Recombinant Human Potassium voltage-gated channel subfamily A member 2 (KCNA2)

Code CSB-CF012007HU
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Source in vitro E.coli expression system
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Product Details

Target Names
KCNA2
Uniprot No.
Alternative Names
KCNA2; 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
Species
Homo sapiens (Human)
Expression Region
1-163
Target Protein Sequence
MTVATGDPADEAAALPGHPQDTYDPEADHECCERVVINISGLRFETQLKTLAQFPETLLGDPKKRMRYFDPLRNEYFFDRNRPSFDAILYYYQSGGRLRRPVNVPLDIFSEEIRFYELGEEAMEMFREDEGYIKEEERPLPENEFQRQVWLLFEYPESSGPAR
Protein Length
Full length protein
Tag Info
Tag type will be determined during the manufacturing process.
The tag type will be determined during production process. If you have specified tag type, please tell us and we will develop the specified tag preferentially.
Form
Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
Buffer before Lyophilization
Tris/PBS-based buffer, 6% Trehalose, pH 8.0
Reconstitution
We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20℃/-80℃. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting and FAQs
Storage Condition
Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life
The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Lead Time
Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Note: All of our proteins are default shipped with normal blue ice packs, if you request to ship with dry ice, please communicate with us in advance and extra fees will be charged.
Notes
Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Datasheet
Please contact us to get it.

