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Protein

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2

Gene

Hcn2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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). Can also transport ammonium in the distal nephron. Produces a large instantaneous current.8 Publications

Enzyme 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. Channel activity is modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages.4 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi581 – 584cAMP2 Publications4
Nucleotide bindingi591 – 592cAMP2 Publications2
Nucleotide bindingi632 – 635cAMP2 Publications4

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

Enzyme and pathway databases

ReactomeiR-MMU-1296061. HCN channels.

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2
Alternative name(s):
Brain cyclic nucleotide-gated channel 2
Short name:
BCNG-2
Hyperpolarization-activated cation channel 1
Short name:
HAC-1
Gene namesi
Name:Hcn2
Synonyms:Bcng2, Hac1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1298210. Hcn2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 188CytoplasmicSequence analysisAdd BLAST188
Transmembranei189 – 209Helical; Name=Segment S1Sequence analysisAdd BLAST21
Topological domaini210 – 213ExtracellularSequence analysis4
Transmembranei214 – 234Helical; Name=Segment S2Sequence analysisAdd BLAST21
Topological domaini235 – 261CytoplasmicSequence analysisAdd BLAST27
Transmembranei262 – 282Helical; Name=Segment S3Sequence analysisAdd BLAST21
Topological domaini283 – 290ExtracellularSequence analysis8
Transmembranei291 – 311Helical; Voltage-sensor; Name=Segment S4Sequence analysisAdd BLAST21
Topological domaini312 – 342CytoplasmicSequence analysisAdd BLAST31
Transmembranei343 – 363Helical; Name=Segment S5Sequence analysisAdd BLAST21
Topological domaini364 – 386ExtracellularSequence analysisAdd BLAST23
Intramembranei387 – 408Pore-forming; Name=Segment H5Sequence analysisAdd BLAST22
Topological domaini409 – 413ExtracellularSequence analysis5
Transmembranei414 – 434Helical; Name=Segment S6Sequence analysisAdd BLAST21
Topological domaini435 – 863CytoplasmicSequence analysisAdd BLAST429

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi225D → N: Abolishes surface expression and channel activity. 1 Publication1
Mutagenesisi231D → N: Reduces surface expression and abolishes channel activity. 1 Publication1
Mutagenesisi267D → N: Reduces surface expression and abolishes channel activity. 1 Publication1
Mutagenesisi275D → N: Reduces surface expression and abolishes channel activity. 1 Publication1
Mutagenesisi291K → Q: Shifts voltage dependence of activation to more negative values. 1 Publication1
Mutagenesisi294R → Q: Shifts voltage dependence of activation to more negative values. 1 Publication1
Mutagenesisi297R → Q: Shifts voltage dependence of activation to more negative values. 1 Publication1
Mutagenesisi300R → Q: Shifts voltage dependence of activation to more negative values. 1 Publication1
Mutagenesisi303K → Q: Decreases current amplitude. 1 Publication1
Mutagenesisi306S → Q: Decreases current amplitude. 2 Publications1
Mutagenesisi309R → Q: Abolishes surface expression and channel activity. 1 Publication1
Mutagenesisi312R → Q: Reduces surface expression and decreases current amplitude. 1 Publication1
Mutagenesisi315R → Q: Reduces surface expression and abolishes channel activity. 1 Publication1
Mutagenesisi318R → Q: Reduces surface expression and disrupts channel closure. 2 Publications1
Mutagenesisi321H → E: Shifts voltage dependence of activation to more positive values and abolishes pH-sensitivity. 1 Publication1
Mutagenesisi321H → Q: Abolishes pH-sensitivity. 1 Publication1
Mutagenesisi321H → R: Abolishes pH-sensitivity. 1 Publication1
Mutagenesisi324E → Q: Disrupts channel closure. 1 Publication1
Mutagenesisi331Y → A: Disrupts channel closure. 1 Publication1
Mutagenesisi331Y → S: Disrupts channel closure. 1 Publication1
Mutagenesisi339R → Q: Disrupts channel closure. 1 Publication1
Mutagenesisi594S → R: Shifts channel activation to more negative voltage, slows channel opening and speeds up channel closure. Reduces sensitivity to activation by cAMP. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL1250408.
GuidetoPHARMACOLOGYi401.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000541121 – 863Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2Add BLAST863

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei119PhosphoserineCombined sources1
Modified residuei134PhosphoserineBy similarity1
Glycosylationi380N-linked (GlcNAc...)Sequence analysis1
Modified residuei641Phosphoserine; by PKG/PRKG21 Publication1
Modified residuei726PhosphoserineBy similarity1
Modified residuei728Omega-N-methylarginineCombined sources1
Modified residuei743PhosphoserineCombined sources1
Modified residuei750PhosphoserineCombined sources1
Modified residuei757PhosphoserineCombined sources1
Modified residuei840PhosphoserineCombined sources1
Modified residuei842PhosphoserineCombined sources1
Modified residuei847PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation at Ser-641 by PRKG2 shifts the voltage-dependence to more negative voltages, hence counteracting the stimulatory effect of cGMP on gating.1 Publication

Keywords - PTMi

Glycoprotein, Methylation, Phosphoprotein

Proteomic databases

MaxQBiO88703.
PaxDbiO88703.
PRIDEiO88703.

