Beryllium copper (T3D0643)
| Record Information | ||||||||||||||||||||||||||||||||||||||||||||||
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| Version | 2.0 | |||||||||||||||||||||||||||||||||||||||||||||
| Creation Date | 2009-03-21 00:59:05 UTC | |||||||||||||||||||||||||||||||||||||||||||||
| Update Date | 2014-12-24 20:22:28 UTC | |||||||||||||||||||||||||||||||||||||||||||||
| Accession Number | T3D0643 | |||||||||||||||||||||||||||||||||||||||||||||
| Identification | ||||||||||||||||||||||||||||||||||||||||||||||
| Common Name | Beryllium copper | |||||||||||||||||||||||||||||||||||||||||||||
| Class | Small Molecule | |||||||||||||||||||||||||||||||||||||||||||||
| Description | Beryllium copper is a metal alloy of beryllium and copper. It is used in springs, load cells, batteries, electrical connectors, tools and intruments. Beryllium is a lightweight alkaline earth metal with the atomic number 4. It is a relatively rare element found naturally only combined with other elements in minerals. Copper is a chemical element with the symbol Cu and atomic number 29. Copper is an essential elements in plants and animals as it is required for the normal functioning of more than 30 enzymes. It occurs naturally throughout the environment in rocks, soil, water, and air. (12, 13, 7, 9) | |||||||||||||||||||||||||||||||||||||||||||||
| Compound Type |
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| Chemical Structure |  | |||||||||||||||||||||||||||||||||||||||||||||
| Synonyms |
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| Chemical Formula | BeCu | |||||||||||||||||||||||||||||||||||||||||||||
| Average Molecular Mass | 72.558 g/mol | |||||||||||||||||||||||||||||||||||||||||||||
| Monoisotopic Mass | 71.942 g/mol | |||||||||||||||||||||||||||||||||||||||||||||
| CAS Registry Number | 11133-98-5 | |||||||||||||||||||||||||||||||||||||||||||||
| IUPAC Name | beryllium copper | |||||||||||||||||||||||||||||||||||||||||||||
| Traditional Name | beryllium copper | |||||||||||||||||||||||||||||||||||||||||||||
| SMILES | [Be].[Cu] | |||||||||||||||||||||||||||||||||||||||||||||
| InChI Identifier | InChI=1S/Be.Cu | |||||||||||||||||||||||||||||||||||||||||||||
| InChI Key | InChIKey=DMFGNRRURHSENX-UHFFFAOYSA-N | |||||||||||||||||||||||||||||||||||||||||||||
| Chemical Taxonomy | ||||||||||||||||||||||||||||||||||||||||||||||
| Description | belongs to the class of inorganic compounds known as miscellaneous mixed metal/non-metals. These are inorganic compounds containing non-metal as well as metal atoms but not belonging to afore mentioned classes. | |||||||||||||||||||||||||||||||||||||||||||||
| Kingdom | Inorganic compounds | |||||||||||||||||||||||||||||||||||||||||||||
| Super Class | Mixed metal/non-metal compounds | |||||||||||||||||||||||||||||||||||||||||||||
| Class | Miscellaneous mixed metal/non-metals | |||||||||||||||||||||||||||||||||||||||||||||
| Sub Class | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| Direct Parent | Miscellaneous mixed metal/non-metals | |||||||||||||||||||||||||||||||||||||||||||||
| Alternative Parents | ||||||||||||||||||||||||||||||||||||||||||||||
| Substituents |
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| Molecular Framework | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| External Descriptors | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| Biological Properties | ||||||||||||||||||||||||||||||||||||||||||||||
| Status | Detected and Not Quantified | |||||||||||||||||||||||||||||||||||||||||||||
| Origin | Exogenous | |||||||||||||||||||||||||||||||||||||||||||||
| Cellular Locations |
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| Biofluid Locations | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| Tissue Locations | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| Pathways | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| Applications | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| Biological Roles | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| Chemical Roles | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| Physical Properties | ||||||||||||||||||||||||||||||||||||||||||||||
| State | Solid | |||||||||||||||||||||||||||||||||||||||||||||
| Appearance | No data. | |||||||||||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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| Predicted Properties |
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| Spectra | ||||||||||||||||||||||||||||||||||||||||||||||
| Spectra | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| Toxicity Profile | ||||||||||||||||||||||||||||||||||||||||||||||
| Route of Exposure | Oral (12) ; inhalation (12) ; dermal (12) | |||||||||||||||||||||||||||||||||||||||||||||
| Mechanism of Toxicity | Once in the body, beryllium acts as a hapten and interacts with human leucocyte antigen (HLA) DP presenting cells in the lungs, becoming physically associated with a major histocompatability (MHC) class II molecule. This MHC class II-beryllium-peptide complex is recognized by the T lymphocyte receptor, triggering CD4+ T lymphocyte activation and proliferation. The resulting inflammatory response is a cell-mediated process orchestrated by cytokines and results in the formation of (usually pulmonary) granulomas. Beryllium's toxicity may be controlled by the iron-storage protein ferritin, which sequesters beryllium by binding it and preventing it from interacting with other enzymes. 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. Copper-induced emesis results from stimulation of the vagus nerve. (12, 6, 3, 15, 8, 1, 2) | |||||||||||||||||||||||||||||||||||||||||||||
