Tmic
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Record Information
Version2.0
Creation Date2009-06-19 21:58:44 UTC
Update Date2014-12-24 20:23:50 UTC
Accession NumberT3D1409
Identification
Common NameNickel arsenate
ClassSmall Molecule
DescriptionNickel arsenate is a chemical compound of nickel and arsenic. Nickel is a chemical compound with the atomic number 28. It is found abundantly in nature in laterite ore minerals, such as limonite, garnierite, and pentlandite. Nickel has a biological role and is found in certain enzymes, including urease, hydrogenase, methylcoenzyme M reductase, and carbon monoxide dehydrogenase. 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. (4, 7, 8)
Compound Type
  • Arsenic Compound
  • Industrial/Workplace Toxin
  • Inorganic Compound
  • Nickel Compound
  • Pollutant
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Arsenic acid (H3aso4), nickel(2+) salt (2:3)
Arsenic acid, nickel(2+) salt (2:3)
Nickel arsenic acid
Trinickel bis(arsenate)
Chemical FormulaAsH3NiO4
Average Molecular Mass200.636 g/mol
Monoisotopic Mass199.860 g/mol
CAS Registry Number13477-70-8
IUPAC Namearsoric acid nickel
Traditional Namearsenic acid nickel
SMILES[Ni].O[As](O)(O)=O
InChI IdentifierInChI=1S/AsH3O4.Ni/c2-1(3,4)5;/h(H3,2,3,4,5);
InChI KeyInChIKey=ZIPTVBOPGBCBMU-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of inorganic compounds known as transition metal arsenates. These are inorganic compounds in which the largest oxoanion is arsenate, and in which the heaviest atom not in an oxoanion is a transition metal.
KingdomInorganic compounds
Super ClassMixed metal/non-metal compounds
ClassTransition metal oxoanionic compounds
Sub ClassTransition metal arsenates
Direct ParentTransition metal arsenates
Alternative Parents
Substituents
  • Transition metal arsenate
  • Arsenate
  • Inorganic oxide
  • Inorganic salt
  • Inorganic metalloid salt
  • Inorganic nickel compound
  • Inorganic arsenic compound
Molecular FrameworkNot Available
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
logP-1.2ChemAxon
pKa (Strongest Acidic)3.15ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area77.76 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity9.14 m³·mol⁻¹ChemAxon
Polarizability7.07 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0090000000-09747a50914e9e1b8f13View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udi-0090000000-09747a50914e9e1b8f13View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udi-0090000000-09747a50914e9e1b8f13View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0900000000-1773b8fee89925702695View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-0900000000-1773b8fee89925702695View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0002-0900000000-1773b8fee89925702695View in MoNA
Toxicity Profile
Route of ExposureOral (5) ; inhalation (5) ; dermal (5)
Mechanism of ToxicityNickel is known to substitute for other essential elements in certain enzmes, such as calcineurin. It is genotoxic, and some nickel compounds have been shown to promote cell proliferation. Nickel has a high affinity for chromatin proteins, particularly histones and protamines. The complexing of nickel ions with heterochromatin results in a number of alterations including condensation, DNA hypermethylation, gene silencing, and inhibition of histone acetylation, which have been shown to disturb gene expression. Nickel has also been shown to alter several transcription factors, including hypoxia-inducible transcription factor, activating transcription factor, and NF-KB transcription factor. There is also evidence that nickel ions inhibit DNA repair, either by directly inhibiting DNA repair enzymes or competing with zinc ions for binding to zinc-finger DNA binding proteins, resulting in structural changes in DNA that prevent repair enzymes from binding. Nickel ions can also complex with a number of cellular ligands including amino acids, peptides, and proteins resulting in the generation of oxygen radicals, which induce base damage, DNA strand breaks, and DNA protein crosslinks. 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. (3, 1, 8, 2)
