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Showing toxin card for Manganese (T3D0117)

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Version 1.0
Creation Date 2009-03-06 18:58:06
Update Date 2010-03-18 21:52:24
Accession Number T3D0117
Name Manganese
Compound Type
  • Cosmetic Toxin
  • Inorganic Compound
  • Manganese Compound
  • Metal
Description Manganese is a naturally occurring metal with the symbol Mn and the atomic number 25. It does not occur naturally in its pure form, but is found in many types of rocks in combination with other substances such as oxygen, sulfur, or chlorine. Manganese occurs naturally in most foods and small amounts are needed to stay healthy, as manganese ions act as cofactors for a number of enzymes. Manganese is used principally in steel production to improve hardness, stiffness, and strength. It may also be used as an additive in gasoline to improve the octane rating of the gas. Manganese ions have various colors and are used industrially as pigments. (R441, R442)
Synonyms
  1. Colloidal manganese
  2. Cutaval
  3. Dienol
  4. Magnacat
  5. Mangan [polish]
  6. Mangan nitridovany [czech]
  7. Manganese fume
  8. Manganese metal alloy
  9. Manganese, elemental
  10. Manganeso
  11. Manganum
  12. Oligostim manganese
  13. Tripart liquid manganese
  14. Tronamang
  15. Tronamang electrolytic manganese metal
Chemical IUPAC Name manganese(2+) ion
Chemical Formula Mn
Chemical Structure Structure
CAS Registry Number 7439-96-5
InChI Identifier InChI=1S/Mn/q+2
InChI Key InChIKey=WAEMQWOKJMHJLA-UHFFFAOYSA-N
PubChem Compound ID 23930 Link Image
KEGG ID C00034 Link Image
UniProt ID Not Available
OMIM ID 153550 173470 Link Image
ChEBI ID 18291 Link Image
BioCyc ID MN%2b3 Link Image
SuperToxic ID Not Available
CTD ID D008345 Link Image
Stitch ID Manganese Link Image
DrugBank ID Not Available
PDB ID Not Available
ACToR ID 6475
Wikipedia Link http://en.wikipedia.org/wiki/Manganese Link Image
Monoisotopic Mass 54.93805
MOL File Show
PDB File Show
SDF File Show
SMILES [Mn++]
Appearance Not Available
Melting Point 1244 °C
Solubility Not Available
Predicted LogP -0.156
Route of Exposure Oral (R441) ; inhalation (R441)
Mechanism of Action Manganese is a cellular toxicant that can impair transport systems, enzyme activities, and receptor functions. It primarily targets the central nervous system, particularily the globus pallidus of the basal ganglia. It is believed that the manganese ion, Mn(II), enhances the autoxidation or turnover of various intracellular catecholamines, leading to increased production of free radicals, reactive oxygen species, and other cytotoxic metabolites, along with a depletion of cellular antioxidant defense mechanisms, leading to oxidative damage and selective destruction of dopaminergic neurons. In addition to dopamine, manganese is thought to interact with other neurotransmitters, such as GABA and glutamate. Manganese overwhelms the manganese superoxide dismutase and produce oxidative damage. The neurotoxicity of Mn(II) has also been linked to its ability to substitute for Ca(II) under physiological conditions. It can enter mitochondria via the calcium uniporter and inhibit mitochondrial oxidative phosphorylation. It may also inhibit the efflux of Ca(II), which can result in a loss of mitochondrial membrane integrity. Mn(II) has been shown to inhibit mitochondrial aconitase activity to a significant level, altering amino acid metabolism and cellular iron homeostasis. (R441)
Metabolism Manganese is mainly absorbed via ingestion, but can also be inhaled. It binds to alpha-2-macroglobulin, albumin, or transferrin in the plasma and is distributed to the brain and all other mammalian tissues, though it tends to accumulate more in the liver, pancreas, and kidney. Manganese exists in a number of oxidation states and is believed to undergo changes in oxidation state within the body. Manganese oxidation state can influence tissue toxicokinetic behavior, and possibly toxicity. Manganese is excreted primarily in the faeces. (R441)
Toxicity Values LD50: 9 g/kg (Oral, Rat) (R293)
Lethal Dose Not Available
Carcinogenicity (IARC Classification) Not Available
Uses/Sources Manganese is used principally in steel production to improve hardness, stiffness, and strength. It may also be used as an additive in gasoline to improve the octane rating of the gas. Manganese ions have various colors and are used industrially as pigments. (R441, R442)
Minimum Risk Level Chronic Inhalation: 0.0003 mg/m3 (R260)
Health Effects Manganese mainly affects the nervous system and may cause behavioral changes and other nervous system effects, which include movements that may become slow and clumsy. This combination of symptoms when sufficiently severe is referred to as “manganism”. High levels of manganese may also cause damage to the reproductive system. (R441)
Symptoms Manganese mainly affects the nervous system and may cause behavioral changes and other nervous system effects, which include movements that may become slow and clumsy. This combination of symptoms when sufficiently severe is referred to as “manganism”. (R441)
Treatment Not Available
General References
  • R442 - Wikipedia. Manganese. Last Updated 26 May 2009.
