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Record Information
Version2.0
Creation Date2009-03-06 18:57:59 UTC
Update Date2014-12-24 20:20:59 UTC
Accession NumberT3D0053
Identification
Common NameNickel
ClassSmall Molecule
DescriptionNickel is a solid, silver-white, hard, malleable transition metal with an atomic number of 28. It resists corrosion even at high temperatures. It is present in many alloys in widespread use, including stainless steels. It may also be present as an impurity in any alloy. Nickel is used in the production of coins, jewellery, and nickel-cadmium batteries, and as a catalyst for the hydrogenation of liquid oils to solid fats such as oleomargarine and vegetable shortening. Nickel-containing dental alloys continue to be used successfully in the provision of various forms of dental care. Many of these alloys have applications in the construction of restorations designed to remain in clinical service for many years, including crowns, fixed bridgework, and removable partial dentures. Furthermore, nickel containing alloys find extensive application in orthodontics, including metallic brackets, arch wires, bands, springs and ligature wires. Many instruments and devises, for example, endodontic instruments also contain nickel. Allergic responses are mediated through the immune system. In a sensitized individual, allergic responses can be initiated by relatively small amounts of the allergen; for example, if nickel ions are released from a nickel plated material following direct and prolonged contact with the skin. Individuals are first sensitized to the allergen. Subsequent exposures, if sufficiently high, may then result in an allergic reaction. A number of allergens are used in the clinical practice of dentistry, notably eugenol, mercury, nickel, chromium, cobalt, components of resin-based materials and a host of other chemical agents. The majority of dental allergies, including allergic responses to nickel-containing dental alloys, comprise Type IV hypersensitivity reactions, cell-mediated by T-lymphocytes. Physiologically, it exists as an ion in the body.(7, 8).
Compound Type
  • Food Toxin
  • Household Toxin
  • Industrial/Workplace Toxin
  • Inorganic Compound
  • Metabolite
  • Metal
  • Natural Compound
  • Nickel Compound
  • Pollutant
Chemical Structure
Thumb
Synonyms
Synonym
Metallic Nickel
Ni(2+)
Ni2+
Nickel ion
Nickel(2+)
Nickel(2+) ion
Nickel(II)
Nickel(II) cation
Nickel(II) ion
Chemical FormulaNi
Average Molecular Mass58.692 g/mol
Monoisotopic Mass57.934 g/mol
CAS Registry Number7440-02-0
IUPAC Namenickel(2+) ion
Traditional Namenickel(2+) ion
SMILES[Ni++]
InChI IdentifierInChI=1S/Ni/q+2
InChI KeyInChIKey=VEQPNABPJHWNSG-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of inorganic compounds known as homogeneous transition metal compounds. These are inorganic compounds containing only metal atoms,with the largest atom being a transition metal atom.
KingdomInorganic compounds
Super ClassHomogeneous metal compounds
ClassHomogeneous transition metal compounds
Sub ClassNot Available
Direct ParentHomogeneous transition metal compounds
Alternative Parents
Substituents
  • Homogeneous transition metal
  • Inorganic nickel compound
Molecular FrameworkNot Available
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceSilvery-white metallic solid.
