Chlorothalonil
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Basic Info
| Common Name | Chlorothalonil(F04333) |
| 2D Structure | |
| Description | Chlorothalonil is a chemical compound of cyanide and a non-systemic fungicide. Chlorothalonil-containing products are sold under the names Bravo, Echo, and Daconil. It is used predominantly on peanuts, potatoes, and tomatoes. It is also used on golf courses and lawns and as an additive in some paints. (L597) |
| FRCD ID | F04333 |
| CAS Number | 1897-45-6 |
| PubChem CID | 15910 |
| Formula | C8Cl4N2 |
| IUPAC Name | 2,4,5,6-tetrachlorobenzene-1,3-dicarbonitrile |
| InChI Key | CRQQGFGUEAVUIL-UHFFFAOYSA-N |
| InChI | InChI=1S/C8Cl4N2/c9-5-3(1-13)6(10)8(12)7(11)4(5)2-14 |
| Canonical SMILES | C(#N)C1=C(C(=C(C(=C1Cl)Cl)Cl)C#N)Cl |
| Isomeric SMILES | C(#N)C1=C(C(=C(C(=C1Cl)Cl)Cl)C#N)Cl |
| Synonyms |
Tetrachloroisophthalonitrile
CHLOROTHALONIL
1897-45-6
Daconil
Bravo
m-Tcpn
Nopcocide
1,3-Dicyanotetrachlorobenzene
meta-TCPN
Chloroalonil
|
| Classifies |
Pollutant
Pesticide
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Benzenoids |
| Class | Benzene and substituted derivatives |
| Subclass | Benzonitriles |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Benzonitriles |
| Alternative Parents | |
| Molecular Framework | Aromatic homomonocyclic compounds |
| Substituents | Benzonitrile - Halobenzene - Chlorobenzene - Aryl halide - Aryl chloride - Nitrile - Carbonitrile - Organic nitrogen compound - Organopnictogen compound - Hydrocarbon derivative - Organonitrogen compound - Organochloride - Organohalogen compound - Aromatic homomonocyclic compound |
| Description | This compound belongs to the class of organic compounds known as benzonitriles. These are organic compounds containing a benzene bearing a nitrile substituent. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 265.902 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 0 |
| Complexity | 284 |
| Monoisotopic Mass | 263.882 |
| Exact Mass | 265.879 |
| XLogP | 2.9 |
| Formal Charge | 0 |
| Heavy Atom Count | 14 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
MRLs
| Food | Product Code | Country | MRLs | Application Date | Notes |
|---|---|---|---|---|---|
| Garlic | Japan | 10ppm | |||
| Onion | Japan | 0.5ppm | |||
| Potato | CAC | 0. 2mg/kg | |||
| Squash | CAC | 5mg/kg | |||
| Grapes | CAC | 0. 5mg/kg | |||
| Currants | CAC | 5mg/kg | |||
| Celery | CAC | 10mg/kg | |||
| Liquorice | 0840010 | European Union | 0.05* | 11/02/2016 | |
| Cranberries (Cloudberries, Crowberries, Crowberries, Crowberries, Crowberries, Muntries, Partridge berries, Small cranberries/European cranberries,) | 0154020 | European Union | 5 | 11/02/2016 | |
| Currants (black, red and white) | 0154030 | European Union | 0.01* | 11/02/2016 | |
| Gooseberries (green, red and yellow) | 0154040 | European Union | 15 | 11/02/2016 | |
| Rose hips | 0154050 | European Union | 0.01* | 11/02/2016 | |
| Mulberries (black and white) | 0154060 | European Union | 0.01* | 11/02/2016 | |
| Azaroles/Mediterranean medlars | 0154070 | European Union | 0.01* | 11/02/2016 | |
| Elderberries (Bayberries, Buffalo berries, Che berries, Dwarf elderberries, Guelder rose berries, Hawberries, Midland hawberries, Phalsa fruits, Riberries, Rowan berries, Saskatoons/saskatoons berr... | 0154080 | European Union | 0.01* | 11/02/2016 | |
| Others (2) | 0154990 | European Union | 0.01* | 11/02/2016 | |
| (a) edible peel | 0161000 | European Union | 0.01* | 11/02/2016 | |
| Dates (Açaí berries, Awara palm fruits, Doum palm fruits,) | 0161010 | European Union | 0.01* | 11/02/2016 | |
| Figs | 0161020 | European Union | 0.01* | 11/02/2016 | |
| Table olives (Chinese black olives, Chinese white olives, Desert dates,) | 0161030 | European Union | 0.01* | 11/02/2016 |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Bioaugmentation of chlorothalonil-contaminated soil with hydrolytically orreductively dehalogenating strain and its effect on soil microbial community. | J Hazard Mater | 2018 Jun 5 | 29550558 |