  • R293 - National Institute for Occupational Safety and Health (2002). RTECS: Registry of Toxic Effects of Chemical Substances.
  • R260 - 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).
  • R441 - ATSDR - Agency for Toxic Substances and Disease Registry (2008). Toxicological profile for manganese. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA).
Targets
  1. Major prion protein
  2. Putative testis-specific prion protein
  3. Aconitate hydratase, mitochondrial
  4. Cytoplasmic aconitate hydratase
  5. Iron-responsive element-binding protein 2
Target 1 [top]
Target 1 ID 633
Target 1 Name Major prion protein
Target 1 Mechanism of Action Manganese binds to the prion protein, altering its conformation, displacing copper, and altering the redox chemistry of the metal-protein complex. These changes are similar to those associated with prion disease. (R443)
Target 1 Description The physiological function of PrP is not known
Target 1 Synonyms
  1. PrP; PrP27-30; PrP33-35C; ASCR; CD230 antigen
Target 1 Gene Name PRNP
Target 1 Protein Sequence >Major prion protein 
MANLGCWMLVLFVATWSDLGLCKKRPKPGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQP
HGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQGGGTHSQWNKPSKPKTNMKHMAGAAAAGA
VVGGLGGYMLGSAMSRPIIHFGSDYEDRYYRENMHRYPNQVYYRPMDEYSNQNNFVHDCV
NITIKQHTVTTTTKGENFTETDVKMMERVVEQMCITQYERESQAYYQRGSSMVLFSSPPV
ILLISFLIFLIVG
Target 1 Number of Residues 253
Target 1 Molecular Weight 27661.2
Target 1 Theoretical pI 9.23
Target 1 GO Classification
Function
Not Available
Process
Not Available
Component
Not Available
Target 1 General Function Carbohydrate transport and metabolism
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Signals
  • 1-22
Target 1 Transmembrane Regions
  • 112-134; 230-252
Target 1 Essentiality Non Essential
Target 1 Domain Function PF00377:Prion PF03991:Prion_octapep
Target 1 GenBank ID Protein Not Available
Target 1 UniProtKB ID P04156 Link Image
Target 1 Cellular Location Cell membrane
Target 1 Gene Sequence >762 bp 
GAGCAGTCATTATGGCGAACCTTGGCTGCTGGATGCTGGTTCTCTTTGTGGCCACATGGA
GTGACCTGGGCCTCTGCAAGAAGCGCCCGAAGCCTGGAGGATGGAACACTGGGGGCAGCC
GATACCCGGGGCAGGGCAGCCCTGGAGGCAACCGCTACCCACCTCAGGGCGGTGGTGGCT
GGGGGCAGCCTCATGGTGGTGGCTGGGGGCAGCCTCATGGTGGTGGCTGGGGGCAGCCCC
ATGGTGGTGGCTGGGGACAGCCTCATGGTGGTGGCTGGGGTCAAGGAGGTGGCACCCACA
GTCAGTGGAACAAGCCGAGTAAGCCAAAAACCAACATGAAGCACATGGCTGGTGCTGCAG
CAGCTGGGGCAGTGGTGGGGGGCCTTGGCGGCTACATGCTGGGAAGTGCCATGAGCAGGC
