Q9JKA7

SS
Gene name
Hcn4
Protein name
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4
Names
Species
Rattus norvegicus (Rat)
KEGG Pathway
rno:59266
EC number
Protein Class

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)

521-594 (C-terminal intracellular region) SS

Target domain

263-522 (Ion transport domain)

Relief mechanism

Ligand binding

Assay

595-710 (CBD domain) SS

Target domain

263-522 (Ion transport domain)

Relief mechanism

Ligand binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for Q9JKA7

Entry ID Method Resolution Chain Position Source
AF-Q9JKA7-F1 Predicted AlphaFoldDB

No variants for Q9JKA7

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q9JKA7

No associated diseases with Q9JKA7

4 regional properties for Q9JKA7

Type Name Position InterPro Accession
domain Cyclic nucleotide-binding domain 595 - 710 IPR000595
domain Ion transport domain 263 - 523 IPR005821
domain Ion transport N-terminal 219 - 261 IPR013621
conserved_site Cyclic nucleotide-binding, conserved site 622 - 638 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

8 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.
basolateral plasma membrane The region of the plasma membrane that includes the basal end and sides of the cell. Often used in reference to animal polarized epithelial membranes, where the basal membrane is the part attached to the extracellular matrix, or in plant cells, where the basal membrane is defined with respect to the zygotic axis.
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.
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.
neuronal cell body The portion of a neuron that includes the nucleus, but excludes cell projections such as axons and dendrites.
perinuclear region of cytoplasm Cytoplasm situated near, or occurring around, the nucleus.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
terminal bouton Terminal inflated portion of the axon, containing the specialized apparatus necessary to release neurotransmitters. The axon terminus is considered to be the whole region of thickening and the terminal bouton is a specialized region of it.

7 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.
potassium channel activity Enables the facilitated diffusion of a potassium ion (by an energy-independent process) involving passage through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism.
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 potassium channel activity involved in SA node cell action potential depolarization Enables the transmembrane transfer of a potassium ion by a voltage-gated channel through the plasma membrane of an SA node cardiac muscle cell contributing to the depolarization phase of an action potential. 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.

19 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.
in utero embryonic development The process whose specific outcome is the progression of the embryo in the uterus over time, from formation of the zygote in the oviduct, to birth. An example of this process is found in Mus musculus.
membrane depolarization during SA node cell action potential The process in which SA node cardiac muscle cell membrane potential changes in the depolarizing direction from the negative resting potential towards the positive membrane potential that will be the peak of the action potential.
modulation of chemical synaptic transmission Any process that modulates the frequency or amplitude of synaptic transmission, the process of communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. Amplitude, in this case, refers to the change in postsynaptic membrane potential due to a single instance of synaptic transmission.
monoatomic cation transport The directed movement of a monoatomic cation, into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. Monatomic cations (also called simple cations) are positively charged ions consisting of exactly one atom.
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 cardiac muscle cell action potential involved in regulation of contraction Any process that modulates the frequency, rate or extent of action potential creation, propagation or termination in a cardiac muscle cell contributing to the regulation of its contraction.
regulation of cardiac muscle contraction Any process that modulates the frequency, rate or extent of cardiac muscle contraction.
regulation of heart contraction Any process that modulates the frequency, rate or extent of heart contraction. Heart contraction is the process in which the heart decreases in volume in a characteristic way to propel blood through the body.
regulation of heart rate Any process that modulates the frequency or rate of heart contraction.
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.
SA node cell action potential An action potential that occurs in a sinoatrial node cardiac muscle cell.
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
Q9UL51 HCN2 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 Homo sapiens (Human) SS
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
Q9Y3Q4 HCN4 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 Homo sapiens (Human) EV
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
O88703 Hcn2 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 Mus musculus (Mouse) EV
O70507 Hcn4 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 Mus musculus (Mouse) SS
Q9JKB0 Hcn1 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 Rattus norvegicus (Rat) SS
Q9JKA9 Hcn2 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 Rattus norvegicus (Rat) SS
Q9JKA8 Hcn3 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 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
MDKLPPSMRK RLYSLPQQVG AKAWIMDEEE DGEEEGAGGL QDPSRRSIRL RPLPSPSPSV
70 80 90 100 110 120
AAGCSESRGA ALGAADSEGP GRSAGKSSTN GDCRRFRGSL ASLGSRGGGS GGAGGGSSLG
130 140 150 160 170 180
HLHDSAEERR LIAAEGDASP GEDRTPPGLA TEPERPGAAA QPAASPPPQQ PPQPASASCE
190 200 210 220 230 240
QPSADTAIKV EGGAAASDQI LPEAEVRLGQ SGFMQRQFGA MLQPGVNKFS LRMFGSQKAV
250 260 270 280 290 300
EREQERVKSA GFWIIHPYSD FRFYWDLTML LLMVGNLIII PVGITFFKDE NTTPWIVFNV
310 320 330 340 350 360
VSDTFFLIDL VLNFRTGIVV EDNTEIILDP QRIKMKYLKS WFVVDFISSI PVDYIFLIVE
370 380 390 400 410 420
TRIDSEVYKT ARALRIVRFT KILSLLRLLR LSRLIRYIHQ WEEIFHMTYD LASAVVRIVN
430 440 450 460 470 480
LIGMMLLLCH WDGCLQFLVP MLQDFPHDCW VSINGMVNNS WGKQYSYALF KAMSHMLCIG
490 500 510 520 530 540
YGRQAPVGMS DVWLTMLSMI VGATCYAMFI GHATALIQSL DSSRRQYQEK YKQVEQYMSF
550 560 570 580 590 600
HKLPPDTRQR IHDYYEHRYQ GKMFDEESIL GELSEPLREE IINFNCRKLV ASMPLFANAD
610 620 630 640 650 660
PNFVTSMLTK LRFEVFQPGD YIIREGTIGK KMYFIQHGVV SVLTKGNKET KLADGSYFGE
670 680 690 700 710 720
ICLLTRGRRT ASVRADTYCR LYSLSVDNFN EVLEEYPMMR RAFETVALDR LDRIGKKNSI
730 740 750 760 770 780
LLHKVQHDLN SGVFNYQENE IIQQIVRHDR EMAHCAHRVQ AAASATPTPT PVIWTPLIQA
790 800 810 820 830 840
PLQAAAATTS VAIALTHHPR LPAAIFRPPP GPGLGNLGAG QTPRHPRRLQ SLIPSALGSA
850 860 870 880 890 900
SPASSPSQVD TPSSSSFHIQ QLAGFSAPPG LSPLLPSSSS SPPPGACSSP PAPTPSTSTA
910 920 930 940 950 960
ATTTGFGHFH KALGGSLSSS DSPLLTPLQP GARSPQAAQP PPPLPGARGG LGLLEHFLPP
970 980 990 1000 1010 1020
PPSSRSPSSS PGQLGQPPGE LSPGLAAGPP STPETPPRPE RPSFMAGASG GASPVAFTPR
1030 1040 1050 1060 1070 1080
GGLSPPGHSP GPPRTFPSAP PRASGSHGSL LLPPASSPPP PQVPQRRGTP PLTPGRLTQD
1090 1100 1110 1120 1130 1140
LKLISASQPA LPQDGAQTLR RASPHSSGES MAAFSLYPRA GGGSGSSGGL GPPGRPYGAI
1150 1160 1170 1180 1190
PGQHVTLPRK TSSGSLPPPL SLFGARAASS GGPPLTAAPQ REPGARSEPV RSKLPSNL