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Target Background

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. 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. 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. In contrast, a heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation. Regulates neuronal excitability and plays a role as pacemaker in the regulation of neuronal action potentials. KCNA2-containing channels play a presynaptic role and prevent hyperexcitability and aberrant action potential firing. 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. Plays a role in the induction of long-term potentiation of neuron excitability in the CA3 layer of the hippocampus. May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons. May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA). Contributes to the regulation of the axonal release of the neurotransmitter dopamine. Reduced KCNA2 expression plays a role in the perception of neuropathic pain after peripheral nerve injury, but not acute pain. Plays a role in the regulation of the time spent in non-rapid eye movement (NREM) sleep.
Gene References into Functions
  1. We identified 3 patients with KCNA2 mutations with novel characteristics PMID: 28806589
  2. study indicates well represented genotype-phenotype associations between three subgroups of patients with KCNA2 encephalopathy according to the electrophysiological features of the mutations. PMID: 29050392
  3. In the asymptomatic mother, the mutated copy of the CDKL5 gene was inactivated in 90% of blood cells. We also identified a premature stop codon (p.Arg926*) in IQSEC2 in a patient with a Rett-like phenotype. Finally, exome sequencing enabled us to characterize a heterozygous de novo missense (p.Val408Ala) in KCNA2 in a girl with infantile-onset seizures variant of Rett syndrome (RTT) PMID: 27062609
  4. Novel recurrent missense mutation within the Kv1.2 voltage sensor associated with variable phenotypes, including hereditary spastic paraplegia, ataxia, and intellectual disability. PMID: 27543892
  5. This study demonstrated that KCNA2 mutation causes episodic ataxia and pharmacoresponsive epilepsy. PMID: 27733563
  6. Use-dependent activation of Kv1.2 channels is mediated by an extrinsic regulator that binds preferentially to the channel closed state, with Thr252 being necessary but not sufficient for this interaction to alter channel function. PMID: 26646078
  7. This gene has not been previously described as a cause of disease in humans, but mutations of the orthologous gene in mice (Kcna2) are known to cause both ataxia and convulsions PMID: 25477152
  8. KCNA2 is a new gene involved in human neurodevelopmental disorders through two different mechanisms, predicting either hyperexcitability or electrical silencing of KV1.2-expressing neurons. PMID: 25751627
  9. the inhibition of two K(+) channel isoforms, Kv1.2 and KCa3.1, by two drug molecules, lidocaine and TRAM-34, is examined in atomic detail using molecular dynamics simulations. PMID: 25300013
  10. isoform betaII plays a central role in the PKC-dependent regulation of Kv1.5/Kvbeta1.2 channels. PMID: 24682423
  11. This study indicated that the T2DM condition leads to potassium channel-mediated peripheral nerve hyperexcitability , thus identifying them as a potential drug target to treat some of the DPN related symptoms. PMID: 22649228
  12. The immunoreactivity of potassium channels (Kv1.2) was markedly reduced in the ventral roots, but normal in the dorsal roots of all the amyotrophic lateral sclerosis patients. PMID: 21906595
  13. Using fluorimetry and gating currents, study of the Kv1.2 voltage sensor domain revealed at least two independent conformational changes in this region in response to depolarization. PMID: 20584892
  14. in addition to its known effect on pore stability, V370 of Kv1.2 is also crucial in controlling ion selectivity. PMID: 20842544
  15. observe for both the open and closed conformations of the Kv1.2 that specific mutations of S4 gating-charge residues destabilize the electrostatic network between helices of the voltage sensor domain PMID: 21044565
  16. analysis of molecular basis for the actions of KVbeta1.2 on the opening and closing of the KV1.2 delayed rectifier channel PMID: 19713757
  17. endocytosis of Kv1.2 from the cell surface is a key mechanism for channel suppression by tyrosine kinases PMID: 15215309
  18. our results demonstrate the multiplicity of gating inhibition of different K(v) channels by Syn-1A and is compatible with versatility of Syntaxin-1A modulation of repolarization in various secretory and nonsecretory (smooth muscle) cell types. PMID: 17234891
  19. MK2-HSP27 pathway regulates the NF-kappaB transcriptional output by switching the activation pattern from high level to low level. PMID: 17576778
  20. Kv1.2 and cortactin interact in vivo PMID: 17959782
  21. Kv1.2 levels at the cell surface are kept in dynamic balance by opposing effects of cAMP PMID: 18003609
  22. Replacement of the N-terminal domain of maurotoxin by the one of the Agitoxin 2 chimera results in reorganization of disulfide bridge arrangements and increase of affinity to the Kv1.2 channel. PMID: 18042681
  23. the numbers of Kv1.2 channels are higher in DRs than VRs. PMID: 18053989
  24. Both receptor-stimulated and steady-state Kv1.2 trafficking modulated by RhoA/ROCK required the activation of dynamin as well as the ROCK effector Lim-kinase, indicating a key role for actin remodeling in RhoA-dependent Kv1.2 regulation. PMID: 19403695
  25. Data show that multivalent calix[4]arene ligands bind to the surface of voltage-dependent potassium channels (K(v)1.2 in a reversible manner. PMID: 19435843
  26. molecular model for how the pre-gating process occurs in sequential steps: Gating charge response, movement and stabilization of the S4 voltage sensor domain, and movement near the base of the S5 region to close the pore domain. PMID: 19883299

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Involvement in disease
Epileptic encephalopathy, early infantile, 32 (EIEE32)
Subcellular Location
Cell membrane; Multi-pass membrane protein. Membrane. Cell projection, axon. Cell junction, synapse. Endoplasmic reticulum membrane. Cell projection, lamellipodium membrane. Cell junction, synapse, synaptosome. Cell junction, synapse, presynaptic cell membrane. Cell projection, dendrite. Cell junction, paranodal septate junction.
Protein Families
Potassium channel family, A (Shaker) (TC 1.A.1.2) subfamily, Kv1.2/KCNA2 sub-subfamily
Tissue Specificity
Detected in brain cortex. Detected in peroneal nerve in the juxtaparanodal regions of the node of Ranvier; expression is decreased in patients with diabetes mellitus that suffer from axonal neuropathy. Detected in paranodal and juxtanodal zones in myelina
Database Links

HGNC: 6220

OMIM: 176262

KEGG: hsa:3737

STRING: 9606.ENSP00000314520

UniGene: Hs.248139

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