beta-Bungarotoxin (T3D2538)
| Record Information | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Version | 2.0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Creation Date | 2009-07-03 22:19:16 UTC | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Update Date | 2014-12-24 20:25:40 UTC | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Accession Number | T3D2538 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Identification | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Common Name | beta-Bungarotoxin | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Class | Protein | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description | beta-Bungarotoxin is a peptide toxin produced by the Many-banded krait (Bungarus multicinctus). It is a neurotoxin and acts at the presynaptic terminal, where it causes release of acetylcholine and subsequent exhaustion of acetylcholine stores in the nerve terminal. (5) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Compound Type |
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| Protein Structure |  | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Synonyms |
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| Chemical Formula | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Average Molecular Mass | 9571.020 g/mol | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAS Registry Number | 12778-32-4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Sequence | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Chemical Taxonomy | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Kingdom | Organic Compounds | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Super Class | Organic Acids | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Class | Carboxylic Acids and Derivatives | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Sub Class | Amino Acids, Peptides, and Analogues | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Direct Parent | Peptides | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alternative Parents | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Substituents | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Molecular Framework | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| External Descriptors | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Biological Properties | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Status | Detected and Not Quantified | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Origin | Exogenous | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cellular Locations |
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| Biofluid Locations | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Tissue Locations | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pathways |
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| Applications | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Biological Roles | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Chemical Roles | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Physical Properties | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| State | Liquid | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Appearance | Clear solution. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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| Predicted Properties | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Spectra | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Spectra |
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| Toxicity Profile | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Route of Exposure | Injection (sting/bite) (6) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mechanism of Toxicity | beta-Bungarotoxin acts at the presynaptic terminal, where it causes release of acetylcholine and subsequent exhaustion of acetylcholine stores in the nerve terminal by binding to proteins, most commonly actin. It can also block voltage-gated potassium channels. (2, 5, 1) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Metabolism | Free toxin may be removed by opsonization via the reticuloendothelial system (primarily the liver and kidneys) or it may be degraded through cellular internalization via the lysosomes. Lysosomes are membrane-enclosed organelles that contain an array of digestive enzymes, including several proteases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Toxicity Values | LD50: 0.108 mg/kg (Subcutaneous, Mouse) (7) LD50: 0.113 mg/kg (Intravenous, Mouse) (7) LD50: 0.08 (Intraperitoneal, Mouse) (7) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lethal Dose | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Carcinogenicity (IARC Classification) | No indication of carcinogenicity to humans (not listed by IARC). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Uses/Sources | beta-Bungarotoxin is a peptide toxin produced by the Many-banded krait (Bungarus multicinctus). (5) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Minimum Risk Level | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Health Effects | Many-banded krait bites can cause paralysis, respiratory failure and death. (4) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Symptoms | Many-banded krait bites can cause paralysis, respiratory failure and death. (4) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Treatment | An antivenom exists for Many-banded krait venom. (3) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Normal Concentrations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abnormal Concentrations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| External Links | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DrugBank ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HMDB ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PubChem Compound ID | 2432 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ChEMBL ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ChemSpider ID | 2338 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| KEGG ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| UniProt ID | P00987 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| OMIM ID | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ChEBI ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BioCyc ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CTD ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Stitch ID | beta-Bungarotoxin | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PDB ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ACToR ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Wikipedia Link | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| References | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Synthesis Reference | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| MSDS | T3D2538.pdf | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| General References |
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| Gene Regulation | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Up-Regulated Genes | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Down-Regulated Genes | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Targets
- General Function:
- Voltage-gated potassium channel activity
- Specific 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 kidney (PubMed:19903818). Contributes to the regulation of the membrane potential and nerve signaling, and prevents neuronal hyperexcitability (PubMed:17156368). 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). 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:12077175, PubMed:17156368). 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 (PubMed:12077175, PubMed:17156368). 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 KCNA1 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:19912772, PubMed:19968958, PubMed:19307729, PubMed:19903818). In contrast, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (PubMed:17156368). Regulates neuronal excitability in hippocampus, especially in mossy fibers and medial perforant path axons, preventing neuronal hyperexcitability. Response to toxins that are selective for KCNA1, respectively for KCNA2, suggests that heteromeric potassium channels composed of both KCNA1 and KCNA2 play a role in pacemaking and regulate the output of deep cerebellar nuclear neurons (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) release (By similarity). Plays a role in regulating the generation of action potentials and preventing hyperexcitability in myelinated axons of the vagus nerve, and thereby contributes to the regulation of heart contraction (By similarity). Required for normal neuromuscular responses (PubMed:11026449, PubMed:17136396). Regulates the frequency of neuronal action potential firing in response to mechanical stimuli, and plays a role in the perception of pain caused by mechanical stimuli, but does not play a role in the perception of pain due to heat stimuli (By similarity). Required for normal responses to auditory stimuli and precise location of sound sources, but not for sound perception (By similarity). The use of toxins that block specific channels suggest that it contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity). Required for normal postnatal brain development and normal proliferation of neuronal precursor cells in the brain (By similarity). Plays a role in the reabsorption of Mg(2+) in the distal convoluted tubules in the kidney and in magnesium ion homeostasis, probably via its effect on the membrane potential (PubMed:23903368, PubMed:19307729).
