtracellularSequence analysis6
Transmembranei163 – 183Helical; Name=Segment S2Sequence analysisAdd BLAST21
Topological domaini184 – 208CytoplasmicSequence analysisAdd BLAST25
Transmembranei209 – 229Helical; Name=Segment S3Sequence analysisAdd BLAST21
Topological domaini230 – 237ExtracellularSequence analysis8
Transmembranei238 – 258Helical; Voltage-sensor; Name=Segment S4Sequence analysisAdd BLAST21
Topological domaini259 – 289CytoplasmicSequence analysisAdd BLAST31
Transmembranei290 – 310Helical; Name=Segment S5Sequence analysisAdd BLAST21
Topological domaini311 – 333ExtracellularSequence analysisAdd BLAST23
Intramembranei334 – 355Pore-forming; Name=Segment H5Sequence analysisAdd BLAST22
Topological domaini356 – 360ExtracellularSequence analysis5
Transmembranei361 – 381Helical; Name=Segment S6Sequence analysisAdd BLAST21
Topological domaini382 – 910CytoplasmicSequence analysisAdd BLAST529

GO - Cellular componenti

  • axon Source: MGI
  • dendrite Source: MGI
  • integral component of plasma membrane Source: UniProtKB
  • plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi303C → S: Abolishes conductivity. 1 Publication1
Mutagenesisi318C → S: Abolishes sensitivity to sulfhydryl modification. 1 Publication1
Mutagenesisi349G → A: Abolishes conductivity; when associated with A-350 and A-351. 1 Publication1
Mutagenesisi350Y → A: Abolishes conductivity; when associated with A-349 and A-351. 1 Publication1
Mutagenesisi351G → A: Abolishes conductivity; when associated with A-349 and A-350. 1 Publication1
Mutagenesisi538R → E: Reduces affinity for cAMP and impairs tetramerization. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL1250401.
GuidetoPHARMACOLOGYi400.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000541081 – 910Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1Add BLAST910

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi327N-linked (GlcNAc...)1 Publication1

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiO88704.
PaxDbiO88704.
PeptideAtlasiO88704.
PRIDEiO88704.

PTM databases

iPTMnetiO88704.
PhosphoSitePlusiO88704.
SwissPalmiO88704.

Expressioni

Tissue specificityi

Predominantly expressed in brain. Highly expressed in apical dendrites of pyramidal neurons in the cortex, in the layer corresponding to the stratum lacunosum-moleculare in the hippocampus and in axons of basket cells in the cerebellum. Expressed in a subset of elongated cells in taste buds.2 Publications

Gene expression databases

BgeeiENSMUSG00000021730.
GenevisibleiO88704. MM.

Interactioni

Subunit structurei

Homotetramer. Heterotetramer with HCN2. The potassium channel is composed of a homo- or heterotetrameric complex of pore-forming subunits. Interacts with KCNE2. Interacts with the SH3 domain of CSK.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-8766347,EBI-8766347

Protein-protein interaction databases

BioGridi200252. 2 interactors.
MINTiMINT-154994.
STRINGi10090.ENSMUSP00000006991.

Chemistry databases

BindingDBiO88704.

Structurei

Secondary structure

1910
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi391 – 410Combined sources20
Helixi414 – 428Combined sources15
Helixi435 – 440Combined sources6
Helixi444 – 454Combined sources11
Helixi456 – 460Combined sources5
Helixi463 – 466Combined sources4
Helixi470 – 478Combined sources9
Beta strandi481 – 485Combined sources5
Beta strandi490 – 492Combined sources3
Beta strandi500 – 506Combined sources7
Beta strandi509 – 512Combined sources4
Beta strandi519 – 521Combined sources3
Beta strandi526 – 528Combined sources3
Helixi529 – 534Combined sources6
Beta strandi540 – 546Combined sources7
Beta strandi548 – 554Combined sources7
Helixi555 – 564Combined sources10
Helixi567 – 583Combined sources17

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3U0ZX-ray2.90A/B390-592[»]
ProteinModelPortaliO88704.
SMRiO88704.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni78 – 129Involved in subunit assemblyBy similarityAdd BLAST52

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1 – 81Gly-richAdd BLAST81
Compositional biasi715 – 777Gln-richAdd BLAST63
Compositional biasi878 – 884Poly-Pro7

Domaini

The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.

