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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

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 – 5424cAMPBy similarity
Nucleotide bindingi549 – 5502cAMPBy similarity
Nucleotide bindingi590 – 5934cAMPBy 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

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 1 Publication; Multi-pass membrane protein 1 Publication

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 1PRO_0000054107Add
BLAST

Amino acid modifications

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

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).By similarity

Protein-protein interaction databases

BioGridi131543. 6 interactions.
STRINGi9606.ENSP00000307342.

Structurei

3D structure databases

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

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 146146CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini168 – 1736ExtracellularSequence Analysis
Topological domaini195 – 21925CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini241 – 2488ExtracellularSequence Analysis
Topological domaini270 – 30031CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini322 – 34423ExtracellularSequence AnalysisAdd
BLAST
Topological domaini367 – 3715ExtracellularSequence Analysis
Topological domaini393 – 890498CytoplasmicSequence AnalysisAdd
BLAST

Intramembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Intramembranei345 – 36622Pore-forming; Name=Segment H5Sequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei147 – 16721Helical; Name=Segment S1Sequence AnalysisAdd
BLAST
Transmembranei174 – 19421Helical; Name=Segment S2Sequence AnalysisAdd
BLAST
Transmembranei220 – 24021Helical; Name=Segment S3Sequence AnalysisAdd
BLAST
Transmembranei249 – 26921Helical; Voltage-sensor; Name=Segment S4Sequence AnalysisAdd
BLAST
Transmembranei301 – 32121Helical; Name=Segment S5Sequence AnalysisAdd
BLAST
Transmembranei372 – 39221Helical; Name=Segment S6Sequence AnalysisAdd
BLAST

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni89 – 14052Involved in subunit assemblyBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi1 – 8080Gly-richAdd
BLAST
Compositional biasi726 – 75631Gln-richAdd
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

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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0664.
GeneTreeiENSGT00760000118772.
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

        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

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti786 – 7861L → F in AAC39759. (PubMed:9630217)Curated
Sequence conflicti789 – 7891S → W in AAC39759. (PubMed:9630217)Curated
Sequence conflicti841 – 8411L → F in AAC39759. (PubMed:9630217)Curated
Sequence conflicti857 – 8571P → L in AAC39759. (PubMed:9630217)Curated
Sequence conflicti861 – 8611P → L in AAC39759. (PubMed:9630217)Curated

Natural variant

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

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...
MobiDBi 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.
GeneTreei ENSGT00760000118772.
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: October 29, 2014
This is version 119 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