MetabolismNickel is absorbed mainly through the lungs and gastrointestinal tract. Once in the body it enters the bloodstream, where it binds to albumin, L-histidine, and _2-macroglobulin. Nickel tends to accumulate in the lungs, thyroid, kidney, heart, and liver. Absorbed nickel is excreted in the urine, wherease unabsorbed nickel is excreted in the faeces. 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. (6, 8)
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)1, carcinogenic to humans. (12)
Uses/SourcesNot Available
Minimum Risk LevelIntermediate Inhalation: 0.0002 mg/m3 (Nickel) (11) Chronic Inhalation: 0.00009 mg/m3 (Nickel) (11) Acute Oral: 0.005 mg/kg/day (Arsenic) (11) Chronic Oral: 0.0003 mg/kg/day (Arsenic) (11) Chronic Inhalation: 0.01 mg/m3 (Arsenic) (11)
Health EffectsThe most common harmful health effect of nickel in humans is an allergic reaction. This usually manifests as a skin rash, although some people experience asthma attacks. Long term inhahation of nickel causes chronic bronchitis and reduced lung function, as well as damage to the naval cavity. Ingestion of excess nickel results in damage to the stomach, blood, liver, kidneys, and immune system, as well as having adverse effects on reproduction and development. 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. (3, 6, 8)
SymptomsSymptoms of nickel poisoning include headache, nausea, vomiting, dizziness, irritability, and difficulty sleeping, followed by chest pains, sweating, rapid heart beat, and a dry cough. 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
TreatmentExcess exposure to nickel is usually handled by preventing further exposure and symptomatic treatment. Nickel poisoning may also be treated using chelation therapy with sodium diethyldithiocarbamate. 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. (6, 9)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID3084152
ChEMBL IDNot Available
ChemSpider ID2341260
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNickel arsenate
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D1409.pdf
General 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. King MM, Huang CY: Activation of calcineurin by nickel ions. Biochem Biophys Res Commun. 1983 Aug 12;114(3):955-61. [6311199 ]
  3. Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.
  4. Emsley, John (2001). Nature's Building Blocks: An A-Z Guide to the Elements. Oxford: Oxford University Press.
  5. 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]
  6. Wikipedia. Arsenic toxicity. Last Updated 22 February 2009. [Link]
  7. Wikipedia. Nickel. Last Updated 22 March 2009. [Link]
  8. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  9. Redmond JC (2008). Nickel Poisoning. LoveToKnow. [Link]
  10. Wikipedia. Metallothionein. Last Updated 20 December 2008. [Link]
  11. 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]
  12. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
General Function:
Ferrous iron binding
Specific Function:
Dioxygenase that repairs alkylated DNA and RNA containing 1-methyladenine and 3-methylcytosine by oxidative demethylation. Can also repair alkylated DNA containing 1-ethenoadenine (in vitro). Has strong preference for double-stranded DNA. Has low efficiency with single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron.
Gene Name:
ALKBH2
Uniprot ID:
Q6NS38
Molecular Weight:
29322.22 Da
References
  1. Chen H, Costa M: Iron- and 2-oxoglutarate-dependent dioxygenases: an emerging group of molecular targets for nickel toxicity and carcinogenicity. Biometals. 2009 Feb;22(1):191-6. doi: 10.1007/s10534-008-9190-3. Epub 2008 Dec 19. [19096759 ]
General Function:
L-ascorbic acid binding
Specific Function:
Dioxygenase that repairs alkylated DNA containing 1-methyladenine (1meA) and 3-methylcytosine (3meC) by oxidative demethylation. Has a strong preference for single-stranded DNA. Able to process alkylated 3mC within double-stranded regions via its interaction with ASCC3, which promotes DNA unwinding to generate single-stranded substrate needed for ALKHB3. May also act on RNA. Requires molecular oxygen, alpha-ketoglutarate and iron.
