Copper
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Basic Info
| Common Name | Copper(F03371) |
| 2D Structure | |
| Description | Copper is an essential nutrient to all higher plants and animals. Physiologically, it exists as an ion in the body. In animals, it is found primarily in the bloodstream, as a cofactor in various enzymes, and in copper-based pigments. In the body, copper shifts between the cuprous (Cu1+) and cupric (Cu2+) forms, though the majority of the body's copper is in the Cu2+ form. The ability of copper to easily accept and donate electrons explains its important role in oxidation-reduction (redox) reactions and in scavenging free radicals. Copper is a critical functional component of a number of essential enzymes known as cuproenzymes. For instance, the copper-dependent enzyme, cytochrome c oxidase, plays a critical role in cellular energy production. By catalyzing the reduction of molecular oxygen (O2) to water (H2O), cytochrome c oxidase generates an electrical gradient used by the mitochondria to create the vital energy-storing molecule, ATP. Another cuproenzyme, lysyl oxidase, is required for the cross-linking of collagen and elastin, which are essential for the formation of strong and flexible connective tissue. Another cuproeznyme, Monoamine oxidase (MAO), plays a role in the metabolism of the neurotransmitters norepinephrine, epinephrine, and dopamine. MAO also functions in the degradation of the neurotransmitter serotonin, which is the basis for the use of MAO inhibitors as antidepressants. One of the most important cuproenzymes is Superoxide dismutase (SOD). SOD functions as an antioxidant by catalyzing the conversion of superoxide radicals (free radicals or ROS) to hydrogen peroxide, which can subsequently be reduced to water by other antioxidant enzymes. Two forms of SOD contain copper: 1) copper/zinc SOD is found within most cells of the body, including red blood cells, and 2) extracellular SOD is a copper-containing enzyme found at high levels in the lungs and low levels in blood plasma. In sufficient amounts, copper can be poisonous or even fatal to organisms. Copper is normally bound to cuproenzymes (such as SOD, MOA) and is thus only toxic when unsequestered and unmediated. It is believed that zinc and copper compete for absorption in the digestive tract so that a diet that is excessive in one of these minerals may result in a deficiency in the other. An imbalance of zinc and copper status might be involved in human hypertension. |
| FRCD ID | F03371 |
| CAS Number | 7440-50-8 |
| PubChem CID | 23978 |
| Formula | Cu |
| IUPAC Name | copper |
| InChI Key | RYGMFSIKBFXOCR-UHFFFAOYSA-N |
| InChI | InChI=1S/Cu |
| Canonical SMILES | [Cu] |
| Isomeric SMILES | [Cu] |
| Wikipedia | Copper |
| Synonyms |
cobre
Copper-airborne
Copper
7440-50-8
cuprum
cuivre
Copper bronze
Kupfer
Blister copper
Cathode copper
|
| Classifies |
Pollutant
Metal
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Inorganic compounds |
| Superclass | Homogeneous metal compounds |
| Class | Homogeneous transition metal compounds |
| Subclass | Not available |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Homogeneous transition metal compounds |
| Alternative Parents | |
| Molecular Framework | Not available |
| Substituents | Homogeneous transition metal |
| Description | This compound 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. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 63.546 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 0 |
| Rotatable Bond Count | 0 |
| Complexity | 0 |
| Monoisotopic Mass | 62.93 |
| Exact Mass | 62.93 |
| Formal Charge | 0 |
| Heavy Atom Count | 1 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9733 |
| Human Intestinal Absorption | HIA+ | 0.9838 |
| Caco-2 Permeability | Caco2+ | 0.7354 |
| P-glycoprotein Substrate | Non-substrate | 0.8810 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9787 |
| Non-inhibitor | 0.9858 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.9110 |
| Distribution | ||
| Subcellular localization | Lysosome | 0.5856 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8466 |
