Copper chromite (T3D1189)
| Record Information | |||||||||||||||||||||||||||||||||||||||||||||||||
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| Version | 2.0 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Creation Date | 2009-06-19 21:58:25 UTC | ||||||||||||||||||||||||||||||||||||||||||||||||
| Update Date | 2014-12-24 20:23:20 UTC | ||||||||||||||||||||||||||||||||||||||||||||||||
| Accession Number | T3D1189 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Identification | |||||||||||||||||||||||||||||||||||||||||||||||||
| Common Name | Copper chromite | ||||||||||||||||||||||||||||||||||||||||||||||||
| Class | Small Molecule | ||||||||||||||||||||||||||||||||||||||||||||||||
| Description | Copper chromite is a chemical compound of copper and chromium. 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. Chromium is a chemical element which has the symbol Cr and atomic number 24. It is found naturally occuring in rocks, animals, plants, and soil, and is usually mined as chromite ore. Chromium is most toxic in its +6 oxidation state (chromium(VI)) due to its greater ability to enter cells and higher redox potential. Trivalent chromium (chromium(III)) however, is biologically necessary for sugar and lipid metabolism in humans. (10, 13, 14) | ||||||||||||||||||||||||||||||||||||||||||||||||
| Compound Type |
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| Chemical Structure |  | ||||||||||||||||||||||||||||||||||||||||||||||||
| Synonyms |
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| Chemical Formula | Cr2Cu2O5 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Average Molecular Mass | 311.081 g/mol | ||||||||||||||||||||||||||||||||||||||||||||||||
| Monoisotopic Mass | 309.715 g/mol | ||||||||||||||||||||||||||||||||||||||||||||||||
| CAS Registry Number | 12053-18-8 | ||||||||||||||||||||||||||||||||||||||||||||||||
| IUPAC Name | oxo[(oxochromio)oxy]chromium; bis(oxocopper) | ||||||||||||||||||||||||||||||||||||||||||||||||
| Traditional Name | chromia; bis(copper(II) oxide) | ||||||||||||||||||||||||||||||||||||||||||||||||
| SMILES | O=[Cu].O=[Cu].O=[Cr]O[Cr]=O | ||||||||||||||||||||||||||||||||||||||||||||||||
| InChI Identifier | InChI=1S/2Cr.2Cu.5O | ||||||||||||||||||||||||||||||||||||||||||||||||
| InChI Key | InChIKey=JGDFBJMWFLXCLJ-UHFFFAOYSA-N | ||||||||||||||||||||||||||||||||||||||||||||||||
| Chemical Taxonomy | |||||||||||||||||||||||||||||||||||||||||||||||||
| Description | belongs to the class of inorganic compounds known as transition metal chromites. These are inorganic compounds in which the largest oxoanion is chromite, and in which the heaviest atom not in an oxoanion is a transition metal. | ||||||||||||||||||||||||||||||||||||||||||||||||
| Kingdom | Inorganic compounds | ||||||||||||||||||||||||||||||||||||||||||||||||
| Super Class | Mixed metal/non-metal compounds | ||||||||||||||||||||||||||||||||||||||||||||||||
| Class | Transition metal oxoanionic compounds | ||||||||||||||||||||||||||||||||||||||||||||||||
| Sub Class | Transition metal chromites | ||||||||||||||||||||||||||||||||||||||||||||||||
| Direct Parent | Transition metal chromites | ||||||||||||||||||||||||||||||||||||||||||||||||
| 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 | White powder. | ||||||||||||||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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| Predicted Properties |
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| Spectra | |||||||||||||||||||||||||||||||||||||||||||||||||
| Spectra | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||
| Toxicity Profile | |||||||||||||||||||||||||||||||||||||||||||||||||
| Route of Exposure | Oral (9) ; inhalation (9) ; dermal (9) | ||||||||||||||||||||||||||||||||||||||||||||||||
| Mechanism of Toxicity | 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. Trivalent chromium may also form complexes with peptides, proteins, and DNA, resulting in DNA-protein crosslinks, DNA strand breaks, DNA-DNA interstrand crosslinks, chromium-DNA adducts, chromosomal aberrations and alterations in cellular signaling pathways. It has been shown to induce carcinogenesis by overstimulating cellular regulatory pathways and increasing peroxide levels by activating certain mitogen-activated protein kinases. It can also cause transcriptional repression by cross-linking histone deacetylase 1-DNA methyltransferase 1 complexes to CYP1A1 promoter chromatin, inhibiting histone modification. Chromium may increase its own toxicity by modifying metal regulatory transcription factor 1, causing the inhibition of zinc-induced metallothionein transcription. (1, 9, 2, 3, 4, 13, 8, 5, 16) | ||||||||||||||||||||||||||||||||||||||||||||||||
| Metabolism | 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. Chromium is absorbed from oral, inhalation, or dermal exposure and distributes to nearly all tissues, with the highest concentrations found in kidney and liver. Bone is also a major storage site and may contribute to long-term retention. Hexavalent chromium's similarity to sulfate and chromate allow it to be transported into cells via sulfate transport mechanisms. Inside the cell, hexavalent chromium is reduced first to pentavalent chromium, then to trivalent chromium by many substances including ascorbate, glutathione, and nicotinamide adenine dinucleotide. Chromium is almost entirely excreted with the urine. (1, 9, 13, 15) | ||||||||||||||||||||||||||||||||||||||||||||||||
