Arsenic (T3D0001)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (46)XML
Targets (46)
Record Information
Version2.0
Creation Date2009-03-06 18:57:53 UTC
Update Date2014-12-24 20:20:50 UTC
Accession NumberT3D0001
Identification
Common NameArsenic
ClassSmall Molecule
DescriptionArsenic(As) is a ubiquitous metalloid found in several forms in food and the environment, such as the soil, air and water. Physiologically, it exists as an ion in the body. The predominant form is inorganic arsenic in drinking water, which is both highly toxic and carcinogenic and rapidly bioavailable. Arsenic is currently one of the most important environmental global contaminants and toxicants, particularly in the developing countries. For decades, very large populations have been and are currently still exposed to inorganic Arsenic through geogenically contaminated drinking water. An increased incidence of disease mediated by this toxicant is the consequence of long-term exposure. In human's chronic ingestion of inorganic arsenic (> 500 mg/L As) has been associated with cardiovascular, nervous, hepatic and renal diseases and diabetes mellitus as well as cancer of the skin, bladder, lung, liver and prostate. Contrary to the earlier view that methylated compounds are innocuous, the methylated metabolites are now recognized to be both toxic and carcinogenic, possibly due to genotoxicity, inhibition of antioxidative enzyme functions, or other mechanisms. Arsenic inhibits indirectly sulfhydryl containing enzymes and interferes with cellular metabolism. Effects involve such phenomena as cytotoxicity, genotoxicity and inhibition of enzymes with antioxidant function. These are all related to nutritional factors directly or indirectly. Nutritional studies both in experimental and epidemiological studies provide convincing evidence that nutritional intervention, including chemoprevention, offers a pragmatic approach to mitigate the health effects of arsenic exposure, particularly cancer, in the relatively resource-poor developing countries. Nutritional intervention, especially with micronutrients, many of which are antioxidants and share the same pathway with Arsenic , appears a host defence against the health effects of arsenic contamination in developing countries and should be embraced as it is pragmatic and inexpensive. (5, 6).
Compound Type
  • Arsenic Compound
  • Cigarette Toxin
  • Food Toxin
  • Household Toxin
  • Inorganic Compound
  • Metabolite
  • Metal
  • Metalloid
  • Natural Compound
  • Pesticide
  • Pollutant
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
Arsenic ion
Arsenic(3+)
Arsenic(3+) ion
Arsenic(III)
Arsenic(III) cation
As
As(3+)
As3+
Chemical FormulaAs
Average Molecular Mass74.920 g/mol
Monoisotopic Mass74.920 g/mol
CAS Registry Number7440-38-2
IUPAC Namearsenic(3+) ion
Traditional Namearsenic(3+) ion
SMILES[As+3]
InChI IdentifierInChI=1S/As/q+3
InChI KeyInChIKey=LULLIKNODDLMDQ-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of inorganic compounds known as homogeneous metalloid compounds. These are inorganic compounds containing only metal atoms,with the largest atom being a metalloid atom.
KingdomInorganic compounds
Super ClassHomogeneous metal compounds
ClassHomogeneous metalloid compounds
Sub ClassNot Available
Direct ParentHomogeneous metalloid compounds
Alternative ParentsNot Available
Substituents
  • Homogeneous metalloid
Molecular FrameworkNot Available
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceGrey metallic solid.
