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Protein

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

Gene

Hcn2

Organism
Rattus norvegicus (Rat)
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.1 Publication

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 (By similarity).By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi581 – 584cAMPBy similarity4
Nucleotide bindingi591 – 592cAMPBy similarity2
Nucleotide bindingi632 – 635cAMPBy similarity4

GO - Molecular functioni

  • cAMP binding Source: UniProtKB-KW
  • intracellular cAMP activated cation channel activity Source: UniProtKB
  • PDZ domain binding Source: RGD
  • protein complex binding Source: RGD
  • protein complex scaffold Source: RGD
  • sodium channel activity Source: UniProtKB-KW
  • voltage-gated potassium channel activity Source: UniProtKB

GO - Biological processi

  • aging Source: RGD
  • brain development Source: RGD
  • cellular response to aldosterone Source: RGD
  • cellular response to cAMP Source: UniProtKB
  • inflammatory response Source: RGD
  • positive regulation of heart contraction Source: RGD
  • potassium ion transmembrane transport Source: UniProtKB
  • regulation of membrane potential Source: GO_Central
  • response to cisplatin Source: RGD
  • response to drug Source: RGD
  • response to hormone 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

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2
Gene namesi
Name:Hcn2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620689. 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

  • axon Source: RGD
  • cytoplasm Source: RGD
  • dendrite membrane Source: RGD
  • dendritic shaft Source: RGD
  • integral component of plasma membrane Source: UniProtKB
  • membrane Source: RGD
  • neuronal cell body Source: RGD
  • plasma membrane Source: RGD
  • somatodendritic compartment Source: RGD
  • synapse Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000541131 – 863Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2Add BLAST863

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei119PhosphoserineCombined sources1
Modified residuei134PhosphoserineCombined sources1
Glycosylationi380N-linked (GlcNAc...)Sequence analysis1
Modified residuei641Phosphoserine; by PKG/PRKG2By similarity1
Modified residuei726PhosphoserineCombined sources1
Modified residuei728Omega-N-methylarginineBy similarity1
Modified residuei743PhosphoserineBy similarity1
Modified residuei750PhosphoserineCombined sources1
Modified residuei757PhosphoserineBy similarity1
Modified residuei840PhosphoserineBy similarity1
Modified residuei842PhosphoserineCombined sources1
Modified residuei847PhosphoserineBy similarity1

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.By similarity

Keywords - PTMi

Glycoprotein, Methylation, Phosphoprotein

Proteomic databases

PaxDbiQ9JKA9.
PRIDEiQ9JKA9.

PTM databases

iPTMnetiQ9JKA9.
PhosphoSitePlusiQ9JKA9.

Expressioni

Tissue specificityi

Highly expressed in neonatal and adult ventricle and in brain. Highly expressed in the pyramidal layer in hippocampus, in anterior dorsal nucleus in thalamus, in the mammillary nucleus in hypothalamus, in red nucleus, in trigeminal mesencephalic, spinal and principal nuclei, in cochlear and trapezoid nuclei and in the dorsal tegemental nucleus.1 Publication

Inductioni

By thyroid hormones in hypothyroid animals.1 Publication

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 (By similarity).By similarity

GO - Molecular functioni

  • PDZ domain binding Source: RGD
  • protein complex binding Source: RGD
  • protein complex scaffold Source: RGD

Protein-protein interaction databases

BioGridi250321. 1 interactor.
STRINGi10116.ENSRNOP00000011837.

Structurei

3D structure databases

ProteinModelPortaliQ9JKA9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

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

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi31 – 58Pro-richAdd BLAST28
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.
HOGENOMiHOG000230717.
HOVERGENiHBG039489.
InParanoidiQ9JKA9.
KOiK04955.
PhylomeDBiQ9JKA9.

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.

Q9JKA9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDARGGGGRP GDSPGTTPAP GPPPPPPPPA PLQLQPPPAP PPNPTTPSHP
60 70 80 90 100
ESADEPGPRS RLCSRDSSCT PGAAKGGANG ECGRGEPQCS PEGPARGPKV
110 120 130 140 150
SFSCRGAASG PAAAEEAGSE 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 GQRVGFFPPP PPRQVRSAIA
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
HGAPAPSPAA SARPASSSTP RLGPAPTTRT AAPSPDRRDS ASPGAASGLD
860
PLDSARSRLS SNL
Length:863
Mass (Da):94,920
Last modified:December 6, 2005 - v3
Checksum:i4EF55435C2384A26
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti16T → A in BAD32628 (PubMed:15265006).Curated1
Sequence conflicti32 – 34LQL → PQP in BAD32628 (PubMed:15265006).Curated3
Sequence conflicti686F → L in BAD32628 (PubMed:15265006).Curated1
Sequence conflicti693R → P in BAD32628 (PubMed:15265006).Curated1
Sequence conflicti696R → T in BAD32628 (PubMed:15265006).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB164197 mRNA. Translation: BAD32628.1.
AF247451 mRNA. Translation: AAF62174.1.
AF155164 mRNA. Translation: AAF01491.1.
RefSeqiNP_446136.1. NM_053684.1.
UniGeneiRn.162907.

Genome annotation databases

GeneIDi114244.
KEGGirno:114244.
UCSCiRGD:620689. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB164197 mRNA. Translation: BAD32628.1.
AF247451 mRNA. Translation: AAF62174.1.
AF155164 mRNA. Translation: AAF01491.1.
RefSeqiNP_446136.1. NM_053684.1.
UniGeneiRn.162907.

3D structure databases

ProteinModelPortaliQ9JKA9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi250321. 1 interactor.
STRINGi10116.ENSRNOP00000011837.

PTM databases

iPTMnetiQ9JKA9.
PhosphoSitePlusiQ9JKA9.

Proteomic databases

PaxDbiQ9JKA9.
PRIDEiQ9JKA9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi114244.
KEGGirno:114244.
UCSCiRGD:620689. rat.

Organism-specific databases

CTDi610.
RGDi620689. Hcn2.

Phylogenomic databases

eggNOGiKOG0498. Eukaryota.
ENOG410XPSE. LUCA.
HOGENOMiHOG000230717.
HOVERGENiHBG039489.
InParanoidiQ9JKA9.
KOiK04955.
PhylomeDBiQ9JKA9.

Miscellaneous databases

PROiQ9JKA9.

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_RAT
AccessioniPrimary (citable) accession number: Q9JKA9
Secondary accession number(s): Q6BCT5, Q9QZW6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: December 6, 2005
Last modified: November 2, 2016
This is version 126 of the entry and version 3 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.