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Protein

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4

Gene

Hcn4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Hyperpolarization-activated ion channel with very slow activation and inactivation exhibiting weak selectivity for potassium over sodium ions. May contribute to the native pacemaker currents in heart (If) that regulate the rhythm of heart beat. May contribute to the native pacemaker currents in neurons (Ih) (By similarity). May mediate responses to sour stimuli.By similarity1 Publication

Enzyme regulationi

Activated by cAMP. cAMP binding causes a conformation change that leads to the assembly of an active tetramer and channel opening (By similarity).By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi659 – 6624cAMPBy similarity
Nucleotide bindingi669 – 6702cAMPBy similarity
Nucleotide bindingi710 – 7134cAMPBy similarity

GO - Molecular functioni

GO - Biological processi

  • cellular response to aldosterone Source: RGD
  • cellular response to cAMP Source: UniProtKB
  • modulation of synaptic transmission Source: RGD
  • potassium ion transmembrane transport Source: UniProtKB
  • regulation of heart rate Source: UniProtKB
  • response to cisplatin Source: RGD
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

ReactomeiR-RNO-1296061. HCN channels.

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4
Gene namesi
Name:Hcn4
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi71065. Hcn4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 266266CytoplasmicSequence analysisAdd
BLAST
Transmembranei267 – 28721Helical; Name=Segment S1Sequence analysisAdd
BLAST
Topological domaini288 – 2936ExtracellularSequence analysis
Transmembranei294 – 31421Helical; Name=Segment S2Sequence analysisAdd
BLAST
Topological domaini315 – 34026CytoplasmicSequence analysisAdd
BLAST
Transmembranei341 – 36121Helical; Name=Segment S3Sequence analysisAdd
BLAST
Topological domaini362 – 3687ExtracellularSequence analysis
Transmembranei369 – 38921Helical; Voltage-sensor; Name=Segment S4Sequence analysisAdd
BLAST
Topological domaini390 – 42031CytoplasmicSequence analysisAdd
BLAST
Transmembranei421 – 44121Helical; Name=Segment S5Sequence analysisAdd
BLAST
Topological domaini442 – 46423ExtracellularSequence analysisAdd
BLAST
Intramembranei465 – 48622Pore-forming; Name=Segment H5Sequence analysisAdd
BLAST
Topological domaini487 – 49610ExtracellularSequence analysis
Transmembranei497 – 51721Helical; Name=Segment S6Sequence analysisAdd
BLAST
Topological domaini518 – 1198681CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • basolateral plasma membrane Source: RGD
  • integral component of membrane Source: UniProtKB-KW
  • intrinsic component of plasma membrane Source: UniProtKB
  • neuronal cell body Source: RGD
  • neuron projection Source: RGD
  • plasma membrane Source: RGD
  • terminal bouton Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11981198Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4PRO_0000054120Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei139 – 1391PhosphoserineCombined sources
Glycosylationi458 – 4581N-linked (GlcNAc...)Sequence analysis
Modified residuei1103 – 11031PhosphoserineBy similarity
Modified residuei1106 – 11061PhosphoserineBy similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ9JKA7.
PRIDEiQ9JKA7.

PTM databases

PhosphoSiteiQ9JKA7.

Expressioni

Tissue specificityi

Highly expressed in pyramidal and granule layer of the hippocampus, in thalamus anterior nucleus, in the supraoptic nucleus in hypothalamus, in cerebellum, and in trapezoid nuclei and superior olivary complex in the auditory system. Detected in a subset of elongated cells in taste buds.2 Publications

Gene expression databases

GenevisibleiQ9JKA7. RN.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000012644.

Structurei

3D structure databases

ProteinModelPortaliQ9JKA7.
SMRiQ9JKA7. Positions 521-721.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni209 – 26052Involved in subunit assemblyBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi799 – 1074276Pro/Ser-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

eggNOGiKOG0498. Eukaryota.
ENOG410XPSE. LUCA.
HOGENOMiHOG000230717.
HOVERGENiHBG039490.
InParanoidiQ9JKA7.
KOiK04957.
OMAiGAIPGQH.
OrthoDBiEOG7VMP6X.
PhylomeDBiQ9JKA7.
TreeFamiTF318250.