CCATCATACATTTCGGCAGTGACTATGAGGACCGTTACTATCGTGAAAACATGCACCGTT
ACCCCAACCAAGTGTACTACAGGCCCATGGATGAGTACAGCAACCAGAACAACTTTGTGC
ACGACTGCGTCAATATCACAATCAAGCAGCACACGGTCACCACAACCACCAAGGGGGAGA
ACTTCACCGAGACCGACGTTAAGATGATGGAGCGCGTGGTTGAGCAGATGTGTATCACCC
AGTACGAGAGGGAATCTCAGGCCTATTACCAGAGAGGATCGAGCATGGTCCTCTTCTCCT
CTCCACCTGTGATCCTCCTGATCTCTTTCCTCATCTTCCTGA
Target 1 GenBank Gene ID Not Available
Target 1 GeneCard ID PRNP Link Image
Target 1 GenAtlas ID PRNP Link Image
Target 1 HGNC ID HGNC:9449 Link Image
Target 1 Chromosome Location Chromosome:20
Target 1 Locus 20p13
Target 1 SNPs SNPJam Report Link Image
Target 1 Toxin References
  • R443 - Brazier MW, Davies P, Player E, Marken F, Viles JH, Brown DR: Manganese binding to the prion protein. J Biol Chem. 2008 May 9;283(19):12831-9. Epub 2008 Mar 10. [PubMed Link Image]
Target 1 General References 3755672; 1678248; 9799790; 10581485; 11780052; 15489334; 3014653; 1363802
Target 2 [top]
Target 2 ID 634
Target 2 Name Putative testis-specific prion protein
Target 2 Mechanism of Action Manganese binds to the prion protein, altering its conformation, displacing copper, and altering the redox chemistry of the metal-protein complex. These changes are similar to those associated with prion disease. (R443)
Target 2 Description Not Available
Target 2 Synonyms
  1. Protein M8
Target 2 Gene Name PRNT
Target 2 Protein Sequence >Putative testis-specific prion protein 
MQHSLVFFFAVILHLSHLLHLDASIHPFRLPFSSKPFLLIPMSNTTLPHTAWPLSFLHQT
VSTLKAVAVTHSLWHLQIPVDCQACNRKSKKIYC
Target 2 Number of Residues 94
Target 2 Molecular Weight 10755.7
Target 2 Theoretical pI 10.00
Target 2 GO Classification
Function
Not Available
Process
Not Available
Component
Not Available
Target 2 General Function Not Available
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Signals
  • 1-18
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non Essential
Target 2 Domain Function Not Available
Target 2 GenBank ID Protein Not Available
Target 2 UniProtKB ID Q86SH4 Link Image
Target 2 Cellular Location Secreted (Potential)
Target 2 Gene Sequence >285 bp 
ATGCAGCATAGTCTTGTTTTCTTTTTTGCAGTGATTCTACATCTTTCCCATCTTCTCCAC
CTGGATGCCTCCATCCATCCTTTCAGACTTCCCTTCTCTAGCAAACCTTTCTTGCTAATT
CCCATGTCTAACACAACACTTCCCCATACTGCATGGCCATTATCCTTTCTGCATCAGACT
GTGAGCACCTTGAAGGCAGTGGCAGTGACTCATTCATTGTGGCATCTGCAGATTCCAGTG
GACTGCCAGGCATGCAATAGAAAATCAAAAAAGATTTACTGCTAA
Target 2 GenBank Gene ID Not Available
Target 2 GeneCard ID PRNT Link Image