Sequence similaritiesi

Belongs to the potassium channel HCN family.Curated
Contains 1 cyclic nucleotide-binding domain.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0498. Eukaryota.
ENOG410XPSE. LUCA.
GeneTreeiENSGT00760000118772.
HOGENOMiHOG000230717.
HOVERGENiHBG039489.
InParanoidiO88704.
KOiK04954.
OMAiEVHRSTQ.
OrthoDBiEOG091G0JQU.
PhylomeDBiO88704.
TreeFamiTF318250.

Family and domain databases

Gene3Di2.60.120.10. 1 hit.
InterProiIPR018490. cNMP-bd-like.
IPR018488. cNMP-bd_CS.
IPR000595. cNMP-bd_dom.
IPR005821. Ion_trans_dom.
IPR013621. Ion_trans_N.
IPR030169. K/Na_HCN1.
IPR003938. K_chnl_volt-dep_EAG/ELK/ERG.
IPR014710. RmlC-like_jellyroll.
[Graphical view]
PANTHERiPTHR10217:SF373. PTHR10217:SF373. 2 hits.
PfamiPF00027. cNMP_binding. 1 hit.
PF00520. Ion_trans. 1 hit.
PF08412. Ion_trans_N. 1 hit.
[Graphical view]
PRINTSiPR01463. EAGCHANLFMLY.
SMARTiSM00100. cNMP. 1 hit.
[Graphical view]
SUPFAMiSSF51206. SSF51206. 1 hit.
PROSITEiPS00888. CNMP_BINDING_1. 1 hit.
PS50042. CNMP_BINDING_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O88704-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEGGGKPNSA SNSRDDGNSV FPSKAPATGP VAADKRLGTP PGGGAAGKEH
60 70 80 90 100
GNSVCFKVDG GGGEEPAGSF EDAEGPRRQY GFMQRQFTSM LQPGVNKFSL
110 120 130 140 150
RMFGSQKAVE KEQERVKTAG FWIIHPYSDF RFYWDLIMLI MMVGNLVIIP
160 170 180 190 200
VGITFFTEQT TTPWIIFNVA SDTVFLLDLI MNFRTGTVNE DSSEIILDPK
210 220 230 240 250
VIKMNYLKSW FVVDFISSIP VDYIFLIVEK GMDSEVYKTA RALRIVRFTK
260 270 280 290 300
ILSLLRLLRL SRLIRYIHQW EEIFHMTYDL ASAVVRIFNL IGMMLLLCHW
310 320 330 340 350
DGCLQFLVPL LQDFPPDCWV SLNEMVNDSW GKQYSYALFK AMSHMLCIGY
360 370 380 390 400
GAQAPVSMSD LWITMLSMIV GATCYAMFVG HATALIQSLD SSRRQYQEKY
410 420 430 440 450
KQVEQYMSFH KLPADMRQKI HDYYEHRYQG KIFDEENILS ELNDPLREEI
460 470 480 490 500
VNFNCRKLVA TMPLFANADP NFVTAMLSKL RFEVFQPGDY IIREGAVGKK
510 520 530 540 550
MYFIQHGVAG VITKSSKEMK LTDGSYFGEI CLLTKGRRTA SVRADTYCRL
560 570 580 590 600
YSLSVDNFNE VLEEYPMMRR AFETVAIDRL DRIGKKNSIL LQKFQKDLNT
610 620 630 640 650
GVFNNQENEI LKQIVKHDRE MVQAIPPINY PQMTALNCTS STTTPTSRMR
660 670 680 690 700
TQSPPVYTAT SLSHSNLHSP SPSTQTPQPS AILSPCSYTT AVCSPPIQSP
710 720 730 740 750
LATRTFHYAS PTASQLSLMQ QPQQQLPQSQ VQQTQTQTQQ QQQQQQQQQQ
760 770 780 790 800
QQQQQQQQQQ QQQQQQQQQQ QQQQQPQTPG SSTPKNEVHK STQALHNTNL
810 820 830 840 850
TKEVRPLSAS QPSLPHEVST LISRPHPTVG ESLASIPQPV AAVHSTGLQA
860 870 880 890 900
GSRSTVPQRV TLFRQMSSGA IPPNRGVPPA PPPPAAVQRE SPSVLNTDPD
910
AEKPRFASNL
Length:910
Mass (Da):102,432
Last modified:November 1, 1998 - v1
Checksum:i56FD5F328DD972E9
GO

