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Record Information
Version2.0
Creation Date2009-03-06 18:58:02 UTC
Update Date2014-12-24 20:21:03 UTC
Accession NumberT3D0077
Identification
Common NameChromium
ClassSmall Molecule
DescriptionChromium is a naturally occurring heavy metal found in the environment commonly in trivalent, Cr(III), and hexavalent, Cr(VI), forms. The reduction of Cr(VI) to Cr(III) results in the formation of reactive intermediates that contribute to the cytotoxicity, genotoxicity and carcinogenicity of Cr(VI)-containing compounds. The major non-occupational source of chromium for humans is food such as vegetables, meat, urban air, hip or knee prostheses and cigarettes. Cr(VI) is a widely used in industrial chemicals, extensively used in paints, metal finishes, steel including stainless steel manufacturing, alloy cast irons, chrome and wood treatment. On the contrary, Cr(III) salts such as chromium polynicotinate, chromium chloride and chromium picolinate (CrP) are used as micronutrients and nutritional supplements and have been demonstrated to exhibit a significant number of health benefits in animals and humans. Physiologically, it exists as an ion in the body. Chromium enters the body through the lungs, gastro-intestinal tract and to a lesser extent through skin. Inhalation is the most important route for occupational exposure, whereas non-occupational exposure occurs via ingestion of chromium-containing food and water. Regardless of route of exposure Cr(III) is poorly absorbed whereas Cr(VI) is more readily absorbed. Further, absorption of Cr(VI) is poorer by oral route, it is thus not very toxic when introduced by the oral route. But chromium is very toxic by dermal and inhalation routes and causes lung cancer, nasal irritation, nasal ulcer, hypersensitivity reactions and contact dermatitis. All the ingested Cr(VI) is reduced to Cr(III) before entering in the blood stream. The main routes for the excretion of chromium are via kidney/urine and the bile/feces. Cr(III) is unable to enter into the cells but Cr(VI) enters through membrane anionic transporters. Intracellular Cr(VI) is metabolically reduced to Cr(III). Cr(VI) does not react with macromolecules such as DNA, RNA, proteins and lipids. However, both Cr(III) and the reductional intermediate Cr(V) are capable of co-ordinate, covalent interactions with macromolecules. Chromium is an essential nutrient required by the human body to promote the action of insulin for the utilization of sugars, proteins and fats. CrP has been used as nutritional supplement; it controls blood sugar in diabetes and may reduce cholesterol and blood pressure levels. Chromium increases insulin binding to cells, insulin receptor number and activates insulin receptor kinase leading to increased insulin sensitivity. But high doses of chromium and long term exposure of it can give rise to various, cytotoxic and genotoxic reactions that affect the immune system of the body. However, the mechanism of the Cr(VI)-induced cytotoxicity is not entirely understood. A series of in vitro and in vivo studies have demonstrated that Cr(VI) induces oxidative stress through enhanced production of reactive oxygen species (ROS) leading to genomic DNA damage and oxidative deterioration of lipids and proteins. A cascade of cellular events occur following Cr(VI)-induced oxidative stress including enhanced production of superoxide anion and hydroxyl radicals, increased lipid peroxidation and genomic DNA fragmentation, modulation of intracellular oxidized states, activation of protein kinase C, apoptotic cell death and altered gene expression. Some of the factors in determining the biological outcome of chromium exposure include the bioavailability, solubility of chromium compounds and chemical speciation, intracellular reduction and interaction with DNA. The chromium genotoxicity manifests as several types of DNA lesions, gene mutations and inhibition of macromolecular synthesis. Further, chromium exposure may lead to apoptosis, premature terminal growth arrest or neoplastic transformation. Chromium-induced tumor suppressor gene p53 and oxidative processes are some of the major factors that may determine the cellular outcome. Studies have utilized these approaches to understand the interrelationship between chromium-induced genotoxicity, apoptosis and effects on immune response. (6).
Compound Type
  • Chromium Compound
  • Cigarette Toxin
  • Food Toxin
  • Household Toxin
  • Industrial/Workplace Toxin
  • Inorganic Compound
  • Metabolite
  • Metal
  • Natural Compound
  • Pollutant
Chemical Structure
Thumb
Synonyms
Synonym
Chromium (VI) cation
Chromium ion
Chromium ion (Cr6+)
Chromium(6+)
Chromium(6+) ion
Chromium(VI)
Cr
Cr(6+)
Cr6+
Chemical FormulaCr
Average Molecular Mass51.993 g/mol
Monoisotopic Mass51.937 g/mol
CAS Registry Number7440-47-3
IUPAC Nameλ⁶-chromium(6+) ion
Traditional Nameλ⁶-chromium(6+) ion
SMILES[Cr+6]
InChI IdentifierInChI=1S/Cr/q+6
InChI KeyInChIKey=JOPOVCBBYLSVDA-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as homogeneous transition metal compounds. These are inorganic compounds containing only metal atoms,with the largest atom being a transition metal atom.
