Cobalt (T3D0049)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (38)XML
Targets (38)
Record Information
Version2.0
Creation Date2009-03-06 18:57:59 UTC
Update Date2014-12-24 20:20:58 UTC
Accession NumberT3D0049
Identification
Common NameCobalt
ClassSmall Molecule
DescriptionCobalt has a molecular weight of 58.9 and an atomic number of 27. In the Periodic Table, close to other transition metals, it is situated in group 8, together with rhodium and iridium and it can occur in four oxidation states (0, +2, +3 and +4). The +2 and the ground state are the most common. Cobalt occurs in the minerals cobaltite (Co, Fe) AsS, smaltite (CoAs2), and erythrite Co3(AsO4)2.8H2O, and is often associated with nickel, silver, lead, copper, and iron ores, from which it is most frequently obtained as a by-product. Depending on the considered species, cobalt has multiple industrial applications including the production of alloys and hard metal, diamond polishing, drying agents, pigments and catalysts. Hard metal or cemented carbide is a powder metallurgical product consisting of hard, wear-resistant carbide particles bound together (cemented) with a ductile metal binder (i.e. metallic Co) by liquid phase sintering. Tungsten carbide (WC) is produced by mixing tungsten powder with pure carbon powder at high temperature; hereafter WC is mixed with Co powder to which paraffin is added as a binder. Depending on specific requirements related to their use, hard metals might additionally contain small quantities of chromium, niobium, molybdenum, titanium, tantalum or vanadium carbides. Inhalation and skin contact are the main occupational exposure routes. Occupational exposure to cobalt may result in adverse health effects in different organs or tissues, including the respiratory tract, the skin, the hemapoietic tissues, the myocardium or the thyroid gland. In addition, teratogenic and carcinogenic effects have been observed in experimental systems and/or in humans. For the general population, the diet constitutes the main route of exposure to cobalt, since it is an essential component of Vitamin B12 (hydroxycolalamin). Cobalt functions as a co-factor in enzyme catalysed reactions and is involved in the production of erythropoietin, a hormone that stimulates the formation of erythrocytes. This last property of cobalt was applied in the past as a therapy for anaemia. The carcinogenic potential of cobalt and its compounds was evaluated in 1991 by the International Agency for Research on Cancer (IARC), which concluded that there was inadequate evidence for carcinogenicity in humans (lung cancer) but sufficient evidence in experimental animal studies. In most experimental studies considered, the routes of exposure were, however, of questionable relevance for cancer risk assessment in humans for example, local sarcomas after intra-muscular injection. The general conclusion was that cobalt and its compounds are possibly carcinogenic to humans (group 2B). Since this evaluation, additional data have been accumulated which generally indicate that, depending on the considered cobalt species, different outcomes regarding toxicity, mutagenicity and carcinogenicity can be observed. Physiologically, it exists as an ion in the body. Co(II) ions are genotoxic in vitro and in vivo, and carcinogenic in rodents. Co metal is genotoxic in vitro. Hard metal dust, of which occupational exposure is linked to an increased lung cancer risk, is proven to be genotoxic in vitro and in vivo. Possibly, production of active oxygen species and/or DNA repair inhibition are mechanisms involved. Given the recently provided proof for in vitro and in vivo genotoxic potential of hard metal dust, the mechanistic evidence of elevated production of active oxygen species and the epidemiological data on increased cancer risk, it may be advisable to consider the possibility of a new evaluation by IARC.(3).
Compound Type
  • Cigarette Toxin
  • Cobalt Compound
  • Food Toxin
  • Household Toxin
  • Industrial/Workplace Toxin
  • Inorganic Compound
  • Metabolite
  • Metal
  • Natural Compound
  • Pollutant
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
Co(2+)
Co2+
Cobalt ion
Cobalt(2+)
Cobalt(2+) ion
Cobalt(II)
Cobalt(II) cation
Cobalt(II) ion
Chemical FormulaCo
Average Molecular Mass58.932 g/mol
Monoisotopic Mass58.932 g/mol
CAS Registry Number7440-48-4
IUPAC Namelambda2-cobalt(2+) ion
Traditional Namelambda2-cobalt(2+) ion
SMILES[Co++]
InChI IdentifierInChI=1S/Co/q+2
InChI KeyInChIKey=XLJKHNWPARRRJB-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 ParentsNot Available
Substituents
  • Homogeneous transition metal
Molecular FrameworkNot Available
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Kidney
  • Skin
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceGrey metallic solid.
