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O60741

- HCN1_HUMAN

UniProt

O60741 - HCN1_HUMAN

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
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    • History
      Entry version 118 (01 Oct 2014)
      Sequence version 3 (05 May 2009)
      Previous versions | rss
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    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

    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

    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.
    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.

    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.
    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

    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 1, 2014
    This is version 118 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