Q9JKB0

EV
Gene name
Hcn1
Protein name
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
Names
Species
Homo sapiens (Human)
KEGG Pathway
rno:84390
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)

390-463 (C-terminal intracellular region) SS

Target domain

132-391 (Ion transport domain)

Relief mechanism

Ligand binding

Assay

464-579 (CBD domain) SS

Target domain

132-391 (Ion transport domain)

Relief mechanism

Ligand binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for Q9JKB0

Entry ID Method Resolution Chain Position Source
AF-Q9JKB0-F1 Predicted AlphaFoldDB

No variants for Q9JKB0

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q9JKB0

No associated diseases with Q9JKB0

5 regional properties for Q9JKB0

Type Name Position InterPro Accession
domain VHS domain 8 - 147 IPR002014
domain GAT domain 171 - 300 IPR004152
domain Clathrin adaptor, alpha/beta/gamma-adaptin, appendage, Ig-like subdomain 507 - 631 IPR008152
domain Gamma-adaptin ear (GAE) domain 510 - 631 IPR008153
domain N-terminal extension of GAT domain 169 - 207 IPR041198

Functions

Description
EC Number
Subcellular Localization
  • Cell membrane ; Multi-pass membrane protein
PANTHER Family PTHR45689 I[[H]] CHANNEL, ISOFORM E
PANTHER Subfamily PTHR45689:SF4 POTASSIUM_SODIUM HYPERPOLARIZATION-ACTIVATED CYCLIC NUCLEOTIDE-GATED CHANNEL 4
PANTHER Protein Class ion channel
transporter
PANTHER Pathway Category No pathway information available

15 GO annotations of cellular component

Name Definition
apical dendrite A dendrite that emerges near the apical pole of a neuron. In bipolar neurons, apical dendrites are located on the opposite side of the soma from the axon.
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.
axon terminus 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 button is a specialized region of it.
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.
cell surface The external part of the cell wall and/or plasma membrane.
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.
glutamatergic synapse A synapse that uses glutamate as a neurotransmitter.
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.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
postsynaptic membrane A specialized area of membrane facing the presynaptic membrane on the tip of the nerve ending and separated from it by a minute cleft (the synaptic cleft). Neurotransmitters cross the synaptic cleft and transmit the signal to the postsynaptic membrane.
presynaptic active zone membrane The membrane portion of the presynaptic active zone; it is the site where docking and fusion of synaptic vesicles occurs for the release of neurotransmitters.
somatodendritic compartment The region of a neuron that includes the cell body (cell soma) and dendrite(s), but excludes the axon.

9 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 involved in regulation of presynaptic membrane potential 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, to regulate the presynaptic membrane potential.
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.
phosphatidylinositol-3,4,5-trisphosphate binding Binding to phosphatidylinositol-3,4,5-trisphosphate, a derivative of phosphatidylinositol in which the inositol ring is phosphorylated at the 3', 4' and 5' positions.
phosphatidylinositol-4,5-bisphosphate binding Binding to phosphatidylinositol-4,5-bisphosphate, a derivative of phosphatidylinositol in which the inositol ring is phosphorylated at the 4' and 5' positions.
voltage-gated monoatomic cation channel activity Enables the transmembrane transfer of a cation by a voltage-gated channel. A cation is a positively charged ion. 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 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.