PTM databases

iPTMnetiO88703.
PhosphoSitePlusiO88703.
SwissPalmiO88703.

Expressioni

Tissue specificityi

Highly expressed in brain. Detected at low levels in heart, in ventricle, atrium and in sinoatrial node (SAN).1 Publication

Gene expression databases

BgeeiENSMUSG00000020331.
GenevisibleiO88703. MM.

Interactioni

Subunit structurei

Homotetramer. Heterotetramer with HCN1. The potassium channel is composed of a homo- or heterotetrameric complex of pore-forming subunits. Forms an obligate 4:4 complex with accessory subunit PEX5L. Interacts with KCNE2.8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
SRCP005235EBI-771231,EBI-848039From a different organism.

Protein-protein interaction databases

BioGridi200253. 1 interactor.
DIPiDIP-29326N.
IntActiO88703. 3 interactors.
MINTiMINT-155013.
STRINGi10090.ENSMUSP00000020581.

Chemistry databases

BindingDBiO88703.

Structurei

Secondary structure

1863
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi444 – 462Combined sources19
Helixi467 – 481Combined sources15
Helixi488 – 494Combined sources7
Helixi497 – 507Combined sources11
Helixi509 – 513Combined sources5
Helixi516 – 519Combined sources4
Helixi523 – 532Combined sources10
Beta strandi534 – 538Combined sources5
Beta strandi543 – 545Combined sources3
Beta strandi553 – 559Combined sources7
Beta strandi561 – 565Combined sources5
Beta strandi567 – 569Combined sources3
Beta strandi572 – 575Combined sources4
Beta strandi579 – 581Combined sources3
Helixi582 – 587Combined sources6
Beta strandi592 – 599Combined sources8
Beta strandi601 – 607Combined sources7
Helixi608 – 617Combined sources10
Helixi619 – 621Combined sources3
Helixi622 – 635Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1Q3EX-ray1.90A/B443-645[»]
1Q43X-ray2.00A/B443-645[»]
1Q5OX-ray2.30A443-645[»]
2Q0AX-ray2.25A/B443-640[»]
3BPZX-ray1.65A/B/C/D443-640[»]
3ETQX-ray1.90A/B443-640[»]
3FFQX-ray2.40A/B443-640[»]
4EQFX-ray3.00B857-863[»]
5KHGX-ray2.24A443-643[»]
5KHHX-ray1.77A443-643[»]
5KHIX-ray2.10A443-643[»]
5KHJX-ray2.01A/B443-643[»]
5KHKX-ray2.07A443-643[»]
ProteinModelPortaliO88703.
SMRiO88703.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO88703.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni131 – 182Involved in subunit assemblyAdd BLAST52

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi10 – 58Pro-richAdd BLAST49
Compositional biasi688 – 835Pro-richAdd BLAST148

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.
GeneTreeiENSGT00760000118772.
HOGENOMiHOG000230717.
HOVERGENiHBG039489.
InParanoidiO88703.
KOiK04955.
OMAiAMSFCPP.
OrthoDBiEOG091G0JQU.
PhylomeDBiO88703.
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.

