FRCD

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

Mechanism of Action:

Arsenic binds to actin.

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 ]

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

Mechanism of Action:

Arsenic binds to actin.

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 ]

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

Mechanism of Action:

Arsenic binds to actin.

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 ]

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

Mechanism of Action:

Arsenic binds to the estrogen receptor.

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 ]

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

Mechanism of Action:

Arsenic binds to the glucocorticoid receptor.

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 ]

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:

Arsenic binds glutathione reductase, which results in the inhibition of essential biochemical reactions, alteration of cellular redox status, and eventual cytotoxicity.

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). : http://www.atsdr.cdc.gov/toxprofiles/tp2.html

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

Mechanism of Action:

Arsenic binds to hemoglobin.

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 ]

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

Mechanism of Action:

Arsenic binds to hemoglobin.

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 ]

Uniprot ID:

A6NKZ8

Mechanism of Action:

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.

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 ]

Uniprot ID:

Q99867

Mechanism of Action:

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.

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 ]

General Function:

Structural constituent of cytoskeleton

Gene Name:

TUBA4B

Uniprot ID:

Q9H853

Molecular Weight:

27551.01 Da

Mechanism of Action:

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.

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 ]

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

Mechanism of Action:

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.

References

1. Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.

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

Mechanism of Action:

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.

References

1. Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.

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

Mechanism of Action:

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.

References

1. Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.

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

Mechanism of Action:

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.

References

1. Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.

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

Mechanism of Action:

Arsenic binds thioredoxin reductase, which results in the inhibition of essential biochemical reactions, alteration of cellular redox status, and eventual cytotoxicity.

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). : http://www.atsdr.cdc.gov/toxprofiles/tp2.html

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

Mechanism of Action:

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.

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 ]

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

Mechanism of Action:

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.

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 ]

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

Mechanism of Action:

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.

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 ]

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

Mechanism of Action:

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.

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 ]

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

Mechanism of Action:

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.

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 ]

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

Mechanism of Action:

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.

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 ]

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

Mechanism of Action:

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.

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 ]

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

Mechanism of Action:

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.

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 ]

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

Mechanism of Action:

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.

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 ]

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

Mechanism of Action:

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.

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 ]

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

Mechanism of Action:

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.

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 ]

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

Mechanism of Action:

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.

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 ]

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

Mechanism of Action:

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.

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 ]

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

Mechanism of Action:

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.

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 ]

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

Mechanism of Action:

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.

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 ]

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

Mechanism of Action:

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.

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 ]

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).

Uniprot ID:

A6NNZ2

Molecular Weight:

49572.265 Da

Mechanism of Action:

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.

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 ]

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

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

Mechanism of Action:

Arsenic binds to actin.

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 ]

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

Mechanism of Action:

Arsenic binds to actin.

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 ]

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

Mechanism of Action:

Arsenic binds to actin.

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 ]

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

Mechanism of Action:

Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.

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 ]

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

Mechanism of Action:

Arsenic binding of XPA is believed to induce carcinogenesis by affecting DNA repair.

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 ]

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

Mechanism of Action:

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.

References

1. Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.

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

Mechanism of Action:

Arsenic binds to haptoglobin.

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 ]

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

Mechanism of Action:

Arsenic binds to kelch-like ECH-associated protein 1.

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 ]

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

Mechanism of Action:

Arsenic binding of PARP-1 is believed to induce carcinogenesis by affecting DNA repair.

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 ]

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

Mechanism of Action:

Arsenic binds thioredoxin reductase, which results in the inhibition of essential biochemical reactions, alteration of cellular redox status, and eventual cytotoxicity.

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). : http://www.atsdr.cdc.gov/toxprofiles/tp2.html