Experimental Properties
PropertyValue
Melting Point> 615°C
Boiling Point614 °C
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
logP0.75ChemAxon
Physiological Charge3ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity0 m³·mol⁻¹ChemAxon
Polarizability1.78 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, Positivesplash10-001i-9000000000-6183cd0482f3420823922016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-9000000000-6183cd0482f3420823922016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001i-9000000000-6183cd0482f3420823922016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-9000000000-30fac8ea879bd5e349662016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-9000000000-30fac8ea879bd5e349662016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-9000000000-30fac8ea879bd5e349662016-08-03View Spectrum
Toxicity Profile
Route of ExposureOral (11); inhalation (11); dermal (11)
Mechanism of ToxicityArsenic and its metabolites disrupt ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits pyruvate dehydrogenase and by competing with phosphate it uncouples oxidative phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration, and ATP synthesis. Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress. Arsenic's carcinogenicity is influenced by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. The binding of other arsenic protein targets may also cause altered DNA repair enzyme activity, altered DNA methylation patterns and cell proliferation. (7, 4)
MetabolismArsenic is absorbed mainly by inhalation or ingestion, as to a lesser extent, dermal exposure. It is then distributed throughout the body, where it is reduced into arsenite if necessary, then methylated into monomethylarsenic (MMA) and dimethylarsenic acid (DMA) by arsenite methyltransferase. Arsenic and its metabolites are primarily excreted in the urine. Arsenic is known to induce the metal-binding protein metallothionein, which decreases the toxic effects of arsenic and other metals by binding them and making them biologically inactive, as well as acting as an antioxidant. (12)
Toxicity ValuesLD50: 763 mg/kg (Oral, Rat) (9) LD50: 13.4 ug/kg (Intraperitoneal, Rat) (9)
Lethal Dose130 mg for an adult human. (10)
Carcinogenicity (IARC Classification)1, carcinogenic to humans. (15)
Uses/SourcesArsenic is used in pesticides, wood preservatives, paints/pigments, and various metal alloys (electronics). Small amounts of arensic can be found in contaminated air, water, and some meat products, especially seafood. (11)
Minimum Risk LevelAcute Oral: 0.005 mg/kg/day (14) Chronic Oral: 0.0003 mg/kg/day (14) Chronic Inhalation: 0.01 mg/m3 (14) The World Health Organization asserts that a level of 0.01 mg/L in drinking water poses a risk of 1/1600 chance of lifetime skin cancer risk.
Health EffectsArsenic poisoning can lead to death from multi-system organ failure, probably from necrotic cell death, not apoptosis. Arsenic is also a known carcinogen, especially in skin, liver, bladder and lung cancers. (7, 12) Arsenic poisoning is has also been associated with heart disease, (hypertension related cardiovascular), stroke (cerebrovascular diseases), chronic lower respiratory diseases and diabetes. Chronic exposure to arsenic can lead to a vitamin A deficiency which is related to heart disease and night blindness.
SymptomsExposure to lower levels of arsenic can cause nausea and vomiting, decreased production of red and white blood cells, abnormal heart rhythm, damage to blood vessels, and a sensation of “pins and needles” in hands and feet. Breathing high levels of inorganic arsenic can give you a sore throat or irritated lungs. Arsenic also affects the brain, causing neurological disturbances such as headaches, confusion, and drowsiness. (1)
TreatmentArsenic poisoning can be treated by chelation therapy, using chelating agents such as dimercaprol, EDTA or DMSA. Charcoal tablets may also be used for less severe cases. In addition, maintaining a diet high in sulfur helps eliminate arsenic from the body. (12)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB02290
PubChem Compound ID104734
ChEMBL IDNot Available
ChemSpider ID94549
KEGG IDC06269
UniProt IDNot Available
OMIM ID
ChEBI ID35828
BioCyc IDCPD-763
CTD IDD001151
Stitch IDArsenic
PDB IDNot Available
ACToR ID6367
Wikipedia LinkArsenic
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Croal LR, Gralnick JA, Malasarn D, Newman DK: The genetics of geochemistry. Annu Rev Genet. 2004;38:175-202. [15568975 ]
  2. Naranmandura H, Suzuki KT: Identification of the major arsenic-binding protein in rat plasma as the ternary dimethylarsinous-hemoglobin-haptoglobin complex. Chem Res Toxicol. 2008 Mar;21(3):678-85. doi: 10.1021/tx700383g. Epub 2008 Feb 2. [18247522 ]
  3. Menzel DB, Hamadeh HK, Lee E, Meacher DM, Said V, Rasmussen RE, Greene H, Roth RN: Arsenic binding proteins from human lymphoblastoid cells. Toxicol Lett. 1999 Mar 29;105(2):89-101. [10221271 ]
  4. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
  5. Anetor JI, Wanibuchi H, Fukushima S: Arsenic exposure and its health effects and risk of cancer in developing countries: micronutrients as host defence. Asian Pac J Cancer Prev. 2007 Jan-Mar;8(1):13-23. [17477765 ]
  6. Jones FT: A broad view of arsenic. Poult Sci. 2007 Jan;86(1):2-14. [17179408 ]
  7. Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.
