Edema factor (T3D2592)
| Record Information | |||||||||||
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| Version | 2.0 | ||||||||||
| Creation Date | 2009-07-06 18:11:23 UTC | ||||||||||
| Update Date | 2014-12-24 20:25:44 UTC | ||||||||||
| Accession Number | T3D2592 | ||||||||||
| Identification | |||||||||||
| Common Name | Edema factor | ||||||||||
| Class | Protein | ||||||||||
| Description | Edema factor (EF) is a component of the anthrax (Bacillus anthracis) toxins, with a calcium- and calmodulin-dependent adenylate cyclase activity. The anthrax toxins consist of three distinct proteins: the protective antigen (PA; 83 kDA), the edema factor (EF; 89 kDA) and the lethal factor (LF; 90 kDa). Individually, none of the three is toxic; PA combined with LF is the lethal toxin (LeTx) and PA combined with EF is the edema toxin (EdTx). (1, 2) | ||||||||||
| Compound Type |
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| Protein Structure |  | ||||||||||
| Synonyms |
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| Chemical Formula | Not Available | ||||||||||
| Average Molecular Mass | 92477.285 g/mol | ||||||||||
| CAS Registry Number | 921236-86-4 | ||||||||||
| 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 | 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 | Ingestion (4) ; inhalation (4) ; dermal (4) | ||||||||||
| Mechanism of Toxicity | After binding to a host cell surface receptor, PA is cleaved by membrane endoproteases of the furin family. Cleaved PA molecules assemble into heptamers, which then associate with EF and LF. PA heptamers are endocytosed into acidic compartments, where a conformational change of the complex allows translocation of LF and EF into the cytosol. LF and EF act enzymatically on intracellular substrates: LF is a zinc-dependent metallo-protease that cleaves and inactivates most isoforms of MEKs (mitogen-activated protein (MAP) kinase kinases), whereas EF is a calcium- and calmodulin-dependent adenylate cyclase that causes a dramatic increase in cytoplasmic cAMP, leading to an imbalance of water homeostasis. (1, 2) | ||||||||||
| 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 | Edema factor (EF) is a component of the anthrax (Bacillus anthracis) toxins. (1, 2) | ||||||||||
| Minimum Risk Level | Not Available | ||||||||||
| Health Effects | Edema factor (EF) is a component of the anthrax (Bacillus anthracis) toxins. Anthrax is an acute diease that may manifest as a pulmonary, gastrointestinal, or cutaneous infection. The toxins are the primary agents of tissue destruction, bleeding, and death of the host. (1, 2, 3) | ||||||||||
| Symptoms | Respiratory infection in humans initially presents with cold or flu-like symptoms. Gastrointestinal infection in causes gastrointestinal difficulty, vomiting of blood, severe diarrhea, acute inflammation of the intestinal tract, and loss of appetite. Some lesions may be found in the intestines and in the mouth and throat. Cutaneous anthrax infection in humans shows up as a boil-like skin lesion that eventually forms an ulcer with a black center (eschar). (3) | ||||||||||
| Treatment | Treatment for anthrax infection includes large doses of intravenous and oral antibiotics, such as fluoroquinolones, like ciprofloxacin (cipro), doxycycline, erythromycin, vancomycin or penicillin. In possible cases of inhalation anthrax, early antibiotic prophylaxis treatment is crucial to prevent possible death. There is an anthrax vaccination licensed under the trade name BioThrax. (3) | ||||||||||
| 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 | P40136 | ||||||||||
| OMIM ID | |||||||||||
| ChEBI ID | Not Available | ||||||||||
| BioCyc ID | Not Available | ||||||||||
| CTD ID | Not Available | ||||||||||
| Stitch ID | Edema factor | ||||||||||
| PDB ID | 1K8T | ||||||||||
| ACToR ID | Not Available | ||||||||||
| Wikipedia Link | Not Available | ||||||||||
| 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:
- Receptor signaling protein tyrosine phosphatase activity
- Specific Function:
- Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis.
- Gene Name:
- MAP2K1
- Uniprot ID:
- Q02750
- Molecular Weight:
- 43438.65 Da
References
- General Function:
- Scaffold protein binding
- Specific Function:
- Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity).
- Gene Name:
- MAP2K2
- Uniprot ID:
- P36507
- Molecular Weight:
- 44423.735 Da
References
- General Function:
- Protein tyrosine kinase activity
- Specific Function:
- Dual specificity kinase. Is activated by cytokines and environmental stress in vivo. Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinase p38.
- Gene Name:
- MAP2K3
- Uniprot ID:
- P46734
- Molecular Weight:
- 39318.05 Da
References
- General Function:
- Protein tyrosine kinase activity
- Specific Function:
- Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14.
- Gene Name:
- MAP2K4
- Uniprot ID:
- P45985
- Molecular Weight:
- 44287.34 Da
References
- General Function:
- Protein tyrosine kinase activity
- Specific Function:
- Acts as a scaffold for the formation of a ternary MAP3K2/MAP3K3-MAP3K5-MAPK7 signaling complex. Activation of this pathway appears to play a critical role in protecting cells from stress-induced apoptosis, neuronal survival and cardiac development and angiogenesis.
- Gene Name:
- MAP2K5
- Uniprot ID:
- Q13163
- Molecular Weight:
- 50111.385 Da
References
- General Function:
- Protein tyrosine kinase activity
- Specific Function:
- Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. With MAP3K3/MKK3, catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 MAPK11, MAPK12, MAPK13 and MAPK14 and plays an important role in the regulation of cellular responses to cytokines and all kinds of stresses. Especially, MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 and MAPK13 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK11 activator in response to TNF. MAP2K6/MKK6 also phosphorylates and activates PAK6. The p38 MAP kinase signal transduction pathway leads to direct activation of transcription factors. Nuclear targets of p38 MAP kinase include the transcription factors ATF2 and ELK1. Within the p38 MAPK signal transduction pathway, MAP3K6/MKK6 mediates phosphorylation of STAT4 through MAPK14 activation, and is therefore required for STAT4 activation and STAT4-regulated gene expression in response to IL-12 stimulation. The pathway is also crucial for IL-6-induced SOCS3 expression and down-regulation of IL-6-mediated gene induction; and for IFNG-dependent gene transcription. Has a role in osteoclast differentiation through NF-kappa-B transactivation by TNFSF11, and in endochondral ossification and since SOX9 is another likely downstream target of the p38 MAPK pathway. MAP2K6/MKK6 mediates apoptotic cell death in thymocytes. Acts also as a regulator for melanocytes dendricity, through the modulation of Rho family GTPases.
- Gene Name:
- MAP2K6
- Uniprot ID:
- P52564
- Molecular Weight:
- 37492.055 Da
References
- General Function:
- Protein tyrosine kinase activity
- Specific Function:
- Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by proinflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis.
- Gene Name:
- MAP2K7
- Uniprot ID:
- O14733
- Molecular Weight:
- 47484.49 Da