Aluminium phosphide (T3D1520)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (23)XML
Targets (23)
Record Information
Version2.0
Creation Date2009-06-19 21:58:54 UTC
Update Date2014-12-24 20:24:05 UTC
Accession NumberT3D1520
Identification
Common NameAluminium phosphide
ClassSmall Molecule
DescriptionAluminium phosphide is a phosphide of aluminum. It is a wide band gap semiconductor and is used as a rodenticide, insecticide and fumigant for stored cereal grains. Aluminum is the most abundant metal in the earth's crust and is always found combined with other elements such as oxygen, silicon, and fluorine. Metal phosphides are hydrolysed to phosphine upon contact with water or stomach acid. Phosphine is a colorless, flammable, explosive, and toxic gas. (11, 8, 9, 10)
Compound Type
  • Aluminum Compound
  • Inorganic Compound
  • Pesticide
  • Phosphide
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
Aluminum phosphide
Aluminum phosphide (alp)
Caswell No. 031
Celphide
Celphine
Celphos
Fumitoxin
Gastion
Phostoxin
Phostoxin-a
RCRA waste number P006
Talunex
Chemical FormulaAlP
Average Molecular Mass57.955 g/mol
Monoisotopic Mass57.955 g/mol
CAS Registry Number20859-73-8
IUPAC Namealumanylidynephosphane
Traditional Namealuminium phosphide
SMILES[Al]#P
InChI IdentifierInChI=1S/Al.P
InChI KeyInChIKey=PPNXXZIBFHTHDM-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of inorganic compounds known as miscellaneous mixed metal/non-metals. These are inorganic compounds containing non-metal as well as metal atoms but not belonging to afore mentioned classes.
KingdomInorganic compounds
Super ClassMixed metal/non-metal compounds
ClassMiscellaneous mixed metal/non-metals
Sub ClassNot Available
Direct ParentMiscellaneous mixed metal/non-metals
Alternative Parents
Substituents
  • Inorganic phosphide
  • Miscellaneous mixed metal/non-metal
Molecular FrameworkNot Available
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceYellow or gray crystals.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
logP0.1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity5.2 m³·mol⁻¹ChemAxon
Polarizability3.59 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-9000000000-734ada5dbbd6ff92d9e82019-02-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-9000000000-734ada5dbbd6ff92d9e82019-02-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-9000000000-734ada5dbbd6ff92d9e82019-02-23View Spectrum
Toxicity Profile
Route of ExposureOral (8) ; Inhalation (8)
Mechanism of ToxicityThe main target organs of aluminum are the central nervous system and bone. Aluminum binds with dietary phosphorus and impairs gastrointestinal absorption of phosphorus. The decreased phosphate body burden results in osteomalacia (softening of the bones due to defective bone mineralization) and rickets. Aluminum's neurotoxicity is believed to involve several mechanisms. Changes in cytoskeletal protein functions as a results of altered phosphorylation, proteolysis, transport, and synthesis are believed to be one cause. Aluminum may induce neurobehavioral effects by affecting permeability of the blood-brain barrier, cholinergic activity, signal transduction pathways, lipid peroxidation, and impair neuronal glutamate nitric oxide-cyclic GMP pathway, as well as interfere with metabolism of essential trace elements because of similar coordination chemistries and consequent competitive interactions. It has been suggested that aluminum's interaction with estrogen receptors increases the expression of estrogen-related genes and thereby contributes to the progression of breast cancer (1), but studies have not been able to establish a clear link between aluminum and increased risk of breast cancer (5). Certain aluminum salts induce immune responses by activating inflammasomes. Phosphine inhibits cytochrome c oxidase, preventing mitochondrial oxidative phosphorylation. This non-competitive inhibition prevents cellular respiration and leads to multi-organ dysfunction. Phosphine can also react with hydrogen peroxide to form the highly reactive hydroxyl radical, which can cause lipid peroxidation. (3, 4, 8, 1, 2)
MetabolismAluminum is poorly absorbed following either oral or inhalation exposure and is essentially not absorbed dermally. The bioavailability of aluminum is strongly influenced by the aluminum compound and the presence of dietary constituents which can complex with aluminum and enhance or inhibit its absorption. Aluminum binds to various ligands in the blood and distributes to every organ, with highest concentrations found in bone and lung tissues. In living organisms, aluminum is believed to exist in four different forms: as free ions, as low-molecular-weight complexes, as physically bound macromolecular complexes, and as covalently bound macromolecular complexes. Absorbed aluminum is excreted principally in the urine and, to a lesser extent, in the bile, while unabsorbed aluminum is excreted in the faeces. Phosphine and metal phosphides may be absorbed following ingestion or inhalation, then distribute to the nervous system, liver, and kidney. In the body, metal phosphides are hydrolysed to phosphine, and phosphine is oxidized to hypophosphite and phosphite. Metabolites are excreted in the urine, while unchanged phosphine is exhaled. (12, 8)
Toxicity ValuesLD50: 11.5 mg/kg (Oral, Rat) (6) LC50: 15.5 mg/m3 over 4 hours (Inhalation, Rat) (6)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Not listed by IARC. IARC classified aluminum production as carcinogenic to humans (Group 1), but did not implicate aluminum itself as a human carcinogen. (13) A link between use of aluminum-containing antiperspirants and increased risk of breast cancer has been proposed (1), but studies have not been able to establish a clear link (5).
