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Protein

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

Gene

Hcn4

Organism
Mus musculus (Mouse)
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. Contributes 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

GO - Molecular functioni

GO - Biological processi

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

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4
Alternative name(s):
Brain cyclic nucleotide-gated channel 3
Short name:
BCNG-3
Gene namesi
Name:Hcn4
Synonyms:Bcng3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1298209. 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 – 1186669CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Chemistry

GuidetoPHARMACOLOGYi403.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11861186Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4PRO_0000054118Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei139 – 1391PhosphoserineBy similarity
Glycosylationi458 – 4581N-linked (GlcNAc...)Sequence analysis
Modified residuei1090 – 10901PhosphoserineCombined sources
Modified residuei1093 – 10931PhosphoserineCombined sources

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiO70507.
PaxDbiO70507.
PeptideAtlasiO70507.
PRIDEiO70507.

PTM databases

iPTMnetiO70507.
PhosphoSiteiO70507.
SwissPalmiO70507.

Expressioni

Tissue specificityi

Detected in a subset of elongated cells in taste buds.1 Publication

Interactioni

Subunit structurei

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

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000034889.

Structurei

3D structure databases

ProteinModelPortaliO70507.
SMRiO70507. Positions 521-701.
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 biasi784 – 1061278Pro/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.
HOVERGENiHBG039490.
InParanoidiO70507.
PhylomeDBiO70507.

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.

O70507-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDKLPPSMRK RLYSLPQQVG AKAWIMDEEE DGEEEGAGGR QDPSRRSIRL
60 70 80 90 100
RPLPSPSPSV AAGCSESRGA ALGATESEGP GRSAGKSSTN GDCRRFRGSL
110 120 130 140 150
ASLGSRGGGS GGAGGGSSLG HLHDSAEERR LIAAEGDASP GEDRTPPGLA
160 170 180 190 200
TEPERPATAA QPAASPPPQQ PPQPASASCE QPSADTAIKV EGGAAAIDHI
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
PVEYIFLIVE TRIDSEVYKT ARAVRIVRFT 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
RLADGSYFGE ICLLTRGRRT ASVRADTYCR LYSLSVDNFN EVLEEYPMMR
710 720 730 740 750
KKNSILLHKV QHDLNSGVFN YQENEIIQQI VRHDREMAHC AHRVQAAASA
760 770 780 790 800
TPTPTPVIWT PLIQAPLQAA AATTSVAIAL THHPRLPAAI FRPPPGPGLG
810 820 830 840 850
NLGAGQTPRH PRRLQSLIPS ALGSASPASS PSQVDTPSSS SFHIQQLAGF
860 870 880 890 900
SAPPGLSPLL PSSSSSPPPG ACGSPPAPTP STSTAAAAST TGFGHFHKAL
910 920 930 940 950
GGSLSSSDSP LLTPLQPGAR SPQAAQPPPP LPGARGGLGL LEHFLPPPPS
960 970 980 990 1000
SRSPSSSPGQ LGQPPGELSL GLAAGPSSTP ETPPRPERPS FMAGASGGAS
1010 1020 1030 1040 1050
PVAFTPRGGL SPPGHSPGPP RTFPSAPPRA SGSHGSLLLP PASSPPPPQV
1060 1070 1080 1090 1100
PQRRGTPPLT PGRLTQDLKL ISASQPALPQ DGAQTLRRAS PHSSGESVAA
1110 1120 1130 1140 1150
FSLYPRAGGG SGSSGGLGPP GRPYGAIPGQ HVTLPRKTSS GSLPPPLSLF
1160 1170 1180
GARAASSGGP PLTTAAPQRE PGARSEPVRS KLPSNL
Length:1,186
Mass (Da):127,414
Last modified:February 28, 2003 - v2
Checksum:iB3DC16818E8697DC
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC110530 Genomic DNA. No translation available.
AF064874 mRNA. Translation: AAC40126.1.
UniGeneiMm.151967.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC110530 Genomic DNA. No translation available.
AF064874 mRNA. Translation: AAC40126.1.
UniGeneiMm.151967.

3D structure databases

ProteinModelPortaliO70507.
SMRiO70507. Positions 521-701.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000034889.

Chemistry

GuidetoPHARMACOLOGYi403.

PTM databases

iPTMnetiO70507.
PhosphoSiteiO70507.
SwissPalmiO70507.

Proteomic databases

MaxQBiO70507.
PaxDbiO70507.
PeptideAtlasiO70507.
PRIDEiO70507.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:1298209. Hcn4.

Phylogenomic databases

eggNOGiKOG0498. Eukaryota.
ENOG410XPSE. LUCA.
HOVERGENiHBG039490.
InParanoidiO70507.
PhylomeDBiO70507.

Miscellaneous databases

PROiO70507.
SOURCEiSearch...

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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  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 179-684.
    Tissue: Brain.
  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. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1090 AND SER-1093, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain.

Entry informationi

Entry nameiHCN4_MOUSE
AccessioniPrimary (citable) accession number: O70507
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: February 28, 2003
Last modified: July 6, 2016
This is version 128 of the entry and version 2 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.