Experimental Properties
PropertyValue
Melting Point1495°C
Boiling Point3100°C (5612°F)
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
logP0.23ChemAxon
pKa (Strongest Acidic)3.09ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity0 m³·mol⁻¹ChemAxon
Polarizability1.78 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-9000000000-5ec55e9e276ff34b918f2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-9000000000-5ec55e9e276ff34b918f2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-9000000000-5ec55e9e276ff34b918f2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-9000000000-c4eed668d3af388c4a952016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-9000000000-c4eed668d3af388c4a952016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9000000000-c4eed668d3af388c4a952016-08-03View Spectrum
Toxicity Profile
Route of ExposureInhalation (9) ; oral (9) ; dermal (9)
Mechanism of ToxicityCobalt is believed to exhibit its toxicity through a oxidant-based and free radical-based processes. It produces oxygen radicals and may be oxidized to ionic cobalt, causing increased lipid peroxidation, DNA damage, and inducing certain enzymes that lead to cell apoptosis. Cobalt has also been shown to block inorganic calcium channels, possibly impairing neurotransmission. Cobalt can also chelate lipoic acids, impairing oxidation of pyruvate or fatty acids. In addition, cobalt may inhibit DNA repair by interacting with zinc finger DNA repair proteins, and has also been shown to inhibit heme synthesis and glucose metabolism. Cobalt may activate specific helper T-lymphocyte cells and interact directly with immunologic proteins, such as antibodies (IgA and IgE) or Fc receptors, resulting in immunosensitization. (9)
MetabolismCobalt is absorbed though the lungs, gastrointestinal tract, and skin. Since it is a component of the vitamin B12 (cyanocobalamin), it is distributed to most tissues of the body. It is transported in the blood, often bound to albumin, with the highest levels being found in the liver and kidney. Cobalt is excreted mainly in the urine and faeces. (9)
Toxicity ValuesLD50: 6170 mg/kg (Oral, Rat) (8) LD50: 100 mg/kg (Intraperitoneal, Rat) (8)
Lethal Dose1 to 2 mg/m3 for an adult human. (13)
Carcinogenicity (IARC Classification)Cobalt metal with tungsten carbide: 2A, probably carcinogenic to humans. Cobalt metal without tungsten carbide: 2B, posiibly carcinogenic to humans. (12)
Uses/SourcesCobalt is used to produce alloys used in the manufacture of aircraft engines, magnets, grinding and cutting tools, artificial hip and knee joints. Cobalt compounds are also used to color glass, ceramics and paints, and used as a drier for porcelain enamel and paints.
Minimum Risk LevelChronic Inhalation: 0.0001 mg/m3 (11) Intermediate Oral: 0.01 mg/kg/day (11)
Health EffectsExposure to high amount of cobalt can cause heart, lung, kidney, and liver damage. Skin contact is known to result in contact dermatitis. Cobalt may also have mutagenic and carcinogenic effects. (9, 10)
SymptomsCobalt inhalation can cause asthma-like breathing problems. Skin contact is known to result in contact dermatitis, which is characterized by irritation and rashes. Ingesting large amounts of cobalt may cause nausea and vomiting. (14)
TreatmentTreatment of cobalt poisoning is symptomatic. (9)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB00608
PubChem Compound ID104729
ChEMBL IDNot Available
ChemSpider ID94546
KEGG IDC00175
UniProt IDNot Available
OMIM ID
ChEBI ID48828
BioCyc IDCOBALT-FACTOR-III
CTD IDD003035
Stitch IDCobalt
PDB IDCO
ACToR ID7202
Wikipedia LinkCobalt
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Ekinci D, Beydemir S, Kufrevioglu OI: In vitro inhibitory effects of some heavy metals on human erythrocyte carbonic anhydrases. J Enzyme Inhib Med Chem. 2007 Dec;22(6):745-50. doi: 10.1080/14756360601176048 . [18237030 ]
  2. Amirtharaj GJ, Natarajan SK, Mukhopadhya A, Zachariah UG, Hegde SK, Kurian G, Balasubramanian KA, Ramachandran A: Fatty acids influence binding of cobalt to serum albumin in patients with fatty liver. Biochim Biophys Acta. 2008 May;1782(5):349-54. doi: 10.1016/j.bbadis.2008.02.006. Epub 2008 Feb 29. [18346470 ]
  3. De Boeck M, Kirsch-Volders M, Lison D: Cobalt and antimony: genotoxicity and carcinogenicity. Mutat Res. 2003 Dec 10;533(1-2):135-52. [14643417 ]
  4. Larese Filon F, Maina G, Adami G, Venier M, Coceani N, Bussani R, Massiccio M, Barbieri P, Spinelli P: In vitro percutaneous absorption of cobalt. Int Arch Occup Environ Health. 2004 Feb;77(2):85-9. Epub 2003 Jun 19. [12819972 ]
  5. Liden C, Skare L, Lind B, Nise G, Vahter M: Assessment of skin exposure to nickel, chromium and cobalt by acid wipe sampling and ICP-MS. Contact Dermatitis. 2006 May;54(5):233-8. [16689805 ]
  6. Fisher JW: A quest for erythropoietin over nine decades. Annu Rev Pharmacol Toxicol. 1998;38:1-20. [9597146 ]
  7. Morales Concepcion JC, Cordies Jackson E, Sandin Hernandez N, Reno Cespedes J, Moreno Diaz ME: [Metachronous bilateral Wilms' tumor]. Arch Esp Urol. 2000 Apr;53(3):245-7. [10851730 ]
  8. National Institute for Occupational Safety and Health (2002). RTECS: Registry of Toxic Effects of Chemical Substances.
