O88704

SS
Gene name
Hcn1 (Bcng1, Hac2)
Protein name
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
Names
Brain cyclic nucleotide-gated channel 1 , BCNG-1 , Hyperpolarization-activated cation channel 2 , HAC-2
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:15165
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)

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

2 structures for O88704

Entry ID Method Resolution Chain Position Source
3U0Z X-ray 290 A A/B 390-592 PDB
AF-O88704-F1 Predicted AlphaFoldDB

28 variants for O88704

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3389277730 250 K>T No EVA
rs3389306683 256 R>L No EVA
rs3389287658 256 R>W No EVA
rs3389304327 260 L>R No EVA
rs3404480023 291 I>S No EVA
rs1132792937 332 K>N No EVA
rs1135268988 333 Q>H No EVA
rs1132593574 334 Y>N No EVA
rs1132997530 341 A>G No EVA
rs1134951338 342 M>V No EVA
rs1131865219 343 S>G No EVA
rs1134287979 345 M>K No EVA
rs3389232420 400 Y>H No EVA
rs3389262381 519 M>T No EVA
rs3389277737 535 K>N No EVA
rs3389306463 551 Y>F No EVA
rs3389270922 556 D>N No EVA
rs3389262417 564 E>D No EVA
rs3411154752 587 N>K No EVA
rs3389277692 606 Q>H No EVA
rs3389301974 623 Q>E No EVA
rs3389302019 628 I>N No EVA
rs3389270988 631 P>R No EVA
rs241512417 645 P>L No EVA
rs3389262353 673 S>N No EVA
rs3389271004 702 A>D No EVA
rs265986383 722 P>T No EVA
rs4230116 727 P>Q No EVA

No associated diseases with O88704

4 regional properties for O88704

Type Name Position InterPro Accession
domain Cyclic nucleotide-binding domain 464 - 580 IPR000595
domain Ion transport domain 132 - 392 IPR005821
domain Ion transport N-terminal 87 - 130 IPR013621
conserved_site Cyclic nucleotide-binding, conserved site 491 - 507 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

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.

14 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.
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.
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 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.
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
O88703 Hcn2 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 Mus musculus (Mouse) EV
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
Q9JKA9 Hcn2 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 Rattus norvegicus (Rat) SS
Q9JKA7 Hcn4 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 Rattus norvegicus (Rat) SS
Q9JKA8 Hcn3 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 Rattus norvegicus (Rat) SS
Q9JKB0 Hcn1 Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 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
MEGGGKPNSA SNSRDDGNSV FPSKAPATGP VAADKRLGTP PGGGAAGKEH GNSVCFKVDG
70 80 90 100 110 120
GGGEEPAGSF EDAEGPRRQY GFMQRQFTSM LQPGVNKFSL RMFGSQKAVE KEQERVKTAG
130 140 150 160 170 180
FWIIHPYSDF RFYWDLIMLI MMVGNLVIIP VGITFFTEQT TTPWIIFNVA SDTVFLLDLI
190 200 210 220 230 240
MNFRTGTVNE DSSEIILDPK VIKMNYLKSW FVVDFISSIP VDYIFLIVEK GMDSEVYKTA
250 260 270 280 290 300
RALRIVRFTK ILSLLRLLRL SRLIRYIHQW EEIFHMTYDL ASAVVRIFNL IGMMLLLCHW
310 320 330 340 350 360
DGCLQFLVPL LQDFPPDCWV SLNEMVNDSW GKQYSYALFK AMSHMLCIGY GAQAPVSMSD
370 380 390 400 410 420
LWITMLSMIV GATCYAMFVG HATALIQSLD SSRRQYQEKY KQVEQYMSFH KLPADMRQKI
430 440 450 460 470 480
HDYYEHRYQG KIFDEENILS ELNDPLREEI VNFNCRKLVA TMPLFANADP NFVTAMLSKL
490 500 510 520 530 540
RFEVFQPGDY IIREGAVGKK MYFIQHGVAG VITKSSKEMK LTDGSYFGEI CLLTKGRRTA
550 560 570 580 590 600
SVRADTYCRL YSLSVDNFNE VLEEYPMMRR AFETVAIDRL DRIGKKNSIL LQKFQKDLNT
610 620 630 640 650 660
GVFNNQENEI LKQIVKHDRE MVQAIPPINY PQMTALNCTS STTTPTSRMR TQSPPVYTAT
670 680 690 700 710 720
SLSHSNLHSP SPSTQTPQPS AILSPCSYTT AVCSPPIQSP LATRTFHYAS PTASQLSLMQ
730 740 750 760 770 780
QPQQQLPQSQ VQQTQTQTQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQPQTPG
790 800 810 820 830 840
SSTPKNEVHK STQALHNTNL TKEVRPLSAS QPSLPHEVST LISRPHPTVG ESLASIPQPV
850 860 870 880 890 900
AAVHSTGLQA GSRSTVPQRV TLFRQMSSGA IPPNRGVPPA PPPPAAVQRE SPSVLNTDPD
AEKPRFASNL