- Gene Name:
- KCNA1
- Uniprot ID:
- Q09470
- Molecular Weight:
- 56465.01 Da
References
- Benishin CG: Potassium channel blockade by the B subunit of beta-bungarotoxin. Mol Pharmacol. 1990 Aug;38(2):164-9. [2385229 ]
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]
- General Function:
- Intracellular cyclic nucleotide activated cation channel activity
- Specific Function:
- Mediates voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient. The channel activity is up-regulated by cAMP.
- Gene Name:
- KCNA10
- Uniprot ID:
- Q16322
- Molecular Weight:
- 57784.47 Da
References
- Benishin CG: Potassium channel blockade by the B subunit of beta-bungarotoxin. Mol Pharmacol. 1990 Aug;38(2):164-9. [2385229 ]
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]
- General Function:
- Voltage-gated potassium channel activity
- Specific 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).
- Gene Name:
- KCNA2
- Uniprot ID:
- P16389
- Molecular Weight:
- 56716.21 Da
References
- Benishin CG: Potassium channel blockade by the B subunit of beta-bungarotoxin. Mol Pharmacol. 1990 Aug;38(2):164-9. [2385229 ]
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]
- General Function:
- Voltage-gated ion channel activity
- Specific Function:
- Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient.
- Gene Name:
- KCNA3
- Uniprot ID:
- P22001
- Molecular Weight:
- 63841.09 Da
References
- Benishin CG: Potassium channel blockade by the B subunit of beta-bungarotoxin. Mol Pharmacol. 1990 Aug;38(2):164-9. [2385229 ]
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]
- General Function:
- Voltage-gated potassium channel activity involved in sa node cell action potential repolarization
- Specific Function:
- Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. 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, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:12130714). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (PubMed:12130714). Homotetrameric channels display rapid activation and slow inactivation (PubMed:8505626, PubMed:12130714). May play a role in regulating the secretion of insulin in normal pancreatic islets. Isoform 2 exhibits a voltage-dependent recovery from inactivation and an excessive cumulative inactivation (PubMed:11524461).
- Gene Name:
- KCNA5
- Uniprot ID:
- P22460
- Molecular Weight:
- 67227.15 Da
References
- Benishin CG: Potassium channel blockade by the B subunit of beta-bungarotoxin. Mol Pharmacol. 1990 Aug;38(2):164-9. [2385229 ]
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]
- General Function:
- Voltage-gated potassium channel activity
- Specific Function:
- Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient (PubMed:2347305, PubMed:14575698). The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:2347305, PubMed:14575698). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA6, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (By similarity). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (By similarity). Homotetrameric channels display rapid activation and slow inactivation (PubMed:2347305).
- Gene Name:
- KCNA6
- Uniprot ID:
- P17658
- Molecular Weight:
- 58728.21 Da
References
- Benishin CG: Potassium channel blockade by the B subunit of beta-bungarotoxin. Mol Pharmacol. 1990 Aug;38(2):164-9. [2385229 ]
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]
- General Function:
- Delayed rectifier potassium channel activity
- Specific Function:
- Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient (By similarity).
