O88703

EV
Gene name
Hcn2 (Bcng2, Hac1)
Protein name
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2
Names
Brain cyclic nucleotide-gated channel 2, BCNG-2, Hyperpolarization-activated cation channel 1, HAC-1
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:15166
EC number
Protein Class
I[[H]] CHANNEL, ISOFORM E (PTHR45689)

Descriptions

Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels contribute to electrical activity in neurons and cardiomyocytes. HCN1-4 share a similar multidomain organization with an N-terminal transmembrane region, a C-terminal intracellular region (IR) and a cyclic nucleotide-binding domain (CBD). Channel opening is primarily stimulated by transmembrane elements that sense membrane hyperpolarization. In the absence of cAMP, the CBD shows steric clashes with the C-linker within IR, which become energetically unfavored. The steric clashes are eliminated by cAMP binding, which selects for a CBD state devoid of steric clashes with the tetrameric C-linker and facilitates channel opening.

Autoinhibitory domains (AIDs)

517-630 (CBD domain) EV

Target domain

184-444 (Ion transport domain)

Relief mechanism

Ligand binding

Assay

Structural analysis, Deletion assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

15 structures for O88703

Entry ID Method Resolution Chain Position Source
1Q3E X-ray 190 A A/B 443-645 PDB
1Q43 X-ray 200 A A/B 443-645 PDB
1Q5O X-ray 230 A A 443-645 PDB
2Q0A X-ray 225 A A/B 443-640 PDB
3BPZ X-ray 165 A A/B/C/D 443-640 PDB
3ETQ X-ray 190 A A/B 443-640 PDB
3FFQ X-ray 240 A A/B 443-640 PDB
4EQF X-ray 300 A B 857-863 PDB
5JON X-ray 204 A A/B 494-640 PDB
5KHG X-ray 224 A A 443-643 PDB
5KHH X-ray 177 A A 443-643 PDB
5KHI X-ray 210 A A 443-643 PDB
5KHJ X-ray 201 A A/B 443-643 PDB
5KHK X-ray 207 A A 443-643 PDB
AF-O88703-F1 Predicted AlphaFoldDB

17 variants for O88703

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3401373082 68 A>T No EVA
rs262363805 112 S>A No EVA
rs3389118299 243 E>D No EVA
rs227492782 260 L>V No EVA
rs247436022 261 R>C No EVA
rs3401625051 265 V>M No EVA
rs3389086224 327 F>I No EVA
rs3389110610 372 W>S No EVA
rs3389077710 373 V>M No EVA
rs3401127974 377 N>S No EVA
rs3400726796 401 I>M No EVA
rs3401454335 401 I>S No EVA
rs3389111522 468 D>H No EVA
rs3400979555 564 V>A No EVA
rs3401454336 564 V>M No EVA
rs3389114256 637 G>R No EVA
rs234251627 742 A>V No EVA

No associated diseases with O88703

4 regional properties for O88703

Type Name Position InterPro Accession
domain Cyclic nucleotide-binding domain 517 - 630 IPR000595
domain Ion transport domain 185 - 444 IPR005821
domain Ion transport N-terminal 141 - 183 IPR013621
conserved_site Cyclic nucleotide-binding, conserved site 544 - 560 IPR018488

Functions

Description
EC Number
Subcellular Localization
  • Cell membrane ; Multi-pass membrane protein
PANTHER Family PTHR45689 I[[H]] CHANNEL, ISOFORM E
PANTHER Subfamily PTHR45689:SF11 POTASSIUM_SODIUM HYPERPOLARIZATION-ACTIVATED CYCLIC NUCLEOTIDE-GATED CHANNEL 2
PANTHER Protein Class ion channel
transporter
PANTHER Pathway Category No pathway information available

12 GO annotations of cellular component

Name Definition
axon The long process of a neuron that conducts nerve impulses, usually away from the cell body to the terminals and varicosities, which are sites of storage and release of neurotransmitter.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
dendrite A neuron projection that has a short, tapering, morphology. Dendrites receive and integrate signals from other neurons or from sensory stimuli, and conduct nerve impulses towards the axon or the cell body. In most neurons, the impulse is conveyed from dendrites to axon via the cell body, but in some types of unipolar neuron, the impulse does not travel via the cell body.
dendrite membrane The portion of the plasma membrane surrounding a dendrite.
dendritic shaft Cylindric portion of the dendrite, directly stemming from the perikaryon, and carrying the dendritic spines.
HCN channel complex A cation ion channel with a preference for K+ over Na+ ions, which is activated by membrane hyperpolarization, and consists of a tetramer of HCN family members. Some members of this family (HCN1, HCN2 and HCN4) are also activated when cAMP binds to their cyclic nucleotide binding domain (CNBD). Channel complexes of this family play an important role in the control of pacemaker activity in the heart.
integral component of plasma membrane The component of the plasma membrane consisting of the gene products and protein complexes having at least some part of their peptide sequence embedded in the hydrophobic region of the membrane.
membrane A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it.
neuronal cell body The portion of a neuron that includes the nucleus, but excludes cell projections such as axons and dendrites.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
somatodendritic compartment The region of a neuron that includes the cell body (cell soma) and dendrite(s), but excludes the axon.
synapse The junction between an axon of one neuron and a dendrite of another neuron, a muscle fiber or a glial cell. As the axon approaches the synapse it enlarges into a specialized structure, the presynaptic terminal bouton, which contains mitochondria and synaptic vesicles. At the tip of the terminal bouton is the presynaptic membrane; facing it, and separated from it by a minute cleft (the synaptic cleft) is a specialized area of membrane on the receiving cell, known as the postsynaptic membrane. In response to the arrival of nerve impulses, the presynaptic terminal bouton secretes molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane.

8 GO annotations of molecular function

Name Definition
cAMP binding Binding to cAMP, the nucleotide cyclic AMP (adenosine 3',5'-cyclophosphate).
identical protein binding Binding to an identical protein or proteins.
intracellular cAMP-activated cation channel activity Enables the transmembrane transfer of a cation by a channel that opens when intracellular cAMP has been bound by the channel complex or one of its constituent parts.
molecular adaptor activity The binding activity of a molecule that brings together two or more molecules through a selective, non-covalent, often stoichiometric interaction, permitting those molecules to function in a coordinated way.
PDZ domain binding Binding to a PDZ domain of a protein, a domain found in diverse signaling proteins.
protein-containing complex binding Binding to a macromolecular complex.
voltage-gated potassium channel activity Enables the transmembrane transfer of a potassium ion by a voltage-gated channel. A voltage-gated channel is a channel whose open state is dependent on the voltage across the membrane in which it is embedded.
voltage-gated sodium channel activity Enables the transmembrane transfer of a sodium ion by a voltage-gated channel. A voltage-gated channel is a channel whose open state is dependent on the voltage across the membrane in which it is embedded.

11 GO annotations of biological process

Name Definition
cellular response to cAMP Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cAMP (cyclic AMP, adenosine 3',5'-cyclophosphate) stimulus.
cellular response to cGMP Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cGMP (cyclic GMP, guanosine 3',5'-cyclophosphate) stimulus.
potassium ion import across plasma membrane The directed movement of potassium ions from outside of a cell, across the plasma membrane and into the cytosol.
potassium ion transmembrane transport A process in which a potassium ion is transported from one side of a membrane to the other.
regulation of cation channel activity Any process that modulates the frequency, rate or extent of cation channel activity.
regulation of heart rate by cardiac conduction A cardiac conduction process that modulates the frequency or rate of heart contraction.
regulation of membrane depolarization Any process that modulates the rate, frequency or extent of membrane depolarization. Membrane depolarization is the process in which membrane potential changes in the depolarizing direction from the resting potential, usually from negative to positive.
regulation of membrane potential Any process that modulates the establishment or extent of a membrane potential, the electric potential existing across any membrane arising from charges in the membrane itself and from the charges present in the media on either side of the membrane.
regulation of SA node cell action potential Any process that modulates the frequency, rate or extent of action potential creation, propagation or termination in an SA node cardiac myocyte. This typically occurs via modulation of the activity or expression of voltage-gated ion channels.
sodium ion import across plasma membrane The directed movement of sodium ions from outside of a cell, across the plasma membrane and into the cytosol.
sodium ion transmembrane transport A process in which a sodium ion is transported from one side of a membrane to the other by means of some agent such as a transporter or pore.

18 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q9Y3Q4 HCN4 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 Homo sapiens (Human) EV
O60741 HCN1 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 Homo sapiens (Human) SS
Q9P1Z3 HCN3 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 Homo sapiens (Human) SS
Q9UL51 HCN2 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 Homo sapiens (Human) SS
O88704 Hcn1 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 Mus musculus (Mouse) SS
O88705 Hcn3 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 Mus musculus (Mouse) SS
O70507 Hcn4 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 Mus musculus (Mouse) SS
Q9JKA7 Hcn4 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 Rattus norvegicus (Rat) SS
Q9JKB0 Hcn1 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 Rattus norvegicus (Rat) SS
Q9JKA8 Hcn3 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 Rattus norvegicus (Rat) SS
Q9JKA9 Hcn2 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 Rattus norvegicus (Rat) SS
A2ZX97 Os01g0718700 Potassium channel KAT6 Oryza sativa subsp japonica (Rice) PR
Q6K3T2 Os02g0245800 Potassium channel KAT1 Oryza sativa subsp japonica (Rice) PR
Q9SKD7 CNGC3 Probable cyclic nucleotide-gated ion channel 3 Arabidopsis thaliana (Mouse-ear cress) PR
Q9LDR2 CNGC19 Putative cyclic nucleotide-gated ion channel 19 Arabidopsis thaliana (Mouse-ear cress) PR
Q9SU64 CNGC16 Probable cyclic nucleotide-gated ion channel 16 Arabidopsis thaliana (Mouse-ear cress) PR
P92960 ATHB-4 Potassium channel KAT3 Arabidopsis thaliana (Mouse-ear cress) PR
Q39128 KAT1 Potassium channel KAT1 Arabidopsis thaliana (Mouse-ear cress) PR
10 20 30 40 50 60
MDARGGGGRP GDSPGTTPAP GPPPPPPPPA PPQPQPPPAP PPNPTTPSHP ESADEPGPRA
70 80 90 100 110 120
RLCSRDSACT PGAAKGGANG ECGRGEPQCS PEGPARGPKV SFSCRGAASG PSAAEEAGSE
130 140 150 160 170 180
EAGPAGEPRG SQASFLQRQF GALLQPGVNK FSLRMFGSQK AVEREQERVK SAGAWIIHPY
190 200 210 220 230 240
SDFRFYWDFT MLLFMVGNLI IIPVGITFFK DETTAPWIVF NVVSDTFFLM DLVLNFRTGI
250 260 270 280 290 300
VIEDNTEIIL DPEKIKKKYL RTWFVVDFVS SIPVDYIFLI VEKGIDSEVY KTARALRIVR
310 320 330 340 350 360
FTKILSLLRL LRLSRLIRYI HQWEEIFHMT YDLASAVMRI CNLISMMLLL CHWDGCLQFL
370 380 390 400 410 420
VPMLQDFPSD CWVSINNMVN HSWSELYSFA LFKAMSHMLC IGYGRQAPES MTDIWLTMLS
430 440 450 460 470 480
MIVGATCYAM FIGHATALIQ SLDSSRRQYQ EKYKQVEQYM SFHKLPADFR QKIHDYYEHR
490 500 510 520 530 540
YQGKMFDEDS ILGELNGPLR EEIVNFNCRK LVASMPLFAN ADPNFVTAML TKLKFEVFQP
550 560 570 580 590 600
GDYIIREGTI GKKMYFIQHG VVSVLTKGNK EMKLSDGSYF GEICLLTRGR RTASVRADTY
610 620 630 640 650 660
CRLYSLSVDN FNEVLEEYPM MRRAFETVAI DRLDRIGKKN SILLHKVQHD LSSGVFNNQE
670 680 690 700 710 720
NAIIQEIVKY DREMVQQAEL GQRVGLFPPP PPPQVTSAIA TLQQAVAMSF CPQVARPLVG
730 740 750 760 770 780
PLALGSPRLV RRAPPGPLPP AASPGPPAAS PPAAPSSPRA PRTSPYGVPG SPATRVGPAL
790 800 810 820 830 840
PARRLSRASR PLSASQPSLP HGVPAPSPAA SARPASSSTP RLGPAPTART AAPSPDRRDS
850 860
ASPGAASGLD PLDSARSRLS SNL