Family and domain databases

Gene3Di2.60.120.10. 1 hit.
InterProiIPR018490. cNMP-bd-like.
IPR018488. cNMP-bd_CS.
IPR000595. cNMP-bd_dom.
IPR030173. HCN4.
IPR005821. Ion_trans_dom.
IPR013621. Ion_trans_N.
IPR003938. K_chnl_volt-dep_EAG/ELK/ERG.
IPR014710. RmlC-like_jellyroll.
[Graphical view]
PANTHERiPTHR10217:SF375. PTHR10217:SF375. 3 hits.
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.

Q9JKA7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDKLPPSMRK RLYSLPQQVG AKAWIMDEEE DGEEEGAGGL QDPSRRSIRL
60 70 80 90 100
RPLPSPSPSV AAGCSESRGA ALGAADSEGP GRSAGKSSTN GDCRRFRGSL
110 120 130 140 150
ASLGSRGGGS GGAGGGSSLG HLHDSAEERR LIAAEGDASP GEDRTPPGLA
160 170 180 190 200
TEPERPGAAA QPAASPPPQQ PPQPASASCE QPSADTAIKV EGGAAASDQI
210 220 230 240 250
LPEAEVRLGQ SGFMQRQFGA MLQPGVNKFS LRMFGSQKAV EREQERVKSA
260 270 280 290 300
GFWIIHPYSD FRFYWDLTML LLMVGNLIII PVGITFFKDE NTTPWIVFNV
310 320 330 340 350
VSDTFFLIDL VLNFRTGIVV EDNTEIILDP QRIKMKYLKS WFVVDFISSI
360 370 380 390 400
PVDYIFLIVE TRIDSEVYKT ARALRIVRFT KILSLLRLLR LSRLIRYIHQ
410 420 430 440 450
WEEIFHMTYD LASAVVRIVN LIGMMLLLCH WDGCLQFLVP MLQDFPHDCW
460 470 480 490 500
VSINGMVNNS WGKQYSYALF KAMSHMLCIG YGRQAPVGMS DVWLTMLSMI
510 520 530 540 550
VGATCYAMFI GHATALIQSL DSSRRQYQEK YKQVEQYMSF HKLPPDTRQR
560 570 580 590 600
IHDYYEHRYQ GKMFDEESIL GELSEPLREE IINFNCRKLV ASMPLFANAD
610 620 630 640 650
PNFVTSMLTK LRFEVFQPGD YIIREGTIGK KMYFIQHGVV SVLTKGNKET
660 670 680 690 700
KLADGSYFGE ICLLTRGRRT ASVRADTYCR LYSLSVDNFN EVLEEYPMMR
710 720 730 740 750
RAFETVALDR LDRIGKKNSI LLHKVQHDLN SGVFNYQENE IIQQIVRHDR
760 770 780 790 800
EMAHCAHRVQ AAASATPTPT PVIWTPLIQA PLQAAAATTS VAIALTHHPR
810 820 830 840 850
LPAAIFRPPP GPGLGNLGAG QTPRHPRRLQ SLIPSALGSA SPASSPSQVD
860 870 880 890 900
TPSSSSFHIQ QLAGFSAPPG LSPLLPSSSS SPPPGACSSP PAPTPSTSTA
910 920 930 940 950
ATTTGFGHFH KALGGSLSSS DSPLLTPLQP GARSPQAAQP PPPLPGARGG
960 970 980 990 1000
LGLLEHFLPP PPSSRSPSSS PGQLGQPPGE LSPGLAAGPP STPETPPRPE
1010 1020 1030 1040 1050
RPSFMAGASG GASPVAFTPR GGLSPPGHSP GPPRTFPSAP PRASGSHGSL
1060 1070 1080 1090 1100
LLPPASSPPP PQVPQRRGTP PLTPGRLTQD LKLISASQPA LPQDGAQTLR
1110 1120 1130 1140 1150
RASPHSSGES MAAFSLYPRA GGGSGSSGGL GPPGRPYGAI PGQHVTLPRK
1160 1170 1180 1190
TSSGSLPPPL SLFGARAASS GGPPLTAAPQ REPGARSEPV RSKLPSNL
Length:1,198
Mass (Da):128,761
Last modified:October 1, 2000 - v1
Checksum:i6B92B8F9452F760F
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti404 – 4041I → V in AAF01493 (PubMed:10400919).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF247453 mRNA. Translation: AAF62176.1.
AF155166 mRNA. Translation: AAF01493.1.
RefSeqiNP_067690.1. NM_021658.1.
UniGeneiRn.41082.