  9. ATSDR - Agency for Toxic Substances and Disease Registry (2004). Toxicological profile for cobalt. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  10. Wikipedia. Cobalt. Last Updated 21 March 2009. [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]
  13. HSDB: Hazardous Substances Data Bank. National Library of Medicine (2001). [Link]
  14. U.S. National Library of Medicine, MedlinePlus: Cobalt poisoning. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

Target Details
1. Carbonic anhydrase 1
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
Gene Name:
CA1
Uniprot ID:
P00915
Molecular Weight:
28870.0 Da
References
  1. Ekinci D, Beydemir S, Kufrevioglu OI: In vitro inhibitory effects of some heavy metals on human erythrocyte carbonic anhydrases. J Enzyme Inhib Med Chem. 2007 Dec;22(6):745-50. doi: 10.1080/14756360601176048 . [18237030 ]
  2. Ul-Hassan M, Scozzafava A, Chohan ZH, Supuran CT: Carbonic anhydrase inhibitors: metal complexes of a sulfanilamide derived Schiff base and their interaction with isozymes I, II and IV. J Enzyme Inhib. 2001 Dec;16(6):499-505. [12164389 ]
Target Details
2. Carbonic anhydrase 2
General Function:
Zinc ion binding
Specific Function:
Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Stimulates the chloride-bicarbonate exchange activity of SLC26A6.
Gene Name:
CA2
Uniprot ID:
P00918
Molecular Weight:
29245.895 Da
References
  1. Ekinci D, Beydemir S, Kufrevioglu OI: In vitro inhibitory effects of some heavy metals on human erythrocyte carbonic anhydrases. J Enzyme Inhib Med Chem. 2007 Dec;22(6):745-50. doi: 10.1080/14756360601176048 . [18237030 ]
  2. Ul-Hassan M, Scozzafava A, Chohan ZH, Supuran CT: Carbonic anhydrase inhibitors: metal complexes of a sulfanilamide derived Schiff base and their interaction with isozymes I, II and IV. J Enzyme Inhib. 2001 Dec;16(6):499-505. [12164389 ]
Target Details
3. Carbonic anhydrase 4
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid.
Gene Name:
CA4
Uniprot ID:
P22748
Molecular Weight:
35032.075 Da
References
  1. Ekinci D, Beydemir S, Kufrevioglu OI: In vitro inhibitory effects of some heavy metals on human erythrocyte carbonic anhydrases. J Enzyme Inhib Med Chem. 2007 Dec;22(6):745-50. doi: 10.1080/14756360601176048 . [18237030 ]
  2. Ul-Hassan M, Scozzafava A, Chohan ZH, Supuran CT: Carbonic anhydrase inhibitors: metal complexes of a sulfanilamide derived Schiff base and their interaction with isozymes I, II and IV. J Enzyme Inhib. 2001 Dec;16(6):499-505. [12164389 ]
Target Details
4. 5-aminolevulinate synthase, erythroid-specific, mitochondrial
General Function:
Pyridoxal phosphate binding
Specific Function:
Not Available
Gene Name:
ALAS2
Uniprot ID:
P22557
Molecular Weight:
64632.86 Da
References
  1. Wikipedia. Mercury poisoning. Last Updated 8 March 2009. [Link]
Target Details
5. 5-aminolevulinate synthase, nonspecific, mitochondrial
General Function:
Pyridoxal phosphate binding
Specific Function:
Not Available
Gene Name:
ALAS1
Uniprot ID:
P13196
Molecular Weight:
70580.325 Da
References
  1. Wikipedia. Mercury poisoning. Last Updated 8 March 2009. [Link]
6. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2004). Toxicological profile for cobalt. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Target Details
7. DNA repair protein complementing XP-A cells
General Function:
Protein homodimerization activity
Specific Function:
Involved in DNA excision repair. Initiates repair by binding to damaged sites with various affinities, depending on the photoproduct and the transcriptional state of the region. Required for UV-induced CHEK1 phosphorylation and the recruitment of CEP164 to cyclobutane pyrimidine dimmers (CPD), sites of DNA damage after UV irradiation.
