Record Information
Version 1.0
Creation Date 2009-03-06 11:58:25 -0700
Update Date 2014-08-11 09:53:27 -0600
Accession Number T3D0275
Identification
Common Name Adamsite
Description Adamsite is an organoarsenic compound which belongs to the group of chemical warfare agents known as vomiting agents or sneeze gases. Due to its toxicity, it is nowadays considered obsolete. Arsenic is a chemical element that has the symbol As and atomic number 33. It is a poisonous metalloid that has many allotropic forms: yellow (molecular non-metallic) and several black and grey forms (metalloids) are a few that are seen. Three metalloidal forms of arsenic with different crystal structures are found free in nature (the minerals arsenopyrite and the much rarer arsenolamprite and pararsenolamprite), but it is more commonly found as a compound with other elements. (L9, T3)
Compound Type
  • Arsenic Compound
  • Organic Compound
Chemical Structure
Thumb
Synonyms
  1. 10-Chloro-5, 10-dihydrophenarsazine
  2. 10-Chloro-5,10-dihydroarsacridine
  3. 5-Aza-10-arsenaanthracene chloride
  4. Adamsit
  5. Adamsite
  6. Chloro diphenylaminearsine
  7. Chlorophenarsazene
  8. DM
  9. Diphenylamine chloroarsine
  10. Diphenylaminechlorarsine
  11. Diphenylaminechloroarsine
  12. Diphenylaminochloroarsine
  13. Fenarsazinchlorid [czech]
  14. Phenarsazine chloride
  15. Phenarsazine chloride (acn)
  16. Phenarsazine, 10-chloro-5,10-dihydro- ( )
  17. Phenazarsine chloride
Chemical Formula C12H9AsClN
Average Molecular Weight 277.581
Monoisotopic Molecular Weight 276.963948417
IUPAC Name
10-chloro-5,10-dihydrophenarsazinine
Traditional IUPAC Name
adamsite
CAS Registry Number 578-94-9
SMILES
Cl[As]1C2=CC=CC=C2NC2=CC=CC=C12
InChI Identifier
InChI=1S/C12H9AsClN/c14-13-9-5-1-3-7-11(9)15-12-8-4-2-6-10(12)13/h1-8,15H
InChI Key InChIKey=PBNSPNYJYOYWTA-UHFFFAOYSA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Heterocyclic Compounds
Class Metalloheterocyclic Compounds
Sub Class Benzazarsines and Derivatives
Direct Parent Benzazarsines and Derivatives
Alternative Parents
  • Benzene and Substituted Derivatives
  • Secondary Amines
  • Organoarsenic Compounds
Molecular Framework Aromatic Heteropolycyclic Compounds
Substituents
  • benzene
  • organonitrogen compound
  • secondary amine
  • organometallic compound
  • organoarsenical-compound
  • organic metalloid moeity
External Descriptors Not Available
Biological Properties
Status Unknown/Not Detected
Origin Not Available
Cellular Locations Not Available
Biofluid Locations Not Available
Tissue Locations Not Available
Pathways Not Available
Physical Properties
State Not Available
Appearance Yellow or green crystals.
Experimental Properties
Property Value
Melting Point 195 C
Boiling Point Not Available
Solubility Not Available
LogP Not Available
Predicted Properties
PropertyValueSource
water solubility4.68e-02 g/lALOGPS
logP3.88ALOGPS
logP3.54ChemAxon
logS-3.8ALOGPS
pKa (strongest acidic)18.83ChemAxon
pKa (strongest basic)0.27ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count1ChemAxon
hydrogen donor count1ChemAxon
polar surface area12.03ChemAxon
rotatable bond count0ChemAxon
refractivity59.51ChemAxon
polarizability24.07ChemAxon
Spectra
Spectra Not Available
Toxicity Profile
Route of Exposure Oral (L2) ; inhalation (L2); dermal (L2)
Mechanism of Toxicity Arsenic 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 carginogenicity 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. (T1, A17)
Metabolism Arsenic 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. (L20)
Toxicity Values LD50: 35 mg/kg (Intravenous, Mouse) (T13)
Lethal Dose Not Available
Carcinogenicity (IARC Classification) 1, carcinogenic to humans. (L135)
Uses/Sources Adamsite is used mainly as a riot control agent. (L9)
Minimum Risk Level Acute Oral: 0.005 mg/kg/day (L134) Chronic Oral: 0.0003 mg/kg/day (L134) Chronic Inhalation: 0.01 mg/m3 (L134)
Health Effects Arsenic poisoning can lead to death from multi-system organ failure, probably from necrotic cell death, not apoptosis. Arsenic is also a known carcinogen, esepcially in skin, liver, bladder and lung cancers. (T1, L20)
Symptoms Exposure 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
Treatment Arsenic 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. (L20)
Normal Concentrations
Not Available
DrugBank ID Not Available
HMDB ID Not Available
PubChem Compound ID 11362
ChEMBL ID Not Available
ChemSpider ID Not Available
KEGG ID Not Available
UniProt ID Not Available
OMIM ID
ChEBI ID Not Available
BioCyc ID Not Available
CTD ID C010283
Stitch ID Adamsite
PDB ID Not Available
ACToR ID Not Available
Wikipedia Link Not Available
References
General References
  • A17 — 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 ]
  • T1 — Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.
  • T3 — Emsley, John (2001). Nature's Building Blocks: An A-Z Guide to the Elements. Oxford: Oxford University Press.
  • T13 — Lewis RJ Sr. (ed) (2004). Sax's Dangerous Properties of Industrial Materials. 11th Edition. Hoboken, NJ: Wiley-Interscience, Wiley & Sons, Inc.
  • L2 — 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]
  • L9 — National Institute for Occupational Safety and Health (2008). Adamsite (DM) Vomiting Agent. [Link]
  • L20 — Wikipedia. Arsenic toxicity. Last Updated 22 February 2009. [Link]
  • L92 — Wikipedia. Metallothionein. Last Updated 20 December 2008. [Link]
  • L134 — 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]
  • L135 — International Agency for Research on Cancer (2009). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]