Target 2 GenAtlas ID PRNT Link Image
Target 2 HGNC ID HGNC:18046 Link Image
Target 2 Chromosome Location Chromosome:20
Target 2 Locus 20p13
Target 2 SNPs SNPJam Report Link Image
Target 2 Toxin References
  • R443 - Brazier MW, Davies P, Player E, Marken F, Viles JH, Brown DR: Manganese binding to the prion protein. J Biol Chem. 2008 May 9;283(19):12831-9. Epub 2008 Mar 10. [PubMed Link Image]
Target 2 General References 12514748; 11780052; 16460908; 17562432; 17199895
Target 3 [top]
Target 3 ID 635
Target 3 Name Aconitate hydratase, mitochondrial
Target 3 Mechanism of Action Manganese interferes with amino acid metabolism by inhibiting aconitase, resulting in an increase in citrate levels. It is also believed that this direct disruption of the catalytic [4Fe-4S] cluster of aconitase by manganese produces iron regulary protein 1, resulting in alterations in cellular iron homeostasis. (R444)
Target 3 Description Citrate = isocitrate
Target 3 Synonyms
  1. Aconitase; Citrate hydro-lyase
Target 3 Gene Name ACO2
Target 3 Protein Sequence >Aconitate hydratase, mitochondrial 
MAPYSLLVTRLQKALGVRQYHVASVLCQRAKVAMSHFEPNEYIHYDLLEKNINIVRKRLN
RPLTLSEKIVYGHLDDPASQEIERGKSYLRLRPDRVAMQDATAQMAMLQFISSGLSKVAV
PSTIHCDHLIEAQVGGEKDLRRAKDINQEVYNFLATAGAKYGVGFWKPGSGIIHQIILEN
YAYPGVLLIGTDSHTPNGGGLGGICIGVGGADAVDVMAGIPWELKCPKVIGVKLTGSLSG
WSSPKDVILKVAGILTVKGGTGAIVEYHGPGVDSISCTGMATICNMGAEIGATTSVFPYN
HRMKKYLSKTGREDIANLADEFKDHLVPDPGCHYDQLIEINLSELKPHINGPFTPDLAHP
VAEVGKVAEKEGWPLDIRVGLIGSCTNSSYEDMGRSAAVAKQALAHGLKCKSQFTITPGS
EQIRATIERDGYAQILRDLGGIVLANACGPCIGQWDRKDIKKGEKNTIVTSYNRNFTGRN
DANPETHAFVTSPEIVTALAIAGTLKFNPETDYLTGTDGKKFRLEAPDADELPKGEFDPG
QDTYQHPPKDSSGQHVDVSPTSQRLQLLEPFDKWDGKDLEDLQILIKVKGKCTTDHISAA
GPWLKFRGHLDNISNNLLIGAINIENGKANSVRNAVTQEFGPVPDTARYYKKHGIRWVVI
GDENYGEGSSREHAALEPRHLGGRAIITKSFARIHETNLKKQGLLPLTFADPADYNKIHP
VDKLTIQGLKDFTPGKPLKCIIKHPNGTQETILLNHTFNETQIEWFRAGSALNRMKELQQ
Target 3 Number of Residues 780
Target 3 Molecular Weight 85424.7
Target 3 Theoretical pI 7.65
Target 3 GO Classification
Function
carbon-oxygen lyase activity
hydro-lyase activity
aconitate hydratase activity
catalytic activity
lyase activity
Process
cellular metabolism
generation of precursor metabolites and energy
energy derivation by oxidation of organic compounds
main pathways of carbohydrate metabolism
tricarboxylic acid cycle
physiological process
metabolism
Component
organelle
membrane-bound organelle
intracellular membrane-bound organelle
mitochondrion