| CYP450 2D6 Substrate | Non-substrate | 0.8259 |
| CYP450 3A4 Substrate | Non-substrate | 0.8158 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.8584 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9241 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9638 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9452 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.9834 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.8820 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9547 |
| Non-inhibitor | 0.9746 | |
| AMES Toxicity | Non AMES toxic | 0.9633 |
| Carcinogens | Carcinogens | 0.6621 |
| Fish Toxicity | Low FHMT | 0.6181 |
| Tetrahymena Pyriformis Toxicity | Low TPT | 0.6631 |
| Honey Bee Toxicity | High HBT | 0.8277 |
| Biodegradation | Ready biodegradable | 0.7326 |
| Acute Oral Toxicity | III | 0.5846 |
| Carcinogenicity (Three-class) | Warning | 0.4769 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -1.0958 | LogS |
| Caco-2 Permeability | 1.6017 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.0135 | LD50, mol/kg |
| Fish Toxicity | 1.5413 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | -0.7156 | pIGC50, ug/L |
MRLs
| Food | Product Code | Country | MRLs | Application Date | Notes |
|---|---|---|---|---|---|
| Kales (Borecoles/collards greens/curly kales, Cow cabbages/stem kales, Cow cabbages/Jersey kales, Kohlrabies leaves (6), Rape kales/Siberian kales, Portuguese kales/tronchuda kales/Portuguese cabba... | 0243020 | European Union | 20 | 01/09/2008 | |
| Basil and edible flowers (Apple mint, Asiatic pennywort, Bergamot mint/eau-de-Cologne mint, Corsican mint, Courgette (edible flowers), Gingermint, Greek bush basil, Hoary basil, Holy basil/tulsi, L... | 0256080 | European Union | 20 | 01/09/2008 | |
| Saffron | 0860010 | European Union | 40 | 01/09/2008 | |
| Capers (Nasturtium pods, Nasturtium pods,) | 0850020 | European Union | 40 | 01/09/2008 | |
| Rye | 0500070 | European Union | 10 | 01/09/2008 | |
| Citrus fruits | 0110000 | European Union | 20 | 01/09/2008 | |
| Grapefruits (Natsudaidais, Shaddocks/pomelos, Sweeties/oroblancos, Tangelolos, Tangelos (except minneolas)/Ugli®, Other hybrids of Citrus paradisi, not elsewhere mentioned,) | 0110010 | European Union | 20 | 01/09/2008 | |
| Oranges (Bergamots, Bitter oranges/sour oranges, Blood oranges, Cara caras, Chinottos, Trifoliate oranges, Other hybrids of Citrus sinensis, not elsewhere mentioned,) | 0110020 | European Union | 20 | 01/09/2008 | |
| Mace | 0870010 | European Union | 40 | 01/09/2008 | |
| Mandarins (Calamondins, Clementines, Cleopatra mandarins, Minneolas, Satsumas/clausellinas, Tangerines/dancy mandarins, Tangors, Other hybrids of Citrus reticulata, not elsewhere mentioned,) | 0110050 | European Union | 20 | 01/09/2008 | |
| Others (2) | 0110990 | European Union | 20 | 01/09/2008 | |
| Tree nuts | 0120000 | European Union | 30 | 01/09/2008 | |
| Others (2) | 0850990 | European Union | 40 | 01/09/2008 | |
| Almonds (Apricot kernels, Bitter almonds, Canarium nuts/galip nuts, Pili nuts, Okari nuts,) | 0120010 | European Union | 30 | 01/09/2008 | |
| Brazil nuts | 0120020 | European Union | 30 | 01/09/2008 | |
| Cashew nuts | 0120030 | European Union | 30 | 01/09/2008 | |
| Chestnuts | 0120040 | European Union | 30 | 01/09/2008 | |
| Coconuts (Areca nuts/betel nuts,) | 0120050 | European Union | 30 | 01/09/2008 | |
| Hazelnuts/cobnuts (Acorns, Filberts,) | 0120060 | European Union | 30 | 01/09/2008 | |
| Macadamias | 0120070 | European Union | 30 | 01/09/2008 |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Establishing a quick screening method by using a microfluidic chip to evaluate cytotoxicity of metal contaminants. | Sci Total Environ | 2019 Feb 15 | 30266051 |
| Simple and fast spectrophotometric determination of low levels of thiabendazoleresidues in fruit and vegetables after pre-concentration with ionic liquid phase microextraction. | Food Addit Contam Part A Chem Anal Control Expo Risk Assess | 2018Jun | 29470140 |
| Evaluation of chemical extractants to assess metals phytoavailability in Brazilian municipal solid waste composts. | Environ Pollut | 2018 Sep 21 | 30267920 |
