Stromatoxin (T3D2502)
| Record Information | |||||||||||
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| Version | 2.0 | ||||||||||
| Creation Date | 2009-07-03 22:19:01 UTC | ||||||||||
| Update Date | 2014-12-24 20:25:37 UTC | ||||||||||
| Accession Number | T3D2502 | ||||||||||
| Identification | |||||||||||
| Common Name | Stromatoxin | ||||||||||
| Class | Protein | ||||||||||
| Description | Stromatoxin is a peptide spider toxin produced by the Featherleg baboon tarantula (Stromatopelma calceatum). This spider lives high in the canopy tops of tropical forests in West Africa. Stromatoxin blocks certain delayed-rectifier and A-type voltage-gated potassium channels. (3) Stromatoxin is a peptide consisting of 34 amino acids that belongs to the structural family of ‘inhibitor cystine knot’ spider peptides. | ||||||||||
| Compound Type |
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| Protein Structure |  | ||||||||||
| Synonyms |
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| Chemical Formula | Not Available | ||||||||||
| Average Molecular Mass | 3798.295 g/mol | ||||||||||
| CAS Registry Number | 1262235-00-6 | ||||||||||
| 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 | Not Available | ||||||||||
| Biofluid Locations | Not Available | ||||||||||
| Tissue Locations | Not Available | ||||||||||
| Pathways | Not Available | ||||||||||
| 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) (4) | ||||||||||
| Mechanism of Toxicity | Stromatoxin blocks the delayed-rectifier type potassium channels Kv2.1, Kv2.2, Kv2.1/9.3 and the A-type potassium channel Kv4.2, with affinity (IC50) of 12.7 nM, 21.4 nM, 7.2 nM and 1.2 nM, respectively. No activity on Kv4.1 and Kv4.3 has been observed. The effect of stromatoxin on potassium channels is voltage-dependent, maximal inhibition is reached between –30 and 0 mV, while inhibition is only partial at values more positive than +10 mV. The toxin therefore acts as a gating modifier, shifting the activation of the channel to more depolarized potentials. Although the channel can still be activated, a much larger depolarization is needed. (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 | Not Available | ||||||||||
| Lethal Dose | Not Available | ||||||||||
| Carcinogenicity (IARC Classification) | No indication of carcinogenicity to humans (not listed by IARC). | ||||||||||
| Uses/Sources | Stromatoxin is a peptide toxin produced by the Featherleg baboon tarantula (Stromatopelma calceatum). (3) | ||||||||||
| Minimum Risk Level | Not Available | ||||||||||
| Health Effects | Bites from the Featherleg baboon tarantula are very painful. There is only one recorded death from a featherleg baboon tarantula bite (a soldier in South Africa). | ||||||||||
| Symptoms | Throbbing pain at site of bite. Redness, swelling, burning sensation, some joint pain near bite. Some cramping may develop in joints. Most symptoms disappear after 1-2 days. | ||||||||||
| Treatment | Minor bites and stings can be treated by: 1) washing the affected area with soap and water; 2) placing a cold compress (a flannel or cloth cooled with cold water) over the affected area to reduce swelling and 3) not scratching the area as it can become infected. If the symptoms of a systemic reaction (SR) appear, it could lead to anaphylactic shock. Anaphylaxis may need to be treated with an adrenaline injection, antihistamines, oxygen or an intravenous drip directly into a vein. | ||||||||||
| Normal Concentrations | |||||||||||
| Not Available | |||||||||||
| Abnormal Concentrations | |||||||||||
| Not Available | |||||||||||
| External Links | |||||||||||
| DrugBank ID | Not Available | ||||||||||
| HMDB ID | Not Available | ||||||||||
| PubChem Compound ID | Not Available | ||||||||||
| ChEMBL ID | Not Available | ||||||||||
| ChemSpider ID | Not Available | ||||||||||
| KEGG ID | Not Available | ||||||||||
| UniProt ID | P60991 | ||||||||||
| OMIM ID | |||||||||||
| ChEBI ID | Not Available | ||||||||||
| BioCyc ID | Not Available | ||||||||||
| CTD ID | Not Available | ||||||||||
| Stitch ID | Not Available | ||||||||||
| PDB ID | Not Available | ||||||||||
| ACToR ID | Not Available | ||||||||||
| Wikipedia Link | Stromatoxin | ||||||||||
| References | |||||||||||
| Synthesis Reference | Not Available | ||||||||||
| MSDS | Not Available | ||||||||||
| General References |
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| Gene Regulation | |||||||||||
| Up-Regulated Genes | Not Available | ||||||||||
| Down-Regulated Genes | Not Available | ||||||||||
Targets
- 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
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| IC50 | 0.0127 uM | Not Available | Not Available |
References
- 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
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| IC50 | 0.0214 uM | Not Available | Not Available |
References
- 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. Mediates the major part of the dendritic A-type current I(SA) in brain neurons (By similarity). This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites. Contributes to the regulation of the circadian rhytm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (By similarity). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (By similarity). Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient (PubMed:10551270, PubMed:15454437, PubMed:14695263, PubMed:14623880, PubMed:14980201, PubMed:16934482, PubMed:24811166, PubMed:24501278). The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:11507158). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes. Interaction with specific isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation, shifts the threshold for channel activation to more negative voltage values, shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation (PubMed:15454437, PubMed:14623880, PubMed:14980201, PubMed:19171772, PubMed:24501278, PubMed:24811166). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (By similarity).
- Gene Name:
- KCND2
- Uniprot ID:
- Q9NZV8
- Molecular Weight:
- 70535.825 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| IC50 | 0.0072 uM | Not Available | Not Available |
References
- General Function:
- Potassium channel regulator activity
- Specific Function:
- Potassium channel subunit that does not form functional channels by itself. Can form functional heterotetrameric channels with KCNB1; modulates the delayed rectifier voltage-gated potassium channel activation and deactivation rates of KCNB1 (PubMed:10484328). Heterotetrameric channel activity formed with KCNB1 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).
- Gene Name:
- KCNS3
- Uniprot ID:
- Q9BQ31
- Molecular Weight:
- 56000.32 Da
Binding/Activity Constants
| Type | Value | Assay Type | Assay Source |
|---|---|---|---|
| IC50 | 0.0012 uM | Not Available | Not Available |