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O60741 (HCN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
Alternative name(s):
Brain cyclic nucleotide-gated channel 1
Short name=BCNG-1
Gene names
Name:HCN1
Synonyms:BCNG1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length890 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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. Ref.3

Enzyme regulation

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. Ref.3

Subunit structure

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 By similarity.

Subcellular location

Cell membrane; Multi-pass membrane protein Ref.3.

Tissue specificity

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. Ref.2

Domain

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

Sequence similarities

Belongs to the potassium channel HCN family.

Contains 1 cyclic nucleotide-binding domain.

Sequence caution

The sequence AAC39759.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence.

Ontologies

Keywords
   Biological processIon transport
Potassium transport
Sodium transport
Transport
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DomainTransmembrane
Transmembrane helix
   LigandcAMP
cAMP-binding
Nucleotide-binding
Potassium
Sodium
   Molecular functionIon channel
Ligand-gated ion channel
Potassium channel
Sodium channel
Voltage-gated channel
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapical protein localization

Inferred from electronic annotation. Source: Ensembl

cellular response to cAMP

Inferred from sequence or structural similarity. Source: UniProtKB

potassium ion transmembrane transport

Inferred from sequence or structural similarity. Source: UniProtKB

potassium ion transport

Non-traceable author statement PubMed 9405696. Source: UniProtKB

regulation of membrane potential

Inferred from mutant phenotype PubMed 22748890. Source: UniProt

retinal cone cell development

Inferred from electronic annotation. Source: Ensembl

sodium ion transmembrane transport

Inferred from mutant phenotype PubMed 22748890. Source: UniProt

synaptic transmission

Traceable author statement. Source: Reactome

   Cellular_componentaxon

Inferred from electronic annotation. Source: Ensembl

dendrite

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Non-traceable author statement PubMed 9405696. Source: UniProtKB

integral component of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 22748890. Source: UniProt

   Molecular_functioncAMP binding

Inferred from sequence or structural similarity. Source: UniProtKB

intracellular cAMP activated cation channel activity

Inferred from sequence or structural similarity. Source: UniProtKB

potassium channel activity

Non-traceable author statement PubMed 9405696. Source: UniProtKB

voltage-gated potassium channel activity

Inferred from sequence or structural similarity. Source: UniProtKB

voltage-gated sodium channel activity

Inferred from mutant phenotype PubMed 22748890. Source: UniProt

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 890890Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
PRO_0000054107

Regions

Topological domain1 – 146146Cytoplasmic Potential
Transmembrane147 – 16721Helical; Name=Segment S1; Potential
Topological domain168 – 1736Extracellular Potential
Transmembrane174 – 19421Helical; Name=Segment S2; Potential
Topological domain195 – 21925Cytoplasmic Potential
Transmembrane220 – 24021Helical; Name=Segment S3; Potential
Topological domain241 – 2488Extracellular Potential
Transmembrane249 – 26921Helical; Voltage-sensor; Name=Segment S4; Potential
Topological domain270 – 30031Cytoplasmic Potential
Transmembrane301 – 32121Helical; Name=Segment S5; Potential
Topological domain322 – 34423Extracellular Potential
Intramembrane345 – 36622Pore-forming; Name=Segment H5; Potential
Topological domain367 – 3715Extracellular Potential
Transmembrane372 – 39221Helical; Name=Segment S6; Potential
Topological domain393 – 890498Cytoplasmic Potential
Nucleotide binding539 – 5424cAMP By similarity
Nucleotide binding549 – 5502cAMP By similarity
Nucleotide binding590 – 5934cAMP By similarity
Region89 – 14052Involved in subunit assembly By similarity
Compositional bias1 – 8080Gly-rich
Compositional bias726 – 75631Gln-rich
Compositional bias857 – 8637Poly-Pro

Amino acid modifications

Glycosylation3381N-linked (GlcNAc...) Potential

Natural variations

Natural variant421P → S.
Corresponds to variant rs56164833 [ dbSNP | Ensembl ].
VAR_061105

Experimental info

Sequence conflict7861L → F in AAC39759. Ref.2
Sequence conflict7891S → W in AAC39759. Ref.2
Sequence conflict8411L → F in AAC39759. Ref.2
Sequence conflict8571P → L in AAC39759. Ref.2
Sequence conflict8611P → L in AAC39759. Ref.2

Sequences

Sequence LengthMass (Da)Tools
O60741 [UniParc].

Last modified May 5, 2009. Version 3.
Checksum: A62F5E79C01257A2

FASTA89098,796
        10         20         30         40         50         60 
MEGGGKPNSS SNSRDDGNSV FPAKASATGA GPAAAEKRLG TPPGGGGAGA KEHGNSVCFK 

        70         80         90        100        110        120 
VDGGGGGGGG GGGGEEPAGG FEDAEGPRRQ YGFMQRQFTS MLQPGVNKFS LRMFGSQKAV 

       130        140        150        160        170        180 
EKEQERVKTA GFWIIHPYSD FRFYWDLIML IMMVGNLVII PVGITFFTEQ TTTPWIIFNV 

       190        200        210        220        230        240 
ASDTVFLLDL IMNFRTGTVN EDSSEIILDP KVIKMNYLKS WFVVDFISSI PVDYIFLIVE 