| Rapid analysis of fungicides in tea infusions using ionic liquid immobilizedfabric phase sorptive extraction with the assistance of surfactant fungicidesanalysis using IL-FPSE assisted with surfactant. | Food Chem | 2018 Jan 15 | 28873637 |
| Antioxidant and antimicrobial properties of dried Portuguese apple variety (Malusdomestica Borkh. cv Bravo de Esmolfe). | Food Chem | 2018 Feb 1 | 28946332 |
| Seasonal Effects and the Impact of In-Hive Pesticide Treatments on Parasite,Pathogens, and Health of Honey Bees. | J Econ Entomol | 2018 Apr 2 | 29471479 |
| Behavioral responses of honey bees (Apis mellifera) to natural and syntheticxenobiotics in food. | Sci Rep | 2017 Nov 21 | 29162843 |
| Contaminants of emerging concern in surface waters in Barbados, West Indies. | Environ Monit Assess | 2017 Nov 14 | 29138943 |
| Production of chlorothalonil hydrolytic dehalogenase from agro-industrialwastewater and its application in raw food cleaning. | J Sci Food Agric | 2017 Jun | 27718236 |
| Simultaneous Determination of Eight Pesticide Residues in Cowpeas by GC-ECD. | J Chromatogr Sci | 2017 Jan | 27993860 |
| Food safety in Thailand. 3: Pesticide residues detected in mangosteen (Garciniamangostana L.), queen of fruits. | J Sci Food Agric | 2017 Feb | 27185538 |
| Multi-residue detection of pesticides using a sensitive immunochip assay based onnanogold enhancement. | Anal Chim Acta | 2016 Sep 28 | 27619097 |
| Conditions Optimizing and Application of Laccase-mediator System (LMS) for theLaccase-catalyzed Pesticide Degradation. | Sci Rep | 2016 Oct 24 | 27775052 |
| Monitoring and probabilistic risk assessment of chlorothalonil residues invegetables from Shandong province (China). | Regul Toxicol Pharmacol | 2016 Oct | 27240750 |
| The identification of the metabolites of chlorothalonil in zebrafish (Daniorerio) and their embryo toxicity and endocrine effects at environmentallyrelevant levels. | Environ Pollut | 2016 Nov | 27541960 |
| Evaluation of ozonation technique for pesticide residue removal and its effect onascorbic acid, cyanidin-3-glucoside, and polyphenols in apple (Malus domesticus) fruits. | Environ Monit Assess | 2016 May | 27098519 |
| Current-use pesticides in seawater and their bioaccumulation in polar bear-ringedseal food chains of the Canadian Arctic. | Environ Toxicol Chem | 2016 Jul | 27027986 |
| Analysis of pesticide residues in tobacco with online size exclusionchromatography with gas chromatography and tandem mass spectrometry. | J Sep Sci | 2016 Jul | 27197809 |
| Aqueous ozone solutions for pesticide removal from potatoes. | Food Sci Technol Int | 2016 Dec | 27188796 |
| Occurrence of pesticide residues in fruiting vegetables from production farms in south-eastern region of Poland | Rocz Panstw Zakl Hig | 2016 | 27925705 |
| Antifungal, Phytotoxic, and Cytotoxic Activities of Metabolites from Epichloëbromicola, a Fungus Obtained from Elymus tangutorum Grass. | J Agric Food Chem | 2015 Oct 14 | 26395226 |
| Food safety in Thailand 2: Pesticide residues found in Chinese kale (Brassicaoleracea), a commonly consumed vegetable in Asian countries. | Sci Total Environ | 2015 Nov 1 | 26093223 |
Targets
- General Function:
- Metal ion binding
- Gene Name:
- ALPPL2
- Uniprot ID:
- P10696
- Molecular Weight:
- 57376.515 Da
- Mechanism of Action:
- Cyanide inhibits alkaline phosphatases.
References
- Gerbitz KD: Human alkaline phosphatases. II. Metalloenzyme properties of the enzyme from human liver. Hoppe Seylers Z Physiol Chem. 1977 Nov;358(11):1491-7. [924371 ]
- General Function:
- Pyrophosphatase activity
- Specific Function:
- This isozyme may play a role in skeletal mineralization.
- Gene Name:
- ALPL
- Uniprot ID:
- P05186
- Molecular Weight:
- 57304.435 Da
- Mechanism of Action:
- Cyanide inhibits alkaline phosphatases.
References
- Gerbitz KD: Human alkaline phosphatases. II. Metalloenzyme properties of the enzyme from human liver. Hoppe Seylers Z Physiol Chem. 1977 Nov;358(11):1491-7. [924371 ]
- 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
- Mechanism of Action:
- Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.