Gene Name:
ALKBH3
Uniprot ID:
Q96Q83
Molecular Weight:
33374.495 Da
References
  1. Chen H, Costa M: Iron- and 2-oxoglutarate-dependent dioxygenases: an emerging group of molecular targets for nickel toxicity and carcinogenicity. Biometals. 2009 Feb;22(1):191-6. doi: 10.1007/s10534-008-9190-3. Epub 2008 Dec 19. [19096759 ]
General Function:
Protein domain specific binding
Specific Function:
Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity.
Gene Name:
PPP3R1
Uniprot ID:
P63098
Molecular Weight:
19299.785 Da
References
  1. King MM, Huang CY: Activation of calcineurin by nickel ions. Biochem Biophys Res Commun. 1983 Aug 12;114(3):955-61. [6311199 ]
General Function:
Calcium ion binding
Specific Function:
Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity (By similarity).
Gene Name:
PPP3R2
Uniprot ID:
Q96LZ3
Molecular Weight:
19533.065 Da
References
  1. King MM, Huang CY: Activation of calcineurin by nickel ions. Biochem Biophys Res Commun. 1983 Aug 12;114(3):955-61. [6311199 ]
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 ]
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.
General Function:
Peptidyl-proline dioxygenase activity
Specific Function:
Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF1B. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality. Target proteins are preferentially recognized via a LXXLAP motif.
Gene Name:
EGLN1
Uniprot ID:
Q9GZT9
Molecular Weight:
46020.585 Da
References
  1. Chen H, Costa M: Iron- and 2-oxoglutarate-dependent dioxygenases: an emerging group of molecular targets for nickel toxicity and carcinogenicity. Biometals. 2009 Feb;22(1):191-6. doi: 10.1007/s10534-008-9190-3. Epub 2008 Dec 19. [19096759 ]
General Function:
Peptidyl-proline 4-dioxygenase activity
Specific Function:
Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF2A. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN2 is involved in regulating hypoxia tolerance and apoptosis in cardiac and skeletal muscle. Also regulates susceptibility to normoxic oxidative neuronal death. Links oxygen sensing to cell cycle and primary cilia formation by hydroxylating the critical centrosome component CEP192 which promotes its ubiquitination and subsequent proteasomal degradation. Hydroxylates IKBKB, mediating NF-kappaB activation in hypoxic conditions. Target proteins are preferentially recognized via a LXXLAP motif.
Gene Name:
EGLN2
Uniprot ID:
Q96KS0
Molecular Weight:
43650.03 Da
References
  1. Chen H, Costa M: Iron- and 2-oxoglutarate-dependent dioxygenases: an emerging group of molecular targets for nickel toxicity and carcinogenicity. Biometals. 2009 Feb;22(1):191-6. doi: 10.1007/s10534-008-9190-3. Epub 2008 Dec 19. [19096759 ]
General Function:
Peptidyl-proline 4-dioxygenase activity
Specific Function:
Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF2A. Hydroxylation on the NODD site by EGLN3 appears to require prior hydroxylation on the CODD site. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN3 is the most important isozyme in limiting physiological activation of HIFs (particularly HIF2A) in hypoxia. Also hydroxylates PKM in hypoxia, limiting glycolysis. Under normoxia, hydroxylates and regulates the stability of ADRB2. Regulator of cardiomyocyte and neuronal apoptosis. In cardiomyocytes, inhibits the anti-apoptotic effect of BCL2 by disrupting the BAX-BCL2 complex. In neurons, has a NGF-induced proapoptotic effect, probably through regulating CASP3 activity. Also essential for hypoxic regulation of neutrophilic inflammation. Plays a crucial role in DNA damage response (DDR) by hydroxylating TELO2, promoting its interaction with ATR which is required for activation of the ATR/CHK1/p53 pathway. Target proteins are preferentially recognized via a LXXLAP motif.
