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Protein

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1

Gene

Hcn1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein 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.5 Publications

Miscellaneous

Inhibited by extracellular cesium ions.

Activity regulationi

Activated by cAMP, and at 10-100 times higher concentrations, also by cGMP. cAMP binding causes a conformation change that leads to the assembly of an active tetramer and channel opening. 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.3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi528 – 531cAMPCombined sources1 Publication4
Nucleotide bindingi538 – 539cAMPCombined sources1 Publication2
Nucleotide bindingi579 – 582cAMPCombined sources1 Publication4

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionIon channel, Ligand-gated ion channel, Potassium channel, Sodium channel, Voltage-gated channel
Biological processIon transport, Potassium transport, Sodium transport, Transport
LigandcAMP, cAMP-binding, Nucleotide-binding, Potassium, Sodium

Enzyme and pathway databases

ReactomeiR-MMU-1296061 HCN channels

Protein family/group databases

TCDBi1.A.1.5.2 the voltage-gated ion channel (vic) superfamily

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
Alternative name(s):
Brain cyclic nucleotide-gated channel 11 Publication
Short name:
BCNG-11 Publication
Hyperpolarization-activated cation channel 21 Publication
Short name:
HAC-21 Publication
Gene namesi
Name:Hcn1
Synonyms:Bcng11 Publication, Hac2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:1096392 Hcn1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 131CytoplasmicBy similarityAdd BLAST131
Transmembranei132 – 153Helical; Name=Segment S1By similarityAdd BLAST22
Topological domaini154 – 162ExtracellularBy similarity9
Transmembranei163 – 183Helical; Name=Segment S2By similarityAdd BLAST21
Topological domaini184 – 204CytoplasmicBy similarityAdd BLAST21
Transmembranei205 – 225Helical; Name=Segment S3By similarityAdd BLAST21
Topological domaini226 – 249ExtracellularBy similarityAdd BLAST24
Transmembranei250 – 270Helical; Voltage-sensor; Name=Segment S4By similarityAdd BLAST21
Topological domaini271 – 284CytoplasmicBy similarityAdd BLAST14
Transmembranei285 – 307Helical; Name=Segment S5By similarityAdd BLAST23
Topological domaini308 – 333ExtracellularBy similarityAdd BLAST26
Intramembranei334 – 355Pore-forming; Name=Segment H5By similarityAdd BLAST22
Topological domaini356 – 360ExtracellularBy similarity5
Transmembranei361 – 381Helical; Name=Segment S6By similarityAdd BLAST21
Topological domaini382 – 910CytoplasmicBy similarityAdd BLAST529

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi303C → S: Abolishes conductivity. 1 Publication1
Mutagenesisi318C → S: Abolishes sensitivity to sulfhydryl modification. 1 Publication1
Mutagenesisi349G → A: Abolishes conductivity; when associated with A-350 and A-351. 1 Publication1
Mutagenesisi350Y → A: Abolishes conductivity; when associated with A-349 and A-351. 1 Publication1
Mutagenesisi351G → A: Abolishes conductivity; when associated with A-349 and A-350. 1 Publication1
Mutagenesisi538R → E: Reduces affinity for cAMP and impairs tetramerization. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL1250401
GuidetoPHARMACOLOGYi400

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000541081 – 910Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1Add BLAST910

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi327N-linked (GlcNAc...) asparagine1 Publication1

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiO88704
PaxDbiO88704
PeptideAtlasiO88704
PRIDEiO88704

PTM databases

iPTMnetiO88704
PhosphoSitePlusiO88704
SwissPalmiO88704

Expressioni

Tissue specificityi

Predominantly expressed in brain. Highly expressed in apical dendrites of pyramidal neurons in the cortex, in the layer corresponding to the stratum lacunosum-moleculare in the hippocampus and in axons of basket cells in the cerebellum. Expressed in a subset of elongated cells in taste buds.2 Publications

Gene expression databases

BgeeiENSMUSG00000021730 Expressed in 116 organ(s), highest expression level in retina
GenevisibleiO88704 MM

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 (PubMed:9405696).5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-8766347,EBI-8766347

GO - Molecular functioni

Protein-protein interaction databases

BioGridi200252, 39 interactors
ComplexPortaliCPX-260 HCN1 channel complex
IntActiO88704, 39 interactors
STRINGi10090.ENSMUSP00000006991

Chemistry databases

BindingDBiO88704

Structurei

Secondary structure

1910
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO88704
SMRiO88704
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 82Intrinsically disorderedBy similarityAdd BLAST82