O88703-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDARGGGGRP GDSPGTTPAP GPPPPPPPPA PPQPQPPPAP PPNPTTPSHP
60 70 80 90 100
ESADEPGPRA RLCSRDSACT PGAAKGGANG ECGRGEPQCS PEGPARGPKV
110 120 130 140 150
SFSCRGAASG PSAAEEAGSE EAGPAGEPRG SQASFLQRQF GALLQPGVNK
160 170 180 190 200
FSLRMFGSQK AVEREQERVK SAGAWIIHPY SDFRFYWDFT MLLFMVGNLI
210 220 230 240 250
IIPVGITFFK DETTAPWIVF NVVSDTFFLM DLVLNFRTGI VIEDNTEIIL
260 270 280 290 300
DPEKIKKKYL RTWFVVDFVS SIPVDYIFLI VEKGIDSEVY KTARALRIVR
310 320 330 340 350
FTKILSLLRL LRLSRLIRYI HQWEEIFHMT YDLASAVMRI CNLISMMLLL
360 370 380 390 400
CHWDGCLQFL VPMLQDFPSD CWVSINNMVN HSWSELYSFA LFKAMSHMLC
410 420 430 440 450
IGYGRQAPES MTDIWLTMLS MIVGATCYAM FIGHATALIQ SLDSSRRQYQ
460 470 480 490 500
EKYKQVEQYM SFHKLPADFR QKIHDYYEHR YQGKMFDEDS ILGELNGPLR
510 520 530 540 550
EEIVNFNCRK LVASMPLFAN ADPNFVTAML TKLKFEVFQP GDYIIREGTI
560 570 580 590 600
GKKMYFIQHG VVSVLTKGNK EMKLSDGSYF GEICLLTRGR RTASVRADTY
610 620 630 640 650
CRLYSLSVDN FNEVLEEYPM MRRAFETVAI DRLDRIGKKN SILLHKVQHD
660 670 680 690 700
LSSGVFNNQE NAIIQEIVKY DREMVQQAEL GQRVGLFPPP PPPQVTSAIA
710 720 730 740 750
TLQQAVAMSF CPQVARPLVG PLALGSPRLV RRAPPGPLPP AASPGPPAAS
760 770 780 790 800
PPAAPSSPRA PRTSPYGVPG SPATRVGPAL PARRLSRASR PLSASQPSLP
810 820 830 840 850
HGVPAPSPAA SARPASSSTP RLGPAPTART AAPSPDRRDS ASPGAASGLD
860
PLDSARSRLS SNL
Length:863
Mass (Da):94,722
Last modified:November 1, 1998 - v1
Checksum:i17CDC4DFF07AC039
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti486F → S in AAC40125 (PubMed:9630217).Curated1
Sequence conflicti642I → T in AAC40125 (PubMed:9630217).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ225122 mRNA. Translation: CAA12406.1.
AF064873 mRNA. Translation: AAC40125.1.
CCDSiCCDS23986.1.
RefSeqiNP_032252.1. NM_008226.2.
UniGeneiMm.12956.

Genome annotation databases

EnsembliENSMUST00000020581; ENSMUSP00000020581; ENSMUSG00000020331.
ENSMUST00000099513; ENSMUSP00000097113; ENSMUSG00000020331.
GeneIDi15166.
KEGGimmu:15166.
UCSCiuc007fzn.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ225122 mRNA. Translation: CAA12406.1.
AF064873 mRNA. Translation: AAC40125.1.
CCDSiCCDS23986.1.
RefSeqiNP_032252.1. NM_008226.2.
UniGeneiMm.12956.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1Q3EX-ray1.90A/B443-645[»]
1Q43X-ray2.00A/B443-645[»]
1Q5OX-ray2.30A443-645[»]
2Q0AX-ray2.25A/B443-640[»]
3BPZX-ray1.65A/B/C/D443-640[»]
3ETQX-ray1.90A/B443-640[»]
3FFQX-ray2.40A/B443-640[»]
4EQFX-ray3.00B857-863[»]
5KHGX-ray2.24A443-643[»]
5KHHX-ray1.77A443-643[»]
5KHIX-ray2.10A443-643[»]
5KHJX-ray2.01A/B443-643[»]
5KHKX-ray2.07A443-643[»]
ProteinModelPortaliO88703.
SMRiO88703.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200253. 1 interactor.
DIPiDIP-29326N.
IntActiO88703. 3 interactors.
MINTiMINT-155013.
STRINGi10090.ENSMUSP00000020581.

Chemistry databases

BindingDBiO88703.
ChEMBLiCHEMBL1250408.
GuidetoPHARMACOLOGYi401.

PTM databases

iPTMnetiO88703.
PhosphoSitePlusiO88703.
SwissPalmiO88703.

Proteomic databases

MaxQBiO88703.
PaxDbiO88703.
PRIDEiO88703.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000020581; ENSMUSP00000020581; ENSMUSG00000020331.
ENSMUST00000099513; ENSMUSP00000097113; ENSMUSG00000020331.
GeneIDi15166.
KEGGimmu:15166.
UCSCiuc007fzn.1. mouse.

Organism-specific databases

CTDi610.
MGIiMGI:1298210. Hcn2.

Phylogenomic databases

eggNOGiKOG0498. Eukaryota.
ENOG410XPSE. LUCA.
GeneTreeiENSGT00760000118772.
HOGENOMiHOG000230717.
HOVERGENiHBG039489.
InParanoidiO88703.
KOiK04955.
OMAiAMSFCPP.
OrthoDBiEOG091G0JQU.
PhylomeDBiO88703.
TreeFamiTF318250.

Enzyme and pathway databases

ReactomeiR-MMU-1296061. HCN channels.

Miscellaneous databases

EvolutionaryTraceiO88703.
PROiO88703.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020331.
GenevisibleiO88703. MM.

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]
ProtoNetiSearch...

Entry informationi

Entry nameiHCN2_MOUSE
AccessioniPrimary (citable) accession number: O88703
Secondary accession number(s): O70506
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: November 1, 1998
Last modified: November 30, 2016
This is version 150 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.