  8. Emsley, John (2001). Nature's Building Blocks: An A-Z Guide to the Elements. Oxford: Oxford University Press.
  9. Lewis RJ (1996). Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold.
  10. US Environmental Protection Agency (2001). OHM/TADS: Oil and Hazardous Materials/Technical Assistance Data System. Washington, DC (Internet Version). Edition expires 2001. Greenwood Village, CO: Thomson Healthcare Inc.
  11. ATSDR - Agency for Toxic Substances and Disease Registry (2007). Toxicological profile for arsenic. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  12. Wikipedia. Arsenic toxicity. Last Updated 22 February 2009. [Link]
  13. Wikipedia. Metallothionein. Last Updated 20 December 2008. [Link]
  14. 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]
  15. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

Target Details
1. Tubulin beta chain
General Function:
Ubiquitin protein ligase binding
Specific 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.
Gene Name:
TUBB
Uniprot ID:
P07437
Molecular Weight:
49670.515 Da
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
  2. Zhang X, Yang F, Shim JY, Kirk KL, Anderson DE, Chen X: Identification of arsenic-binding proteins in human breast cancer cells. Cancer Lett. 2007 Sep 18;255(1):95-106. Epub 2007 May 17. [17499915 ]
Target Details
2. Actin, alpha cardiac muscle 1
General Function:
Myosin binding
Specific Function:
Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
Gene Name:
ACTC1
Uniprot ID:
P68032
Molecular Weight:
42018.6 Da
References
  1. Menzel DB, Hamadeh HK, Lee E, Meacher DM, Said V, Rasmussen RE, Greene H, Roth RN: Arsenic binding proteins from human lymphoblastoid cells. Toxicol Lett. 1999 Mar 29;105(2):89-101. [10221271 ]
Target Details
3. Actin, alpha skeletal muscle
General Function:
Structural constituent of cytoskeleton
Specific Function:
Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
Gene Name:
ACTA1
Uniprot ID:
P68133
Molecular Weight:
42050.67 Da
References
  1. Menzel DB, Hamadeh HK, Lee E, Meacher DM, Said V, Rasmussen RE, Greene H, Roth RN: Arsenic binding proteins from human lymphoblastoid cells. Toxicol Lett. 1999 Mar 29;105(2):89-101. [10221271 ]
Target Details
4. Actin, aortic smooth muscle
General Function:
Protein kinase binding
Specific Function:
Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
Gene Name:
ACTA2
Uniprot ID:
P62736
Molecular Weight:
42008.57 Da
References
  1. Menzel DB, Hamadeh HK, Lee E, Meacher DM, Said V, Rasmussen RE, Greene H, Roth RN: Arsenic binding proteins from human lymphoblastoid cells. Toxicol Lett. 1999 Mar 29;105(2):89-101. [10221271 ]
Target Details
5. Actin, cytoplasmic 1
General Function:
Tat protein binding
Specific Function:
Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
Gene Name:
ACTB
Uniprot ID:
P60709
Molecular Weight:
41736.37 Da
References
  1. Menzel DB, Hamadeh HK, Lee E, Meacher DM, Said V, Rasmussen RE, Greene H, Roth RN: Arsenic binding proteins from human lymphoblastoid cells. Toxicol Lett. 1999 Mar 29;105(2):89-101. [10221271 ]
Target Details
6. Actin, cytoplasmic 2
General Function:
Ubiquitin protein ligase binding
Specific Function:
Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
Gene Name:
ACTG1
Uniprot ID:
P63261
Molecular Weight:
41792.48 Da
References
  1. Menzel DB, Hamadeh HK, Lee E, Meacher DM, Said V, Rasmussen RE, Greene H, Roth RN: Arsenic binding proteins from human lymphoblastoid cells. Toxicol Lett. 1999 Mar 29;105(2):89-101. [10221271 ]
Target Details
7. Actin, gamma-enteric smooth muscle
General Function:
Atp binding
Specific Function:
Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
Gene Name:
ACTG2
Uniprot ID:
P63267
Molecular Weight:
41876.495 Da
References
  1. Menzel DB, Hamadeh HK, Lee E, Meacher DM, Said V, Rasmussen RE, Greene H, Roth RN: Arsenic binding proteins from human lymphoblastoid cells. Toxicol Lett. 1999 Mar 29;105(2):89-101. [10221271 ]
Target Details
8. DNA repair protein complementing XP-A cells
General Function:
Protein homodimerization activity
Specific Function:
Involved in DNA excision repair. Initiates repair by binding to damaged sites with various affinities, depending on the photoproduct and the transcriptional state of the region. Required for UV-induced CHEK1 phosphorylation and the recruitment of CEP164 to cyclobutane pyrimidine dimmers (CPD), sites of DNA damage after UV irradiation.