References
- Wikipedia. Cyanide poisoning. Last Updated 30 March 2009. : http://en.wikipedia.org/wiki/Cyanide_poisoning
- 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
- Mechanism of Action:
- Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.
References
- Wikipedia. Cyanide poisoning. Last Updated 30 March 2009. : http://en.wikipedia.org/wiki/Cyanide_poisoning
- 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
- Mechanism of Action:
- Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.
References
- Wikipedia. Cyanide poisoning. Last Updated 30 March 2009. : http://en.wikipedia.org/wiki/Cyanide_poisoning
- 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
- Mechanism of Action:
- Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.
References
- Wikipedia. Cyanide poisoning. Last Updated 30 March 2009. : http://en.wikipedia.org/wiki/Cyanide_poisoning
- General Function:
- Ubiquinone binding
- Specific Function:
- Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
- Gene Name:
- SDHD
- Uniprot ID:
- O14521
- Molecular Weight:
- 17042.82 Da
- Mechanism of Action:
- Cyanide inhibits succinate dehydrogenases.
References
- Ardelt BK, Borowitz JL, Isom GE: Brain lipid peroxidation and antioxidant protectant mechanisms following acute cyanide intoxication. Toxicology. 1989 Jun 1;56(2):147-54. [2734799 ]
- 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
- Mechanism of Action:
- Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.
References
- Wikipedia. Cyanide poisoning. Last Updated 30 March 2009. : http://en.wikipedia.org/wiki/Cyanide_poisoning
- 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
- Mechanism of Action:
- Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.
References
- Wikipedia. Cyanide poisoning. Last Updated 30 March 2009. : http://en.wikipedia.org/wiki/Cyanide_poisoning
- 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
- Mechanism of Action:
- Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.
References
- Wikipedia. Cyanide poisoning. Last Updated 30 March 2009. : http://en.wikipedia.org/wiki/Cyanide_poisoning
- 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
- Mechanism of Action:
- Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.
References
- Wikipedia. Cyanide poisoning. Last Updated 30 March 2009. : http://en.wikipedia.org/wiki/Cyanide_poisoning
- 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
- Mechanism of Action:
- Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.
References
- Wikipedia. Cyanide poisoning. Last Updated 30 March 2009. : http://en.wikipedia.org/wiki/Cyanide_poisoning
- 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
- Mechanism of Action:
- Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.
References
- Wikipedia. Cyanide poisoning. Last Updated 30 March 2009. : http://en.wikipedia.org/wiki/Cyanide_poisoning
- 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
- Mechanism of Action:
- Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.
References
- Wikipedia. Cyanide poisoning. Last Updated 30 March 2009. : http://en.wikipedia.org/wiki/Cyanide_poisoning
- 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
- Mechanism of Action:
- Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.
References
- Wikipedia. Cyanide poisoning. Last Updated 30 March 2009. : http://en.wikipedia.org/wiki/Cyanide_poisoning
- 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
- Mechanism of Action:
- Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.
References
- Wikipedia. Cyanide poisoning. Last Updated 30 March 2009. : http://en.wikipedia.org/wiki/Cyanide_poisoning
- 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
- Mechanism of Action:
- Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.
References
- Wikipedia. Cyanide poisoning. Last Updated 30 March 2009. : http://en.wikipedia.org/wiki/Cyanide_poisoning
- 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
- Mechanism of Action:
- Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.
References
- Wikipedia. Cyanide poisoning. Last Updated 30 March 2009. : http://en.wikipedia.org/wiki/Cyanide_poisoning
- 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
- Mechanism of Action:
- Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.
References
- Wikipedia. Cyanide poisoning. Last Updated 30 March 2009. : http://en.wikipedia.org/wiki/Cyanide_poisoning
- General Function:
- Glutathione peroxidase activity
- Specific Function:
- Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione. May constitute a glutathione peroxidase-like protective system against peroxide damage in sperm membrane lipids.
- Gene Name:
- GPX5
- Uniprot ID:
- O75715
- Molecular Weight:
- 25202.14 Da
- Mechanism of Action:
- Cyanide inhibits glutathione peroxidases.
References
- Kraus RJ, Ganther HE: Reaction of cyanide with glutathione peroxidase. Biochem Biophys Res Commun. 1980 Oct 16;96(3):1116-22. [7437059 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Protect the extracellular space from toxic effect of reactive oxygen intermediates by converting superoxide radicals into hydrogen peroxide and oxygen.
- Gene Name:
- SOD3
- Uniprot ID:
- P08294
- Molecular Weight:
- 25850.675 Da
- Mechanism of Action:
- Cyanide inhibits superoxide dismutase [Cu-Zn].