| Toxicity Values | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||
| Lethal Dose | 10 to 20 grams for an adult human (copper salts). (7) | ||||||||||||||||||||||||||||||||||||||||||||||||
| Carcinogenicity (IARC Classification) | 3, not classifiable as to its carcinogenicity to humans. (12) | ||||||||||||||||||||||||||||||||||||||||||||||||
| Uses/Sources | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||
| Minimum Risk Level | Acute Oral: 0.01 mg/kg/day (11) Intermediate Oral: 0.01 mg/kg/day (11) | ||||||||||||||||||||||||||||||||||||||||||||||||
| Health Effects | 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. (14, 15) | ||||||||||||||||||||||||||||||||||||||||||||||||
| Symptoms | 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. (14, 15) | ||||||||||||||||||||||||||||||||||||||||||||||||
| Treatment | There is no know antidote for chromium poisoning. Exposure is usually handled with symptomatic treatment. (9) | ||||||||||||||||||||||||||||||||||||||||||||||||
| Normal Concentrations | |||||||||||||||||||||||||||||||||||||||||||||||||
| Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||
| Abnormal Concentrations | |||||||||||||||||||||||||||||||||||||||||||||||||
| Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||
| External Links | |||||||||||||||||||||||||||||||||||||||||||||||||
| DrugBank ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||
| HMDB ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||
| PubChem Compound ID | 3084101 | ||||||||||||||||||||||||||||||||||||||||||||||||
| ChEMBL ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||
| ChemSpider ID | 2341215 | ||||||||||||||||||||||||||||||||||||||||||||||||
| KEGG ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||
| UniProt ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||
| OMIM ID | |||||||||||||||||||||||||||||||||||||||||||||||||
| ChEBI ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||
| BioCyc ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||
| CTD ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||
| Stitch ID | Copper chromite | ||||||||||||||||||||||||||||||||||||||||||||||||
| PDB ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||
| ACToR ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||
| Wikipedia Link | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||
| References | |||||||||||||||||||||||||||||||||||||||||||||||||
| Synthesis Reference | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||
| MSDS | T3D1189.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:
- 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 ]
7. 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
- ATSDR - Agency for Toxic Substances and Disease Registry (2008). Toxicological profile for chromium. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
- General Function:
- Transcription regulatory region sequence-specific dna 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. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Deacetylates 'Lys-310' in RELA and thereby inhibits the transcriptional activity of NF-kappa-B. Deacetylates NR1D2 and abrogates the effect of KAT5-mediated relieving of NR1D2 transcription repression activity. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Involved in CIART-mediated transcriptional repression of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex or CRY1 through histone deacetylation.
- Gene Name:
- HDAC1
- Uniprot ID:
- Q13547
- Molecular Weight:
- 55102.615 Da
References
- Schnekenburger M, Talaska G, Puga A: Chromium cross-links histone deacetylase 1-DNA methyltransferase 1 complexes to chromatin, inhibiting histone-remodeling marks critical for transcriptional activation. Mol Cell Biol. 2007 Oct;27(20):7089-101. Epub 2007 Aug 6. [17682057 ]
- General Function:
- Transcriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
- Specific Function:
- Activates the metallothionein I promoter. Binds to the metal responsive element (MRE).
- Gene Name:
- MTF1
- Uniprot ID:
- Q14872
- Molecular Weight:
- 80956.22 Da
References
- Kimura T: [Molecular mechanism involved in chromium(VI) toxicity]. Yakugaku Zasshi. 2007 Dec;127(12):1957-65. [18057785 ]
- General Function:
- Rna polymerase ii carboxy-terminal domain kinase activity
- Specific Function:
- Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in respons to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation.Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.
- Gene Name:
- MAPK1
- Uniprot ID:
- P28482
- Molecular Weight:
- 41389.265 Da
References
- Kim G, Yurkow EJ: Chromium induces a persistent activation of mitogen-activated protein kinases by a redox-sensitive mechanism in H4 rat hepatoma cells. Cancer Res. 1996 May 1;56(9):2045-51. [8616849 ]
- General Function:
- Phosphatase binding
- Specific Function:
- Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade.
- Gene Name:
- MAPK3
- Uniprot ID:
- P27361
- Molecular Weight:
- 43135.16 Da
References
- Kim G, Yurkow EJ: Chromium induces a persistent activation of mitogen-activated protein kinases by a redox-sensitive mechanism in H4 rat hepatoma cells. Cancer Res. 1996 May 1;56(9):2045-51. [8616849 ]