Experimental Properties
PropertyValue
Melting Point1455°C
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
logP0.16ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity0 m3·mol-1ChemAxon
Polarizability1.78 Å3ChemAxon
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, Positivesplash10-0a4i-9000000000-08256b3c9e2cc1750f60View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-9000000000-08256b3c9e2cc1750f60View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-9000000000-08256b3c9e2cc1750f60View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-9000000000-4648ffc6f53552c41503View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-9000000000-4648ffc6f53552c41503View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9000000000-4648ffc6f53552c41503View in MoNA
Toxicity Profile
Route of ExposureOral (14) ; inhalation (14) ; dermal (14)
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. (14, 1)
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 α2-macroglobulin. Nickel tends to accumulate in the lungs, thyroid, kidney, heart, and liver. Absorbed nickel is excreted in the urine, whereas unabsorbed nickel is excreted in the faeces. (14)
Toxicity ValuesLD50: 250 mg/kg (Intraperitoneal, Rat) (12)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Metallic nickel is possibly carcinogenic to humons (Group 2B). Nickel compounds are carcinogenic to humans (Group 1). (17)
Uses/SourcesPure nickel is mainly used to make alloys, which are found in items such as coins, jewelry, valves and heat exchangers. Nickel compounds are used for nickel plating, to color ceramics, to make some batteries, and as catalysts. (14)
Minimum Risk LevelIntermediate Inhalation: 0.0002 mg/m3 (16) Chronic Inhalation: 0.00009 mg/m3 (16)
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. (14)
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. (15)
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. (15)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB02457
PubChem Compound ID934
ChEMBL IDNot Available
ChemSpider ID909
KEGG IDC19609
UniProt IDNot Available
OMIM ID
ChEBI ID49786
BioCyc IDCPD-7425
CTD IDD009532
Stitch IDNickel
PDB IDNI
ACToR ID946
Wikipedia LinkNickel
References
Synthesis ReferenceLightner, David A.; Crist, B. Vincent; Kalyanam, Nagabushanam; May, Leslie M.; Jackman, Dennis E. The octant rule. 15. Antioctant effects: synthesis and circular dichroism of 2-exo- and 2-endo-alkylbicyclo[2.2.1]heptan-7-ones and bicyclo[3.2.1]octan-8-one
MSDST3D0053.pdf
General References
  1. King MM, Huang CY: Activation of calcineurin by nickel ions. Biochem Biophys Res Commun. 1983 Aug 12;114(3):955-61. [6311199 ]
  2. Zoroddu MA, Schinocca L, Kowalik-Jankowska T, Kozlowski H, Salnikow K, Costa M: Molecular mechanisms in nickel carcinogenesis: modeling Ni(II) binding site in histone H4. Environ Health Perspect. 2002 Oct;110 Suppl 5:719-23. [12426119 ]
  3. Bal W, Jezowska-Bojczuk M, Kasprzak KS: Binding of nickel(II) and copper(II) to the N-terminal sequence of human protamine HP2. Chem Res Toxicol. 1997 Aug;10(8):906-14. [9282840 ]
  4. Salnikow K, Davidson T, Zhang Q, Chen LC, Su W, Costa M: The involvement of hypoxia-inducible transcription factor-1-dependent pathway in nickel carcinogenesis. Cancer Res. 2003 Jul 1;63(13):3524-30. [12839937 ]
  5. Cruz MT, Goncalo M, Figueiredo A, Carvalho AP, Duarte CB, Lopes MC: Contact sensitizer nickel sulfate activates the transcription factors NF-kB and AP-1 and increases the expression of nitric oxide synthase in a skin dendritic cell line. Exp Dermatol. 2004 Jan;13(1):18-26. [15009112 ]
  6. Salnikow K, Wang S, Costa M: Induction of activating transcription factor 1 by nickel and its role as a negative regulator of thrombospondin I gene expression. Cancer Res. 1997 Nov 15;57(22):5060-6. [9371503 ]
  7. Hostynek JJ: Sensitization to nickel: etiology, epidemiology, immune reactions, prevention, and therapy. Rev Environ Health. 2006 Oct-Dec;21(4):253-80. [17243350 ]
  8. Setcos JC, Babaei-Mahani A, Silvio LD, Mjor IA, Wilson NH: The safety of nickel containing dental alloys. Dent Mater. 2006 Dec;22(12):1163-8. Epub 2006 Jan 6. [16405986 ]
  9. Nielsen FH: How should dietary guidance be given for mineral elements with beneficial actions or suspected of being essential? J Nutr. 1996 Sep;126(9 Suppl):2377S-2385S. [8811801 ]
  10. Biego GH, Joyeux M, Hartemann P, Debry G: Daily intake of essential minerals and metallic micropollutants from foods in France. Sci Total Environ. 1998 Jun 30;217(1-2):27-36. [9695171 ]
  11. Uthus EO, Seaborn CD: Deliberations and evaluations of the approaches, endpoints and paradigms for dietary recommendations of the other trace elements. J Nutr. 1996 Sep;126(9 Suppl):2452S-2459S. [8811811 ]
  12. National Institute for Occupational Safety and Health (2002). RTECS: Registry of Toxic Effects of Chemical Substances.