Uses/SourcesAluminium phosphide is a wide band gap semiconductor and is used as a rodenticide, insecticide and fumigant for stored cereal grains. (10)
Minimum Risk LevelIntermediate Oral: 1.0 mg/kg/day (7) Chronic Oral: 1.0 mg/kg/day (7)
Health EffectsAluminum targets the nervous system and causes decreased nervous system performance and is associated with altered function of the blood-brain barrier. The accumulation of aluminum in the body may cause bone or brain diseases. High levels of aluminum have been linked to Alzheimer's disease. A small percentage of people are allergic to aluminium and experience contact dermatitis, digestive disorders, vomiting or other symptoms upon contact or ingestion of products containing aluminium. Inhalation of phosphine may cause severe pulmonary irritation leading to acute pulmonary oedema, cardiovascular dysfunction, CNS excitation, coma and death. Gastrointestinal disorders, renal damage and leukopenia may also occur. Chronic exposure to phosphine can result in anemia, bronchitis, gastrointestinal effects, and visual, speech and motor problems. (11, 12, 8, 9)
SymptomsInhalating aluminum dust causes coughing and abnormal chest X-rays. A small percentage of people are allergic to aluminium and experience contact dermatitis, digestive disorders, vomiting or other symptoms upon contact or ingestion of products containing aluminium. Early symptoms of acute phosphine intoxication include pain in the diaphragm, nausea, vomiting, excitement, and a phosphorus smell on the breath. Higher levels can cause weakness, bronchitis, pulmonary edema, shortness of breath, convulsions, and death. Some effects, such as pulmonary edema, convulsions, and liver injury, may appear or continue to be present days after an exposure. Ingestion of metal phosphides results in release of phosphine in your stomach which can cause nausea, vomiting, abdominal pain, and diarrhea. (11, 8, 9)
TreatmentAs there is no antidote for phosphine poisoning, treatment is mainly symptomatic. Artificial respiration, gastric lavage, and/or administration of activated charcoal may be necessary. (12)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID30332
ChEMBL IDNot Available
ChemSpider ID28171
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID38495
BioCyc IDNot Available
CTD IDC001864
Stitch IDAluminium phosphide
PDB IDNot Available
ACToR ID6355
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D1520.pdf
General References
  1. Darbre PD: Metalloestrogens: an emerging class of inorganic xenoestrogens with potential to add to the oestrogenic burden of the human breast. J Appl Toxicol. 2006 May-Jun;26(3):191-7. [16489580 ]
  2. Aimanianda V, Haensler J, Lacroix-Desmazes S, Kaveri SV, Bayry J: Novel cellular and molecular mechanisms of induction of immune responses by aluminum adjuvants. Trends Pharmacol Sci. 2009 Jun;30(6):287-95. doi: 10.1016/j.tips.2009.03.005. Epub 2009 May 11. [19439372 ]
  3. Singh S, Bhalla A, Verma SK, Kaur A, Gill K: Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin Toxicol (Phila). 2006;44(2):155-8. [16615671 ]
  4. Proudfoot AT: Aluminium and zinc phosphide poisoning. Clin Toxicol (Phila). 2009 Feb;47(2):89-100. doi: 10.1080/15563650802520675. [19280425 ]
  5. Willhite CC, Karyakina NA, Yokel RA, Yenugadhati N, Wisniewski TM, Arnold IM, Momoli F, Krewski D: Systematic review of potential health risks posed by pharmaceutical, occupational and consumer exposures to metallic and nanoscale aluminum, aluminum oxides, aluminum hydroxide and its soluble salts. Crit Rev Toxicol. 2014 Oct;44 Suppl 4:1-80. doi: 10.3109/10408444.2014.934439. [25233067 ]
  6. Bingham, E, Cohrssen, B, and Powell, CH (2001). Patty's Toxicology Volumes 1-9. 5th ed. New York, N.Y: John Wiley & Sons.