Target 3 General Function Energy production and conversion
Target 3 Pathways Carbohydrate metabolism; tricarboxylic acid cycle
Target 3 Reactions Not Available
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • None
Target 3 Essentiality Non Essential
Target 3 Domain Function PF00330:Aconitase PF00694:Aconitase_C
Target 3 GenBank ID Protein Not Available
Target 3 UniProtKB ID Q99798 Link Image
Target 3 Cellular Location Mitochondrion (By similarity)
Target 3 Gene Sequence >2343 bp 
ATGGCGCCCTACAGCCTACTGGTGACTCGGCTGCAGAAAGCTCTGGGTGTGCGGCAGTAC
CATGTGGCCTCAGTCCTGTGCCAACGGGCCAAGGTGGCGATGACGCATTTTGAGCCCAAC
GAGTACATCCATTATGACCTGCTAGAGAAGAACATTAACATTGTTCGCAAACGACTGAAC
CGGCCGCTGACACTCTCGGAGAAGATTGTGTATGGACACCTGGATGACCCCGCCAGCCAG
GAAATTGAGCGAGGCAAGTCGTACCTGCGGCTGCGGCCCGACCGTGTGGCCATGCAGGAT
GCGACGGCCCAGATGGCCATGCTCCAGTTCATCAGCAGCGGGCTGTCCAAGGTGGCTGTG
CCATCCACCATCCACTGTGACCATCTGATTGAAGCCCAGGTTGGGGACGAGAAAGACCTG
CGCCGGGCCAAGGACATCAACCAGGAAGTTTATAATTTCCTGGCAACTGCAGGTGACAAG
TATGGCGTGGGCTTCTGGAGCCCTGGATCTGGAATCATTCACCAGATTATTCTCGAAAAC
TATGCGTACCCTGGAGTTCTTCTGATTGGAACTGACTCCCACACCCCCAATGGTGGTGGC
CTAGGAGGCATCTGCATTGGAGTAGGGGGTGCAGATGCTGTGGATGTCATGGCTGGGATC
CCCTGGGAGCTGAAGTGCCCCAAGGTGATTGGCGTGAAGCTGACGGGCTCTCTCTCCGGT
TGGACCTCACCCAAAGATGTGATCCTGAAGGTGGCAGGCATCCTCACGGTGAAAGGTGGC
ACAGGTGCAATCGTGGAATACCACGGGCCTGGTGTAGACTCCATGTCCTGCACTGGCATG
GCGACAATCTGCAACATGGGTGCAGAAATTGGGGCCACCACTTCCGTGTTCCCTTACAAC
CACAGGATGAAGAAGTACCTGAGCAAGACCGGCCGGGAAGACATTGCCAATCTAGCTGAT
GAATTCAAGGATCACTTGGTGCCTGACCCTGGCTGCCATTATGACCAACTAATTGAAATT
AACCTCAGTGAGCTGAAGCCACACATCAATGGGCCCTTCACCCCTGACCTGGCTCACCCT
GTGGCAGAAGTGGGCAAGGTGGCAGAGAAGGAAGGATGGCCTCTGGACATCCGAGTGGGT
CTAATTGGTAGCTGCACCAATTCAAGCTATGAAGATATGGGGCGCTCAGCAGCTGTGGCC
AAGCAGGCACTGGCCCATGGACTCAAGTGCAAGTCCCAGTTCACCATCACTCCAGGTTCC
GAGCAGATCCGCGCCACCATTGAGCGGGACGGCTATGCACAGATCCTGAGGGATCTGGGT
GGCATTGTCCTGGCCAATGCCTGCGGGCCCTGCATTGGCCAGTGGGACAGAAAGGACATC
AAGAAGGGGGAGAAGAACACAATCGTCACCTCCTACAACAGGAACTTCACGGGCCGCAAC
GACGCAAACCCCGAGACCCATGCCTTTGTCACGTCCCCAGAGATTGTCACAGCCCTGGCC
ATTGCAGGAACCCTCAAGTTCAACCCAGAGACCGACTACCTGACAGGCAAGGATGGCAAG
AAGTTCAGGCTGGAAGCTCCGGATGCAGATGAGCTTCCCAAAGGGGAGTTTGACCCAGGG
CAGGACACCTACCAGCACCCCCCAAAGGACAGCAGCAGGCAGCATGTGGACGTGAGCCCC
ACCAGCCAGCGCCTGCAGCTCCTGGAGCCTTTTGACAAGTGGGATGGCAAGGACCTGGAG
GACCTGCAGATCCTCATCAAGGTCAAAGGGAAGTGTACCACTGACCACATCTCAGCTGCT
GGCCCCTGGCTCAAGTTCCGTGGGCACTTGGATAACATCTCCAACAACCTGCTCATTGGT
GCCATCAACATTGAAAACGGCAAGGCCAACTCCGTGCGCAATGCCGTCACTCAGGAGTTT