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi347 – 351Selectivity filter1 Publication5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1 – 81Gly-richAdd BLAST81
Compositional biasi715 – 777Gln-richAdd BLAST63
Compositional biasi878 – 884Poly-Pro7

Domaini

The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.By similarity

Sequence similaritiesi

Belongs to the potassium channel HCN family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0498 Eukaryota
ENOG410XPSE LUCA
GeneTreeiENSGT00900000140801
HOGENOMiHOG000230717
HOVERGENiHBG039489
InParanoidiO88704
KOiK04954
OMAiTRTFHYA
OrthoDBiEOG091G0JQU
PhylomeDBiO88704
TreeFamiTF318250

Family and domain databases

CDDicd00038 CAP_ED, 1 hit
Gene3Di1.20.120.350, 1 hit
2.60.120.10, 1 hit
InterProiView protein in InterPro
IPR018490 cNMP-bd-like
IPR018488 cNMP-bd_CS
IPR000595 cNMP-bd_dom
IPR005821 Ion_trans_dom
IPR013621 Ion_trans_N
IPR030169 K/Na_HCN1
IPR003938 K_chnl_volt-dep_EAG/ELK/ERG
IPR014710 RmlC-like_jellyroll
IPR027359 Volt_channel_dom_sf
PANTHERiPTHR10217:SF373 PTHR10217:SF373, 1 hit
PfamiView protein in Pfam
PF00027 cNMP_binding, 1 hit
PF00520 Ion_trans, 1 hit
PF08412 Ion_trans_N, 1 hit
PRINTSiPR01463 EAGCHANLFMLY
SMARTiView protein in SMART
SM00100 cNMP, 1 hit
SUPFAMiSSF51206 SSF51206, 1 hit
PROSITEiView protein in PROSITE
PS00888 CNMP_BINDING_1, 1 hit
PS50042 CNMP_BINDING_3, 1 hit

Sequencei

Sequence statusi: Complete.

O88704-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MEGGGKPNSA SNSRDDGNSV FPSKAPATGP VAADKRLGTP PGGGAAGKEH
60 70 80 90 100
GNSVCFKVDG GGGEEPAGSF EDAEGPRRQY GFMQRQFTSM LQPGVNKFSL
110 120 130 140 150
RMFGSQKAVE KEQERVKTAG FWIIHPYSDF RFYWDLIMLI MMVGNLVIIP
160 170 180 190 200
VGITFFTEQT TTPWIIFNVA SDTVFLLDLI MNFRTGTVNE DSSEIILDPK
210 220 230 240 250
VIKMNYLKSW FVVDFISSIP VDYIFLIVEK GMDSEVYKTA RALRIVRFTK
260 270 280 290 300
ILSLLRLLRL SRLIRYIHQW EEIFHMTYDL ASAVVRIFNL IGMMLLLCHW
310 320 330 340 350
DGCLQFLVPL LQDFPPDCWV SLNEMVNDSW GKQYSYALFK AMSHMLCIGY
360 370 380 390 400
GAQAPVSMSD LWITMLSMIV GATCYAMFVG HATALIQSLD SSRRQYQEKY
410 420 430 440 450
KQVEQYMSFH KLPADMRQKI HDYYEHRYQG KIFDEENILS ELNDPLREEI
460 470 480 490 500
VNFNCRKLVA TMPLFANADP NFVTAMLSKL RFEVFQPGDY IIREGAVGKK
510 520 530 540 550
MYFIQHGVAG VITKSSKEMK LTDGSYFGEI CLLTKGRRTA SVRADTYCRL
560 570 580 590 600
YSLSVDNFNE VLEEYPMMRR AFETVAIDRL DRIGKKNSIL LQKFQKDLNT
610 620 630 640 650
GVFNNQENEI LKQIVKHDRE MVQAIPPINY PQMTALNCTS STTTPTSRMR
660 670 680 690 700
TQSPPVYTAT SLSHSNLHSP SPSTQTPQPS AILSPCSYTT AVCSPPIQSP
710 720 730 740 750
LATRTFHYAS PTASQLSLMQ QPQQQLPQSQ VQQTQTQTQQ QQQQQQQQQQ
760 770 780 790 800
QQQQQQQQQQ QQQQQQQQQQ QQQQQPQTPG SSTPKNEVHK STQALHNTNL
810 820 830 840 850
TKEVRPLSAS QPSLPHEVST LISRPHPTVG ESLASIPQPV AAVHSTGLQA
860 870 880 890 900
GSRSTVPQRV TLFRQMSSGA IPPNRGVPPA PPPPAAVQRE SPSVLNTDPD
910
AEKPRFASNL
Length:910
Mass (Da):102,432
Last modified:November 1, 1998 - v1
Checksum:i56FD5F328DD972E9
GO