Targets

1. Actin, alpha cardiac muscle 1

Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

Arsenic binds to actin. (A16)
UniProt ID: P68032
Gene: ACTC1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A16 — 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 ]

2. Actin, alpha skeletal muscle

Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

Arsenic binds to actin. (A16)
UniProt ID: P68133
Gene: ACTA1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A16 — 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 ]

3. Actin, aortic smooth muscle

Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

Arsenic binds to actin. (A16)
UniProt ID: P62736
Gene: ACTA2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A16 — 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. Actin, cytoplasmic 1

Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

Arsenic binds to actin. (A16)
UniProt ID: P60709
Gene: ACTB
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A16 — 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 ]

5. Actin, cytoplasmic 2

Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

Arsenic binds to actin. (A16)
UniProt ID: P63261
Gene: ACTG1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A16 — 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 ]

6. Actin, gamma-enteric smooth muscle

Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

Arsenic binds to actin. (A16)
UniProt ID: P63267
Gene: ACTG2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A16 — 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 ]

7. Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial

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.

Arsenic disrupts 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. (T1)
UniProt ID: P10515
Gene: DLAT
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T1 — Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.

8. DNA repair protein complementing XP-A cells

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.

Arsenic binding of XPA is believed to induce carcinogenesis by affecting DNA repair. (A17)
UniProt ID: P23025
Gene: XPA
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

9. Estrogen receptor

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. Isoform 3 can bind to ERE and inhibit isoform 1.

Arsenic binds to the estrogen receptor. (A17)
UniProt ID: P03372
Gene: ESR1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

10. Glucocorticoid receptor

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. Plays a significant role in transactivation.

Arsenic binds to the glucocorticoid receptor. (A17)
UniProt ID: P04150
Gene: NR3C1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

11. Glutathione reductase, mitochondrial

Maintains high levels of reduced glutathione in the cytosol.

Arsenic binds glutathione reductase, which results in the inhibition of essential biochemical reactions, alteration of cellular redox status, and eventual cytotoxicity. (L2)
UniProt ID: P00390
Gene: GSR
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • L2 — 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. Haptoglobin

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.

Arsenic binds to haptoglobin. (A15)
UniProt ID: P00738
Gene: HP
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A15 — 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 ]

13. Hemoglobin subunit alpha

Involved in oxygen transport from the lung to the various peripheral tissues.

Arsenic binds to hemoglobin. (A15)
UniProt ID: P69905
Gene: HBA1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A15 — 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 ]

14. Hemoglobin subunit beta

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.

Arsenic binds to hemoglobin. (A15)
UniProt ID: P68871
Gene: HBB
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A15 — 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 ]

15. Kelch-like ECH-associated protein 1

Retains NFE2L2/NRF2 in the cytosol. Functions as substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1. 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. May also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome.

Arsenic binds to kelch-like ECH-associated protein 1. (A17)
UniProt ID: Q14145
Gene: KEAP1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

16. Poly [ADP-ribose] polymerase 1

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.

Arsenic binding of PARP-1 is believed to induce carcinogenesis by affecting DNA repair. (A17)
UniProt ID: P09874
Gene: PARP1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

17. Putative tubulin beta chain-like protein ENSP00000290377

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).