Gene Name:
EGLN3
Uniprot ID:
Q9H6Z9
Molecular Weight:
27261.06 Da
References
  1. Chen H, Costa M: Iron- and 2-oxoglutarate-dependent dioxygenases: an emerging group of molecular targets for nickel toxicity and carcinogenicity. Biometals. 2009 Feb;22(1):191-6. doi: 10.1007/s10534-008-9190-3. Epub 2008 Dec 19. [19096759 ]
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 ]
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 ]
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]
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 ]
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 ]
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 ]
General Function:
Poly(a) rna binding
Specific Function:
Histones H1 are necessary for the condensation of nucleosome chains into higher-order structures. The H1F0 histones are found in cells that are in terminal stages of differentiation or that have low rates of cell division.
Gene Name:
H1F0
Uniprot ID:
P07305
Molecular Weight:
20862.775 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Chromatin dna binding
Specific Function:
Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Acts also as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation (By similarity).
Gene Name:
HIST1H1A
Uniprot ID:
Q02539
Molecular Weight:
21841.89 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Poly(a) rna binding
Specific Function:
Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Acts also as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation (By similarity).
Gene Name:
HIST1H1C
Uniprot ID:
P16403
Molecular Weight:
21364.57 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Poly(a) rna binding
Specific Function:
Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Acts also as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation (By similarity).
Gene Name:
HIST1H1D
Uniprot ID:
P16402
Molecular Weight:
22349.71 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Poly(a) rna binding
Specific Function:
Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Acts also as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation (By similarity).
Gene Name:
HIST1H1E
Uniprot ID:
P10412
Molecular Weight:
21865.02 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Poly(a) rna binding
Specific Function:
Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Acts also as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation (By similarity).
Gene Name:
HIST1H1B
Uniprot ID:
P16401
Molecular Weight:
22579.945 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Nucleosomal dna binding
Specific Function:
May play a key role in the control of gene expression during oogenesis and early embryogenesis, presumably through the perturbation of chromatin structure. Essential for meiotic maturation of germinal vesicle-stage oocytes. The somatic type linker histone H1c is rapidly replaced by H1oo in a donor nucleus transplanted into an oocyte. The greater mobility of H1oo as compared to H1c may contribute to this rapid replacement and increased instability of the embryonic chromatin structure. The rapid replacement of H1c with H1oo may play an important role in nuclear remodeling (By similarity).
Gene Name:
H1FOO
Uniprot ID:
Q8IZA3
Molecular Weight:
35813.185 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Histones H1 are necessary for the condensation of nucleosome chains into higher-order structures.
Gene Name:
HIST1H1T
Uniprot ID:
P22492
Molecular Weight:
22018.82 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Poly(a) rna binding
Specific Function:
Histones H1 are necessary for the condensation of nucleosome chains into higher-order structures.
Gene Name:
H1FX
Uniprot ID:
Q92522
Molecular Weight:
22487.0 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Enzyme binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST1H2AG
Uniprot ID:
P0C0S8
Molecular Weight:
14091.375 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST1H2AA
Uniprot ID:
Q96QV6
Molecular Weight:
14233.39 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST1H2AB
Uniprot ID:
P04908
Molecular Weight:
14135.385 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST1H2AC
Uniprot ID:
Q93077
Molecular Weight:
14105.355 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST1H2AD
Uniprot ID:
P20671
Molecular Weight:
14107.375 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST1H2AH
Uniprot ID:
Q96KK5
Molecular Weight:
13906.145 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST1H2AJ
Uniprot ID:
Q99878
Molecular Weight:
13936.175 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST2H2AA3
Uniprot ID:
Q6FI13
Molecular Weight:
14095.385 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST2H2AB
Uniprot ID:
Q8IUE6
Molecular Weight:
13995.205 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST2H2AC
Uniprot ID:
Q16777
Molecular Weight:
13988.26 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST3H2A
Uniprot ID:
Q7L7L0
Molecular Weight:
14121.355 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Atypical histone H2A which can replace conventional H2A in some nucleosomes and is associated with active transcription and mRNA processing (PubMed:22795134). Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability (PubMed:15257289, PubMed:16287874, PubMed:16957777, PubMed:17591702, PubMed:17726088, PubMed:18329190, PubMed:22795134). Nucleosomes containing this histone are less rigid and organize less DNA than canonical nucleosomes in vivo (PubMed:15257289, PubMed:16957777, PubMed:17591702, PubMed:24336483). They are enriched in actively transcribed genes and associate with the elongating form of RNA polymerase (PubMed:17591702, PubMed:24753410). They associate with spliceosome components and are required for mRNA splicing (PubMed:22795134).
