Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

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

Gene

HCN1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions (PubMed:28086084). Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). May mediate responses to sour stimuli.2 Publications

Activity regulationi

Activated by cAMP, and at 10-100 times higher concentrations, also by cGMP. cAMP binding promotes tetramerization and formation of an active channel. 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. Inhibited by Cs1+, zatebradine, capsazepine and ZD7288.2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi539 – 542cAMPCombined sources1 Publication4
Nucleotide bindingi549 – 550cAMPCombined sources1 Publication2
Nucleotide bindingi590 – 593cAMPBy similarity4

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionIon channel, Ligand-gated ion channel, Potassium channel, Sodium channel, Voltage-gated channel
Biological processIon transport, Potassium transport, Sodium transport, Transport
LigandcAMP, cAMP-binding, Nucleotide-binding, Potassium, Sodium

Enzyme and pathway databases

ReactomeiR-HSA-1296061 HCN channels

Protein family/group databases

TCDBi1.A.1.5.32 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
Gene namesi
Name:HCN1
Synonyms:BCNG1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000164588.5
HGNCiHGNC:4845 HCN1
MIMi602780 gene
neXtProtiNX_O60741

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 142Cytoplasmic1 PublicationAdd BLAST142
Transmembranei143 – 164Helical; Name=Segment S11 PublicationAdd BLAST22
Topological domaini165 – 173Extracellular1 Publication9
Transmembranei174 – 194Helical; Name=Segment S21 PublicationAdd BLAST21
Topological domaini195 – 215Cytoplasmic1 PublicationAdd BLAST21
Transmembranei216 – 236Helical; Name=Segment S31 PublicationAdd BLAST21
Topological domaini237 – 260Extracellular1 PublicationAdd BLAST24
Transmembranei261 – 281Helical; Voltage-sensor; Name=Segment S41 PublicationAdd BLAST21
Topological domaini282 – 295Cytoplasmic1 PublicationAdd BLAST14
Transmembranei296 – 318Helical; Name=Segment S51 PublicationAdd BLAST23
Topological domaini319 – 344Extracellular1 PublicationAdd BLAST26
Intramembranei345 – 366Pore-forming; Name=Segment H51 PublicationAdd BLAST22
Topological domaini367 – 371Extracellular1 Publication5
Transmembranei372 – 392Helical; Name=Segment S61 PublicationAdd BLAST21
Topological domaini393 – 890Cytoplasmic1 PublicationAdd BLAST498

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Epileptic encephalopathy, early infantile, 24 (EIEE24)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by early-onset seizures, intellectual disability of varying degrees, and behavioral disturbances or autistic features in most individuals.
See also OMIM:615871
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07182547G → V in EIEE24; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs544994462EnsemblClinVar.1
Natural variantiVAR_071826100S → F in EIEE24; dominant-negative mutation resulting in gain of channel function. 1 PublicationCorresponds to variant dbSNP:rs587777492EnsemblClinVar.1
Natural variantiVAR_078216153M → I in EIEE24. 1 PublicationCorresponds to variant dbSNP:rs1057519548Ensembl.1
Natural variantiVAR_071827272S → P in EIEE24; dominant-negative mutation resulting in loss of channel currents. 1 PublicationCorresponds to variant dbSNP:rs587777493EnsemblClinVar.1
Natural variantiVAR_071828279H → Y in EIEE24; results in a gain of channel function. 1 PublicationCorresponds to variant dbSNP:rs587777495EnsemblClinVar.1
Natural variantiVAR_071829297R → T in EIEE24; dominant-negative mutation resulting in loss of channel currents. 1 PublicationCorresponds to variant dbSNP:rs587777494EnsemblClinVar.1
Natural variantiVAR_078217391G → D in EIEE24. 1 PublicationCorresponds to variant dbSNP:rs1057519547Ensembl.1
Natural variantiVAR_071830401D → H in EIEE24; results in a gain of channel function. 1 PublicationCorresponds to variant dbSNP:rs587777491EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Epilepsy