| Carcinogenic and Non-carcinogenic Risk Assessment of Heavy Metals in Groundwater Wells in Neyshabur Plain, Iran. | Biol Trace Elem Res | 2018 Sep 17 | 30225757 |
| Effects of cadmium and copper mixtures to carrot and pakchoi under greenhouse cultivation condition. | Ecotoxicol Environ Saf | 2018 Sep 15 | 29751225 |
| Different forms of copper and kinetin impacted element accumulation andmacromolecule contents in kidney bean (Phaseolus vulgaris) seeds. | Sci Total Environ | 2018 Sep 15 | 29913614 |
| Concentration of heavy metals in seafood (fishes, shrimp, lobster and crabs) and human health assessment in Saint Martin Island, Bangladesh. | Ecotoxicol Environ Saf | 2018 Sep 15 | 29747150 |
| Source identification and spatial distribution of arsenic and heavy metals inagricultural soil around Hunan industrial estate by positive matrix factorizationmodel, principle components analysis and geo statistical analysis. | Ecotoxicol Environ Saf | 2018 Sep 15 | 29778047 |
| Biomass decaying and elemental release of aquatic macrophyte detritus inwaterways of the Indian River Lagoon basin, South Florida, USA. | Sci Total Environ | 2018 Sep 1 | 29710610 |
| A new perspective of using sequential extraction: To predict the deficiency oftrace elements during anaerobic digestion. | Water Res | 2018 Sep 1 | 29747126 |
| Patterns of toxic metals bioaccumulation in a cross-border freshwater reservoir. | Chemosphere | 2018 Sep | 29800819 |
| Development, validation and application of an ICP-MS/MS method to quantify minerals and (ultra-)trace elements in human serum. | J Trace Elem Med Biol | 2018 Sep | 29895367 |
| Validation of a dilute and shoot method for quantification of 12 elements byinductively coupled plasma tandem mass spectrometry in human milk and in cow milkpreparations. | J Trace Elem Med Biol | 2018 Sep | 29895368 |
| Combined toxicity of microcystin-LR and copper on lettuce (Lactuca sativa L.). | Chemosphere | 2018 Sep | 29775940 |
| Assessment of Cu sub-lethal toxicity (LC50) in the cold-water gorgonianDentomuricea meteor under a deep-sea mining activity scenario. | Environ Pollut | 2018 Sep | 29793198 |
| Selective and sensitive spectrophotometric method to determine trace amounts ofcopper metal ions using Amaranth food dye. | Spectrochim Acta A Mol Biomol Spectrosc | 2018 Oct 5 | 29894959 |
| Rice flakes produced from commercial wild rice: Chemical compositions, vitamin B compounds, mineral and trace element contents and their dietary intake evaluation. | Food Chem | 2018 Oct 30 | 29853391 |
| Organic cattle products: Authenticating production origin by analysis of serummineral content. | Food Chem | 2018 Oct 30 | 29853367 |
| New insights into chelator recycling by a chelating resin: From molecular mechanisms to applicability. | Chemosphere | 2018 Oct 15 | 30359949 |
| Hydrologic and water quality performance of permeable pavement with internalwater storage over a clay soil in Durham, North Carolina. | J Environ Manage | 2018 Oct 15 | 30055460 |
Targets
- 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
- Mechanism of Action:
- Copper binds the N-terminal region of amyloid precursor protein, promoting the generation of β-amyloid from the protein. This is believed to contribute to the development of the neurodegenerative disorders Parkinson's disease and Alzheimer's disease.
References
- Davies P, Fontaine SN, Moualla D, Wang X, Wright JA, Brown DR: Amyloidogenic metal-binding proteins: new investigative pathways. Biochem Soc Trans. 2008 Dec;36(Pt 6):1299-303. doi: 10.1042/BST0361299. [19021544 ]
- General Function:
- Copper-exporting atpase activity
- Specific Function:
- Involved in the export of copper out of the cells, such as the efflux of hepatic copper into the bile.
- Gene Name:
- ATP7B
- Uniprot ID:
- P35670
- Molecular Weight:
- 157261.34 Da
References
- Niemiec MS, Weise CF, Wittung-Stafshede P: In vitro thermodynamic dissection of human copper transfer from chaperone to target protein. PLoS One. 2012;7(5):e36102. doi: 10.1371/journal.pone.0036102. Epub 2012 May 4. [22574136 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Delivers copper to copper zinc superoxide dismutase (SOD1).