References
- Lee WG, Hwang JH, Na BK, Cho JH, Lee HW, Cho SH, Kong Y, Song CY, Kim TS: Functional expression of a recombinant copper/zinc superoxide dismutase of filarial nematode, Brugia malayi. J Parasitol. 2005 Feb;91(1):205-8. [15856906 ]
- General Function:
- Sh3 domain binding
- Specific Function:
- Protects the hemoglobin in erythrocytes from oxidative breakdown.
- Gene Name:
- GPX1
- Uniprot ID:
- P07203
- Molecular Weight:
- 22087.94 Da
- Mechanism of Action:
- Cyanide inhibits glutathione peroxidases.
References
- Kraus RJ, Ganther HE: Reaction of cyanide with glutathione peroxidase. Biochem Biophys Res Commun. 1980 Oct 16;96(3):1116-22. [7437059 ]
- General Function:
- Glutathione peroxidase activity
- Specific Function:
- Could play a major role in protecting mammals from the toxicity of ingested organic hydroperoxides. Tert-butyl hydroperoxide, cumene hydroperoxide and linoleic acid hydroperoxide but not phosphatidycholine hydroperoxide, can act as acceptors.
- Gene Name:
- GPX2
- Uniprot ID:
- P18283
- Molecular Weight:
- 21953.835 Da
- Mechanism of Action:
- Cyanide inhibits glutathione peroxidases.
References
- Kraus RJ, Ganther HE: Reaction of cyanide with glutathione peroxidase. Biochem Biophys Res Commun. 1980 Oct 16;96(3):1116-22. [7437059 ]
- General Function:
- Transcription factor binding
- Specific Function:
- Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione.
- Gene Name:
- GPX3
- Uniprot ID:
- P22352
- Molecular Weight:
- 25552.185 Da
- Mechanism of Action:
- Cyanide inhibits glutathione peroxidases.
References
- Kraus RJ, Ganther HE: Reaction of cyanide with glutathione peroxidase. Biochem Biophys Res Commun. 1980 Oct 16;96(3):1116-22. [7437059 ]
- General Function:
- Glutathione peroxidase activity
- Gene Name:
- GPX6
- Uniprot ID:
- P59796
- Molecular Weight:
- 24970.46 Da
- Mechanism of Action:
- Cyanide inhibits glutathione peroxidases.
References
- Kraus RJ, Ganther HE: Reaction of cyanide with glutathione peroxidase. Biochem Biophys Res Commun. 1980 Oct 16;96(3):1116-22. [7437059 ]
- General Function:
- Peroxidase activity
- Specific Function:
- It protects esophageal epithelia from hydrogen peroxide-induced oxidative stress. It suppresses acidic bile acid-induced reactive oxigen species (ROS) and protects against oxidative DNA damage and double-strand breaks.
- Gene Name:
- GPX7
- Uniprot ID:
- Q96SL4
- Molecular Weight:
- 20995.88 Da
- Mechanism of Action:
- Cyanide inhibits glutathione peroxidases.
References
- Kraus RJ, Ganther HE: Reaction of cyanide with glutathione peroxidase. Biochem Biophys Res Commun. 1980 Oct 16;96(3):1116-22. [7437059 ]
- General Function:
- Nadp binding
- Specific Function:
- Maintains high levels of reduced glutathione in the cytosol.
- Gene Name:
- GSR
- Uniprot ID:
- P00390
- Molecular Weight:
- 56256.565 Da
- Mechanism of Action:
- Cyanide inhibits glutathione reductase.
References
- Ardelt BK, Borowitz JL, Isom GE: Brain lipid peroxidation and antioxidant protectant mechanisms following acute cyanide intoxication. Toxicology. 1989 Jun 1;56(2):147-54. [2734799 ]
- General Function:
- Peroxidase activity
- Gene Name:
- GPX8
- Uniprot ID:
- Q8TED1
- Molecular Weight:
- 23880.83 Da
- Mechanism of Action:
- Cyanide inhibits glutathione peroxidases.
References
- Kraus RJ, Ganther HE: Reaction of cyanide with glutathione peroxidase. Biochem Biophys Res Commun. 1980 Oct 16;96(3):1116-22. [7437059 ]
- General Function:
- Succinate dehydrogenase activity
- Specific Function:
- Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q). Can act as a tumor suppressor.
- Gene Name:
- SDHA
- Uniprot ID:
- P31040
- Molecular Weight:
- 72690.975 Da
- Mechanism of Action:
- Cyanide inhibits succinate dehydrogenases.
References
- Ardelt BK, Borowitz JL, Isom GE: Brain lipid peroxidation and antioxidant protectant mechanisms following acute cyanide intoxication. Toxicology. 1989 Jun 1;56(2):147-54. [2734799 ]
- General Function:
- Ubiquinone binding
- Specific Function:
- Iron-sulfur protein (IP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
- Gene Name:
- SDHB
- Uniprot ID:
- P21912
- Molecular Weight:
- 31629.365 Da
- Mechanism of Action:
- Cyanide inhibits succinate dehydrogenases.
