General Information of This Target
Target ID
BTDT00126
Target Name
Potassium voltage-gated channel subfamily B member 1 (Kcnb1)
Target Bioclass
Transporter and channel
Uniprot ID
Q03717
3D Structure
Download
2D Sequence
3D Structure
Source
Predict by Alphafold2
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Alphafold Parameters: msa_mode: mmseqs2_uniref_env model_type: auto num_recycles: auto
Gene Name
Kcnb1
Gene ID
16500
Synonym
Voltage-gated potassium channel subunit Kv2.1; mShab
Sequence
MPAGMTKHGSRSTSSLPPEPMEIVRSKACSRRVRLNVGGLAHEVLWRTLDRLPRTRLGKL
RDCNTHDSLLQVCDDYSLEDNEYFFDRHPGAFTSILNFYRTGRLHMMEEMCALSFSQELD
YWGIDEIYLESCCQARYHQKKEQMNEELKREAETLREREGEEFDNTCCAEKRKKLWDLLE
KPNSSVAAKILAIISIMFIVLSTIALSLNTLPELQSLDEFGQSTDNPQLAHVEAVCIAWF
TMEYLLRFLSSPKKWKFFKGPLNAIDLLAILPYYVTIFLTESNKSVLQFQNVRRVVQIFR
IMRILRILKLARHSTGLQSLGFTLRRSYNELGLLILFLAMGIMIFSSLVFFAEKDEDDTK
FKSIPASFWWATITMTTVGYGDIYPKTLLGKIVGGLCCIAGVLVIALPIPIIVNNFSEFY
KEQKRQEKAIKRREALERAKRNGSIVSMNMKDAFARSIEMMDIVVEKNGEGVAKKDKVQD
NHLSPNKWKWTKRALSETSSSKSFETKEQGSPEKARSSSSPQHLNVQQLQDMYSKMAKTQ
SQPILNTKEMAPQSQPQEELEMGSMPSPVAPLPTRTEGVIDMRSMSSIDSFISCATDFPE
ATRFSHSPLASLSGKSGGSTAPEVGWRGALGASGGRLMETNPIPEASRSGFFVESPRSSM
KTHNPMKLRALKVNFLEGDPTPLLPALGLYHDPLRNRGGAAAAVAGLECASLLDKPVLSP
ESSIYTTASARTPPRSPEKHTAIAFNFEAGVHQYIDTDTDDEGQLLYSVDSSPPKSLHGS
TSPKFSLGARTEKNHFESSPLPTSPKFLRPNCVYASEGLPGKGPGAQEKCKLENHTSPDV
HMLPGGGAHGSTRDQSI

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Family
the potassium channel family
Function
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in the pancreas and cardiovascular system. Contributes to the regulation of the action potential (AP) repolarization, duration and frequency of repetitive AP firing in neurons, muscle cells and endocrine cells and plays a role in homeostatic attenuation of electrical excitability throughout the brain. Also plays a role in the regulation of exocytosis independently of its electrical function. 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. Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization. Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB2; channel properties depend on the type of alpha subunits that are part of the channel. Can also form functional heterotetrameric channels with other alpha subunits that are non-conducting when expressed alone, such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1, creating a functionally diverse range of channel complexes. Heterotetrameric channel activity formed with KCNS3 show increased current amplitude with the threshold for action potential activation shifted towards more negative values in hypoxic-treated pulmonary artery smooth muscle cells. Channel properties are also modulated by cytoplasmic ancillary beta subunits, such as AMIGO1, KCNE1, KCNE2 and KCNE3, slowing activation and inactivation rate of the 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. Major contributor to the delayed-rectifier voltage-gated potassium current in neurons of the central nervous system, sympathetic ganglion neurons, neuroendocrine cells, pancreatic beta cells, cardiomyocytes and smooth muscle. Mediates the major part of the somatodendritic delayed-rectifier potassium current in hippocampal and cortical pyramidal neurons and sympathetic superior cervical ganglion (CGC) neurons that acts to slow down periods of firing, especially during high frequency stimulation. Plays a role in the induction of long-term potentiation (LTP) of neuron excitability in the CA3 layer of the hippocampus. Contributes to the regulation of the glucose-induced amplitude and duration of action potentials in pancreatic beta-cells, hence limiting calcium influx and insulin secretion. Plays a role in the regulation of resting membrane potential and contraction in hypoxia-treated pulmonary artery smooth muscle cells. May contribute to the regulation of the duration of both the action potential of cardiomyocytes and the heart ventricular repolarization QT interval. Contributes to the pronounced pro-apoptotic potassium current surge during neuronal apoptotic cell death in response to oxidative injury. May confer neuroprotection in response to hypoxia/ischemic insults by suppressing pyramidal neurons hyperexcitability in hippocampal and cortical regions. Promotes trafficking of KCNG3, KCNH1 and KCNH2 to the cell surface membrane, presumably by forming heterotetrameric channels with these subunits. Plays a role in the calcium-dependent recruitment and release of fusion-competent vesicles from the soma of neurons, neuroendocrine and glucose-induced pancreatic beta cells by binding key components of the fusion machinery in a pore-independent manner.

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Taxonomy ID
10090
        Click to Show/Hide the Complete Species Lineage
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Rodentia
Family: Muridae
Genus: Mus
Species: Mus musculus
Toxin Information Related to This Target
                           Toxin Name Activity Data Type Activity Data Reference
 Toxin Info    Toxin (3D,F4D,N6G,L7K,R8L,R9F,C10S,E11G,L12C,S13D,C14T,R15N,S16A,L17D,G18C,L19C,L20E,K22Y,C23V,I24C,G25R,E26L,E27W,C30L,V31D,P32W) Inhibition rate . [1]
 Toxin Info    Kappa-theraphotoxin-Hm2a Inhibition rate
18 %
[2]
 Toxin Info    Delta-theraphotoxin-Hm1a Inhibition rate
23 %
[2], [3], [4], [5]
 Toxin Info    Kappa-theraphotoxin-Sc1a IC50
12.7 nM
[2]
References
Ref 1 Heteropoda toxin 2 is a gating modifier toxin specific for voltage-gated K+ channels of the Kv4 family. Toxicon. 2005 Mar 15;45(4):431-42. doi: 10.1016/j.toxicon.2004.11.015.
Ref 2 Novel tarantula toxins for subtypes of voltage-dependent potassium channels in the Kv2 and Kv4 subfamilies. Mol Pharmacol. 2002 Jul;62(1):48-57. doi: 10.1124/mol.62.1.48.
Ref 3 Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain. Nature. 2016 Jun 23;534(7608):494-9. doi: 10.1038/nature17976. Epub 2016 Jun 6.
Ref 4 A selective Na(V)1.1 activator with potential for treatment of Dravet syndrome epilepsy. Biochem Pharmacol. 2020 Nov;181:113991. doi: 10.1016/j.bcp.2020.113991. Epub 2020 Apr 23.
Ref 5 Selective Na(V)1.1 activation rescues Dravet syndrome mice from seizures and premature death. Proc Natl Acad Sci U S A. 2018 Aug 21;115(34):E8077-E8085. doi: 10.1073/pnas.1804764115. Epub 2018 Aug 3.
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