  7. ATSDR - Agency for Toxic Substances and Disease Registry (2001). Minimal Risk Levels (MRLs) for Hazardous Substances. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  8. ATSDR - Agency for Toxic Substances and Disease Registry (2008). Toxicological profile for aluminum. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  9. Wikipedia. Aluminium. Last Updated 16 June 2009. [Link]
  10. Wikipedia. Aluminium phosphide. Last Updated 25 May 2009. [Link]
  11. ATSDR - Agency for Toxic Substances and Disease Registry (2002). ToxFAQ for phosphine. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  12. International Programme on Chemical Safety (IPCS) INCHEM (1996). Poison Information Monograph for Phosphine. [Link]
  13. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Cytochrome c oxidase subunit 1
General Function:
Iron ion binding
Specific Function:
Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. CO I is the catalytic subunit of the enzyme. Electrons originating in cytochrome c are transferred via the copper A center of subunit 2 and heme A of subunit 1 to the bimetallic center formed by heme A3 and copper B.
Gene Name:
MT-CO1
Uniprot ID:
P00395
Molecular Weight:
57040.91 Da
References
  1. Singh S, Bhalla A, Verma SK, Kaur A, Gill K: Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin Toxicol (Phila). 2006;44(2):155-8. [16615671 ]
Target Details
2. Cytochrome c oxidase subunit 2
General Function:
Cytochrome-c oxidase activity
Specific Function:
Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Subunit 2 transfers the electrons from cytochrome c via its binuclear copper A center to the bimetallic center of the catalytic subunit 1.
Gene Name:
MT-CO2
Uniprot ID:
P00403
Molecular Weight:
25564.73 Da
References
  1. Singh S, Bhalla A, Verma SK, Kaur A, Gill K: Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin Toxicol (Phila). 2006;44(2):155-8. [16615671 ]
Target Details
3. Cytochrome c oxidase subunit 3
General Function:
Cytochrome-c oxidase activity
Specific Function:
Subunits I, II and III form the functional core of the enzyme complex.
Gene Name:
MT-CO3
Uniprot ID:
P00414
Molecular Weight:
29950.6 Da
References
  1. Singh S, Bhalla A, Verma SK, Kaur A, Gill K: Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin Toxicol (Phila). 2006;44(2):155-8. [16615671 ]
Target Details
4. Cytochrome c oxidase subunit 4 isoform 1, mitochondrial
General Function:
Cytochrome-c oxidase activity
Specific Function:
This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport.
Gene Name:
COX4I1
Uniprot ID:
P13073
Molecular Weight:
19576.6 Da
References
  1. Singh S, Bhalla A, Verma SK, Kaur A, Gill K: Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin Toxicol (Phila). 2006;44(2):155-8. [16615671 ]
Target Details
5. Cytochrome c oxidase subunit 4 isoform 2, mitochondrial
General Function:
Cytochrome-c oxidase activity
Specific Function:
This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport.
Gene Name:
COX4I2
Uniprot ID:
Q96KJ9
Molecular Weight:
20010.02 Da
References
  1. Singh S, Bhalla A, Verma SK, Kaur A, Gill K: Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin Toxicol (Phila). 2006;44(2):155-8. [16615671 ]
Target Details
6. Cytochrome c oxidase subunit 5A, mitochondrial
General Function:
Metal ion binding
Specific Function:
This is the heme A-containing chain of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport.