Genome annotation databases

GeneIDi59266.
KEGGirno:59266.
UCSCiRGD:71065. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF247453 mRNA. Translation: AAF62176.1.
AF155166 mRNA. Translation: AAF01493.1.
RefSeqiNP_067690.1. NM_021658.1.
UniGeneiRn.41082.

3D structure databases

ProteinModelPortaliQ9JKA7.
SMRiQ9JKA7. Positions 521-721.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000012644.

PTM databases

PhosphoSiteiQ9JKA7.

Proteomic databases

PaxDbiQ9JKA7.
PRIDEiQ9JKA7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi59266.
KEGGirno:59266.
UCSCiRGD:71065. rat.

Organism-specific databases

CTDi10021.
RGDi71065. Hcn4.

Phylogenomic databases

eggNOGiKOG0498. Eukaryota.
ENOG410XPSE. LUCA.
HOGENOMiHOG000230717.
HOVERGENiHBG039490.
InParanoidiQ9JKA7.
KOiK04957.
OMAiGAIPGQH.
OrthoDBiEOG7VMP6X.
PhylomeDBiQ9JKA7.
TreeFamiTF318250.

Enzyme and pathway databases

ReactomeiR-RNO-1296061. HCN channels.

Miscellaneous databases

NextBioi611789.
PROiQ9JKA7.

Gene expression databases

GenevisibleiQ9JKA7. RN.

Family and domain databases

Gene3Di2.60.120.10. 1 hit.
InterProiIPR018490. cNMP-bd-like.
IPR018488. cNMP-bd_CS.
IPR000595. cNMP-bd_dom.
IPR030173. HCN4.
IPR005821. Ion_trans_dom.
IPR013621. Ion_trans_N.
IPR003938. K_chnl_volt-dep_EAG/ELK/ERG.
IPR014710. RmlC-like_jellyroll.
[Graphical view]
PANTHERiPTHR10217:SF375. PTHR10217:SF375. 3 hits.
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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and localization of the hyperpolarization-activated cyclic nucleotide-gated channel family in rat brain."
    Monteggia L.M., Eisch A.J., Tang M.D., Kaczmarek L.K., Nestler E.J.
    Brain Res. Mol. Brain Res. 81:129-139(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    Strain: Sprague-Dawley.
    Tissue: Brain.
  2. "Distribution and prevalence of hyperpolarization-activated cation channel (HCN) mRNA expression in cardiac tissues."
    Shi W., Wymore R., Yu H., Wu J., Wymore R.T., Pan Z., Robinson R.B., Dixon J.E., McKinnon D., Cohen I.S.
    Circ. Res. 85:1-6(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 262-428.
    Tissue: Heart.
  3. "Hyperpolarization-activated channels HCN1 and HCN4 mediate responses to sour stimuli."
    Stevens D.R., Seifert R., Bufe B., Mueller F., Kremmer E., Gauss R., Meyerhof W., Kaupp U.B., Lindemann B.
    Nature 413:631-635(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  4. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-139, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiHCN4_RAT
AccessioniPrimary (citable) accession number: Q9JKA7
Secondary accession number(s): Q9QZW4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: October 1, 2000
Last modified: May 11, 2016
This is version 121 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.