Gene Name:
XPA
Uniprot ID:
P23025
Molecular Weight:
31367.71 Da
References
  1. Hartwig A, Asmuss M, Ehleben I, Herzer U, Kostelac D, Pelzer A, Schwerdtle T, Burkle A: Interference by toxic metal ions with DNA repair processes and cell cycle control: molecular mechanisms. Environ Health Perspect. 2002 Oct;110 Suppl 5:797-9. [12426134 ]
Target Details
8. Estrogen receptor
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66215.45 Da
References
  1. Payne JC, Rous BW, Tenderholt AL, Godwin HA: Spectroscopic determination of the binding affinity of zinc to the DNA-binding domains of nuclear hormone receptors. Biochemistry. 2003 Dec 9;42(48):14214-24. [14640689 ]
Target Details
9. Fas-binding factor 1
General Function:
Not Available
Specific Function:
Keratin-binding protein required for epithelial cell polarization. Involved in apical junction complex (AJC) assembly via its interaction with PARD3. Required for ciliogenesis.
Gene Name:
FBF1
Uniprot ID:
Q8TES7
Molecular Weight:
125445.19 Da
References
  1. Mothes E, Faller P: Evidence that the principal CoII-binding site in human serum albumin is not at the N-terminus: implication on the albumin cobalt binding test for detecting myocardial ischemia. Biochemistry. 2007 Feb 27;46(8):2267-74. Epub 2007 Feb 3. [17274600 ]
Target Details
10. Histone deacetylase 8
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 ]
Target Details
11. Ig alpha-1 chain C region
General Function:
Antigen binding
Specific Function:
Ig alpha is the major immunoglobulin class in body secretions. It may serve both to defend against local infection and to prevent access of foreign antigens to the general immunologic system.
Gene Name:
IGHA1
Uniprot ID:
P01876
Molecular Weight:
37654.29 Da
References
  1. Bencko V, Wagner V, Wagnerova M, Reichrtova E: Immuno-biochemical findings in groups of individuals occupationally and non-occupationally exposed to emissions containing nickel and cobalt. J Hyg Epidemiol Microbiol Immunol. 1983;27(4):387-94. [6663071 ]
Target Details
12. Ig alpha-2 chain C region
General Function:
Antigen binding
Specific Function:
Ig alpha is the major immunoglobulin class in body secretions. It may serve both to defend against local infection and to prevent access of foreign antigens to the general immunologic system.
Gene Name:
IGHA2
Uniprot ID:
P01877
Molecular Weight:
36526.005 Da
References
  1. Bencko V, Wagner V, Wagnerova M, Reichrtova E: Immuno-biochemical findings in groups of individuals occupationally and non-occupationally exposed to emissions containing nickel and cobalt. J Hyg Epidemiol Microbiol Immunol. 1983;27(4):387-94. [6663071 ]
Target Details
13. Ig epsilon chain C region
General Function:
Immunoglobulin receptor binding
Specific Function:
Not Available
Gene Name:
IGHE
Uniprot ID:
P01854
Molecular Weight:
47018.665 Da
References
  1. Shirakawa T, Kusaka Y, Fujimura N, Goto S, Morimoto K: The existence of specific antibodies to cobalt in hard metal asthma. Clin Allergy. 1988 Sep;18(5):451-60. [3233723 ]
Target Details
14. Poly [ADP-ribose] polymerase 1
General Function:
Zinc ion binding
Specific Function:
Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production. Required for PARP9 and DTX3L recruitment to DNA damage sites. PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites.