Gene Name:
COX5A
Uniprot ID:
P20674
Molecular Weight:
16761.985 Da
References
  1. Singh S, Bhalla A, Verma SK, Kaur A, Gill K: Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin Toxicol (Phila). 2006;44(2):155-8. [16615671 ]
Target Details
7. Cytochrome c oxidase subunit 5B, mitochondrial
General Function:
Metal ion binding
Specific Function:
This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport.
Gene Name:
COX5B
Uniprot ID:
P10606
Molecular Weight:
13695.57 Da
References
  1. Singh S, Bhalla A, Verma SK, Kaur A, Gill K: Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin Toxicol (Phila). 2006;44(2):155-8. [16615671 ]
Target Details
8. Cytochrome c oxidase subunit 6A1, mitochondrial
General Function:
Cytochrome-c oxidase activity
Specific Function:
This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport.
Gene Name:
COX6A1
Uniprot ID:
P12074
Molecular Weight:
12154.8 Da
References
  1. Singh S, Bhalla A, Verma SK, Kaur A, Gill K: Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin Toxicol (Phila). 2006;44(2):155-8. [16615671 ]
Target Details
9. Cytochrome c oxidase subunit 6A2, mitochondrial
General Function:
Cytochrome-c oxidase activity
Specific Function:
This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport.
Gene Name:
COX6A2
Uniprot ID:
Q02221
Molecular Weight:
10815.32 Da
References
  1. Singh S, Bhalla A, Verma SK, Kaur A, Gill K: Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin Toxicol (Phila). 2006;44(2):155-8. [16615671 ]
Target Details
10. Cytochrome c oxidase subunit 6B1
General Function:
Cytochrome-c oxidase activity
Specific Function:
Connects the two COX monomers into the physiological dimeric form.
Gene Name:
COX6B1
Uniprot ID:
P14854
Molecular Weight:
10192.345 Da
References
  1. Singh S, Bhalla A, Verma SK, Kaur A, Gill K: Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin Toxicol (Phila). 2006;44(2):155-8. [16615671 ]
Target Details
11. Cytochrome c oxidase subunit 6B2
General Function:
Cytochrome-c oxidase activity
Specific Function:
Connects the two COX monomers into the physiological dimeric form.
Gene Name:
COX6B2
Uniprot ID:
Q6YFQ2
Molecular Weight:
10528.905 Da
References
  1. Singh S, Bhalla A, Verma SK, Kaur A, Gill K: Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin Toxicol (Phila). 2006;44(2):155-8. [16615671 ]
Target Details
12. Cytochrome c oxidase subunit 6C
General Function:
Cytochrome-c oxidase activity
Specific Function:
This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport.
Gene Name:
COX6C
Uniprot ID:
P09669
Molecular Weight:
8781.36 Da
References
  1. Singh S, Bhalla A, Verma SK, Kaur A, Gill K: Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin Toxicol (Phila). 2006;44(2):155-8. [16615671 ]
Target Details
13. Cytochrome c oxidase subunit 7A1, mitochondrial
General Function:
Cytochrome-c oxidase activity
Specific Function:
This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport.
Gene Name:
COX7A1
Uniprot ID:
P24310
Molecular Weight:
9117.44 Da
References
  1. Singh S, Bhalla A, Verma SK, Kaur A, Gill K: Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin Toxicol (Phila). 2006;44(2):155-8. [16615671 ]
Target Details
14. Cytochrome c oxidase subunit 7A2, mitochondrial
General Function:
Cytochrome-c oxidase activity
Specific Function:
This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport.
Gene Name:
COX7A2
Uniprot ID:
P14406
Molecular Weight:
9395.89 Da
References
  1. Singh S, Bhalla A, Verma SK, Kaur A, Gill K: Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin Toxicol (Phila). 2006;44(2):155-8. [16615671 ]
Target Details
15. Cytochrome c oxidase subunit 7B, mitochondrial
General Function:
Cytochrome-c oxidase activity
Specific Function:
This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport. Plays a role in proper central nervous system (CNS) development in vertebrates.
Gene Name:
COX7B
Uniprot ID:
P24311
Molecular Weight:
9160.485 Da
References
  1. Singh S, Bhalla A, Verma SK, Kaur A, Gill K: Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin Toxicol (Phila). 2006;44(2):155-8. [16615671 ]
Target Details
16. Cytochrome c oxidase subunit 7B2, mitochondrial
General Function:
Cytochrome-c oxidase activity
Specific Function:
This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport.