References
- Ardelt BK, Borowitz JL, Isom GE: Brain lipid peroxidation and antioxidant protectant mechanisms following acute cyanide intoxication. Toxicology. 1989 Jun 1;56(2):147-54. [2734799 ]
- General Function:
- Succinate dehydrogenase activity
- Specific Function:
- Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
- Gene Name:
- SDHC
- Uniprot ID:
- Q99643
- Molecular Weight:
- 18610.03 Da
- Mechanism of Action:
- Cyanide inhibits succinate dehydrogenases.
References
- Ardelt BK, Borowitz JL, Isom GE: Brain lipid peroxidation and antioxidant protectant mechanisms following acute cyanide intoxication. Toxicology. 1989 Jun 1;56(2):147-54. [2734799 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
- Gene Name:
- SOD1
- Uniprot ID:
- P00441
- Molecular Weight:
- 15935.685 Da
- Mechanism of Action:
- Cyanide inhibits superoxide dismutase [Cu-Zn].
References
- Lee WG, Hwang JH, Na BK, Cho JH, Lee HW, Cho SH, Kong Y, Song CY, Kim TS: Functional expression of a recombinant copper/zinc superoxide dismutase of filarial nematode, Brugia malayi. J Parasitol. 2005 Feb;91(1):205-8. [15856906 ]
- General Function:
- Protein homodimerization activity
- Specific Function:
- This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the rate-limiting conversions of tyrosine to DOPA, DOPA to DOPA-quinone and possibly 5,6-dihydroxyindole to indole-5,6 quinone.
- Gene Name:
- TYR
- Uniprot ID:
- P14679
- Molecular Weight:
- 60392.69 Da
- Mechanism of Action:
- Cyanide inhibits tyrosinase.
References
- Laufer Z, Beckett RP, Minibayeva FV: Co-occurrence of the multicopper oxidases tyrosinase and laccase in lichens in sub-order peltigerineae. Ann Bot. 2006 Nov;98(5):1035-42. Epub 2006 Sep 1. [16950829 ]
- General Function:
- Transmembrane signaling receptor activity
- Specific Function:
- Thrombomodulin is a specific endothelial cell receptor that forms a 1:1 stoichiometric complex with thrombin. This complex is responsible for the conversion of protein C to the activated protein C (protein Ca). Once evolved, protein Ca scissions the activated cofactors of the coagulation mechanism, factor Va and factor VIIIa, and thereby reduces the amount of thrombin generated.
- Gene Name:
- THBD
- Uniprot ID:
- P07204
- Molecular Weight:
- 60328.72 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic genes expression.
- Gene Name:
- NR3C1
- Uniprot ID:
- P04150
- Molecular Weight:
- 85658.57 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Transcription regulatory region sequence-specific dna binding
- Specific Function:
- Transcription factor that binds to the octamer motif (5'-ATTTGCAT-3') and activates the promoters of the genes for some small nuclear RNAs (snRNA) and of genes such as those for histone H2B and immunoglobulins. Modulates transcription transactivation by NR3C1, AR and PGR (By similarity). In case of human herpes simplex virus (HSV) infection, POU2F1 forms a multiprotein-DNA complex with the viral transactivator protein VP16 and HCFC1 thereby enabling the transcription of the viral immediate early genes.
- Gene Name:
- POU2F1
- Uniprot ID:
- P14859
- Molecular Weight:
- 76470.82 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Iron ion binding
- Specific Function:
- Catalyzes the conversion of 25-hydroxyvitamin D3 (25(OH)D) to 1-alpha,25-dihydroxyvitamin D3 (1,25(OH)2D) plays an important role in normal bone growth, calcium metabolism, and tissue differentiation.
- Gene Name:
- CYP27B1
- Uniprot ID:
- O15528
- Molecular Weight:
- 56503.475 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Recruited to promoters via its interaction with BAZ1B/WSTF which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.
- Gene Name:
- VDR
- Uniprot ID:
- P11473
- Molecular Weight:
- 48288.64 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- Uniprot ID:
- P05184
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Serine-type endopeptidase activity
- Specific Function:
- Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
- Gene Name:
- PLAU
- Uniprot ID:
- P00749
- Molecular Weight:
- 48507.09 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Atp binding
- Specific Function:
- Involved in DNA damage response. Involved in a RAD9A-related damage checkpoint, a pathway that is important in determining whether DNA damage is compatible with cell survival or whether it requires cell elimination by apoptosis. Modulates the RAD9A interaction with BCL2 and thereby induces DNA damages-induced apoptosis.