- Gene Name:
- KCNA7
- Uniprot ID:
- Q96RP8
- Molecular Weight:
- 50558.415 Da
References
- Benishin CG: Potassium channel blockade by the B subunit of beta-bungarotoxin. Mol Pharmacol. 1990 Aug;38(2):164-9. [2385229 ]
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]
- General Function:
- Ubiquitin-like protein binding
- Specific 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 (PubMed:23161216). Plays also a role in the regulation of exocytosis independently of its electrical function (By similarity). 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 (PubMed:8081723, PubMed:1283219, PubMed:10484328, PubMed:12560340, PubMed:19074135, PubMed:19717558, PubMed:24901643). 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 (By similarity). 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 (PubMed:10484328, PubMed:11852086, PubMed:12060745, PubMed:19074135, PubMed:19717558, PubMed:24901643). 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 (By similarity). 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 (By similarity). 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 slowly inactivating 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 cells. 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 (By similarity). Contributes to the regulation of glucose-induced action potential amplitude and duration in pancreatic beta cells, hence limiting calcium influx and insulin secretion (PubMed:23161216). 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 (By similarity). Promotes trafficking of KCNG3, KCNH1 and KCNH2 to the cell surface membrane, presumably by forming heterotetrameric channels with these subunits (PubMed:12060745). 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 (By similarity).
- Gene Name:
- KCNB1
- Uniprot ID:
- Q14721
- Molecular Weight:
- 95876.615 Da
References
- Benishin CG: Potassium channel blockade by the B subunit of beta-bungarotoxin. Mol Pharmacol. 1990 Aug;38(2):164-9. [2385229 ]
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]
- General Function:
- Protein heterodimerization activity
- Specific Function:
- Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and smooth muscle cells. Channels open or close in response to the voltage difference across the membrane, letting potassium ions pass in accordance with their electrochemical gradient. 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 KCNB1; 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 KCNS1 and KCNS2, creating a functionally diverse range of channel complexes. 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. Contributes to the delayed-rectifier voltage-gated potassium current in cortical pyramidal neurons and smooth muscle cells.
- Gene Name:
- KCNB2
- Uniprot ID:
- Q92953
- Molecular Weight:
- 102561.99 Da
References
- Benishin CG: Potassium channel blockade by the B subunit of beta-bungarotoxin. Mol Pharmacol. 1990 Aug;38(2):164-9. [2385229 ]
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]
- General Function:
- Voltage-gated potassium channel activity
- Specific Function:
- Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient. Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNC2, and possibly other family members as well. Contributes to fire sustained trains of very brief action potentials at high frequency in pallidal neurons.
- Gene Name:
- KCNC1
- Uniprot ID:
- P48547
- Molecular Weight:
- 57941.87 Da
References
- Benishin CG: Potassium channel blockade by the B subunit of beta-bungarotoxin. Mol Pharmacol. 1990 Aug;38(2):164-9. [2385229 ]
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]
- General Function:
- Voltage-gated potassium channel activity
- Specific Function:
- Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Contributes to the regulation of the fast action potential repolarization and in sustained high-frequency firing in neurons of the central nervous system. Homotetramer channels mediate delayed-rectifier voltage-dependent potassium currents that activate rapidly at high-threshold voltages and inactivate slowly. Forms tetrameric 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:15709110). Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNC1, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel. Channel properties may be modulated either by the association with ancillary subunits, such as KCNE1, KCNE2 or KCNE3 or indirectly by nitric oxide (NO) through a cGMP- and PKG-mediated signaling cascade, slowing channel activation and deactivation of delayed rectifier potassium channels (By similarity). Contributes to fire sustained trains of very brief action potentials at high frequency in retinal ganglion cells, thalamocortical and suprachiasmatic nucleus (SCN) neurons and in hippocampal and neocortical interneurons (PubMed:15709110). Sustained maximal action potential firing frequency in inhibitory hippocampal interneurons is negatively modulated by histamine H2 receptor activation in a cAMP- and protein kinase (PKA) phosphorylation-dependent manner. Plays a role in maintaining the fidelity of synaptic transmission in neocortical GABAergic interneurons by generating action potential (AP) repolarization at nerve terminals, thus reducing spike-evoked calcium influx and GABA neurotransmitter release. Required for long-range synchronization of gamma oscillations over distance in the neocortex. Contributes to the modulation of the circadian rhythm of spontaneous action potential firing in suprachiasmatic nucleus (SCN) neurons in a light-dependent manner (By similarity).