Organism-specific databases

DisGeNETi348980
MalaCardsiHCN1
MIMi615871 phenotype
OpenTargetsiENSG00000164588
Orphaneti442835 Undetermined early-onset epileptic encephalopathy
PharmGKBiPA77

Chemistry databases

ChEMBLiCHEMBL1795171
GuidetoPHARMACOLOGYi400

Polymorphism and mutation databases

BioMutaiHCN1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000541071 – 890Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1Add BLAST890

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi338N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiO60741
PaxDbiO60741
PeptideAtlasiO60741
PRIDEiO60741
ProteomicsDBi49583

PTM databases

iPTMnetiO60741
PhosphoSitePlusiO60741

Expressioni

Tissue specificityi

Detected in brain, in particular in amygdala and hippocampus, while expression in caudate nucleus, corpus callosum, substantia nigra, subthalamic nucleus and thalamus is very low or not detectable. Detected at very low levels in muscle and pancreas.1 Publication

Gene expression databases

BgeeiENSG00000164588 Expressed in 78 organ(s), highest expression level in primary visual cortex
CleanExiHS_HCN1
ExpressionAtlasiO60741 baseline and differential
GenevisibleiO60741 HS

Organism-specific databases

HPAiHPA019195

Interactioni

Subunit structurei

Homotetramer (PubMed:28086084). 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 (By similarity).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Shank3Q4ACU6-14EBI-11173743,EBI-16201983From a different organism.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi131543, 5 interactors
ComplexPortaliCPX-261 HCN1 channel complex
DIPiDIP-62038N
IntActiO60741, 1 interactor
STRINGi9606.ENSP00000307342

Chemistry databases

BindingDBiO60741

Structurei

Secondary structure

1890
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO60741
SMRiO60741
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 93Intrinsically disordered1 PublicationAdd BLAST93

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi358 – 362Selectivity filter1 Publication5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1 – 80Gly-richAdd BLAST80
Compositional biasi726 – 756Gln-richAdd BLAST31
Compositional biasi857 – 863Poly-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.1 Publication

Sequence similaritiesi

Belongs to the potassium channel HCN family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0498 Eukaryota
ENOG410XPSE LUCA
GeneTreeiENSGT00900000140801
HOGENOMiHOG000230717
HOVERGENiHBG039489
InParanoidiO60741
KOiK04954
OMAiTRTFHYA
OrthoDBiEOG091G0JQU
PhylomeDBiO60741
TreeFamiTF318250

Family and domain databases

CDDicd00038 CAP_ED, 1 hit
Gene3Di2.60.120.10, 1 hit
InterProiView protein in InterPro
IPR018490 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
PANTHERiPTHR10217:SF373 PTHR10217:SF373, 1 hit
PfamiView protein in Pfam
PF00027 cNMP_binding, 1 hit
PF00520 Ion_trans, 1 hit
PF08412 Ion_trans_N, 1 hit
PRINTSiPR01463 EAGCHANLFMLY
SMARTiView protein in SMART
SM00100 cNMP, 1 hit
SUPFAMiSSF51206 SSF51206, 1 hit
PROSITEiView protein in PROSITE
PS00888 CNMP_BINDING_1, 1 hit
PS50042 CNMP_BINDING_3, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