- Gene Name:
- ATAD5
- Uniprot ID:
- Q96QE3
- Molecular Weight:
- 207568.185 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels (By similarity).
- Gene Name:
- PPARG
- Uniprot ID:
- P37231
- Molecular Weight:
- 57619.58 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Transcriptional activator activity, rna polymerase ii transcription factor binding
- Specific Function:
- Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3'. Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation.
- Gene Name:
- JUN
- Uniprot ID:
- P05412
- Molecular Weight:
- 35675.32 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- Gene Name:
- TP53
- Uniprot ID:
- P04637
- Molecular Weight:
- 43652.79 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Transferase activity
- Specific Function:
- Synthesizes the second messagers cyclic ADP-ribose and nicotinate-adenine dinucleotide phosphate, the former a second messenger for glucose-induced insulin secretion. Also has cADPr hydrolase activity. Also moonlights as a receptor in cells of the immune system.
- Gene Name:
- CD38
- Uniprot ID:
- P28907
- Molecular Weight:
- 34328.145 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- Gene Name:
- CCL2
- Uniprot ID:
- P13500
- Molecular Weight:
- 11024.87 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Chemokine activity
- Specific Function:
- Chemotactic for eosinophils and basophils. Binds to CCR3.
- Gene Name:
- CCL26
- Uniprot ID:
- Q9Y258
- Molecular Weight:
- 10647.495 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Receptor binding
- Specific Function:
- Chemotactic for monocytes and T-lymphocytes. Binds to CXCR3.
- Gene Name:
- CXCL10
- Uniprot ID:
- P02778
- Molecular Weight:
- 10880.915 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Cytokine activity
- Specific Function:
- Cytokine that affects the growth, movement, or activation state of cells that participate in immune and inflammatory response. Chemotactic for activated T-cells. Binds to CXCR3.
- Gene Name:
- CXCL9
- Uniprot ID:
- Q07325
- Molecular Weight:
- 14018.72 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Transmembrane signaling receptor activity
- Specific Function:
- Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with PSGL1/SELPLG. May have a role in capillary morphogenesis.
- Gene Name:
- SELE
- Uniprot ID:
- P16581
- Molecular Weight:
- 66654.575 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Transmembrane signaling receptor activity
- Specific Function:
- Involved in lymphocyte proliferation and functions as a signal transmitting receptor in lymphocytes, natural killer (NK) cells, and platelets.
- Gene Name:
- CD69
- Uniprot ID:
- Q07108
- Molecular Weight:
- 22559.25 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Cytokine activity
- Specific Function:
- Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.
- Gene Name:
- IL1A
- Uniprot ID:
- P01583
- Molecular Weight:
- 30606.29 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Interleukin-8 receptor binding
- Specific Function:
- IL-8 is a chemotactic factor that attracts neutrophils, basophils, and T-cells, but not monocytes. It is also involved in neutrophil activation. It is released from several cell types in response to an inflammatory stimulus. IL-8(6-77) has a 5-10-fold higher activity on neutrophil activation, IL-8(5-77) has increased activity on neutrophil activation and IL-8(7-77) has a higher affinity to receptors CXCR1 and CXCR2 as compared to IL-8(1-77), respectively.
- Gene Name:
- CXCL8
- Uniprot ID:
- P10145
- Molecular Weight:
- 11097.98 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.
- Gene Name:
- MMP9
- Uniprot ID:
- P14780
- Molecular Weight:
- 78457.51 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Protease binding
- Specific Function:
- Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-13, MMP-14, MMP-15, MMP-16 and MMP-19.
- Gene Name:
- TIMP2
- Uniprot ID:
- P16035
- Molecular Weight:
- 24398.995 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Sialic acid binding
- Specific Function:
- Ca(2+)-dependent receptor for myeloid cells that binds to carbohydrates on neutrophils and monocytes. Mediates the interaction of activated endothelial cells or platelets with leukocytes. The ligand recognized is sialyl-Lewis X. Mediates rapid rolling of leukocyte rolling over vascular surfaces during the initial steps in inflammation through interaction with PSGL1.
- Gene Name:
- SELP
- Uniprot ID:
- P16109
- Molecular Weight:
- 90833.105 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Serine-type endopeptidase inhibitor activity
- Specific Function:
- Serine protease inhibitor. This inhibitor acts as 'bait' for tissue plasminogen activator, urokinase, protein C and matriptase-3/TMPRSS7. Its rapid interaction with PLAT may function as a major control point in the regulation of fibrinolysis.
- Gene Name:
- SERPINE1
- Uniprot ID:
- P05121
- Molecular Weight:
- 45059.695 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Prostaglandin e receptor activity
- Specific Function:
- Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. The subsequent raise in intracellular cAMP is responsible for the relaxing effect of this receptor on smooth muscle.