- Gene Name:
- CCS
- Uniprot ID:
- O14618
- Molecular Weight:
- 29040.445 Da
References
- Stasser JP, Eisses JF, Barry AN, Kaplan JH, Blackburn NJ: Cysteine-to-serine mutants of the human copper chaperone for superoxide dismutase reveal a copper cluster at a domain III dimer interface. Biochemistry. 2005 Mar 8;44(9):3143-52. [15736924 ]
- General Function:
- Metallochaperone activity
- Specific Function:
- Binds and deliver cytosolic copper to the copper ATPase proteins. May be important in cellular antioxidant defense.
- Gene Name:
- ATOX1
- Uniprot ID:
- O00244
- Molecular Weight:
- 7401.575 Da
References
- Banci L, Bertini I, Cantini F, DellaMalva N, Herrmann T, Rosato A, Wuthrich K: Solution structure and intermolecular interactions of the third metal-binding domain of ATP7A, the Menkes disease protein. J Biol Chem. 2006 Sep 29;281(39):29141-7. Epub 2006 Jul 26. [16873374 ]
- Gene Name:
- SNCA
- Uniprot ID:
- P37840
- Molecular Weight:
- 14460.155 Da
- Mechanism of Action:
- Copper binds to alpha-synuclein, initiating protein aggregation and likely contributing to the development of the neurodegenerative disorders Parkinson's disease and Alzheimer's disease.
References
- Davies P, Fontaine SN, Moualla D, Wang X, Wright JA, Brown DR: Amyloidogenic metal-binding proteins: new investigative pathways. Biochem Soc Trans. 2008 Dec;36(Pt 6):1299-303. doi: 10.1042/BST0361299. [19021544 ]
- General Function:
- Superoxide dismutase copper chaperone activity
- Specific Function:
- May supply copper to copper-requiring proteins within the secretory pathway, when localized in the trans-Golgi network. Under conditions of elevated extracellular copper, it relocalized to the plasma membrane where it functions in the efflux of copper from cells.
- Gene Name:
- ATP7A
- Uniprot ID:
- Q04656
- Molecular Weight:
- 163372.275 Da
References
- Banci L, Bertini I, Cantini F, DellaMalva N, Herrmann T, Rosato A, Wuthrich K: Solution structure and intermolecular interactions of the third metal-binding domain of ATP7A, the Menkes disease protein. J Biol Chem. 2006 Sep 29;281(39):29141-7. Epub 2006 Jul 26. [16873374 ]
- Gene Name:
- NEIL1
- Uniprot ID:
- Q96FI4
- Molecular Weight:
- 43683.625 Da
References
- Hegde ML, Hegde PM, Holthauzen LM, Hazra TK, Rao KS, Mitra S: Specific Inhibition of NEIL-initiated repair of oxidized base damage in human genome by copper and iron: potential etiological linkage to neurodegenerative diseases. J Biol Chem. 2010 Sep 10;285(37):28812-25. doi: 10.1074/jbc.M110.126664. Epub 2010 Jul 9. [20622253 ]
- General Function:
- Protein homodimerization activity
- Specific Function:
- Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine.
- Gene Name:
- ADRB2
- Uniprot ID:
- P07550
- Molecular Weight:
- 46458.32 Da
References
- Elling CE, Frimurer TM, Gerlach LO, Jorgensen R, Holst B, Schwartz TW: Metal ion site engineering indicates a global toggle switch model for seven-transmembrane receptor activation. J Biol Chem. 2006 Jun 23;281(25):17337-46. Epub 2006 Mar 27. [16567806 ]
- 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
- Wells MA, Jackson GS, Jones S, Hosszu LL, Craven CJ, Clarke AR, Collinge J, Waltho JP: A reassessment of copper(II) binding in the full-length prion protein. Biochem J. 2006 Nov 1;399(3):435-44. [16824036 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Binds heavy metals. Contains three zinc and three copper atoms per polypeptide chain and only a negligible amount of cadmium. Inhibits survival and neurite formation of cortical neurons in vitro.
- Gene Name:
- MT3
- Uniprot ID:
- P25713
- Molecular Weight:
- 6926.855 Da
References
- Zheng WJ, Wu F, Zhuang HQ, Lu C, Yang F, Ma WL, Hua ZC: Expression of human metallothionein III and its metalloabsorption capability in Escherichia coli. Prep Biochem Biotechnol. 2004 Aug;34(3):265-78. [15461142 ]
- General Function:
- Protein homodimerization activity
- Specific Function:
- Has low activity towards the organophosphate paraxon and aromatic carboxylic acid esters. Rapidly hydrolyzes lactones such as statin prodrugs (e.g. lovastatin). Hydrolyzes aromatic lactones and 5- or 6-member ring lactones with aliphatic substituents but not simple lactones or those with polar substituents.
