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Q9P1Z3

- HCN3_HUMAN

UniProt

Q9P1Z3 - HCN3_HUMAN

Protein

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3

Gene

HCN3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 124 (01 Oct 2014)
      Sequence version 2 (28 Feb 2003)
      Previous versions | rss
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    Functioni

    Hyperpolarization-activated potassium channel. May also facilitate the permeation of sodium ions.1 Publication

    Enzyme regulationi

    Inhibited by Cs1+ and ZD7288. Is apparently not activated by cAMP.1 Publication

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi492 – 4954cAMPBy similarity
    Nucleotide bindingi502 – 5032cAMPBy similarity
    Nucleotide bindingi543 – 5464cAMPBy similarity

    GO - Molecular functioni

    1. cAMP binding Source: UniProtKB-KW
    2. voltage-gated potassium channel activity Source: UniProt
    3. voltage-gated sodium channel activity Source: UniProt

    GO - Biological processi

    1. potassium ion transmembrane transport Source: UniProt
    2. regulation of membrane potential Source: UniProt
    3. sodium ion transmembrane transport Source: UniProt
    4. 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 3
    Gene namesi
    Name:HCN3
    Synonyms:KIAA1535
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:19183. HCN3.

    Subcellular locationi

    Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication

    GO - Cellular componenti

    1. integral component of plasma membrane Source: RefGenome
    2. plasma membrane Source: UniProt

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA38821.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 774774Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3PRO_0000054114Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi291 – 2911N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    PaxDbiQ9P1Z3.
    PRIDEiQ9P1Z3.

    PTM databases

    PhosphoSiteiQ9P1Z3.

    Expressioni

    Tissue specificityi

    Detected in brain.1 Publication

    Gene expression databases

    BgeeiQ9P1Z3.
    CleanExiHS_HCN3.
    GenevestigatoriQ9P1Z3.

    Organism-specific databases

    HPAiHPA026584.

    Interactioni

    Subunit structurei

    Homotetramer. The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming subunits By similarity.By similarity

    Protein-protein interaction databases

    BioGridi121691. 3 interactions.
    STRINGi9606.ENSP00000357342.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9P1Z3.
    SMRiQ9P1Z3. Positions 295-550.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 9797CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini119 – 1246ExtracellularSequence Analysis
    Topological domaini146 – 17126CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini193 – 2019ExtracellularSequence Analysis
    Topological domaini223 – 25331CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini275 – 29723ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini320 – 32910ExtracellularSequence Analysis
    Topological domaini351 – 774424CytoplasmicSequence AnalysisAdd
    BLAST

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei298 – 31922Pore-forming; Name=Segment H5Sequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei98 – 11821Helical; Name=Segment S1Sequence AnalysisAdd
    BLAST
    Transmembranei125 – 14521Helical; Name=Segment S2Sequence AnalysisAdd
    BLAST
    Transmembranei172 – 19221Helical; Name=Segment S3Sequence AnalysisAdd
    BLAST
    Transmembranei202 – 22221Helical; Voltage-sensor; Name=Segment S4Sequence AnalysisAdd
    BLAST
    Transmembranei254 – 27421Helical; Name=Segment S5Sequence AnalysisAdd
    BLAST
    Transmembranei330 – 35021Helical; Name=Segment S6Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni46 – 9146Involved in subunit assemblyBy similarityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi696 – 76570Pro-richAdd
    BLAST

    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.
    InParanoidiQ9P1Z3.
    KOiK04956.
    OMAiRMVNHSW.
    OrthoDBiEOG7VMP6X.
    PhylomeDBiQ9P1Z3.
    TreeFamiTF318250.

    Family and domain databases

    Gene3Di2.60.120.10. 1 hit.
    InterProiIPR018490. cNMP-bd-like.
    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.
    PROSITEiPS50042. CNMP_BINDING_3. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9P1Z3-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEAEQRPAAG ASEGATPGLE AVPPVAPPPA TAASGPIPKS GPEPKRRHLG    50
    TLLQPTVNKF SLRVFGSHKA VEIEQERVKS AGAWIIHPYS DFRFYWDLIM 100
    LLLMVGNLIV LPVGITFFKE ENSPPWIVFN VLSDTFFLLD LVLNFRTGIV 150
    VEEGAEILLA PRAIRTRYLR TWFLVDLISS IPVDYIFLVV ELEPRLDAEV 200
    YKTARALRIV RFTKILSLLR LLRLSRLIRY IHQWEEIFHM TYDLASAVVR 250
    IFNLIGMMLL LCHWDGCLQF LVPMLQDFPP DCWVSINHMV NHSWGRQYSH 300
    ALFKAMSHML CIGYGQQAPV GMPDVWLTML SMIVGATCYA MFIGHATALI 350
    QSLDSSRRQY QEKYKQVEQY MSFHKLPADT RQRIHEYYEH RYQGKMFDEE 400
    SILGELSEPL REEIINFTCR GLVAHMPLFA HADPSFVTAV LTKLRFEVFQ 450
    PGDLVVREGS VGRKMYFIQH GLLSVLARGA RDTRLTDGSY FGEICLLTRG 500
    RRTASVRADT YCRLYSLSVD HFNAVLEEFP MMRRAFETVA MDRLLRIGKK 550
    NSILQRKRSE PSPGSSGGIM EQHLVQHDRD MARGVRGRAP STGAQLSGKP 600
    VLWEPLVHAP LQAAAVTSNV AIALTHQRGP LPLSPDSPAT LLARSAWRSA 650
    GSPASPLVPV RAGPWASTSR LPAPPARTLH ASLSRAGRSQ VSLLGPPPGG 700
    GGRRLGPRGR PLSASQPSLP QRATGDGSPG RKGSGSERLP PSGLLAKPPR 750
    TAQPPRPPVP EPATPRGLQL SANM 774
    Length:774
    Mass (Da):86,032
    Last modified:February 28, 2003 - v2
    Checksum:i37B9BC13E5E2C097
    GO