| Metabolism | Beryllium is absorbed mainly through the lungs, where it enters the bloodstream and is transported throughout the body by binding to prealbumins and gamma-globulins. Beryllium accumulates in lung tissue and the skeleton. It is excreted mainly in the urine. Copper is mainly absorbed through the gastrointestinal tract, but it can also be inhalated and absorbed dermally. It passes through the basolateral membrane, possibly via regulatory copper transporters, and is transported to the liver and kidney bound to serum albumin. The liver is the critical organ for copper homoeostasis. In the liver and other tissues, copper is stored bound to metallothionein, amino acids, and in association with copper-dependent enzymes, then partitioned for excretion through the bile or incorporation into intra- and extracellular proteins. The transport of copper to the peripheral tissues is accomplished through the plasma attached to serum albumin, ceruloplasmin or low-molecular-weight complexes. Copper may induce the production of metallothionein and ceruloplasmin. The membrane-bound copper transporting adenosine triphosphatase (Cu-ATPase) transports copper ions into and out of cells. Physiologically normal levels of copper in the body are held constant by alterations in the rate and amount of copper absorption, compartmental distribution, and excretion. (12, 14, 8) | |||||||||||||||||||||||||||||||||||||||||||||
| Toxicity Values | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| Lethal Dose | 10 to 20 grams for an adult human (copper salts). (5) | |||||||||||||||||||||||||||||||||||||||||||||
| Carcinogenicity (IARC Classification) | 1, carcinogenic to humans. (11) | |||||||||||||||||||||||||||||||||||||||||||||
| Uses/Sources | Beryllium copper is used in springs, load cells, batteries, electrical connectors, tools and intruments. (9) | |||||||||||||||||||||||||||||||||||||||||||||
| Minimum Risk Level | Chronic Oral: 0.002 mg/kg/day (Beryllium) (10) Acute Oral: 0.01 mg/kg/day (Copper) (10) Intermediate Oral: 0.01 mg/kg/day (Copper) (10) | |||||||||||||||||||||||||||||||||||||||||||||
| Health Effects | Acute inhalation of a high level of beryllium can result in a pneumonia-like condition called acute beryllium disease. Chronic inhalation of beryllium can cause an inflammatory reaction in the respiratory system called chronic beryllium disease. Chronic beryllium disease may result in anorexia and weight loss, as well as right side heart enlargement and heart disease in advanced cases. Chronic exposure can also increase the risk of lung cancer. Skin contact with beryllium results in contact dermatitus. People must absorb small amounts of copper every day because copper is essential for good health, however, high levels of copper can be harmful. Very-high doses of copper can cause damage to your liver and kidneys, and can even cause death. Copper may induce allergic responses in sensitive individuals. (13, 14, 7, 8) | |||||||||||||||||||||||||||||||||||||||||||||
| Symptoms | Chronic beryllium disease causes fatigue, weakness, difficulty breathing, and a persistent dry cough. Breathing high levels of copper can cause irritation of the nose and throat. Ingesting high levels of copper can cause nausea, vomiting, diarrhea, headache, dizziness, and respiratory difficulty. (13, 14, 7, 8) | |||||||||||||||||||||||||||||||||||||||||||||
| Treatment | Chronic beryllium disease is treated with immunosuppressive medicines, usually of the glucocorticoid class. (7) | |||||||||||||||||||||||||||||||||||||||||||||
| Normal Concentrations | ||||||||||||||||||||||||||||||||||||||||||||||
| Not Available | ||||||||||||||||||||||||||||||||||||||||||||||
| Abnormal Concentrations | ||||||||||||||||||||||||||||||||||||||||||||||
| Not Available | ||||||||||||||||||||||||||||||||||||||||||||||
| External Links | ||||||||||||||||||||||||||||||||||||||||||||||
| DrugBank ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| HMDB ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| PubChem Compound ID | 21871507 | |||||||||||||||||||||||||||||||||||||||||||||
| ChEMBL ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| ChemSpider ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| KEGG ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| UniProt ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| OMIM ID | ||||||||||||||||||||||||||||||||||||||||||||||
| ChEBI ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| BioCyc ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| CTD ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| Stitch ID | Beryllium copper | |||||||||||||||||||||||||||||||||||||||||||||
| PDB ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| ACToR ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| Wikipedia Link | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| References | ||||||||||||||||||||||||||||||||||||||||||||||
| Synthesis Reference | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| MSDS | T3D0643.pdf | |||||||||||||||||||||||||||||||||||||||||||||
| General References |
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| Gene Regulation | ||||||||||||||||||||||||||||||||||||||||||||||
| Up-Regulated Genes | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
| Down-Regulated Genes | Not Available | |||||||||||||||||||||||||||||||||||||||||||||
Targets
- 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
References
- Brewer GJ: A brand new mechanism for copper toxicity. J Hepatol. 2007 Oct;47(4):621-2. Epub 2007 Jul 23. [17697726 ]
- Baxter PJ, Adams PH, & Aw TC (2000). Hunter's Diseases of Occupations. 9th ed. New York, NY: Oxford University Press Inc.