Gene Name:
XPA
Uniprot ID:
P23025
Molecular Weight:
31367.71 Da
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
9. Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial
General Function:
Dihydrolipoyllysine-residue acetyltransferase activity
Specific Function:
The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
Gene Name:
DLAT
Uniprot ID:
P10515
Molecular Weight:
68996.03 Da
References
  1. Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.
Target Details
10. 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. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
11. Glucocorticoid receptor
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
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
12. Glutathione reductase, mitochondrial
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
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2007). Toxicological profile for arsenic. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Target Details
13. Haptoglobin
General Function:
Serine-type endopeptidase activity
Specific Function:
As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of heme iron and to prevent kidney damage. Haptoglobin also acts as an Antimicrobial; Antioxidant, has antibacterial activity and plays a role in modulating many aspects of the acute phase response. Hemoglobin/haptoglobin complexes are rapidely cleared by the macrophage CD163 scavenger receptor expressed on the surface of liver Kupfer cells through an endocytic lysosomal degradation pathway.Uncleaved haptoglogin, also known as zonulin, plays a role in intestinal permeability, allowing intercellular tight junction disassembly, and controlling the equilibrium between tolerance and immunity to non-self antigens.
Gene Name:
HP
Uniprot ID:
P00738
Molecular Weight:
45205.065 Da
References
  1. Naranmandura H, Suzuki KT: Identification of the major arsenic-binding protein in rat plasma as the ternary dimethylarsinous-hemoglobin-haptoglobin complex. Chem Res Toxicol. 2008 Mar;21(3):678-85. doi: 10.1021/tx700383g. Epub 2008 Feb 2. [18247522 ]
Target Details
14. Hemoglobin subunit alpha
General Function:
Oxygen transporter activity
Specific Function:
Involved in oxygen transport from the lung to the various peripheral tissues.
Gene Name:
HBA1
Uniprot ID:
P69905
Molecular Weight:
15257.405 Da
References
  1. Naranmandura H, Suzuki KT: Identification of the major arsenic-binding protein in rat plasma as the ternary dimethylarsinous-hemoglobin-haptoglobin complex. Chem Res Toxicol. 2008 Mar;21(3):678-85. doi: 10.1021/tx700383g. Epub 2008 Feb 2. [18247522 ]
Target Details
15. Hemoglobin subunit beta
General Function:
Oxygen transporter activity
Specific Function:
Involved in oxygen transport from the lung to the various peripheral tissues.LVV-hemorphin-7 potentiates the activity of bradykinin, causing a decrease in blood pressure.Spinorphin: functions as an endogenous inhibitor of enkephalin-degrading enzymes such as DPP3, and as a selective antagonist of the P2RX3 receptor which is involved in pain signaling, these properties implicate it as a regulator of pain and inflammation.
Gene Name:
HBB
Uniprot ID:
P68871
Molecular Weight:
15998.34 Da
References
  1. Naranmandura H, Suzuki KT: Identification of the major arsenic-binding protein in rat plasma as the ternary dimethylarsinous-hemoglobin-haptoglobin complex. Chem Res Toxicol. 2008 Mar;21(3):678-85. doi: 10.1021/tx700383g. Epub 2008 Feb 2. [18247522 ]
Target Details
16. Kelch-like ECH-associated protein 1
General Function:
Transcription factor binding
Specific Function:
Acts as a substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1 and targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. Retains NFE2L2/NRF2 and may also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome.
Gene Name:
KEAP1
Uniprot ID:
Q14145
Molecular Weight:
69665.765 Da
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
17. Metallothionein-1A
General Function:
Zinc ion binding
Specific Function:
Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.