- Gene Name:
- PON3
- Uniprot ID:
- Q15166
- Molecular Weight:
- 39607.185 Da
- Mechanism of Action:
- Excess copper is sequestered within hepatocyte lysosomes, where it is complexed with metallothionein. Copper hepatotoxicity is believed to occur when the lysosomes become saturated and copper accumulates in the nucleus, causing nuclear damage. This damage is possibly a result of oxidative damage, including lipid peroxidation. Copper inhibits the sulfhydryl group enzymes such as glucose-6-phosphate 1-dehydrogenase, glutathione reductase, and paraoxonases, which protect the cell from free oxygen radicals. It also influences gene expression and is a co-factor for oxidative enzymes such as cytochrome C oxidase and lysyl oxidase. In addition, the oxidative stress induced by copper is thought to activate acid sphingomyelinase, which lead to the production of ceramide, an apoptotic signal, as well as cause hemolytic anemia.
References
- Brewer GJ: A brand new mechanism for copper toxicity. J Hepatol. 2007 Oct;47(4):621-2. Epub 2007 Jul 23. [17697726 ]
- General Function:
- Ferroxidase activity
- Specific Function:
- Ceruloplasmin is a blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron transport across the cell membrane. Provides Cu(2+) ions for the ascorbate-mediated deaminase degradation of the heparan sulfate chains of GPC1. May also play a role in fetal lung development or pulmonary antioxidant defense (By similarity).
- Gene Name:
- CP
- Uniprot ID:
- P00450
- Molecular Weight:
- 122204.45 Da
References
- Bento I, Peixoto C, Zaitsev VN, Lindley PF: Ceruloplasmin revisited: structural and functional roles of various metal cation-binding sites. Acta Crystallogr D Biol Crystallogr. 2007 Feb;63(Pt 2):240-8. Epub 2007 Jan 16. [17242517 ]
- 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
- 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 ]
- General Function:
- Ferroxidase activity
- Specific Function:
- May function as a ferroxidase and may be involved in copper transport and homeostasis.
- Gene Name:
- HEPHL1
- Uniprot ID:
- Q6MZM0
- Molecular Weight:
- 131601.67 Da
References
- Chen H, Attieh ZK, Syed BA, Kuo YM, Stevens V, Fuqua BK, Andersen HS, Naylor CE, Evans RW, Gambling L, Danzeisen R, Bacouri-Haidar M, Usta J, Vulpe CD, McArdle HJ: Identification of zyklopen, a new member of the vertebrate multicopper ferroxidase family, and characterization in rodents and human cells. J Nutr. 2010 Oct;140(10):1728-35. doi: 10.3945/jn.109.117531. Epub 2010 Aug 4. [20685892 ]
- General Function:
- Copper ion binding
- Specific Function:
- Thought to play a role in cellular copper homeostasis, mitochondrial redox signaling or insertion of copper into the active site of COX.
- Gene Name:
- SCO1
- Uniprot ID:
- O75880
- Molecular Weight:
- 33813.69 Da
References
- Banci L, Bertini I, Ciofi-Baffoni S, Leontari I, Martinelli M, Palumaa P, Sillard R, Wang S: Human Sco1 functional studies and pathological implications of the P174L mutant. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):15-20. Epub 2006 Dec 20. [17182746 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
- Gene Name:
- SOD1
- Uniprot ID:
- P00441
- Molecular Weight:
- 15935.685 Da
References
- Lapenna D, Ciofani G, Pierdomenico SD, Giamberardino MA, Cuccurullo F: Copper, zinc superoxide dismutase plus hydrogen peroxide: a catalytic system for human lipoprotein oxidation. FEBS Lett. 2005 Jan 3;579(1):245-50. [15620721 ]
- General Function:
- Protein homodimerization activity
- Specific Function:
- Catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis. The main function of this enzyme is to provide reducing power (NADPH) and pentose phosphates for fatty acid and nucleic acid synthesis.