Specific Function:
Dna binding
Gene Name:
H2AFB1
Uniprot ID:
P0C5Y9
Molecular Weight:
12697.21 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Atypical histone H2A which can replace conventional H2A in some nucleosomes and is associated with active transcription and mRNA processing. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. Nucleosomes containing this histone are less rigid and organize less DNA than canonical nucleosomes in vivo. They are enriched in actively transcribed genes and associate with the elongating form of RNA polymerase. They associate with spliceosome components and are required for mRNA splicing. May participate in spermatogenesis.
Gene Name:
H2AFB2
Uniprot ID:
P0C5Z0
Molecular Weight:
12713.25 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
H2AFJ
Uniprot ID:
Q9BTM1
Molecular Weight:
14019.3 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. May be involved in the formation of constitutive heterochromatin. May be required for chromosome segregation during cell division (By similarity).
Gene Name:
H2AFV
Uniprot ID:
Q71UI9
Molecular Weight:
13508.575 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Rna polymerase ii distal enhancer sequence-specific dna binding
Specific Function:
Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. May be involved in the formation of constitutive heterochromatin. May be required for chromosome segregation during cell division.
Gene Name:
H2AFZ
Uniprot ID:
P0C0S5
Molecular Weight:
13552.635 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Histone binding
Specific Function:
Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Required for checkpoint-mediated arrest of cell cycle progression in response to low doses of ionizing radiation and for efficient repair of DNA double strand breaks (DSBs) specifically when modified by C-terminal phosphorylation.
Gene Name:
H2AFX
Uniprot ID:
P16104
Molecular Weight:
15144.45 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Variant histone specifically required to direct the transformation of dissociating nucleosomes to protamine in male germ cells. Entirely replaces classical histone H2B prior nucleosome to protamine transition and probably acts as a nucleosome dissociating factor that creates a more dynamic chromatin, facilitating the large-scale exchange of histones. Also expressed maternally and is present in the female pronucleus, suggesting a similar role in protamine replacement by nucleosomes at fertilization (By similarity). Also found in fat cells, its function and the presence of post-translational modifications specific to such cells are still unclear. Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST1H2BA
Uniprot ID:
Q96A08
Molecular Weight:
14167.38 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST1H2BB
Uniprot ID:
P33778
Molecular Weight:
13950.075 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid.
Gene Name:
HIST1H2BC
Uniprot ID:
P62807
Molecular Weight:
13906.035 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST1H2BD
Uniprot ID:
P58876
Molecular Weight:
13936.065 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST1H2BH
Uniprot ID:
Q93079
Molecular Weight:
13892.005 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid.
Gene Name:
HIST1H2BJ
Uniprot ID:
P06899
Molecular Weight:
13904.055 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid.
Gene Name:
HIST1H2BK
Uniprot ID:
O60814
Molecular Weight:
13890.035 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST1H2BL
Uniprot ID:
Q99880
Molecular Weight:
13952.095 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST1H2BM
Uniprot ID:
Q99879
Molecular Weight:
13989.175 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST1H2BN
Uniprot ID:
Q99877
Molecular Weight:
13922.035 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST1H2BO
Uniprot ID:
P23527
Molecular Weight:
13906.025 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid.