Sequence cautioni

The sequence AK014722 differs from that shown. Reason: Frameshift at position 381.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti42G → R in AAC53518 (PubMed:9405696).Curated1
Sequence conflicti394R → S in AK014722 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF028737 mRNA. Translation: AAC53518.1.
AJ225123 mRNA. Translation: CAA12407.1.
AK014722 mRNA. No translation available.
CCDSiCCDS26793.1.
RefSeqiNP_034538.2. NM_010408.3.
UniGeneiMm.343429.

Genome annotation databases

EnsembliENSMUST00000006991; ENSMUSP00000006991; ENSMUSG00000021730.
GeneIDi15165.
KEGGimmu:15165.
UCSCiuc007ryo.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF028737 mRNA. Translation: AAC53518.1.
AJ225123 mRNA. Translation: CAA12407.1.
AK014722 mRNA. No translation available.
CCDSiCCDS26793.1.
RefSeqiNP_034538.2. NM_010408.3.
UniGeneiMm.343429.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3U0ZX-ray2.90A/B390-592[»]
ProteinModelPortaliO88704.
SMRiO88704.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200252. 2 interactors.
MINTiMINT-154994.
STRINGi10090.ENSMUSP00000006991.

Chemistry databases

BindingDBiO88704.
ChEMBLiCHEMBL1250401.
GuidetoPHARMACOLOGYi400.

Protein family/group databases

TCDBi1.A.1.5.2. the voltage-gated ion channel (vic) superfamily.

PTM databases

iPTMnetiO88704.
PhosphoSitePlusiO88704.
SwissPalmiO88704.

Proteomic databases

MaxQBiO88704.
PaxDbiO88704.
PeptideAtlasiO88704.
PRIDEiO88704.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000006991; ENSMUSP00000006991; ENSMUSG00000021730.
GeneIDi15165.
KEGGimmu:15165.
UCSCiuc007ryo.2. mouse.

Organism-specific databases

CTDi348980.
MGIiMGI:1096392. Hcn1.

Phylogenomic databases

eggNOGiKOG0498. Eukaryota.
ENOG410XPSE. LUCA.
GeneTreeiENSGT00760000118772.
HOGENOMiHOG000230717.
HOVERGENiHBG039489.
InParanoidiO88704.
KOiK04954.
OMAiEVHRSTQ.
OrthoDBiEOG091G0JQU.
PhylomeDBiO88704.
TreeFamiTF318250.

Enzyme and pathway databases

ReactomeiR-MMU-1296061. HCN channels.

Miscellaneous databases

PROiO88704.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000021730.
GenevisibleiO88704. MM.

Family and domain databases

Gene3Di2.60.120.10. 1 hit.
InterProiIPR018490. cNMP-bd-like.
IPR018488. cNMP-bd_CS.
IPR000595. cNMP-bd_dom.
IPR005821. Ion_trans_dom.
IPR013621. Ion_trans_N.
IPR030169. K/Na_HCN1.
IPR003938. K_chnl_volt-dep_EAG/ELK/ERG.
IPR014710. RmlC-like_jellyroll.
[Graphical view]
PANTHERiPTHR10217:SF373. PTHR10217:SF373. 2 hits.
PfamiPF00027. cNMP_binding. 1 hit.
PF00520. Ion_trans. 1 hit.
PF08412. Ion_trans_N. 1 hit.
[Graphical view]
PRINTSiPR01463. EAGCHANLFMLY.
SMARTiSM00100. cNMP. 1 hit.
[Graphical view]
SUPFAMiSSF51206. SSF51206. 1 hit.
PROSITEiPS00888. CNMP_BINDING_1. 1 hit.
PS50042. CNMP_BINDING_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHCN1_MOUSE
AccessioniPrimary (citable) accession number: O88704
Secondary accession number(s): O54899, Q9D613
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: November 1, 1998
Last modified: November 2, 2016
This is version 155 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Inhibited by extracellular cesium ions.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.