- Gene Name:
- PTGER2
- Uniprot ID:
- P43116
- Molecular Weight:
- 39759.945 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
- Specific Function:
- Gtp binding
- Gene Name:
- TUBA1A
- Uniprot ID:
- Q71U36
- Molecular Weight:
- 50135.25 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Tumor necrosis factor receptor binding
- Specific Function:
- Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key 'Ser-418' residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line (PubMed:22517918).The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.
- Gene Name:
- TNF
- Uniprot ID:
- P01375
- Molecular Weight:
- 25644.15 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Ubiquitin protein ligase binding
- Specific Function:
- Receptor for TNFSF5/CD40LG. Transduces TRAF6- and MAP3K8-mediated signals that activate ERK in macrophages and B cells, leading to induction of immunoglobulin secretion.
- Gene Name:
- CD40
- Uniprot ID:
- P25942
- Molecular Weight:
- 30618.76 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Urokinase plasminogen activator receptor activity
- Specific Function:
- Acts as a receptor for urokinase plasminogen activator. Plays a role in localizing and promoting plasmin formation. Mediates the proteolysis-independent signal transduction activation effects of U-PA. It is subject to negative-feedback regulation by U-PA which cleaves it into an inactive form.
- Gene Name:
- PLAUR
- Uniprot ID:
- Q03405
- Molecular Weight:
- 36977.62 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Primary amine oxidase activity
- Specific Function:
- Important in cell-cell recognition. Appears to function in leukocyte-endothelial cell adhesion. Interacts with integrin alpha-4/beta-1 (ITGA4/ITGB1) on leukocytes, and mediates both adhesion and signal transduction. The VCAM1/ITGA4/ITGB1 interaction may play a pathophysiologic role both in immune responses and in leukocyte emigration to sites of inflammation.
- Gene Name:
- VCAM1
- Uniprot ID:
- P19320
- Molecular Weight:
- 81275.43 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- 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
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Cholesterol binding
- Specific Function:
- Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism (PubMed:24814875), but its precise physiological role is controversial. It is apparently not required for steroid hormone biosynthesis. Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides (PubMed:1847678).
- Gene Name:
- TSPO
- Uniprot ID:
- P30536
- Molecular Weight:
- 18827.81 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Interleukin-6 receptor binding
- Specific Function:
- Cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig-secreting cells Involved in lymphocyte and monocyte differentiation. Acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells and cells of the CNS. Required for the generation of T(H)17 cells. Also acts as a myokine. It is discharged into the bloodstream after muscle contraction and acts to increase the breakdown of fats and to improve insulin resistance. It induces myeloma and plasmacytoma growth and induces nerve cells differentiation.
- Gene Name:
- IL6
- Uniprot ID:
- P05231
- Molecular Weight:
- 23717.965 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Steroid hydroxylase activity
- Specific Function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
- Gene Name:
- CYP2B6
- Uniprot ID:
- P20813
- Molecular Weight:
- 56277.81 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Hydroxymethylglutaryl-coa synthase activity
- Specific Function:
- This enzyme condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is the substrate for HMG-CoA reductase.
- Gene Name:
- HMGCS2
- Uniprot ID:
- P54868
- Molecular Weight:
- 56634.915 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Receptor binding
- Specific Function:
- Occurs in almost all aerobically respiring organisms and serves to protect cells from the toxic effects of hydrogen peroxide. Promotes growth of cells including T-cells, B-cells, myeloid leukemia cells, melanoma cells, mastocytoma cells and normal and transformed fibroblast cells.
- Gene Name:
- CAT
- Uniprot ID:
- P04040
- Molecular Weight:
- 59755.82 Da
- Mechanism of Action:
- Cyanide inhibits catalase.
References
- Kang YS, Lee DH, Yoon BJ, Oh DC: Purification and characterization of a catalase from photosynthetic bacterium Rhodospirillum rubrum S1 grown under anaerobic conditions. J Microbiol. 2006 Apr;44(2):185-91. [16728955 ]
- 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
- Mechanism of Action:
- Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.
References
- Wikipedia. Cyanide poisoning. Last Updated 30 March 2009. : http://en.wikipedia.org/wiki/Cyanide_poisoning
- 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
- Mechanism of Action:
- Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.
References
- Wikipedia. Cyanide poisoning. Last Updated 30 March 2009. : http://en.wikipedia.org/wiki/Cyanide_poisoning
- 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
- Mechanism of Action:
- Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.