- Wikipedia. Copper. Last Updated 29 May 2009. [Link]
- US Environmental Protection Agency (2008). Drinking Water Health Advisory for 2,4-Dinitrotoluene and 2,6-Dinitrotoluene. [Link]
- General Function:
- Nadp binding
- Specific Function:
- Maintains high levels of reduced glutathione in the cytosol.
- Gene Name:
- GSR
- Uniprot ID:
- P00390
- Molecular Weight:
- 56256.565 Da
References
- Brewer GJ: A brand new mechanism for copper toxicity. J Hepatol. 2007 Oct;47(4):621-2. Epub 2007 Jul 23. [17697726 ]
- Baxter PJ, Adams PH, & Aw TC (2000). Hunter's Diseases of Occupations. 9th ed. New York, NY: Oxford University Press Inc.
- Wikipedia. Copper. Last Updated 29 May 2009. [Link]
- US Environmental Protection Agency (2008). Drinking Water Health Advisory for 2,4-Dinitrotoluene and 2,6-Dinitrotoluene. [Link]
- 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
References
- Brewer GJ: A brand new mechanism for copper toxicity. J Hepatol. 2007 Oct;47(4):621-2. Epub 2007 Jul 23. [17697726 ]
- Baxter PJ, Adams PH, & Aw TC (2000). Hunter's Diseases of Occupations. 9th ed. New York, NY: Oxford University Press Inc.
- Wikipedia. Copper. Last Updated 29 May 2009. [Link]
- US Environmental Protection Agency (2008). Drinking Water Health Advisory for 2,4-Dinitrotoluene and 2,6-Dinitrotoluene. [Link]
- 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
References
- Brewer GJ: A brand new mechanism for copper toxicity. J Hepatol. 2007 Oct;47(4):621-2. Epub 2007 Jul 23. [17697726 ]
- Baxter PJ, Adams PH, & Aw TC (2000). Hunter's Diseases of Occupations. 9th ed. New York, NY: Oxford University Press Inc.
- Wikipedia. Copper. Last Updated 29 May 2009. [Link]
- US Environmental Protection Agency (2008). Drinking Water Health Advisory for 2,4-Dinitrotoluene and 2,6-Dinitrotoluene. [Link]
- General Function:
- Peptide antigen binding
- Specific Function:
- Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading.
- Gene Name:
- HLA-DPA1
- Uniprot ID:
- P20036
- Molecular Weight:
- 29380.345 Da
References
- Amicosante M, Berretta F, Dweik R, Saltini C: Role of high-affinity HLA-DP specific CLIP-derived peptides in beryllium binding to the HLA-DPGlu69 berylliosis-associated molecules and presentation to beryllium-sensitized T cells. Immunology. 2009 Sep;128(1 Suppl):e462-70. doi: 10.1111/j.1365-2567.2008.03000.x. Epub 2008 Dec 23. [19191908 ]
- ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for beryllium. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
- General Function:
- Peptide antigen binding
- Specific Function:
- Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading.
- Gene Name:
- HLA-DPB1
- Uniprot ID:
- P04440
- Molecular Weight:
- 29159.195 Da
References
- Amicosante M, Berretta F, Dweik R, Saltini C: Role of high-affinity HLA-DP specific CLIP-derived peptides in beryllium binding to the HLA-DPGlu69 berylliosis-associated molecules and presentation to beryllium-sensitized T cells. Immunology. 2009 Sep;128(1 Suppl):e462-70. doi: 10.1111/j.1365-2567.2008.03000.x. Epub 2008 Dec 23. [19191908 ]
- ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for beryllium. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
- General Function:
- Peptide antigen binding
- Specific Function:
- Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading.
- Gene Name:
- HLA-DPB1
- Uniprot ID:
- P04440
- Molecular Weight:
- 29159.195 Da
References
- Amicosante M, Berretta F, Dweik R, Saltini C: Role of high-affinity HLA-DP specific CLIP-derived peptides in beryllium binding to the HLA-DPGlu69 berylliosis-associated molecules and presentation to beryllium-sensitized T cells. Immunology. 2009 Sep;128(1 Suppl):e462-70. doi: 10.1111/j.1365-2567.2008.03000.x. Epub 2008 Dec 23. [19191908 ]
- ATSDR - Agency for Toxic Substances and Disease Registry (2002). Toxicological profile for beryllium. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
- General Function:
- Not Available
- Specific Function:
- Not Available
- Gene Name:
- SNCA
- Uniprot ID:
- P37840
- Molecular Weight:
- 14460.155 Da
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:
- 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
- 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 ]