    Sequence cautioni

    The sequence AAH28024.2 differs from that shown. Reason: Erroneous initiation.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti206 – 2061A → G in AAH00066. (PubMed:15489334)Curated
    Sequence conflicti734 – 7341S → T in BAA96059. (PubMed:10819331)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti630 – 6301P → L.
    Corresponds to variant rs35001694 [ dbSNP | Ensembl ].
    VAR_048746

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AL713999 Genomic DNA. Translation: CAI95100.1.
    AB040968 mRNA. Translation: BAA96059.2.
    CH471121 Genomic DNA. Translation: EAW53084.1.
    CH471121 Genomic DNA. Translation: EAW53086.1.
    BC000066 mRNA. Translation: AAH00066.1.
    BC028024 mRNA. Translation: AAH28024.2. Different initiation.
    CCDSiCCDS1108.1.
    RefSeqiNP_065948.1. NM_020897.2.
    UniGeneiHs.706960.

    Genome annotation databases

    EnsembliENST00000368358; ENSP00000357342; ENSG00000143630.
    ENST00000575670; ENSP00000458364; ENSG00000263324.
    GeneIDi57657.
    KEGGihsa:57657.
    UCSCiuc001fjz.2. human.

    Polymorphism databases

    DMDMi29840780.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AL713999 Genomic DNA. Translation: CAI95100.1 .
    AB040968 mRNA. Translation: BAA96059.2 .
    CH471121 Genomic DNA. Translation: EAW53084.1 .
    CH471121 Genomic DNA. Translation: EAW53086.1 .
    BC000066 mRNA. Translation: AAH00066.1 .
    BC028024 mRNA. Translation: AAH28024.2 . Different initiation.
    CCDSi CCDS1108.1.
    RefSeqi NP_065948.1. NM_020897.2.
    UniGenei Hs.706960.

    3D structure databases

    ProteinModelPortali Q9P1Z3.
    SMRi Q9P1Z3. Positions 295-550.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 121691. 3 interactions.
    STRINGi 9606.ENSP00000357342.

    Chemistry

    ChEMBLi CHEMBL1795173.
    GuidetoPHARMACOLOGYi 402.

    PTM databases

    PhosphoSitei Q9P1Z3.

    Polymorphism databases

    DMDMi 29840780.

    Proteomic databases

    PaxDbi Q9P1Z3.
    PRIDEi Q9P1Z3.

    Protocols and materials databases

    DNASUi 57657.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000368358 ; ENSP00000357342 ; ENSG00000143630 .
    ENST00000575670 ; ENSP00000458364 ; ENSG00000263324 .
    GeneIDi 57657.
    KEGGi hsa:57657.
    UCSCi uc001fjz.2. human.

    Organism-specific databases

    CTDi 57657.
    GeneCardsi GC01P155247.
    H-InvDB HIX0001125.
    HGNCi HGNC:19183. HCN3.
    HPAi HPA026584.
    MIMi 609973. gene.
    neXtProti NX_Q9P1Z3.
    PharmGKBi PA38821.
    HUGEi Search...
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0664.
    HOGENOMi HOG000230717.
    HOVERGENi HBG039489.
    InParanoidi Q9P1Z3.
    KOi K04956.
    OMAi RMVNHSW.
    OrthoDBi EOG7VMP6X.
    PhylomeDBi Q9P1Z3.
    TreeFami TF318250.

    Enzyme and pathway databases

    Reactomei REACT_75862. HCN channels.

    Miscellaneous databases

    GeneWikii HCN3.
    GenomeRNAii 57657.
    NextBioi 64413.
    PROi Q9P1Z3.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q9P1Z3.
    CleanExi HS_HCN3.
    Genevestigatori Q9P1Z3.

    Family and domain databases

    Gene3Di 2.60.120.10. 1 hit.
    InterProi IPR018490. cNMP-bd-like.
    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 PS50042. CNMP_BINDING_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
      Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.
      DNA Res. 7:143-150(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 64-774.
      Tissue: Brain.
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 204-774.
      Tissue: Brain.
    5. Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ENZYME REGULATION.

    Entry informationi

    Entry nameiHCN3_HUMAN
    AccessioniPrimary (citable) accession number: Q9P1Z3
    Secondary accession number(s): D3DV90
    , Q4VX12, Q8N6W6, Q9BWQ2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 28, 2003
    Last sequence update: February 28, 2003
    Last modified: October 1, 2014
    This is version 124 of the entry and version 2 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 1
      Human chromosome 1: 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