- Gene Name:
- KCNC2
- Uniprot ID:
- Q96PR1
- Molecular Weight:
- 70224.915 Da
References
- Benishin CG: Potassium channel blockade by the B subunit of beta-bungarotoxin. Mol Pharmacol. 1990 Aug;38(2):164-9. [2385229 ]
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]
- General Function:
- Phosphorelay sensor kinase activity
- Specific Function:
- Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel (PubMed:22732247). Channel properties may be modulated by subunit assembly, but not by cyclic nucleotides (By similarity). Mediates IK(NI) current in myoblasts (PubMed:9738473). Involved in the regulation of cell proliferation and differentiation, in particular adipogenic and osteogenic differentiation in bone marrow-derived mesenchymal stem cells (MSCs) (PubMed:23881642).
- Gene Name:
- KCNH1
- Uniprot ID:
- O95259
- Molecular Weight:
- 111421.76 Da
References
- Benishin CG: Potassium channel blockade by the B subunit of beta-bungarotoxin. Mol Pharmacol. 1990 Aug;38(2):164-9. [2385229 ]
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]
- General Function:
- Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
- Specific Function:
- Potassium channel that plays an important role in a number of tissues, including heart, inner ear, stomach and colon (By similarity) (PubMed:10646604). Associates with KCNE beta subunits that modulates current kinetics (By similarity) (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505, PubMed:19687231). Induces a voltage-dependent by rapidly activating and slowly deactivating potassium-selective outward current (By similarity) (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505). Promotes also a delayed voltage activated potassium current showing outward rectification characteristic (By similarity). During beta-adrenergic receptor stimulation participates in cardiac repolarization by associating with KCNE1 to form the I(Ks) cardiac potassium current that increases the amplitude and slows down the activation kinetics of outward potassium current I(Ks) (By similarity) (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505). Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current (PubMed:10713961). When associated with KCNE3, forms the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions (PubMed:10646604). This interaction with KCNE3 is reduced by 17beta-estradiol, resulting in the reduction of currents (By similarity). During conditions of increased substrate load, maintains the driving force for proximal tubular and intestinal sodium ions absorption, gastric acid secretion, and cAMP-induced jejunal chloride ions secretion (By similarity). Allows the provision of potassium ions to the luminal membrane of the secretory canaliculus in the resting state as well as during stimulated acid secretion (By similarity). When associated with KCNE2, forms an heterooligomer complex leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (PubMed:11101505). When associated with KCNE4, inhibits voltage-gated potassium channel activity (PubMed:19687231). When associated with KCNE5, this complex only conducts current upon strong and continued depolarization (PubMed:12324418). Also forms an heterotetramer with KCNQ5; has a voltage-gated potassium channel activity (PubMed:24855057). Binds with phosphatidylinositol 4,5-bisphosphate (PubMed:25037568).Isoform 2: Non-functional alone but modulatory when coexpressed with the full-length isoform 1.
- Gene Name:
- KCNQ1
- Uniprot ID:
- P51787
- Molecular Weight:
- 74697.925 Da
References
- Benishin CG: Potassium channel blockade by the B subunit of beta-bungarotoxin. Mol Pharmacol. 1990 Aug;38(2):164-9. [2385229 ]
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]
- General Function:
- Voltage-gated potassium channel activity
- Specific Function:
- Probably important in the regulation of neuronal excitability. Associates with KCNQ3 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs. KCNQ2/KCNQ3 current is blocked by linopirdine and XE991, and activated by the anticonvulsant retigabine. Muscarinic agonist oxotremorine-M strongly suppress KCNQ2/KCNQ3 current in cells in which cloned KCNQ2/KCNQ3 channels were coexpressed with M1 muscarinic receptors.