Gene Name:
PARP1
Uniprot ID:
P09874
Molecular Weight:
113082.945 Da
References
  1. Hartwig A, Asmuss M, Ehleben I, Herzer U, Kostelac D, Pelzer A, Schwerdtle T, Burkle A: Interference by toxic metal ions with DNA repair processes and cell cycle control: molecular mechanisms. Environ Health Perspect. 2002 Oct;110 Suppl 5:797-9. [12426134 ]
Target Details
15. Voltage-dependent L-type calcium channel subunit alpha-1C
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in excitation-contraction coupling in the heart. The various isoforms display marked differences in the sensitivity to DHP compounds. Binding of calmodulin or CABP1 at the same regulatory sites results in an opposit effects on the channel function.
Gene Name:
CACNA1C
Uniprot ID:
Q13936
Molecular Weight:
248974.1 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
16. Voltage-dependent L-type calcium channel subunit alpha-1D
General Function:
Voltage-gated calcium channel activity involved sa node cell action potential
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA).
Gene Name:
CACNA1D
Uniprot ID:
Q01668
Molecular Weight:
245138.75 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
17. Voltage-dependent L-type calcium channel subunit alpha-1F
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1F gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA).
Gene Name:
CACNA1F
Uniprot ID:
O60840
Molecular Weight:
220675.9 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
18. Voltage-dependent L-type calcium channel subunit alpha-1S
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1S gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle.
Gene Name:
CACNA1S
Uniprot ID:
Q13698
Molecular Weight:
212348.1 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
19. Voltage-dependent L-type calcium channel subunit beta-1
General Function:
Voltage-gated calcium channel activity
Specific Function:
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
Gene Name:
CACNB1
Uniprot ID:
Q02641
Molecular Weight:
65712.995 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
20. Voltage-dependent L-type calcium channel subunit beta-2
General Function:
Voltage-gated calcium channel activity
Specific Function:
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
Gene Name:
CACNB2
Uniprot ID:
Q08289
Molecular Weight:
73579.925 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
21. Voltage-dependent L-type calcium channel subunit beta-3
General Function:
Voltage-gated calcium channel activity
Specific Function:
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
Gene Name:
CACNB3
Uniprot ID:
P54284
Molecular Weight:
54531.425 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
22. Voltage-dependent L-type calcium channel subunit beta-4
General Function:
Voltage-gated calcium channel activity
Specific Function:
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
Gene Name:
CACNB4
Uniprot ID:
O00305
Molecular Weight:
58168.625 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
23. Voltage-dependent N-type calcium channel subunit alpha-1B
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1B gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by omega-conotoxin-GVIA (omega-CTx-GVIA) and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to dihydropyridines (DHP), and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons.
Gene Name:
CACNA1B
Uniprot ID:
Q00975
Molecular Weight:
262493.84 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
24. Voltage-dependent P/Q-type calcium channel subunit alpha-1A
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1A gives rise to P and/or Q-type calcium currents. P/Q-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by the funnel toxin (Ftx) and by the omega-agatoxin-IVA (omega-Aga-IVA). They are however insensitive to dihydropyridines (DHP), and omega-conotoxin-GVIA (omega-CTx-GVIA).
Gene Name:
CACNA1A
Uniprot ID:
O00555
Molecular Weight:
282362.39 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
25. Voltage-dependent R-type calcium channel subunit alpha-1E
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1E gives rise to R-type calcium currents. R-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by nickel, and partially by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to dihydropyridines (DHP), omega-conotoxin-GVIA (omega-CTx-GVIA), and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing alpha-1E subunit could be involved in the modulation of firing patterns of neurons which is important for information processing.
Gene Name:
CACNA1E
Uniprot ID:
Q15878
Molecular Weight:
261729.05 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
26. Voltage-dependent calcium channel gamma-1 subunit
General Function:
Voltage-gated calcium channel activity
Specific Function:
This protein is a subunit of the dihydropyridine (DHP) sensitive calcium channel. Plays a role in excitation-contraction coupling. The skeletal muscle DHP-sensitive Ca(2+) channel may function only as a multiple subunit complex.
Gene Name:
CACNG1
Uniprot ID:
Q06432
Molecular Weight:
25028.105 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
27. Voltage-dependent calcium channel gamma-2 subunit
General Function:
Voltage-gated calcium channel activity
Specific Function:
Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits. Thought to stabilize the calcium channel in an inactivated (closed) state.