References
- Wikipedia. Cyanide poisoning. Last Updated 30 March 2009. : http://en.wikipedia.org/wiki/Cyanide_poisoning
- General Function:
- Phospholipid-hydroperoxide glutathione peroxidase activity
- Specific Function:
- Protects cells against membrane lipid peroxidation and cell death. Required for normal sperm development and male fertility. Could play a major role in protecting mammals from the toxicity of ingested lipid hydroperoxides. Essential for embryonic development. Protects from radiation and oxidative damage.
- Gene Name:
- GPX4
- Uniprot ID:
- P36969
- Molecular Weight:
- 22174.52 Da
- Mechanism of Action:
- Cyanide inhibits glutathione peroxidases.
References
- Kraus RJ, Ganther HE: Reaction of cyanide with glutathione peroxidase. Biochem Biophys Res Commun. 1980 Oct 16;96(3):1116-22. [7437059 ]
- General Function:
- Cytochrome-c oxidase activity
- Gene Name:
- COX7A2P2
- Uniprot ID:
- O60397
- Molecular Weight:
- 11840.715 Da
- Mechanism of Action:
- Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.
References
- Wikipedia. Cyanide poisoning. Last Updated 30 March 2009. : http://en.wikipedia.org/wiki/Cyanide_poisoning
- General Function:
- Zinc ion binding
- Specific Function:
- Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Regulates expression of target genes in a ligand-dependent manner by recruiting chromatin complexes containing KMT2E/MLL5. Mediates retinoic acid-induced granulopoiesis.
- Gene Name:
- RARA
- Uniprot ID:
- P10276
- Molecular Weight:
- 50770.805 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
- Gene Name:
- NR1I2
- Uniprot ID:
- O75469
- Molecular Weight:
- 49761.245 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Vitamin d3 25-hydroxylase activity
- Specific Function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
- Gene Name:
- CYP3A4
- Uniprot ID:
- P08684
- Molecular Weight:
- 57342.67 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
- Gene Name:
- CYP1A2
- Uniprot ID:
- P05177
- Molecular Weight:
- 58293.76 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Peptide antigen binding
- Specific Function:
- Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading.
- Gene Name:
- HLA-DRA
- Uniprot ID:
- P01903
- Molecular Weight:
- 28606.685 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Virus receptor activity
- Specific Function:
- ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical cups through ARHGEF26/SGEF and RHOG activation.(Microbial infection) Acts as a receptor for major receptor group rhinovirus A-B capsid proteins (PubMed:1968231, PubMed:2538243). Acts as a receptor for Coxsackievirus A21 capsid proteins (PubMed:11160747, PubMed:16004874, PubMed:9539703). Upon Kaposi's sarcoma-associated herpesvirus/HHV-8 infection, is degraded by viral E3 ubiquitin ligase MIR2, presumably to prevent lysis of infected cells by cytotoxic T-lymphocytes and NK cell (PubMed:11413168).
- Gene Name:
- ICAM1
- Uniprot ID:
- P05362
- Molecular Weight:
- 57824.785 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Protein homodimerization activity
- Specific Function:
- Cytokine that plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone development. Required for normal male and female fertility. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration. Plays a role in lipoprotein clearance.
- Gene Name:
- CSF1
- Uniprot ID:
- P09603
- Molecular Weight:
- 60178.885 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Protease binding
- Specific Function:
- Initiates blood coagulation by forming a complex with circulating factor VII or VIIa. The [TF:VIIa] complex activates factors IX or X by specific limited protolysis. TF plays a role in normal hemostasis by initiating the cell-surface assembly and propagation of the coagulation protease cascade.
- Gene Name:
- F3
- Uniprot ID:
- P13726
- Molecular Weight:
- 33067.3 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Type iii transforming growth factor beta receptor binding
- Specific Function:
- Multifunctional protein that controls proliferation, differentiation and other functions in many cell types. Many cells synthesize TGFB1 and have specific receptors for it. It positively and negatively regulates many other growth factors. It plays an important role in bone remodeling as it is a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts. Can promote either T-helper 17 cells (Th17) or regulatory T-cells (Treg) lineage differentiation in a concentration-dependent manner. At high concentrations, leads to FOXP3-mediated suppression of RORC and down-regulation of IL-17 expression, favoring Treg cell development. At low concentrations in concert with IL-6 and IL-21, leads to expression of the IL-17 and IL-23 receptors, favoring differentiation to Th17 cells.
- Gene Name:
- TGFB1
- Uniprot ID:
- P01137
- Molecular Weight:
- 44340.685 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Histone binding
- Specific Function:
- Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Required for checkpoint-mediated arrest of cell cycle progression in response to low doses of ionizing radiation and for efficient repair of DNA double strand breaks (DSBs) specifically when modified by C-terminal phosphorylation.
- Gene Name:
- H2AFX
- Uniprot ID:
- P16104
- Molecular Weight:
- 15144.45 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]