Gene Name:
MT1A
Uniprot ID:
P04731
Molecular Weight:
6120.19 Da
References
  1. Ngu TT, Stillman MJ: Arsenic binding to human metallothionein. J Am Chem Soc. 2006 Sep 27;128(38):12473-83. [16984198 ]
Target Details
18. Poly [ADP-ribose] polymerase 1
General Function:
Zinc ion binding
Specific Function:
Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production. Required for PARP9 and DTX3L recruitment to DNA damage sites. PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites.
Gene Name:
PARP1
Uniprot ID:
P09874
Molecular Weight:
113082.945 Da
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
19. Putative tubulin beta chain-like protein ENSP00000290377
General Function:
Not Available
Specific Function:
Not Available
Gene Name:
Not Available
Uniprot ID:
A6NKZ8
Molecular Weight:
Not Available
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
20. Putative tubulin beta-4q chain
General Function:
Not Available
Specific Function:
Not Available
Gene Name:
Not Available
Uniprot ID:
Q99867
Molecular Weight:
Not Available
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
21. Putative tubulin-like protein alpha-4B
General Function:
Structural constituent of cytoskeleton
Specific Function:
Not Available
Gene Name:
TUBA4B
Uniprot ID:
Q9H853
Molecular Weight:
27551.01 Da
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
22. Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial
General Function:
Pyruvate dehydrogenase activity
Specific Function:
The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
Gene Name:
PDHA1
Uniprot ID:
P08559
Molecular Weight:
43295.255 Da
References
  1. Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.
Target Details
23. Pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial
General Function:
Pyruvate dehydrogenase (acetyl-transferring) activity
Specific Function:
The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
Gene Name:
PDHA2
Uniprot ID:
P29803
Molecular Weight:
42932.855 Da
References
  1. Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.
Target Details
24. Pyruvate dehydrogenase E1 component subunit beta, mitochondrial
General Function:
Pyruvate dehydrogenase activity
Specific Function:
The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
Gene Name:
PDHB
Uniprot ID:
P11177
Molecular Weight:
39233.1 Da
References
  1. Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.
Target Details
25. Pyruvate dehydrogenase protein X component, mitochondrial
General Function:
Transferase activity, transferring acyl groups
Specific Function:
Required for anchoring dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide transacetylase (E2) core of the pyruvate dehydrogenase complexes of eukaryotes. This specific binding is essential for a functional PDH complex.
Gene Name:
PDHX
Uniprot ID:
O00330
Molecular Weight:
54121.76 Da
References
  1. Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.
Target Details
26. Pyruvate kinase PKM
General Function:
Pyruvate kinase activity
Specific Function:
Glycolytic enzyme that catalyzes the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP. Stimulates POU5F1-mediated transcriptional activation. Plays a general role in caspase independent cell death of tumor cells. The ratio betwween the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production. The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival.
Gene Name:
PKM
Uniprot ID:
P14618
Molecular Weight:
57936.38 Da
References
  1. Zhang X, Yang F, Shim JY, Kirk KL, Anderson DE, Chen X: Identification of arsenic-binding proteins in human breast cancer cells. Cancer Lett. 2007 Sep 18;255(1):95-106. Epub 2007 May 17. [17499915 ]
Target Details
27. Thioredoxin reductase 1, cytoplasmic
General Function:
Thioredoxin-disulfide reductase activity
Specific Function:
Isoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity and induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Isoform 4 enhances the transcriptional activity of estrogen receptors alpha and beta while isoform 5 enhances the transcriptional activity of the beta receptor only. Isoform 5 also mediates cell death induced by a combination of interferon-beta and retinoic acid.
Gene Name:
TXNRD1
Uniprot ID:
Q16881
Molecular Weight:
70905.58 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2007). Toxicological profile for arsenic. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Target Details
28. Thioredoxin reductase 2, mitochondrial
General Function:
Thioredoxin-disulfide reductase activity
Specific Function:
Maintains thioredoxin in a reduced state. Implicated in the defenses against oxidative stress. May play a role in redox-regulated cell signaling.
Gene Name:
TXNRD2
Uniprot ID:
Q9NNW7
Molecular Weight:
56506.275 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2007). Toxicological profile for arsenic. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Target Details
29. Thioredoxin reductase 3
General Function:
Thioredoxin-disulfide reductase activity
Specific Function:
Displays thioredoxin reductase, glutaredoxin and glutathione reductase activities. Catalyzes disulfide bond isomerization. Promotes disulfide bond formation between GPX4 and various sperm proteins and may play a role in sperm maturation by promoting formation of sperm structural components (By similarity).
