KCNA2 - Potassium voltage-gated channel subfamily A member 2 - human protein (Function)
 
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KCNA2 »  Potassium voltage-gated channel subfamily A member 2
 
Protein also known as:  Voltage-gated potassium channel subunit Kv1.2.
Gene name:  KCNA2
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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 (PubMed19912772, PubMed8495559, PubMed11211111, PubMed23769686). 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 (PubMed8495559, PubMed20220134). 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 (PubMed19912772, PubMed23769686). In contrast, a heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation (PubMed8495559). 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).  
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  • UniProtKB
According to TCDB this is a transporter from family:
the voltage-gated ion channel (vic) superfamily  1.A.1.2.10  
GO molecular function 
Delayed rectifier potassium channel activitydefinition[GO:0005251]  
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  • Ortholog Curator
  • RefGenome
Outward rectifier potassium channel activitydefinition[GO:0015271] silver  
1
  • Ortholog Compara
Potassium channel activitydefinition[GO:0005267]  
1
  • PINC
Protein bindingdefinition[GO:0005515]  
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  • IntAct
Voltage-gated potassium channel activitydefinition[GO:0005249]  
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  • UniProtKB
  • Ortholog Curator
GO biological process 
Neuronal action potentialdefinition[GO:0019228]  
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  • Ortholog Curator
Optic nerve structural organizationdefinition[GO:0021633] silver  
1
  • Ortholog Compara
Potassium ion transmembrane transportdefinition[GO:0071805]  
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  • UniProtKB
  • Ortholog Curator
  • RefGenome
Potassium ion transportdefinition[GO:0006813]  
1
  • PINC
Protein homooligomerizationdefinition[GO:0051260] silver  
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  • InterPro 2 GO
Regulation of dopamine secretiondefinition[GO:0014059]  
1
  • Ortholog Curator
Regulation of ion transmembrane transportdefinition[GO:0034765]  
1
  • UniProtKB KW
Sensory perception of paindefinition[GO:0019233]  
1
  • Ortholog Curator
Enzymatic activity 
It is regulated in the following manner
Inhibited by 4-aminopyridine (4-AP) and charybdotoxin (CTX), but not by tetraethylammonium (TEA) (PubMed19912772). 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 (PubMed20220134).  
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  • UniProtKB
Pathways 
According to Reactome, this protein belongs to the following pathway:
Voltage gated Potassium channels  REACT_75770  
Note 
The delay or D-type current observed in hippocampus pyramidal neurons is probably mediated by potassium channels containing KCNA2 plus KCNA1 or other family members. It is activated at about -50 mV, i.e. Below the action potential threshold, and is characterized by slow inactivation, extremely slow recovery from inactivation, sensitivity to dendrotoxin (DTX) and to 4-aminopyridine (4-AP).  
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  • UniProtKB
 

Keywords

Biological process 
Ion transport  definition   [KW-0406]
Potassium transport  definition   [KW-0633]
Transport  definition   [KW-0813]
Molecular function 
Ion channel  definition   [KW-0407]
Potassium channel  definition   [KW-0631]
Voltage-gated channel  definition   [KW-0851]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: KCNA2
GenomeRNAi: 3737
PRO: PR:P16389
Chemistry
GuidetoPHARMACOLOGY: 539