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. (A17)
UniProt ID: A6NKZ8
Protein Sequence: FASTA
References:
  • A17 — 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 ]

18. Putative tubulin beta-4q chain

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)

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. (A17)
UniProt ID: Q99867
Gene: TUBB4Q
Protein Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

19. Putative tubulin-like protein alpha-4B

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. (A17)
UniProt ID: Q9H853
Gene: TUBA4B
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

20. Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial

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.

Arsenic disrupts 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. (T1)
UniProt ID: P08559
Gene: PDHA1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T1 — Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.

21. Pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial

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.

Arsenic disrupts 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. (T1)
UniProt ID: P29803
Gene: PDHA2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T1 — Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.

22. Pyruvate dehydrogenase E1 component subunit beta, mitochondrial

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.

Arsenic disrupts 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. (T1)
UniProt ID: P11177
Gene: PDHB
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T1 — Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.

23. Pyruvate dehydrogenase protein X component, mitochondrial

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.

Arsenic disrupts 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. (T1)
UniProt ID: O00330
Gene: PDHX
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • T1 — Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.

24. Thioredoxin reductase 1, cytoplasmic

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.

Arsenic binds thioredoxin reductase, which results in the inhibition of essential biochemical reactions, alteration of cellular redox status, and eventual cytotoxicity. (L2)
UniProt ID: Q16881
Gene: TXNRD1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • L2 — 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]

25. Thioredoxin reductase 2, mitochondrial

Maintains thioredoxin in a reduced state. Implicated in the defenses against oxidative stress. May play a role in redox-regulated cell signaling.

Arsenic binds thioredoxin reductase, which results in the inhibition of essential biochemical reactions, alteration of cellular redox status, and eventual cytotoxicity. (L2)
UniProt ID: Q9NNW7
Gene: TXNRD2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • L2 — 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]

26. Thioredoxin reductase 3

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).

Arsenic binds thioredoxin reductase, which results in the inhibition of essential biochemical reactions, alteration of cellular redox status, and eventual cytotoxicity. (L2)
UniProt ID: Q86VQ6
Gene: TXNRD3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • L2 — 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]

27. Tubulin alpha chain-like 3

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).

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. (A17)
UniProt ID: A6NHL2
Gene: TUBAL3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

28. Tubulin alpha-1A chain

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.

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. (A17)
UniProt ID: Q71U36
Gene: TUBA1A
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

29. Tubulin alpha-1B chain

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.

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. (A17)
UniProt ID: P68363
Gene: TUBA1B
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

30. Tubulin alpha-1C chain

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.

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. (A17)
UniProt ID: Q9BQE3
Gene: TUBA1C
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

31. Tubulin alpha-3C/D chain

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.

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. (A17)
UniProt ID: Q13748
Gene: TUBA3C
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

32. Tubulin alpha-3E chain

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).

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. (A17)
UniProt ID: Q6PEY2
Gene: TUBA3E
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

33. Tubulin alpha-4A chain

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.

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. (A17)
UniProt ID: P68366
Gene: TUBA4A
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

34. Tubulin alpha-8 chain

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.

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. (A17)
UniProt ID: Q9NY65
Gene: TUBA8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

35. Tubulin beta chain

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.

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. (A17)
UniProt ID: P07437
Gene: TUBB
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

36. Tubulin beta-1 chain

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).

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. (A17)
UniProt ID: Q9H4B7
Gene: TUBB1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

37. Tubulin beta-2A chain

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).

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. (A17)
UniProt ID: Q13885
Gene: TUBB2A
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

38. Tubulin beta-2B chain

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.

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. (A17)
UniProt ID: Q9BVA1
Gene: TUBB2B
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

39. Tubulin beta-4B chain

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.

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. (A17)
UniProt ID: P68371
Gene: TUBB4B
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

40. Tubulin beta-3 chain

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.

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. (A17)
UniProt ID: Q13509
Gene: TUBB3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

41. Tubulin beta-4A chain

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.

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. (A17)
UniProt ID: P04350
Gene: TUBB4A
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

42. Tubulin beta-6 chain

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).

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. (A17)
UniProt ID: Q9BUF5
Gene: TUBB6
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

43. Tubulin beta-8 chain

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).

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. (A17)
UniProt ID: Q3ZCM7
Gene: TUBB8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A17 — 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 ]

44. Tubulin beta-8 chain-like protein LOC260334

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).

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. (A17)
UniProt ID: A6NNZ2
Protein Sequence: FASTA
References:
  • A17 — 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 ]

45. Transient receptor potential cation channel subfamily A member 1

Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function. Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes. Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana. Not involved in menthol sensation. May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).

Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function. Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes. Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana. Not involved in menthol sensation. May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).
UniProt ID: O75762
Gene: TRPA1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • L1991 — Lachrymation [Link]