  13. Wikipedia. Nickel. Last Updated 22 March 2009. [Link]
  14. 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]
  15. Redmond JC (2008). Nickel Poisoning. LoveToKnow. [Link]
  16. 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]
  17. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5025 uMNot AvailableBindingDB 50361477
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 ]
  2. Suzuki T, Miyata N: Lysine demethylases inhibitors. J Med Chem. 2011 Dec 22;54(24):8236-50. doi: 10.1021/jm201048w. Epub 2011 Oct 7. [21955276 ]
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:
Transition metal ion binding
Specific Function:
Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Beta-amyloid 42 is a more effective reductant than beta-amyloid 40. Beta-amyloid peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity. Also binds GPC1 in lipid rafts.Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain.The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).
Gene Name:
APP
Uniprot ID:
P05067
Molecular Weight:
86942.715 Da
References
  1. da Silva GF, Tay WM, Ming LJ: Catechol oxidase-like oxidation chemistry of the 1-20 and 1-16 fragments of Alzheimer's disease-related beta-amyloid peptide: their structure-activity correlation and the fate of hydrogen peroxide. J Biol Chem. 2005 Apr 29;280(17):16601-9. Epub 2005 Feb 7. [15699049 ]
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 c-terminus binding
Specific Function:
Required for full ubiquitin ligase activity of the anaphase promoting complex/cyclosome (APC/C) and may confer substrate specificity upon the complex. Is regulated by MAD2L1: in metaphase the MAD2L1-CDC20-APC/C ternary complex is inactive and in anaphase the CDC20-APC/C binary complex is active in degrading substrates. The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. CDC20-APC/C-induced degradation of NEUROD2 induces presynaptic differentiation.
Gene Name:
CDC20
Uniprot ID:
Q12834
Molecular Weight:
54722.15 Da
References
  1. Mondal G, Baral RN, Roychoudhury S: A new Mad2-interacting domain of Cdc20 is critical for the function of Mad2-Cdc20 complex in the spindle assembly checkpoint. Biochem J. 2006 Jun 1;396(2):243-53. [16497171 ]
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:
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:
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Also involved in the deacetylation of cohesin complex protein SMC3 regulating release of cohesin complexes from chromatin. May play a role in smooth muscle cell contractility.
Gene Name:
HDAC8
Uniprot ID:
Q9BY41
Molecular Weight:
41757.29 Da
References
  1. Gantt SL, Gattis SG, Fierke CA: Catalytic activity and inhibition of human histone deacetylase 8 is dependent on the identity of the active site metal ion. Biochemistry. 2006 May 16;45(19):6170-8. [16681389 ]
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:
Tubulin binding
Specific Function:
Its primary physiological function is unclear. Has cytoprotective activity against internal or environmental stresses. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May play a role in iron uptake and iron homeostasis. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro) (PubMed:12732622, PubMed:19936054, PubMed:20564047). Association with GPC1 (via its heparan sulfate chains) targets PRNP to lipid rafts. Also provides Cu(2+) or ZN(2+) for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains (By similarity).
Gene Name:
PRNP
Uniprot ID:
P04156
Molecular Weight:
27661.21 Da
References
  1. Shearer J, Soh P: Ni K-edge XAS suggests that coordination of Ni(II) to the unstructured amyloidogenic region of the human prion protein produces a Ni(2) bis-mu-hydroxo dimer. J Inorg Biochem. 2007 Feb;101(2):370-3. Epub 2006 Oct 20. [17126907 ]
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:
HIST2H2BC
Uniprot ID:
Q6DN03
Molecular Weight:
21471.81 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:
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]