18 GO annotations of biological process

Name Definition
apical protein localization Any process in which a protein is transported to, or maintained in, apical regions of the cell.
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 interferon-beta 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 interferon-beta stimulus. Interferon-beta is a type I interferon.
general adaptation syndrome, behavioral process The set of behavioral processes that occur as part of the general adaptation syndrome, the response of the body to a strong, stressful stimulus.
maternal behavior Female behaviors associated with the care and rearing of offspring.
negative regulation of action potential Any process that stops, prevents, or reduces the frequency, rate or extent of action potential creation, propagation or termination. This typically occurs via modulation of the activity or expression of voltage-gated ion channels.
neuronal action potential An action potential that occurs in a neuron.
positive regulation of membrane hyperpolarization Any process that activates or increases the frequency, rate or extent of membrane hyperpolarization.
potassium ion transmembrane transport A process in which a potassium ion is transported from one side of a membrane to the other.
protein homotetramerization The formation of a protein homotetramer, a macromolecular structure consisting of four noncovalently associated identical subunits.
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 hyperpolarization Any process that modulates the frequency, rate or extent of membrane hyperpolarization.
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 postsynaptic membrane potential Any process that modulates the potential difference across a post-synaptic membrane.
response to calcium ion 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 calcium ion stimulus.
response to L-glutamate 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 an L-glutamate stimulus.
retinal cone cell development Development of a cone cell, one of the sensory cells in the eye that reacts to the presence of light. Cone cells contain the photopigment iodopsin or cyanopsin and are responsible for photopic (daylight) vision.
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
Q9Y3Q4 HCN4 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 Homo sapiens (Human) EV
Q9P1Z3 HCN3 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 Homo sapiens (Human) SS
O60741 HCN1 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 Homo sapiens (Human) 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
O88704 Hcn1 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 Mus musculus (Mouse) 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
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
MDKLPPSMRK RLYSLPQQVG AKAWIMDEEE DAEEEGAGGR QDPSRRSIRL RPLPSPSPSA
70 80 90 100 110 120
AAGGTESRSS ALGAADSEGP ARGAGKSSTN GDCRRFRGSL ASLGSRGGGS GGTGSGSSHG
130 140 150 160 170 180
HLHDSAEERR LIAEGDASPG EDRTPPGLAA EPERPGASAQ PAASPPPPQQ PPQPASASCE
190 200 210 220 230 240
QPSVDTAIKV EGGAAAGDQI LPEAEVRLGQ AGFMQRQFGA MLQPGVNKFS LRMFGSQKAV
250 260 270 280 290 300
EREQERVKSA GFWIIHPYSD FRFYWDLTML LLMVGNLIII PVGITFFKDE NTTPWIVFNV
310 320 330 340 350 360
VSDTFFLIDL VLNFRTGIVV EDNTEIILDP QRIKMKYLKS WFMVDFISSI PVDYIFLIVE
370 380 390 400 410 420
TRIDSEVYKT ARALRIVRFT KILSLLRLLR LSRLIRYIHQ WEEIFHMTYD LASAVVRIVN
430 440 450 460 470 480
LIGMMLLLCH WDGCLQFLVP MLQDFPDDCW VSINNMVNNS 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 IIQQIVQHDR EMAHCAHRVQ AAASATPTPT PVIWTPLIQA
790 800 810 820 830 840
PLQAAAATTS VAIALTHHPR LPAAIFRPPP GSGLGNLGAG QTPRHLKRLQ SLIPSALGSA
850 860 870 880 890 900
SPASSPSQVD TPSSSSFHIQ QLAGFSAPAG LSPLLPSSSS SPPPGACGSP SAPTPSAGVA
910 920 930 940 950 960
ATTIAGFGHF HKALGGSLSS SDSPLLTPLQ PGARSPQAAQ PSPAPPGARG GLGLPEHFLP
970 980 990 1000 1010 1020
PPPSSRSPSS SPGQLGQPPG ELSLGLATGP LSTPETPPRQ PEPPSLVAGA SGGASPVGFT
1030 1040 1050 1060 1070 1080
PRGGLSPPGH SPGPPRTFPS APPRASGSHG SLLLPPASSP PPPQVPQRRG TPPLTPGRLT
1090 1100 1110 1120 1130 1140
QDLKLISASQ PALPQDGAQT LRRASPHSSG ESMAAFPLFP RAGGGSGGSG SSGGLGPPGR
1150 1160 1170 1180 1190 1200
PYGAIPGQHV TLPRKTSSGS LPPPLSLFGA RATSSGGPPL TAGPQREPGA RPEPVRSKLP
SNL