KingdomChemical entities
Super ClassInorganic compounds
ClassHomogeneous metal compounds
Sub ClassHomogeneous transition metal compounds
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
  • Erythrocyte
  • Hair
  • Liver
  • Lymphocyte
  • Skin
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point1900°C
Boiling Point2642°C (4787.6°F)
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
logP-0.16ChemAxon
Physiological Charge6ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity0 m3·mol-1ChemAxon
Polarizability1.78 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-9000000000-ad2780f1f48b7aca8012View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udi-9000000000-ad2780f1f48b7aca8012View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udi-9000000000-ad2780f1f48b7aca8012View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-9000000000-f010964c6795d9f5713aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-9000000000-f010964c6795d9f5713aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0udi-9000000000-f010964c6795d9f5713aView in MoNA
Toxicity Profile
Route of ExposureOral (27) ; inhalation (27); dermal (27)
Mechanism of ToxicityHexavalent chromium's carcinogenic effects are caused by its metabolites, pentavalent and trivalent chromium. The DNA damage may be caused by hydroxyl radicals produced during reoxidation of pentavalent chromium by hydrogen peroxide molecules present in the cell. 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, 27, 2, 3, 4)
MetabolismChromium 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 allows 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 different pathways including ascorbate, glutathione, and nicotinamide adenine dinucleotide. Chromium is almost entirely excreted in the urine. (1, 27)
Toxicity ValuesNot Available
Lethal Dose1 to 3 grams of hexavalent chromium for an adult human. (5)
Carcinogenicity (IARC Classification)3, not classifiable as to its carcinogenicity to humans. (30)
Uses/SourcesElemental chromium is used mainly for making steel. Hexavalent chromium is used for chrome plating, dyes and pigments, leather tanning, and wood preserving. (1, 28)
Minimum Risk LevelIntermediate Oral: 0.005 mg/kg/day (Hexavalent chromium) (29) Chronic Oral: 0.001 mg/kg/day (Hexavalent chromium) (29)
Health EffectsHexavalent chromium is a known carcinogen. Chronic inhalation especially has been linked to lung cancer. Hexavalent chromium has also been shown to affect reproduction and development. (1)
SymptomsBreathing hexavalent chromium can cause irritation to the lining of the nose, nose ulcers, runny nose, and breathing problems, such as asthma, cough, shortness of breath, or wheezing. Ingestion of hexavalent chromium causes irritation and ulcers in the stomach and small intestine, as well as anemia. Skin contact can cause skin ulcers. (27)
TreatmentThere is no known antidote for chromium poisoning. Exposure is usually handled with symptomatic treatment. (27)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB00599
PubChem Compound ID23976
ChEMBL IDNot Available
ChemSpider ID25743
KEGG IDC06268
UniProt IDNot Available
OMIM ID271400
ChEBI ID28073
BioCyc IDNot Available
CTD IDD002857
Stitch IDChromium
PDB IDCR
ACToR ID7192
Wikipedia LinkChromium
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Salnikow K, Zhitkovich A: Genetic and epigenetic mechanisms in metal carcinogenesis and cocarcinogenesis: nickel, arsenic, and chromium. Chem Res Toxicol. 2008 Jan;21(1):28-44. Epub 2007 Oct 30. [17970581 ]
  2. 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 ]
  3. 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 ]
  4. Kimura T: [Molecular mechanism involved in chromium(VI) toxicity]. Yakugaku Zasshi. 2007 Dec;127(12):1957-65. [18057785 ]
  5. Barceloux DG: Chromium. J Toxicol Clin Toxicol. 1999;37(2):173-94. [10382554 ]
  6. Shrivastava R, Upreti RK, Seth PK, Chaturvedi UC: Effects of chromium on the immune system. FEMS Immunol Med Microbiol. 2002 Sep 6;34(1):1-7. [12208600 ]
  7. Gambelunghe A, Piccinini R, Ambrogi M, Villarini M, Moretti M, Marchetti C, Abbritti G, Muzi G: Primary DNA damage in chrome-plating workers. Toxicology. 2003 Jun 30;188(2-3):187-95. [12767690 ]
  8. Agaoglu G, Arun T, Izgi B, Yarat A: Nickel and chromium levels in the saliva and serum of patients with fixed orthodontic appliances. Angle Orthod. 2001 Oct;71(5):375-9. [11605871 ]
  9. Kim H, Cho SH, Chung MH: Exposure to hexavalent chromium does not increase 8-hydroxydeoxyguanosine levels in Korean chromate pigment workers. Ind Health. 1999 Jul;37(3):335-41. [10441906 ]