- Gene Name:
- KCNQ2
- Uniprot ID:
- O43526
- Molecular Weight:
- 95846.575 Da
References
- Benishin CG: Potassium channel blockade by the B subunit of beta-bungarotoxin. Mol Pharmacol. 1990 Aug;38(2):164-9. [2385229 ]
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]
- General Function:
- Voltage-gated potassium channel activity
- Specific Function:
- Probably important in the regulation of neuronal excitability. Associates with KCNQ2 or KCNQ5 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs.
- Gene Name:
- KCNQ3
- Uniprot ID:
- O43525
- Molecular Weight:
- 96741.515 Da
References
- Benishin CG: Potassium channel blockade by the B subunit of beta-bungarotoxin. Mol Pharmacol. 1990 Aug;38(2):164-9. [2385229 ]
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]
- General Function:
- Potassium channel activity
- Specific Function:
- Probably important in the regulation of neuronal excitability. May underlie a potassium current involved in regulating the excitability of sensory cells of the cochlea. KCNQ4 channels are blocked by linopirdin, XE991 and bepridil, whereas clofilium is without significant effect. Muscarinic agonist oxotremorine-M strongly suppress KCNQ4 current in CHO cells in which cloned KCNQ4 channels were coexpressed with M1 muscarinic receptors.
- Gene Name:
- KCNQ4
- Uniprot ID:
- P56696
- Molecular Weight:
- 77099.99 Da
References
- Benishin CG: Potassium channel blockade by the B subunit of beta-bungarotoxin. Mol Pharmacol. 1990 Aug;38(2):164-9. [2385229 ]
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]
- General Function:
- Voltage-gated potassium channel activity
- Specific Function:
- Probably important in the regulation of neuronal excitability. Associates with KCNQ3 to form a potassium channel which contributes to M-type current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons. May contribute, with other potassium channels, to the molecular diversity of a heterogeneous population of M-channels, varying in kinetic and pharmacological properties, which underlie this physiologically important current. Insensitive to tetraethylammonium, but inhibited by barium, linopirdine and XE991. Activated by niflumic acid and the anticonvulsant retigabine. Muscarine suppresses KCNQ5 current in Xenopus oocytes in which cloned KCNQ5 channels were coexpressed with M(1) muscarinic receptors.
- Gene Name:
- KCNQ5
- Uniprot ID:
- Q9NR82
- Molecular Weight:
- 102178.015 Da
References
- Benishin CG: Potassium channel blockade by the B subunit of beta-bungarotoxin. Mol Pharmacol. 1990 Aug;38(2):164-9. [2385229 ]
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]
- General Function:
- Myosin binding
- Specific Function:
- Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
- Gene Name:
- ACTC1
- Uniprot ID:
- P68032
- Molecular Weight:
- 42018.6 Da
References
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
- Gene Name:
- ACTA1
- Uniprot ID:
- P68133
- Molecular Weight:
- 42050.67 Da
References
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]
- General Function:
- Protein kinase binding
- Specific Function:
- Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
- Gene Name:
- ACTA2
- Uniprot ID:
- P62736
- Molecular Weight:
- 42008.57 Da
References
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]
- General Function:
- Tat protein binding
- Specific Function:
- Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
- Gene Name:
- ACTB
- Uniprot ID:
- P60709
- Molecular Weight:
- 41736.37 Da
References
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]
- General Function:
- Ubiquitin protein ligase binding
- Specific Function:
- Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
- Gene Name:
- ACTG1
- Uniprot ID:
- P63261
- Molecular Weight:
- 41792.48 Da
References
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]
- General Function:
- Atp binding
- Specific Function:
- Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
- Gene Name:
- ACTG2
- Uniprot ID:
- P63267
- Molecular Weight:
- 41876.495 Da
References
- Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
- The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
- Wikipedia. Beta-Bungarotoxin. Last Updated 7 October 2009. [Link]