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O60741

- HCN1_HUMAN

UniProt

O60741 - HCN1_HUMAN

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Protein
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
Gene
HCN1, BCNG1
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript 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.1 Publication

Enzyme 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 ZD7288.1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi539 – 5424cAMP By similarity
Nucleotide bindingi549 – 5502cAMP By similarity
Nucleotide bindingi590 – 5934cAMP By similarity

GO - Molecular functioni

  1. cAMP binding Source: UniProtKB
  2. intracellular cAMP activated cation channel activity Source: UniProtKB
  3. potassium channel activity Source: UniProtKB
  4. voltage-gated potassium channel activity Source: UniProtKB
  5. voltage-gated sodium channel activity Source: UniProt
Complete GO annotation...

GO - Biological processi

  1. apical protein localization Source: Ensembl
  2. cellular response to cAMP Source: UniProtKB
  3. potassium ion transmembrane transport Source: UniProtKB
  4. potassium ion transport Source: UniProtKB
  5. regulation of membrane potential Source: UniProt
  6. retinal cone cell development Source: Ensembl
  7. sodium ion transmembrane transport Source: UniProt
  8. synaptic transmission Source: Reactome
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

ReactomeiREACT_75862. HCN channels.

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
ProteomesiUP000005640: Chromosome 5

Organism-specific databases

HGNCiHGNC:4845. HCN1.

Subcellular locationi

Cell membrane; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 146146Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei147 – 16721Helical; Name=Segment S1; Reviewed prediction
Add
BLAST
Topological domaini168 – 1736Extracellular Reviewed prediction
Transmembranei174 – 19421Helical; Name=Segment S2; Reviewed prediction
Add
BLAST
Topological domaini195 – 21925Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei220 – 24021Helical; Name=Segment S3; Reviewed prediction
Add
BLAST
Topological domaini241 – 2488Extracellular Reviewed prediction
Transmembranei249 – 26921Helical; Voltage-sensor; Name=Segment S4; Reviewed prediction
Add
BLAST
Topological domaini270 – 30031Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei301 – 32121Helical; Name=Segment S5; Reviewed prediction
Add
BLAST
Topological domaini322 – 34423Extracellular Reviewed prediction
Add
BLAST
Intramembranei345 – 36622Pore-forming; Name=Segment H5; Reviewed prediction
Add
BLAST
Topological domaini367 – 3715Extracellular Reviewed prediction
Transmembranei372 – 39221Helical; Name=Segment S6; Reviewed prediction
Add
BLAST
Topological domaini393 – 890498Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. axon Source: Ensembl
  2. dendrite Source: Ensembl
  3. integral component of membrane Source: UniProtKB
  4. integral component of plasma membrane Source: UniProtKB
  5. plasma membrane Source: UniProt
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA77.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 890890Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
PRO_0000054107Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi338 – 3381N-linked (GlcNAc...) Reviewed prediction

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiO60741.
PaxDbiO60741.
PRIDEiO60741.

PTM databases

PhosphoSiteiO60741.

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

BgeeiO60741.
CleanExiHS_HCN1.
GenevestigatoriO60741.

Organism-specific databases

HPAiHPA019195.

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 By similarity.

Protein-protein interaction databases

BioGridi131543. 6 interactions.
STRINGi9606.ENSP00000307342.

Structurei

3D structure databases

ProteinModelPortaliO60741.
SMRiO60741. Positions 344-394, 401-599.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni89 – 14052Involved in subunit assembly By similarity
Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi1 – 8080Gly-rich
Add
BLAST
Compositional biasi726 – 75631Gln-rich
Add
BLAST
Compositional biasi857 – 8637Poly-Pro

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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0664.
HOGENOMiHOG000230717.
HOVERGENiHBG039489.
InParanoidiO60741.
KOiK04954.
OMAiIPPNRGV.
OrthoDBiEOG7VMP6X.
PhylomeDBiO60741.
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.
IPR003938. K_chnl_volt-dep_EAG/ELK/ERG.
IPR014710. RmlC-like_jellyroll.
[Graphical view]
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.