O60741-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MEGGGKPNSS SNSRDDGNSV FPAKASATGA GPAAAEKRLG TPPGGGGAGA
60 70 80 90 100
KEHGNSVCFK VDGGGGGGGG GGGGEEPAGG FEDAEGPRRQ YGFMQRQFTS
110 120 130 140 150
MLQPGVNKFS LRMFGSQKAV EKEQERVKTA GFWIIHPYSD FRFYWDLIML
160 170 180 190 200
IMMVGNLVII PVGITFFTEQ TTTPWIIFNV ASDTVFLLDL IMNFRTGTVN
210 220 230 240 250
EDSSEIILDP KVIKMNYLKS WFVVDFISSI PVDYIFLIVE KGMDSEVYKT
260 270 280 290 300
ARALRIVRFT KILSLLRLLR LSRLIRYIHQ WEEIFHMTYD LASAVVRIFN
310 320 330 340 350
LIGMMLLLCH WDGCLQFLVP LLQDFPPDCW VSLNEMVNDS WGKQYSYALF
360 370 380 390 400
KAMSHMLCIG YGAQAPVSMS DLWITMLSMI VGATCYAMFV GHATALIQSL
410 420 430 440 450
DSSRRQYQEK YKQVEQYMSF HKLPADMRQK IHDYYEHRYQ GKIFDEENIL
460 470 480 490 500
NELNDPLREE IVNFNCRKLV ATMPLFANAD PNFVTAMLSK LRFEVFQPGD
510 520 530 540 550
YIIREGAVGK KMYFIQHGVA GVITKSSKEM KLTDGSYFGE ICLLTKGRRT
560 570 580 590 600
ASVRADTYCR LYSLSVDNFN EVLEEYPMMR RAFETVAIDR LDRIGKKNSI
610 620 630 640 650
LLQKFQKDLN TGVFNNQENE ILKQIVKHDR EMVQAIAPIN YPQMTTLNST
660 670 680 690 700
SSTTTPTSRM RTQSPPVYTA TSLSHSNLHS PSPSTQTPQP SAILSPCSYT
710 720 730 740 750
TAVCSPPVQS PLAARTFHYA SPTASQLSLM QQQPQQQVQQ SQPPQTQPQQ
760 770 780 790 800
PSPQPQTPGS STPKNEVHKS TQALHNTNLT REVRPLSASQ PSLPHEVSTL
810 820 830 840 850
ISRPHPTVGE SLASIPQPVT AVPGTGLQAG GRSTVPQRVT LFRQMSSGAI
860 870 880 890
PPNRGVPPAP PPPAAALPRE SSSVLNTDPD AEKPRFASNL
Length:890
Mass (Da):98,796
Last modified:May 5, 2009 - v3
Checksum:iA62F5E79C01257A2
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0U1RQR7A0A0U1RQR7_HUMAN
Potassium/sodium hyperpolarization-...
HCN1
295Annotation score:

Sequence cautioni

The sequence AAC39759 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti786L → F in AAC39759 (PubMed:9630217).Curated1
Sequence conflicti789S → W in AAC39759 (PubMed:9630217).Curated1
Sequence conflicti841L → F in AAC39759 (PubMed:9630217).Curated1
Sequence conflicti857P → L in AAC39759 (PubMed:9630217).Curated1
Sequence conflicti861P → L in AAC39759 (PubMed:9630217).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06110542P → S. Corresponds to variant dbSNP:rs56164833EnsemblClinVar.1
Natural variantiVAR_07182547G → V in EIEE24; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs544994462EnsemblClinVar.1
Natural variantiVAR_071826100S → F in EIEE24; dominant-negative mutation resulting in gain of channel function. 1 PublicationCorresponds to variant dbSNP:rs587777492EnsemblClinVar.1
Natural variantiVAR_078216153M → I in EIEE24. 1 PublicationCorresponds to variant dbSNP:rs1057519548Ensembl.1
Natural variantiVAR_071827272S → P in EIEE24; dominant-negative mutation resulting in loss of channel currents. 1 PublicationCorresponds to variant dbSNP:rs587777493EnsemblClinVar.1
Natural variantiVAR_071828279H → Y in EIEE24; results in a gain of channel function. 1 PublicationCorresponds to variant dbSNP:rs587777495EnsemblClinVar.1
Natural variantiVAR_071829297R → T in EIEE24; dominant-negative mutation resulting in loss of channel currents. 1 PublicationCorresponds to variant dbSNP:rs587777494EnsemblClinVar.1
Natural variantiVAR_078217391G → D in EIEE24. 1 PublicationCorresponds to variant dbSNP:rs1057519547Ensembl.1
Natural variantiVAR_071830401D → H in EIEE24; results in a gain of channel function. 1 PublicationCorresponds to variant dbSNP:rs587777491EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC099514 Genomic DNA No translation available.
AC114975 Genomic DNA No translation available.
AC117529 Genomic DNA No translation available.
AC138520 Genomic DNA No translation available.
AF064876 mRNA Translation: AAC39759.1 Sequence problems.
CCDSiCCDS3952.1
RefSeqiNP_066550.2, NM_021072.3
UniGeneiHs.353176