Gene Name:
TXNRD3
Uniprot ID:
Q86VQ6
Molecular Weight:
70682.52 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2007). Toxicological profile for arsenic. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Target Details
30. Tubulin alpha chain-like 3
General Function:
Structural constituent of cytoskeleton
Specific 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 (By similarity).
Gene Name:
TUBAL3
Uniprot ID:
A6NHL2
Molecular Weight:
49908.305 Da
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
31. Tubulin alpha-1A chain
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
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
32. Tubulin alpha-1B chain
General Function:
Ubiquitin protein ligase binding
Specific 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.
Gene Name:
TUBA1B
Uniprot ID:
P68363
Molecular Weight:
50151.24 Da
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
33. Tubulin alpha-1C chain
General Function:
Structural molecule activity
Specific 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.
Gene Name:
TUBA1C
Uniprot ID:
Q9BQE3
Molecular Weight:
49894.93 Da
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
34. Tubulin alpha-3C/D chain
General Function:
Structural constituent of cytoskeleton
Specific 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.
Gene Name:
TUBA3C
Uniprot ID:
Q13748
Molecular Weight:
49959.145 Da
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
35. Tubulin alpha-3E chain
General Function:
Structural constituent of cytoskeleton
Specific 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 (By similarity).
Gene Name:
TUBA3E
Uniprot ID:
Q6PEY2
Molecular Weight:
49858.135 Da
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
36. Tubulin alpha-4A chain
General Function:
Structural constituent of cytoskeleton
Specific 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.
Gene Name:
TUBA4A
Uniprot ID:
P68366
Molecular Weight:
49923.995 Da
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
37. Tubulin alpha-8 chain
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:
TUBA8
Uniprot ID:
Q9NY65
Molecular Weight:
50093.12 Da
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
38. Tubulin beta-1 chain
General Function:
Structural constituent of cytoskeleton
Specific 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 (By similarity).
Gene Name:
TUBB1
Uniprot ID:
Q9H4B7
Molecular Weight:
50326.56 Da
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
39. Tubulin beta-2A chain
General Function:
Structural constituent of cytoskeleton
Specific 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 (By similarity).
Gene Name:
TUBB2A
Uniprot ID:
Q13885
Molecular Weight:
49906.67 Da
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
40. Tubulin beta-2B chain
General Function:
Structural constituent of cytoskeleton
Specific 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 (By similarity). TUBB2B is implicated in neuronal migration.
Gene Name:
TUBB2B
Uniprot ID:
Q9BVA1
Molecular Weight:
49952.76 Da
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
41. Tubulin beta-3 chain
General Function:
Structural constituent of cytoskeleton
Specific 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. TUBB3 plays a critical role in proper axon guidance and mantainance.
Gene Name:
TUBB3
Uniprot ID:
Q13509
Molecular Weight:
50432.355 Da
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
42. Tubulin beta-4A chain
General Function:
Structural constituent of cytoskeleton
Specific 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.
Gene Name:
TUBB4A
Uniprot ID:
P04350
Molecular Weight:
49585.475 Da
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
43. Tubulin beta-4B chain
General Function:
Unfolded protein binding
Specific 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.
Gene Name:
TUBB4B
Uniprot ID:
P68371
Molecular Weight:
49830.72 Da
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
44. Tubulin beta-6 chain
General Function:
Structural constituent of cytoskeleton
Specific 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 (By similarity).
Gene Name:
TUBB6
Uniprot ID:
Q9BUF5
Molecular Weight:
49856.785 Da
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
45. Tubulin beta-8 chain
General Function:
Structural constituent of cytoskeleton
Specific 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 (By similarity).
Gene Name:
TUBB8
Uniprot ID:
Q3ZCM7
Molecular Weight:
49775.655 Da
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
Target Details
46. Tubulin beta-8 chain-like protein LOC260334
General Function:
Structural constituent of cytoskeleton
Specific 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 (By similarity).
Gene Name:
Not Available
Uniprot ID:
A6NNZ2
Molecular Weight:
49572.265 Da
References
  1. Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]