Gene Name:
CACNG2
Uniprot ID:
Q9Y698
Molecular Weight:
35965.44 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
28. Voltage-dependent calcium channel gamma-3 subunit
General Function:
Voltage-gated calcium channel activity
Specific Function:
Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits. Thought to stabilize the calcium channel in an inactivated (closed) state (By similarity).
Gene Name:
CACNG3
Uniprot ID:
O60359
Molecular Weight:
35548.14 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
29. Voltage-dependent calcium channel gamma-4 subunit
General Function:
Voltage-gated calcium channel activity
Specific Function:
Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization and by mediating their resensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits. Thought to stabilize the calcium channel in an inactivated (closed) state.
Gene Name:
CACNG4
Uniprot ID:
Q9UBN1
Molecular Weight:
36578.39 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
30. Voltage-dependent calcium channel gamma-5 subunit
General Function:
Voltage-gated calcium channel activity
Specific Function:
Regulates the gating properties of AMPA-selective glutamate receptors (AMPARs). Modulates their gating properties by accelerating their rates of activation, deactivation and desensitization. Displays subunit-specific AMPA receptor regulation. Shows specificity for GRIA1, GRIA4 and the long isoform of GRIA2. Thought to stabilize the calcium channel in an inactivated (closed) state (By similarity).
Gene Name:
CACNG5
Uniprot ID:
Q9UF02
Molecular Weight:
30902.44 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
31. Voltage-dependent calcium channel gamma-6 subunit
General Function:
Voltage-gated calcium channel activity
Specific Function:
Thought to stabilize the calcium channel in an inactivated (closed) state.
Gene Name:
CACNG6
Uniprot ID:
Q9BXT2
Molecular Weight:
28128.745 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
32. Voltage-dependent calcium channel gamma-7 subunit
General Function:
Voltage-gated calcium channel activity
Specific Function:
Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization and by mediating their resensitization. Displays subunit-specific AMPA receptor regulation. Shows specificity only for GRIA1 and GRIA2. Thought to stabilize the calcium channel in an inactivated (closed) state.
Gene Name:
CACNG7
Uniprot ID:
P62955
Molecular Weight:
31002.29 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
33. Voltage-dependent calcium channel gamma-8 subunit
General Function:
Voltage-gated calcium channel activity
Specific Function:
Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization and by mediating their resensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits. Thought to stabilize the calcium channel in an inactivated (closed) state.
Gene Name:
CACNG8
Uniprot ID:
Q8WXS5
Molecular Weight:
43312.44 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
34. Voltage-dependent calcium channel gamma-like subunit
General Function:
Voltage-gated ion channel activity
Specific Function:
Thought to stabilize the calcium channel in an inactivated (closed) state. Modulates calcium current when coexpressed with CACNA1G (By similarity).
Gene Name:
TMEM37
Uniprot ID:
Q8WXS4
Molecular Weight:
20931.565 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
35. Voltage-dependent calcium channel subunit alpha-2/delta-1
General Function:
Voltage-gated calcium channel activity
Specific Function:
The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Plays an important role in excitation-contraction coupling (By similarity).
Gene Name:
CACNA2D1
Uniprot ID:
P54289
Molecular Weight:
124566.93 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
36. Voltage-dependent calcium channel subunit alpha-2/delta-2
General Function:
Voltage-gated calcium channel activity
Specific Function:
The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) and possibly T-type (CACNA1G). Overexpression induces apoptosis.
Gene Name:
CACNA2D2
Uniprot ID:
Q9NY47
Molecular Weight:
129816.095 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
37. Voltage-dependent calcium channel subunit alpha-2/delta-3
General Function:
Voltage-gated ion channel activity
Specific Function:
The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) but not T-type (CACNA1G) (By similarity).
Gene Name:
CACNA2D3
Uniprot ID:
Q8IZS8
Molecular Weight:
123010.22 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]
Target Details
38. Voltage-dependent calcium channel subunit alpha-2/delta-4
General Function:
Voltage-gated calcium channel activity
Specific Function:
The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel.
Gene Name:
CACNA2D4
Uniprot ID:
Q7Z3S7
Molecular Weight:
127936.93 Da
References
  1. Castelli L, Tanzi F, Taglietti V, Magistretti J: Cu2+, Co2+, and Mn2+ modify the gating kinetics of high-voltage-activated Ca2+ channels in rat palaeocortical neurons. J Membr Biol. 2003 Oct 1;195(3):121-36. [14724759 ]