       250        260        270        280        290        300 
KGMDSEVYKT ARALRIVRFT KILSLLRLLR LSRLIRYIHQ WEEIFHMTYD LASAVVRIFN 

       310        320        330        340        350        360 
LIGMMLLLCH WDGCLQFLVP LLQDFPPDCW VSLNEMVNDS WGKQYSYALF KAMSHMLCIG 

       370        380        390        400        410        420 
YGAQAPVSMS DLWITMLSMI VGATCYAMFV GHATALIQSL DSSRRQYQEK YKQVEQYMSF 

       430        440        450        460        470        480 
HKLPADMRQK IHDYYEHRYQ GKIFDEENIL NELNDPLREE IVNFNCRKLV ATMPLFANAD 

       490        500        510        520        530        540 
PNFVTAMLSK LRFEVFQPGD YIIREGAVGK KMYFIQHGVA GVITKSSKEM KLTDGSYFGE 

       550        560        570        580        590        600 
ICLLTKGRRT ASVRADTYCR LYSLSVDNFN EVLEEYPMMR RAFETVAIDR LDRIGKKNSI 

       610        620        630        640        650        660 
LLQKFQKDLN TGVFNNQENE ILKQIVKHDR EMVQAIAPIN YPQMTTLNST SSTTTPTSRM 

       670        680        690        700        710        720 
RTQSPPVYTA TSLSHSNLHS PSPSTQTPQP SAILSPCSYT TAVCSPPVQS PLAARTFHYA 

       730        740        750        760        770        780 
SPTASQLSLM QQQPQQQVQQ SQPPQTQPQQ PSPQPQTPGS STPKNEVHKS TQALHNTNLT 

       790        800        810        820        830        840 
REVRPLSASQ PSLPHEVSTL ISRPHPTVGE SLASIPQPVT AVPGTGLQAG GRSTVPQRVT 

       850        860        870        880        890 
LFRQMSSGAI PPNRGVPPAP PPPAAALPRE SSSVLNTDPD AEKPRFASNL 

« Hide

References

« Hide 'large scale' references
[1]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]"Identification of a gene encoding a hyperpolarization-activated 'pacemaker' channel of brain."
Santoro B., Liu D.T., Yao H., Bartsch D., Kandel E.R., Siegelbaum S.A., Tibbs G.R.
Cell 93:717-729(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 122-862, TISSUE SPECIFICITY.
Tissue: Brain.
[3]"Characterization of the human HCN1 channel and its inhibition by capsazepine."
Gill C.H., Randall A., Bates S.A., Hill K., Owen D., Larkman P.M., Cairns W., Yusaf S.P., Murdock P.R., Strijbos P.J., Powell A.J., Benham C.D., Davies C.H.
Br. J. Pharmacol. 143:411-421(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_066550.2. NM_021072.3.
UniGeneHs.353176.

3D structure databases

ProteinModelPortalO60741.
SMRO60741. Positions 344-398, 401-599.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid131543. 5 interactions.
STRING9606.ENSP00000307342.

Chemistry

ChEMBLCHEMBL1795171.
GuidetoPHARMACOLOGY400.

PTM databases

PhosphoSiteO60741.

Proteomic databases

PaxDbO60741.
PRIDEO60741.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000303230; ENSP00000307342; ENSG00000164588.
GeneID348980.
KEGGhsa:348980.
UCSCuc003jok.3. human.

Organism-specific databases

CTD348980.
GeneCardsGC05M045260.
H-InvDBHIX0004850.
HGNCHGNC:4845. HCN1.
HPAHPA019195.
MIM602780. gene.
neXtProtNX_O60741.
PharmGKBPA77.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0664.
HOGENOMHOG000230717.
HOVERGENHBG039489.
InParanoidO60741.
KOK04954.
OMATPKNEVH.
OrthoDBEOG7VMP6X.
PhylomeDBO60741.
TreeFamTF318250.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.

Gene expression databases

BgeeO60741.
CleanExHS_HCN1.
GenevestigatorO60741.

Family and domain databases

Gene3D2.60.120.10. 1 hit.
InterProIPR018490. cNMP-bd-like.
IPR018488. cNMP-bd_CS.
IPR000595. cNMP-bd_dom.
IPR005821. Ion_trans_dom.
IPR013621. Ion_trans_N.
IPR003938. K_chnl_volt-dep_EAG/ELK/ERG.
IPR014710. RmlC-like_jellyroll.
[Graphical view]
PfamPF00027. cNMP_binding. 1 hit.
PF00520. Ion_trans. 1 hit.
PF08412. Ion_trans_N. 1 hit.
[Graphical view]
PRINTSPR01463. EAGCHANLFMLY.
SMARTSM00100. cNMP. 1 hit.
[Graphical view]
SUPFAMSSF51206. SSF51206. 1 hit.
PROSITEPS00888. CNMP_BINDING_1. 1 hit.
PS50042. CNMP_BINDING_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiHCN1.
GenomeRNAi348980.
NextBio99467.
PROO60741.
SOURCESearch...

Entry information

Entry nameHCN1_HUMAN
AccessionPrimary (citable) accession number: O60741
Entry history
Integrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: May 5, 2009
Last modified: April 16, 2014
This is version 113 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM