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)

Target domain

185-444 (Ion transport domain)

Relief mechanism

Ligand binding

Assay

Target domain

185-444 (Ion transport domain)

Relief mechanism

Ligand binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for Q9JKA9

Entry ID Method Resolution Chain Position Source
AF-Q9JKA9-F1 Predicted AlphaFoldDB

No variants for Q9JKA9

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q9JKA9

No associated diseases with Q9JKA9

4 regional properties for Q9JKA9

Type Name Position InterPro Accession
domain Cyclic nucleotide-binding domain 517 - 630 IPR000595
domain Ion transport domain 185 - 445 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
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

9 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.
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.
membrane A lipid bilayer along with all the proteins and protein complexes embedded in it and 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.

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.
intracellularly 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 aldosterone 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 an aldosterone stimulus.
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 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.
response to hormone Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hormone stimulus.
response to xenobiotic stimulus Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a xenobiotic, a compound foreign to the organim exposed to it. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical.
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
O88703 Hcn2 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 Mus musculus (Mouse) EV
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
Q9JKA7 Hcn4 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 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 PLQLQPPPAP PPNPTTPSHP ESADEPGPRS
70 80 90 100 110 120
RLCSRDSSCT PGAAKGGANG ECGRGEPQCS PEGPARGPKV SFSCRGAASG PAAAEEAGSE
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 GQRVGFFPPP PPRQVRSAIA TLQQAVAMSF CPQVARPLVG
730 740 750 760 770 780
PLALGSPRLV RRAPPGPLPP AASPGPPAAS PPAAPSSPRA PRTSPYGVPG SPATRVGPAL
790 800 810 820 830 840
PARRLSRASR PLSASQPSLP HGAPAPSPAA SARPASSSTP RLGPAPTTRT AAPSPDRRDS
850 860
ASPGAASGLD PLDSARSRLS SNL