Gene Name:
HIST2H2BE
Uniprot ID:
Q16778
Molecular Weight:
13920.055 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST2H2BF
Uniprot ID:
Q5QNW6
Molecular Weight:
13920.065 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST3H2BB
Uniprot ID:
Q8N257
Molecular Weight:
13908.005 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
H2BFM
Uniprot ID:
P0C1H6
Molecular Weight:
17001.165 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid.
Gene Name:
H2BFS
Uniprot ID:
P57053
Molecular Weight:
13944.085 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Atypical histone H2B. Nucleosomes containing it are structurally and dynamically indistinguishable from those containing conventional H2B. However, unlike conventional H2B, does not recruit chromosome condensation factors and does not participate in the assembly of mitotic chromosomes. May be important for telomere function.
Gene Name:
H2BFWT
Uniprot ID:
Q7Z2G1
Molecular Weight:
19618.3 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Histone H3-like variant which exclusively replaces conventional H3 in the nucleosome core of centromeric chromatin at the inner plate of the kinetochore. Required for recruitment and assembly of kinetochore proteins, mitotic progression and chromosome segregation. May serve as an epigenetic mark that propagates centromere identity through replication and cell division. The CENPA-H4 heterotetramer can bind DNA by itself (in vitro).
Gene Name:
CENPA
Uniprot ID:
P49450
Molecular Weight:
15990.395 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Histone binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST1H3A
Uniprot ID:
P68431
Molecular Weight:
15403.925 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Histone binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST3H3
Uniprot ID:
Q16695
Molecular Weight:
15508.105 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Histone binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST2H3A
Uniprot ID:
Q71DI3
Molecular Weight:
15387.865 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Rna polymerase ii distal enhancer sequence-specific dna binding
Specific Function:
Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes. Constitutes the predominant form of histone H3 in non-dividing cells and is incorporated into chromatin independently of DNA synthesis. Deposited at sites of nucleosomal displacement throughout transcribed genes, suggesting that it represents an epigenetic imprint of transcriptionally active chromatin. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
H3F3A
Uniprot ID:
P84243
Molecular Weight:
15327.745 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Nucleosomal dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Hominid-specific H3.5/H3F3C preferentially colocalizes with euchromatin, and it is associated with actively transcribed genes.
Gene Name:
H3F3C
Uniprot ID:
Q6NXT2
Molecular Weight:
15213.57 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Protein domain specific binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST1H4A
Uniprot ID:
P62805
Molecular Weight:
11367.3 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling (By similarity).
Gene Name:
HIST1H4G
Uniprot ID:
Q99525
Molecular Weight:
11009.065 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
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 ]
General Function:
Transcription regulatory region sequence-specific dna binding
Specific Function:
Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Preferentially demethylates mono- and dimethylated H3 'Lys-9' residue, with a preference for dimethylated residue, while it has weak or no activity on trimethylated H3 'Lys-9'. Demethylation of Lys residue generates formaldehyde and succinate. Involved in hormone-dependent transcriptional activation, by participating in recruitment to androgen-receptor target genes, resulting in H3 'Lys-9' demethylation and transcriptional activation. Involved in spermatogenesis by regulating expression of target genes such as PRM1 and TMP1 which are required for packaging and condensation of sperm chromatin. Involved in obesity resistance through regulation of metabolic genes such as PPARA and UCP1.
Gene Name:
KDM3A
Uniprot ID:
Q9Y4C1
Molecular Weight:
147339.98 Da
References
  1. Chen H, Costa M: Iron- and 2-oxoglutarate-dependent dioxygenases: an emerging group of molecular targets for nickel toxicity and carcinogenicity. Biometals. 2009 Feb;22(1):191-6. doi: 10.1007/s10534-008-9190-3. Epub 2008 Dec 19. [19096759 ]
General Function:
Zinc ion binding
Specific Function:
Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. Participates in transcriptional repression of ASCL2 and E2F-responsive promoters via the recruitment of histone deacetylases and NCOR1, respectively.Isoform 2: Crucial for muscle differentiation, promotes transcriptional activation of the Myog gene by directing the removal of repressive chromatin marks at its promoter. Lacks the N-terminal demethylase domain.