- Gene Name:
- G6PD
- Uniprot ID:
- P11413
- Molecular Weight:
- 59256.31 Da
- Mechanism of Action:
- Excess copper is sequestered within hepatocyte lysosomes, where it is complexed with metallothionein. Copper hepatotoxicity is believed to occur when the lysosomes become saturated and copper accumulates in the nucleus, causing nuclear damage. This damage is possibly a result of oxidative damage, including lipid peroxidation. Copper inhibits the sulfhydryl group enzymes such as glucose-6-phosphate 1-dehydrogenase, glutathione reductase, and paraoxonases, which protect the cell from free oxygen radicals. It also influences gene expression and is a co-factor for oxidative enzymes such as cytochrome C oxidase and lysyl oxidase. In addition, the oxidative stress induced by copper is thought to activate acid sphingomyelinase, which lead to the production of ceramide, an apoptotic signal, as well as cause hemolytic anemia.
References
- Brewer GJ: A brand new mechanism for copper toxicity. J Hepatol. 2007 Oct;47(4):621-2. Epub 2007 Jul 23. [17697726 ]
- General Function:
- Nadp binding
- Specific Function:
- Maintains high levels of reduced glutathione in the cytosol.
- Gene Name:
- GSR
- Uniprot ID:
- P00390
- Molecular Weight:
- 56256.565 Da
- Mechanism of Action:
- Excess copper is sequestered within hepatocyte lysosomes, where it is complexed with metallothionein. Copper hepatotoxicity is believed to occur when the lysosomes become saturated and copper accumulates in the nucleus, causing nuclear damage. This damage is possibly a result of oxidative damage, including lipid peroxidation. Copper inhibits the sulfhydryl group enzymes such as glucose-6-phosphate 1-dehydrogenase, glutathione reductase, and paraoxonases, which protect the cell from free oxygen radicals. It also influences gene expression and is a co-factor for oxidative enzymes such as cytochrome C oxidase and lysyl oxidase. In addition, the oxidative stress induced by copper is thought to activate acid sphingomyelinase, which lead to the production of ceramide, an apoptotic signal, as well as cause hemolytic anemia.
References
- Brewer GJ: A brand new mechanism for copper toxicity. J Hepatol. 2007 Oct;47(4):621-2. Epub 2007 Jul 23. [17697726 ]
- General Function:
- Protein homodimerization activity
- Specific Function:
- Hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. Capable of hydrolyzing a broad spectrum of organophosphate substrates and lactones, and a number of aromatic carboxylic acid esters. Mediates an enzymatic protection of low density lipoproteins against oxidative modification and the consequent series of events leading to atheroma formation.
- Gene Name:
- PON1
- Uniprot ID:
- P27169
- Molecular Weight:
- 39730.99 Da
- Mechanism of Action:
- Excess copper is sequestered within hepatocyte lysosomes, where it is complexed with metallothionein. Copper hepatotoxicity is believed to occur when the lysosomes become saturated and copper accumulates in the nucleus, causing nuclear damage. This damage is possibly a result of oxidative damage, including lipid peroxidation. Copper inhibits the sulfhydryl group enzymes such as glucose-6-phosphate 1-dehydrogenase, glutathione reductase, and paraoxonases, which protect the cell from free oxygen radicals. It also influences gene expression and is a co-factor for oxidative enzymes such as cytochrome C oxidase and lysyl oxidase. In addition, the oxidative stress induced by copper is thought to activate acid sphingomyelinase, which lead to the production of ceramide, an apoptotic signal, as well as cause hemolytic anemia.
References
- Brewer GJ: A brand new mechanism for copper toxicity. J Hepatol. 2007 Oct;47(4):621-2. Epub 2007 Jul 23. [17697726 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Has DNA glycosylase activity towards 5-hydroxyuracil and other oxidized derivatives of cytosine with a preference for mismatched double-stranded DNA (DNA bubbles). Has low or no DNA glycosylase activity towards thymine glycol, 2-hydroxyadenine, hypoxanthine and 8-oxoguanine. Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates.
- Gene Name:
- NEIL2
- Uniprot ID:
- Q969S2
- Molecular Weight:
- 36826.285 Da
References
- Hegde ML, Hegde PM, Holthauzen LM, Hazra TK, Rao KS, Mitra S: Specific Inhibition of NEIL-initiated repair of oxidized base damage in human genome by copper and iron: potential etiological linkage to neurodegenerative diseases. J Biol Chem. 2010 Sep 10;285(37):28812-25. doi: 10.1074/jbc.M110.126664. Epub 2010 Jul 9. [20622253 ]