Gene Name:
COX7B2
Uniprot ID:
Q8TF08
Molecular Weight:
9077.43 Da
References
  1. Singh S, Bhalla A, Verma SK, Kaur A, Gill K: Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin Toxicol (Phila). 2006;44(2):155-8. [16615671 ]
Target Details
17. Cytochrome c oxidase subunit 7C, mitochondrial
General Function:
Cytochrome-c oxidase activity
Specific Function:
This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport.
Gene Name:
COX7C
Uniprot ID:
P15954
Molecular Weight:
7245.45 Da
References
  1. Singh S, Bhalla A, Verma SK, Kaur A, Gill K: Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin Toxicol (Phila). 2006;44(2):155-8. [16615671 ]
Target Details
18. Cytochrome c oxidase subunit 8A, mitochondrial
General Function:
Cytochrome-c oxidase activity
Specific Function:
This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport.
Gene Name:
COX8A
Uniprot ID:
P10176
Molecular Weight:
7579.0 Da
References
  1. Singh S, Bhalla A, Verma SK, Kaur A, Gill K: Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin Toxicol (Phila). 2006;44(2):155-8. [16615671 ]
Target Details
19. Cytochrome c oxidase subunit 8C, mitochondrial
General Function:
Cytochrome-c oxidase activity
Specific Function:
This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport.
Gene Name:
COX8C
Uniprot ID:
Q7Z4L0
Molecular Weight:
8128.575 Da
References
  1. Singh S, Bhalla A, Verma SK, Kaur A, Gill K: Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin Toxicol (Phila). 2006;44(2):155-8. [16615671 ]
Target Details
20. Estrogen receptor
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66215.45 Da
References
  1. Darbre PD: Metalloestrogens: an emerging class of inorganic xenoestrogens with potential to add to the oestrogenic burden of the human breast. J Appl Toxicol. 2006 May-Jun;26(3):191-7. [16489580 ]
Target Details
21. NACHT, LRR and PYD domains-containing protein 3
General Function:
Transcription factor binding
Specific Function:
As the sensor component of the NLRP3 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens and other damage-associated signals, initiates the formation of the inflammasome polymeric complex, made of NLRP3, PYCARD and CASP1 (and possibly CASP4 and CASP5). Recruitement of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu. Activation of NLRP3 inflammasome is also required for HMGB1 secretion (PubMed:22801494). The active cytokines and HMGB1 stimulate inflammatory responses. Inflammasomes can also induce pyroptosis, an inflammatory form of programmed cell death. Under resting conditions, NLRP3 is autoinhibited. NLRP3 activation stimuli include extracellular ATP, reactive oxygen species, K(+) efflux, crystals of monosodium urate or cholesterol, beta-amyloid fibers, environmental or industrial particles and nanoparticles, etc. However, it is unclear what constitutes the direct NLRP3 activator. Independently of inflammasome activation, regulates the differentiation of T helper 2 (Th2) cells and has a role in Th2 cell-dependent asthma and tumor growth (By similarity). During Th2 differentiation, required for optimal IRF4 binding to IL4 promoter and for IRF4-dependent IL4 transcription. Binds to the consensus DNA sequence 5'-GRRGGNRGAG-3'. May also participate in the transcription of IL5, IL13, GATA3, CCR3, CCR4 and MAF (By similarity).
Gene Name:
NLRP3
Uniprot ID:
Q96P20
Molecular Weight:
118171.375 Da
References
  1. Aimanianda V, Haensler J, Lacroix-Desmazes S, Kaveri SV, Bayry J: Novel cellular and molecular mechanisms of induction of immune responses by aluminum adjuvants. Trends Pharmacol Sci. 2009 Jun;30(6):287-95. doi: 10.1016/j.tips.2009.03.005. Epub 2009 May 11. [19439372 ]
Target Details
22. Phosphorus
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2008). Toxicological profile for aluminum. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Target Details
23. Putative cytochrome c oxidase subunit 7A3, mitochondrial
General Function:
Cytochrome-c oxidase activity
Specific Function:
Not Available
Gene Name:
COX7A2P2
Uniprot ID:
O60397
Molecular Weight:
11840.715 Da
References
  1. Singh S, Bhalla A, Verma SK, Kaur A, Gill K: Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin Toxicol (Phila). 2006;44(2):155-8. [16615671 ]