O60741-1 [UniParc]FASTAAdd to Basket

« Hide

MEGGGKPNSS SNSRDDGNSV FPAKASATGA GPAAAEKRLG TPPGGGGAGA    50
KEHGNSVCFK VDGGGGGGGG GGGGEEPAGG FEDAEGPRRQ YGFMQRQFTS 100
MLQPGVNKFS LRMFGSQKAV EKEQERVKTA GFWIIHPYSD FRFYWDLIML 150
IMMVGNLVII PVGITFFTEQ TTTPWIIFNV ASDTVFLLDL IMNFRTGTVN 200
EDSSEIILDP KVIKMNYLKS WFVVDFISSI PVDYIFLIVE KGMDSEVYKT 250
ARALRIVRFT KILSLLRLLR LSRLIRYIHQ WEEIFHMTYD LASAVVRIFN 300
LIGMMLLLCH WDGCLQFLVP LLQDFPPDCW VSLNEMVNDS WGKQYSYALF 350
KAMSHMLCIG YGAQAPVSMS DLWITMLSMI VGATCYAMFV GHATALIQSL 400
DSSRRQYQEK YKQVEQYMSF HKLPADMRQK IHDYYEHRYQ GKIFDEENIL 450
NELNDPLREE IVNFNCRKLV ATMPLFANAD PNFVTAMLSK LRFEVFQPGD 500
YIIREGAVGK KMYFIQHGVA GVITKSSKEM KLTDGSYFGE ICLLTKGRRT 550
ASVRADTYCR LYSLSVDNFN EVLEEYPMMR RAFETVAIDR LDRIGKKNSI 600
LLQKFQKDLN TGVFNNQENE ILKQIVKHDR EMVQAIAPIN YPQMTTLNST 650
SSTTTPTSRM RTQSPPVYTA TSLSHSNLHS PSPSTQTPQP SAILSPCSYT 700
TAVCSPPVQS PLAARTFHYA SPTASQLSLM QQQPQQQVQQ SQPPQTQPQQ 750
PSPQPQTPGS STPKNEVHKS TQALHNTNLT REVRPLSASQ PSLPHEVSTL 800
ISRPHPTVGE SLASIPQPVT AVPGTGLQAG GRSTVPQRVT LFRQMSSGAI 850
PPNRGVPPAP PPPAAALPRE SSSVLNTDPD AEKPRFASNL 890
Length:890
Mass (Da):98,796
Last modified:May 5, 2009 - v3
Checksum:iA62F5E79C01257A2
GO

Sequence cautioni

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

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti42 – 421P → S.
Corresponds to variant rs56164833 [ dbSNP | Ensembl ].
VAR_061105

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti786 – 7861L → F in AAC39759. 1 Publication
Sequence conflicti789 – 7891S → W in AAC39759. 1 Publication
Sequence conflicti841 – 8411L → F in AAC39759. 1 Publication
Sequence conflicti857 – 8571P → L in AAC39759. 1 Publication
Sequence conflicti861 – 8611P → L in AAC39759. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
CCDSi CCDS3952.1.
RefSeqi NP_066550.2. NM_021072.3.
UniGenei Hs.353176.

3D structure databases

ProteinModelPortali O60741.
SMRi O60741. Positions 344-394, 401-599.
ModBasei Search...

Protein-protein interaction databases

BioGridi 131543. 6 interactions.
STRINGi 9606.ENSP00000307342.

Chemistry

ChEMBLi CHEMBL1795171.
GuidetoPHARMACOLOGYi 400.

PTM databases

PhosphoSitei O60741.

Proteomic databases

MaxQBi O60741.
PaxDbi O60741.
PRIDEi O60741.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000303230 ; ENSP00000307342 ; ENSG00000164588 .
GeneIDi 348980.
KEGGi hsa:348980.
UCSCi uc003jok.3. human.

Organism-specific databases

CTDi 348980.
GeneCardsi GC05M045260.
H-InvDB HIX0004850.
HGNCi HGNC:4845. HCN1.
HPAi HPA019195.
MIMi 602780. gene.
neXtProti NX_O60741.
PharmGKBi PA77.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0664.
HOGENOMi HOG000230717.
HOVERGENi HBG039489.
InParanoidi O60741.
KOi K04954.
OMAi IPPNRGV.
OrthoDBi EOG7VMP6X.
PhylomeDBi O60741.
TreeFami TF318250.

Enzyme and pathway databases

Reactomei REACT_75862. HCN channels.

Miscellaneous databases

GeneWikii HCN1.
GenomeRNAii 348980.
NextBioi 99467.
PROi O60741.
SOURCEi Search...

Gene expression databases

Bgeei O60741.
CleanExi HS_HCN1.
Genevestigatori O60741.

Family and domain databases

Gene3Di 2.60.120.10. 1 hit.
InterProi IPR018490. 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 ]
Pfami PF00027. cNMP_binding. 1 hit.
PF00520. Ion_trans. 1 hit.
PF08412. Ion_trans_N. 1 hit.
[Graphical view ]
PRINTSi PR01463. EAGCHANLFMLY.
SMARTi SM00100. cNMP. 1 hit.
[Graphical view ]
SUPFAMi SSF51206. SSF51206. 1 hit.
PROSITEi PS00888. CNMP_BINDING_1. 1 hit.
PS50042. CNMP_BINDING_3. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. Cited for: FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION.

Entry informationi

Entry nameiHCN1_HUMAN
AccessioniPrimary (citable) accession number: O60741
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: May 5, 2009
Last modified: September 3, 2014
This is version 117 of the entry and version 3 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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