Genome annotation databases

EnsembliENST00000303230; ENSP00000307342; ENSG00000164588
GeneIDi348980
KEGGihsa:348980
UCSCiuc003jok.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC099514 Genomic DNA No translation available.
AC114975 Genomic DNA No translation available.
AC117529 Genomic DNA No translation available.
AC138520 Genomic DNA No translation available.
AF064876 mRNA Translation: AAC39759.1 Sequence problems.
CCDSiCCDS3952.1
RefSeqiNP_066550.2, NM_021072.3
UniGeneiHs.353176

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5U6Oelectron microscopy3.50A/B/C/D1-890[»]
5U6Pelectron microscopy3.51A/B/C/D1-890[»]
ProteinModelPortaliO60741
SMRiO60741
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi131543, 5 interactors
ComplexPortaliCPX-261 HCN1 channel complex
DIPiDIP-62038N
IntActiO60741, 1 interactor
STRINGi9606.ENSP00000307342

Chemistry databases

BindingDBiO60741
ChEMBLiCHEMBL1795171
GuidetoPHARMACOLOGYi400

Protein family/group databases

TCDBi1.A.1.5.32 the voltage-gated ion channel (vic) superfamily

PTM databases

iPTMnetiO60741
PhosphoSitePlusiO60741

Polymorphism and mutation databases

BioMutaiHCN1

Proteomic databases

MaxQBiO60741
PaxDbiO60741
PeptideAtlasiO60741
PRIDEiO60741
ProteomicsDBi49583

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000303230; ENSP00000307342; ENSG00000164588
GeneIDi348980
KEGGihsa:348980
UCSCiuc003jok.4 human

Organism-specific databases

CTDi348980
DisGeNETi348980
EuPathDBiHostDB:ENSG00000164588.5
GeneCardsiHCN1
H-InvDBiHIX0004850
HGNCiHGNC:4845 HCN1
HPAiHPA019195
MalaCardsiHCN1
MIMi602780 gene
615871 phenotype
neXtProtiNX_O60741
OpenTargetsiENSG00000164588
Orphaneti442835 Undetermined early-onset epileptic encephalopathy
PharmGKBiPA77
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0498 Eukaryota
ENOG410XPSE LUCA
GeneTreeiENSGT00900000140801
HOGENOMiHOG000230717
HOVERGENiHBG039489
InParanoidiO60741
KOiK04954
OMAiTRTFHYA
OrthoDBiEOG091G0JQU
PhylomeDBiO60741
TreeFamiTF318250

Enzyme and pathway databases

ReactomeiR-HSA-1296061 HCN channels

Miscellaneous databases

ChiTaRSiHCN1 human
GeneWikiiHCN1
GenomeRNAii348980
PROiPR:O60741
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164588 Expressed in 78 organ(s), highest expression level in primary visual cortex
CleanExiHS_HCN1
ExpressionAtlasiO60741 baseline and differential
GenevisibleiO60741 HS

Family and domain databases

CDDicd00038 CAP_ED, 1 hit
Gene3Di2.60.120.10, 1 hit
InterProiView protein in InterPro
IPR018490 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
PANTHERiPTHR10217:SF373 PTHR10217:SF373, 1 hit
PfamiView protein in Pfam
PF00027 cNMP_binding, 1 hit
PF00520 Ion_trans, 1 hit
PF08412 Ion_trans_N, 1 hit
PRINTSiPR01463 EAGCHANLFMLY
SMARTiView protein in SMART
SM00100 cNMP, 1 hit
SUPFAMiSSF51206 SSF51206, 1 hit
PROSITEiView protein in PROSITE
PS00888 CNMP_BINDING_1, 1 hit
PS50042 CNMP_BINDING_3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHCN1_HUMAN
AccessioniPrimary (citable) accession number: O60741
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: May 5, 2009
Last modified: November 7, 2018
This is version 152 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again