Names & Taxonomy
- Uniprot ID:
- P16389
- Entry Name:
- KCNA2_HUMAN
- Status:
- reviewed
- Protein Names:
- Potassium voltage-gated channel subfamily A member 2 (NGK1) (Voltage-gated K(+) channel HuKIV) (Voltage-gated potassium channel HBK5) (Voltage-gated potassium channel subunit Kv1.2)
- Gene Names:
- KCNA2
- Gene Names Primary:
- KCNA2
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 499
- Sequence:
- MTVATGDPADEAAALPGHPQDTYDPEADHECCERVVINISGLRFETQLKTLAQFPETLLGDPKKRMRYFDPLRNEYFFDRNRPSFDAILYYYQSGGRLRRPVNVPLDIFSEEIRFYELGEEAMEMFREDEGYIKEEERPLPENEFQRQVWLLFEYPESSGPARIIAIVSVMVILISIVSFCLETLPIFRDENEDMHGSGVTFHTYSNSTIGYQQSTSFTDPFFIVETLCIIWFSFEFLVRFFACPSKAGFFTNIMNIIDIVAIIPYFITLGTELAEKPEDAQQGQQAMSLAILRVIRLVRVFRIFKLSRHSKGLQILGQTLKASMRELGLLIFFLFIGVILFSSAVYFAEADERESQFPSIPDAFWWAVVSMTTVGYGDMVPTTIGGKIVGSLCAIAGVLTIALPVPVIVSNFNYFYHRETEGEEQAQYLQVTSCPKIPSSPDLKKSRSASTISKSDYMEIQEGVNNSNEDFREENLKTANCTLANTNYVNITKMLTDV
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cell membrane
- Intramembrane:
- INTRAMEM 362 373 Helical; Name=Pore helix.
Function
- Function:
- Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the cardiovascular system. Prevents aberrant action potential firing and regulates neuronal output. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:19912772, PubMed:8495559, PubMed:11211111, PubMed:23769686). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:8495559, PubMed:20220134). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA2 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:19912772, PubMed:23769686). In contrast, a heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation (PubMed:8495559). Regulates neuronal excitability and plays a role as pacemaker in the regulation of neuronal action potentials (By similarity). KCNA2-containing channels play a presynaptic role and prevent hyperexcitability and aberrant action potential firing (By similarity). Response to toxins that are selective for KCNA2-containing potassium channels suggests that in Purkinje cells, dendritic subthreshold KCNA2-containing potassium channels prevent random spontaneous calcium spikes, suppressing dendritic hyperexcitability without hindering the generation of somatic action potentials, and thereby play an important role in motor coordination (By similarity). Plays a role in the induction of long-term potentiation of neuron excitability in the CA3 layer of the hippocampus (By similarity). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) (By similarity). Contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity). Reduced KCNA2 expression plays a role in the perception of neuropathic pain after peripheral nerve injury, but not acute pain (By similarity). Plays a role in the regulation of the time spent in non-rapid eye movement (NREM) sleep (By similarity).
- Kinetics:
- BIOPHYSICOCHEMICAL PROPERTIES: ; Kinetic parameters: Note=Homotetrameric channels activate rapidly, i.e within a few msec, but inactivation is very slow, with only a marginal decrease in conductance over several seconds. The voltage-dependence of activation and inactivation and other channel characteristics vary depending on the experimental conditions, the expression system, post-translational modifications and the presence or absence of ancillary subunits. For the activation of homotetrameric channels expressed in xenopus oocytes, the threshold is at about -30 mV and the midpoint at about -5 mV.
- Enzyme Regulation:
- ENZYME REGULATION: Inhibited by 4-aminopyridine (4-AP) and charybdotoxin (CTX), but not by tetraethylammonium (TEA) (PubMed:19912772). Inhibited by dendrotoxin (DTX) (By similarity). Inhibited by tityustoxin-K alpha (TsTX-Kalpha), a toxin that is highly specific for KCNA2 (By similarity). Inhibited by maurotoxin (By similarity). Inhibited by kappaM conotoxins kappaM-RIIIJ and kappaM-RIIIK; kappaM-RIIIJ has much higher affinity for channels containing KCNA2 than kappaM-RIIIK, with the exception of heterodimers formed by KCNA2 and KCNA7 where the opposite is true (PubMed:20220134).
- Cross Reference Drug Bank:
- DB06637
- Gene Ontology Go:
- axon
axon terminus
cell junction
dendrite
endoplasmic reticulum membrane
integral component of plasma membrane
juxtaparanode region of axon
lamellipodium
lamellipodium membrane
neuronal cell body membrane
perikaryon
plasma membrane
presynaptic membrane
voltage-gated potassium channel complex
delayed rectifier potassium channel activity
potassium channel activity
voltage-gated potassium channel activity
neuronal action potential
optic nerve structural organization
potassium ion transmembrane transport
potassium ion transport
protein homooligomerization
regulation of circadian sleep/wake cycle, non-REM sleep
regulation of dopamine secretion
sensory perception of pain
synaptic transmission - Gene Ontology Biological Process:
- neuronal action potential
optic nerve structural organization
potassium ion transmembrane transport
potassium ion transport
protein homooligomerization
regulation of circadian sleep/wake cycle, non-REM sleep
regulation of dopamine secretion
sensory perception of pain
synaptic transmission - Gene Ontology Molecular Function:
- delayed rectifier potassium channel activity
potassium channel activity
voltage-gated potassium channel activity - Gene Ontology Cellular Component:
- axon
axon terminus
cell junction
dendrite
endoplasmic reticulum membrane
integral component of plasma membrane
juxtaparanode region of axon
lamellipodium
lamellipodium membrane
neuronal cell body membrane
perikaryon
plasma membrane
presynaptic membrane
voltage-gated potassium channel complex - Keywords:
- Alternative splicing
Cell junction
Cell membrane
Cell projection
Complete proteome
Disease mutation
Endoplasmic reticulum
Epilepsy
Glycoprotein
Ion channel
Ion transport
Lipoprotein
Membrane
Palmitate
Phosphoprotein
Potassium
Potassium channel
Potassium transport
Reference proteome
Synapse
Synaptosome
Transmembrane
Transmembrane helix
Transport
Voltage-gated channel - Interacts With:
- P49069