Gene Name:
KDM4A
Uniprot ID:
O75164
Molecular Weight:
120661.265 Da
References
  1. Chen H, Costa M: Iron- and 2-oxoglutarate-dependent dioxygenases: an emerging group of molecular targets for nickel toxicity and carcinogenicity. Biometals. 2009 Feb;22(1):191-6. doi: 10.1007/s10534-008-9190-3. Epub 2008 Dec 19. [19096759 ]
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 ]
General Function:
Dna binding
Specific Function:
Protamines substitute for histones in the chromatin of sperm during the haploid phase of spermatogenesis. They compact sperm DNA into a highly condensed, stable and inactive complex.
Gene Name:
PRM2
Uniprot ID:
P04554
Molecular Weight:
13050.695 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Protamines substitute for histones in the chromatin of sperm during the haploid phase of spermatogenesis. They compact sperm DNA into a highly condensed, stable and inactive complex (By similarity).
Gene Name:
PRM3
Uniprot ID:
Q9NNZ6
Molecular Weight:
11232.01 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Gene Name:
HIST2H2BD
Uniprot ID:
Q6DRA6
Molecular Weight:
18017.875 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
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 ]
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 ]
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 ]
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.
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.
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.
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.
General Function:
Protein serine/threonine phosphatase activity
Specific Function:
Calcium-dependent, calmodulin-stimulated protein phosphatase. Many of the substrates contain a PxIxIT motif. This subunit may have a role in the calmodulin activation of calcineurin. Dephosphorylates DNM1L, HSPB1 and SSH1.
Gene Name:
PPP3CA
Uniprot ID:
Q08209
Molecular Weight:
58687.27 Da
References
  1. King MM, Huang CY: Activation of calcineurin by nickel ions. Biochem Biophys Res Commun. 1983 Aug 12;114(3):955-61. [6311199 ]
General Function:
Protein serine/threonine phosphatase activity
Specific Function:
Calcium-dependent, calmodulin-stimulated protein phosphatase. This subunit may have a role in the calmodulin activation of calcineurin.
Gene Name:
PPP3CB
Uniprot ID:
P16298
Molecular Weight:
59023.735 Da
References
  1. King MM, Huang CY: Activation of calcineurin by nickel ions. Biochem Biophys Res Commun. 1983 Aug 12;114(3):955-61. [6311199 ]
General Function:
Phosphoprotein phosphatase activity
Specific Function:
Calcium-dependent, calmodulin-stimulated protein phosphatase. This subunit may have a role in the calmodulin activation of calcineurin.
Gene Name:
PPP3CC
Uniprot ID:
P48454
Molecular Weight:
58128.865 Da
References
  1. King MM, Huang CY: Activation of calcineurin by nickel ions. Biochem Biophys Res Commun. 1983 Aug 12;114(3):955-61. [6311199 ]
General Function:
Dna binding
Specific Function:
Protamines substitute for histones in the chromatin of sperm during the haploid phase of spermatogenesis. They compact sperm DNA into a highly condensed, stable and inactive complex.
Gene Name:
PRM1
Uniprot ID:
P04553
Molecular Weight:
6822.9 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Dna binding
Specific Function:
Essential for normal spermatogenesis and male fertility. Required for proper cell restructuring and DNA condensation during the elongation phase of spermiogenesis. Involved in the histone-protamine transition of sperm chromatin and the subsequent production of functional sperm. Binds both double-stranded and single-stranded DNA, ATP and protamine-1 (By similarity).
Gene Name:
H1FNT
Uniprot ID:
Q75WM6
Molecular Weight:
28115.69 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for nickel. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
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]
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]
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]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]