Grammotoxin (T3D2498)
| Record Information | |||||||||||
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| Version | 2.0 | ||||||||||
| Creation Date | 2009-07-03 22:19:00 UTC | ||||||||||
| Update Date | 2014-12-24 20:25:37 UTC | ||||||||||
| Accession Number | T3D2498 | ||||||||||
| Identification | |||||||||||
| Common Name | Grammotoxin | ||||||||||
| Class | Protein | ||||||||||
| Description | Grammotoxin is a peptide toxin produced by the Chilean rose tarantula (Grammostola rosea). It inhibits voltage-gated calcium channels in neurons. (1) | ||||||||||
| Compound Type |
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| Protein Structure |  | ||||||||||
| Synonyms |
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| Chemical Formula | Not Available | ||||||||||
| Average Molecular Mass | 9600.980 g/mol | ||||||||||
| CAS Registry Number | 152617-90-8 | ||||||||||
| 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) (2) | ||||||||||
| Mechanism of Toxicity | Grammotoxin inhibits P-, Q- and N-type voltage-gated calcium channels in neurons. Binding to the calcium channels modifies their voltage-dependent gating. This makes it more difficult for channels to be opened by depolarization, so much larger depolarisations are required for channel activation. Grammotoxin also binds to potassium channels, but with lower affinity than to the calcium channels. (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 | Grammotoxin is a peptide toxin produced by the Chilean rose tarantula (Grammostola rosea). (1) | ||||||||||
| Minimum Risk Level | Not Available | ||||||||||
| Health Effects | Grammotoxin is neurotoxic. (1) | ||||||||||
| Symptoms | Tarantula bites can be very painful. In some individuals they may cause an allergic reaction, which is usually anaphylactic and will have symptoms such as breathing difficulties or chest pain. (3) | ||||||||||
| Treatment | Not Available | ||||||||||
| 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 | P60590 | ||||||||||
| OMIM ID | |||||||||||
| ChEBI ID | Not Available | ||||||||||
| BioCyc ID | Not Available | ||||||||||
| CTD ID | Not Available | ||||||||||
| Stitch ID | Not Available | ||||||||||
| PDB ID | 1KOZ | ||||||||||
| ACToR ID | Not Available | ||||||||||
| Wikipedia Link | Not Available | ||||||||||
| References | |||||||||||
| Synthesis Reference | Not Available | ||||||||||
| MSDS | Not Available | ||||||||||
| General References | |||||||||||
| 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
References
- Wikipedia. Grammotoxin. Last Updated 28 April 2009. [Link]
- General Function:
- Voltage-gated calcium channel activity
- Specific Function:
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1B gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by omega-conotoxin-GVIA (omega-CTx-GVIA) and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to dihydropyridines (DHP), and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons.
- Gene Name:
- CACNA1B
- Uniprot ID:
- Q00975
- Molecular Weight:
- 262493.84 Da
References
- Wikipedia. Grammotoxin. Last Updated 28 April 2009. [Link]
- General Function:
- Voltage-gated calcium channel activity
- Specific Function:
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1A gives rise to P and/or Q-type calcium currents. P/Q-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by the funnel toxin (Ftx) and by the omega-agatoxin-IVA (omega-Aga-IVA). They are however insensitive to dihydropyridines (DHP), and omega-conotoxin-GVIA (omega-CTx-GVIA).
- Gene Name:
- CACNA1A
- Uniprot ID:
- O00555
- Molecular Weight:
- 282362.39 Da
References
- Wikipedia. Grammotoxin. Last Updated 28 April 2009. [Link]