Sequence cautioni

The sequence AK014722 differs from that shown. Reason: Frameshift at position 381.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti42G → R in AAC53518 (PubMed:9405696).Curated1
Sequence conflicti394R → S in AK014722 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF028737 mRNA Translation: AAC53518.1
AJ225123 mRNA Translation: CAA12407.1
AK014722 mRNA No translation available.
CCDSiCCDS26793.1
RefSeqiNP_034538.2, NM_010408.3
UniGeneiMm.343429

Genome annotation databases

EnsembliENSMUST00000006991; ENSMUSP00000006991; ENSMUSG00000021730
GeneIDi15165
KEGGimmu:15165
UCSCiuc007ryo.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF028737 mRNA Translation: AAC53518.1
AJ225123 mRNA Translation: CAA12407.1
AK014722 mRNA No translation available.
CCDSiCCDS26793.1
RefSeqiNP_034538.2, NM_010408.3
UniGeneiMm.343429

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3U0ZX-ray2.90A/B390-592[»]
ProteinModelPortaliO88704
SMRiO88704
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200252, 39 interactors
ComplexPortaliCPX-260 HCN1 channel complex
IntActiO88704, 39 interactors
STRINGi10090.ENSMUSP00000006991

Chemistry databases

BindingDBiO88704
ChEMBLiCHEMBL1250401
GuidetoPHARMACOLOGYi400

Protein family/group databases

TCDBi1.A.1.5.2 the voltage-gated ion channel (vic) superfamily

PTM databases

iPTMnetiO88704
PhosphoSitePlusiO88704
SwissPalmiO88704

Proteomic databases

MaxQBiO88704
PaxDbiO88704
PeptideAtlasiO88704
PRIDEiO88704

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000006991; ENSMUSP00000006991; ENSMUSG00000021730
GeneIDi15165
KEGGimmu:15165
UCSCiuc007ryo.2 mouse

Organism-specific databases

CTDi348980
MGIiMGI:1096392 Hcn1

Phylogenomic databases

eggNOGiKOG0498 Eukaryota
ENOG410XPSE LUCA
GeneTreeiENSGT00900000140801
HOGENOMiHOG000230717
HOVERGENiHBG039489
InParanoidiO88704
KOiK04954
OMAiTRTFHYA
OrthoDBiEOG091G0JQU
PhylomeDBiO88704
TreeFamiTF318250

Enzyme and pathway databases

ReactomeiR-MMU-1296061 HCN channels

Miscellaneous databases

PROiPR:O88704
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000021730 Expressed in 116 organ(s), highest expression level in retina
GenevisibleiO88704 MM

Family and domain databases

CDDicd00038 CAP_ED, 1 hit
Gene3Di1.20.120.350, 1 hit
2.60.120.10, 1 hit
InterProiView protein in InterPro
IPR018490 cNMP-bd-like
IPR018488 cNMP-bd_CS
IPR000595 cNMP-bd_dom
IPR005821 Ion_trans_dom
IPR013621 Ion_trans_N
IPR030169 K/Na_HCN1
IPR003938 K_chnl_volt-dep_EAG/ELK/ERG
IPR014710 RmlC-like_jellyroll
IPR027359 Volt_channel_dom_sf
PANTHERiPTHR10217:SF373 PTHR10217:SF373, 1 hit
PfamiView protein in Pfam
PF00027 cNMP_binding, 1 hit
PF00520 Ion_trans, 1 hit
PF08412 Ion_trans_N, 1 hit
PRINTSiPR01463 EAGCHANLFMLY
SMARTiView protein in SMART
SM00100 cNMP, 1 hit
SUPFAMiSSF51206 SSF51206, 1 hit
PROSITEiView protein in PROSITE
PS00888 CNMP_BINDING_1, 1 hit
PS50042 CNMP_BINDING_3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHCN1_MOUSE
AccessioniPrimary (citable) accession number: O88704
Secondary accession number(s): O54899, Q9D613
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: November 1, 1998
Last modified: October 10, 2018
This is version 173 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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