  10. MacDonald SJ, McCalden RW, Chess DG, Bourne RB, Rorabeck CH, Cleland D, Leung F: Metal-on-metal versus polyethylene in hip arthroplasty: a randomized clinical trial. Clin Orthop Relat Res. 2003 Jan;(406):282-96. [12579029 ]
  11. Vanoirbeek JA, Hoet PH, Nemery B, Verbeken EK, Haufroid V, Lison D, Dinsdale D: Kinetics of an intratracheally administered chromium catalyst in rats. J Toxicol Environ Health A. 2003 Feb 28;66(4):393-409. [12554544 ]
  12. Seifert B, Becker K, Hoffmann K, Krause C, Schulz C: The German Environmental Survey 1990/1992 (GerES II): a representative population study. J Expo Anal Environ Epidemiol. 2000 Mar-Apr;10(2):103-14. [10791592 ]
  13. Aguilar MV, Mateos CJ, Martinez Para MC: Determination of chromium in cerebrospinal fluid using electrothermal atomisation atomic absorption spectrometry. J Trace Elem Med Biol. 2002;16(4):221-5. [12530583 ]
  14. Chuang IC, Lee PN, Lin TH, Chen GS: Determination of some elements in the cervical mucus of healthy Taiwanese women, by GF-AAS. Biol Trace Elem Res. 2002 May;86(2):137-43. [12008976 ]
  15. Gaggelli E, Berti F, D'Amelio N, Gaggelli N, Valensin G, Bovalini L, Paffetti A, Trabalzini L: Metabolic pathways of carcinogenic chromium. Environ Health Perspect. 2002 Oct;110 Suppl 5:733-8. [12426122 ]
  16. Ravina A, Slezak L, Mirsky N, Bryden NA, Anderson RA: Reversal of corticosteroid-induced diabetes mellitus with supplemental chromium. Diabet Med. 1999 Feb;16(2):164-7. [10229312 ]
  17. Torra M, Rodamilans M, Corbella J, Ferrer R, Mazzara R: Blood chromium determination in assessing reference values in an unexposed Mediterranean population. Biol Trace Elem Res. 1999 Nov;70(2):183-9. [10535527 ]
  18. Kocadereli L, Atac PA, Kale PS, Ozer D: Salivary nickel and chromium in patients with fixed orthodontic appliances. Angle Orthod. 2000 Dec;70(6):431-4. [11138646 ]
  19. Kang EK, Lee S, Park JH, Joo KM, Jeong HJ, Chang IS: Determination of hexavalent chromium in cosmetic products by ion chromatography and postcolumn derivatization. Contact Dermatitis. 2006 May;54(5):244-8. [16689807 ]
  20. 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 ]
  21. Shigeta A, Ratanamaneechat S, Srisukho S, Tanaka M, Moriyama Y, Suwanagool S, Miki M: Epidemiological correlation between chromium content in gallstones and cholesterol in blood. J Med Assoc Thai. 2002 Feb;85(2):183-94. [12081118 ]
  22. Medeiros MG, Rodrigues AS, Batoreu MC, Laires A, Rueff J, Zhitkovich A: Elevated levels of DNA-protein crosslinks and micronuclei in peripheral lymphocytes of tannery workers exposed to trivalent chromium. Mutagenesis. 2003 Jan;18(1):19-24. [12473731 ]
  23. Vaglenov A, Nosko M, Georgieva R, Carbonell E, Creus A, Marcos R: Genotoxicity and radioresistance in electroplating workers exposed to chromium. Mutat Res. 1999 Oct 29;446(1):23-34. [10613183 ]
  24. Iarmarcovai G, Sari-Minodier I, Chaspoul F, Botta C, De Meo M, Orsiere T, Berge-Lefranc JL, Gallice P, Botta A: Risk assessment of welders using analysis of eight metals by ICP-MS in blood and urine and DNA damage evaluation by the comet and micronucleus assays; influence of XRCC1 and XRCC3 polymorphisms. Mutagenesis. 2005 Nov;20(6):425-32. Epub 2005 Oct 18. [16234265 ]
  25. Kolacinski Z, Kostrzewski P, Kruszewska S, Razniewska G, Mielczarska J: Acute potassium dichromate poisoning: a toxicokinetic case study. J Toxicol Clin Toxicol. 1999;37(6):785-91. [10584593 ]
  26. Morris BW, MacNeil S, Hardisty CA, Heller S, Burgin C, Gray TA: Chromium homeostasis in patients with type II (NIDDM) diabetes. J Trace Elem Med Biol. 1999 Jul;13(1-2):57-61. [10445219 ]
  27. 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]
  28. Wikipedia. Chromium. Last Updated 5 March 2009. [Link]
  29. 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]
  30. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

1. 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 (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
  1. 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
  1. 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
  1. 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
  1. 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:
Transferrin receptor binding
Specific Function:
Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation.
Gene Name:
TF
Uniprot ID:
P02787
Molecular Weight:
77063.195 Da
References
  1. Moshtaghie AA, Ani M, Bazrafshan MR: Comparative binding study of aluminum and chromium to human transferrin. Effect of iron. Biol Trace Elem Res. 1992 Jan-Mar;32:39-46. [1375080 ]