O88705

SS
Gene name
Hcn3 (Hac3)
Protein name
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3
Names
Hyperpolarization-activated cation channel 3 , HAC-3
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:15168
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)

353-426 (C-terminal intracellular region) SS

Target domain

93-354 (Ion transport domain)

Relief mechanism

Ligand binding

Assay

427-542 (CBD domain) SS

Target domain

93-354 (Ion transport domain)

Relief mechanism

Ligand binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for O88705

Entry ID Method Resolution Chain Position Source
AF-O88705-F1 Predicted AlphaFoldDB

33 variants for O88705

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3388644665 110 L>M No EVA
rs3388629449 133 D>G No EVA
rs3388631523 186 F>S No EVA
rs228097029 251 F>V No EVA
rs3388645273 281 C>R No EVA
rs3388639283 290 N>D No EVA
rs3388635316 316 Q>* No EVA
rs3388643845 340 M>V No EVA
rs3388643857 377 A>V No EVA
rs3413089316 404 E>G No EVA
rs3388635776 404 E>K No EVA
rs3388635758 415 N>T No EVA
rs3388643880 437 T>I No EVA
rs3388645260 476 A>T No EVA
rs3388645256 498 R>Q No EVA
rs3388639230 519 D>N No EVA
rs3388629455 521 F>S No EVA
rs3388639274 527 E>D No EVA
rs3388634727 549 K>R No EVA
rs3388641726 567 G>D No EVA
rs3388639248 574 V>L No EVA
rs3388643840 575 Q>* No EVA
rs3388635736 576 H>R No EVA
rs3388635310 578 R>I No EVA
rs3388634726 579 D>G No EVA
rs3388639266 588 A>P No EVA
rs3388634783 645 A>T No EVA
rs3388642109 654 S>F No EVA
rs3388634786 656 L>V No EVA
rs3388642174 668 G>E No EVA
rs3388643884 673 T>A No EVA
rs3388643851 684 L>I No EVA
rs3388645244 717 L>F No EVA

No associated diseases with O88705

3 regional properties for O88705

Type Name Position InterPro Accession
domain Cyclic nucleotide-binding domain 427 - 540 IPR000595
domain Ion transport domain 93 - 355 IPR005821
domain Ion transport N-terminal 49 - 91 IPR013621

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

7 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.
cone cell pedicle A specialized axon terminus which is produced by retinal cone cells. Pedicles are large, conical, flat end-feet (8-10 micrometers diameter) of the retinal cone axon that lie more or less side by side on the same plane at the outer edge of the outer plexiform layer (OPL).
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.
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.

3 GO annotations of molecular function

Name Definition
cAMP binding Binding to cAMP, the nucleotide cyclic AMP (adenosine 3',5'-cyclophosphate).
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.

4 GO annotations of biological process

Name Definition
cellular response to dopamine 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 dopamine stimulus.
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.
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
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
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
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
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
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
MEEEARPAAG AGEAATPARE TPPAAPAQAR AASGGVPESA PEPKRRQLGT LLQPTVNKFS
70 80 90 100 110 120
LRVFGSHKAV EIEQERVKSA GAWIIHPYSD FRFYWDLIML LLMVGNLIVL PVGITFFKEE
130 140 150 160 170 180
NSPPWIVFNV LSDTFFLLDL VLNFRTGIVV EEGAEILLAP RAIRTRYLRT WFLVDLISSI
190 200 210 220 230 240
PVDYIFLVVE LEPRLDAEVY KTARALRIVR FTKILSLLRL LRLSRLIRYI HQWEEIFHMT
250 260 270 280 290 300
YDLASAVVRI FNLIGMMLLL CHWDGCLQFL VPMLQDFPSD CWVSMNRMVN HSWGRQYSHA
310 320 330 340 350 360
LFKAMSHMLC IGYGQQAPVG MPDVWLTMLS MIVGATCYAM FIGHATALIQ SLDSSRRQYQ
370 380 390 400 410 420
EKYKQVEQYM SFHKLPADTR QRIHEYYEHR YQGKMFDEES ILGELSEPLR EEIINFTCRG
430 440 450 460 470 480
LVAHMPLFAH ADPSFVTAVL TKLRFEVFQP GDLVVREGSV GRKMYFIQHG LLSVLARGAR
490 500 510 520 530 540
DTRLTDGSYF GEICLLTRGR RTASVRADTY CRLYSLSVDH FNAVLEEFPM MRRAFETVAM
550 560 570 580 590 600
DRLRRIGKKN SILQRKRSEP SPGSSGGVME QHLVQHDRDM ARGVRGLAPG TGARLSGKPV
610 620 630 640 650 660
LWEPLVHAPL QAAAVTSNVA IALTHQRGPL PLSPDSPATL LARSARRSAG SPASPLVPVR
670 680 690 700 710 720
AGPLLARGPW ASTSRLPAPP ARTLHASLSR TGRSQVSLLG PPPGGGARRL GPRGRPLSAS
730 740 750 760 770
QPSLPQRATG DGSPRRKGSG SERLPPSGLL AKPPGTVQPP RSSVPEPVTP RGPQISANM