GGCCCCGTCCCTGACACTGCCCGCTACTACAAGAAACATGGCATCAGGTGGGTGGTGATC
GGAGACGAGAACTACGGCGAGGGCTCGAGCCGGGAGCATGCAGCTCTGGAGCCTCGCCAC
CTTGGGGGCCGGGCCATCATCACCAAGAGCTTTGCCAGGATCCACGAGACCAACCTGAAG
AAACAGGGCCTGCTGCCTCTGACCTTCGCTGACCCGGCTGACTACAACAAGATTCACCCT
GTGGACAAGCTGACCATTCAGGGCCTGAAGGACTTCACCCCTGGCAAGCCCCTGAAGTGC
ATCATCAAGCACCCCAACGGGACCCAGGAGACCATCCTCCTGAACCACACCTTCAACGAG
ACGCAGATTGAGTGGTTCCGCGCTGGCAGTGCCCTCAACAGAATGAAGGAACTGCAACAG
TGA
Target 3 GenBank Gene ID Not Available
Target 3 GeneCard ID ACO2 Link Image
Target 3 GenAtlas ID ACO2 Link Image
Target 3 HGNC ID HGNC:118 Link Image
Target 3 Chromosome Location Chromosome:22
Target 3 Locus 22q11.2-q13.31|22q13.2|22q13.2-q13.31
Target 3 SNPs SNPJam Report Link Image
Target 3 Toxin References
  • R444 - Crooks DR, Ghosh MC, Braun-Sommargren M, Rouault TA, Smith DR: Manganese targets m-aconitase and activates iron regulatory protein 2 in AF5 GABAergic cells. J Neurosci Res. 2007 Jun;85(8):1797-809. [PubMed Link Image]
Target 3 General References 9630632; 15461802; 10591208; 15489334; 1946331; 16959974
Target 4 [top]
Target 4 ID 636
Target 4 Name Cytoplasmic aconitate hydratase
Target 4 Mechanism of Action Manganese interferes with amino acid metabolism by inhibiting aconitase, resulting in an increase in citrate levels. It is also believed that this direct disruption of the catalytic [4Fe-4S] cluster of aconitase by manganese produces iron regulary protein 1, resulting in alterations in cellular iron homeostasis. (R444)
Target 4 Description Binds to iron-responsive elements (IRES), which are stem-loop structures found in the 5'-UTR of ferritin, and delta aminolevulinic acid synthase mRNAs, and in the 3'-UTR of transferrin receptor mRNA. Binding to the IRE element in ferritin results in the repression of its mRNA translation. Binding of the protein to the transferrin receptor mRNA inhibits the degradation of this otherwise rapidly degraded mRNA. This protein also expresses aconitase activity
Target 4 Synonyms
  1. Aconitase; Citrate hydro-lyase; Iron-responsive element-binding protein 1; IRE-BP 1; Iron regulatory protein 1; IRP1; Ferritin repressor protein
Target 4 Gene Name ACO1
Target 4 Protein Sequence >Cytoplasmic aconitate hydratase 
MSNPFAHLAEPLDPVQPGKKFFNLNKLEDSRYGRLPFSIRVLLEAAIRNCDEFLVKKQDI
ENILHWNVTQHKNIEVPFKPARVILQDFTGVPAVVDFAAMRDAVKKLGGDPEKINPVCPA
DLVIDHSIQVDFNRRADSLQKNQDLEFERNRERFEFLKWGSQAFHNMRIIPPGSGIIHQV
NLEYLARVVFDQDGYYYPDSLVGTDSHTTMIDGLGILGWGVGGIEAEAVMLGQPISMVLP
QVIGYRLMGKPHPLVTSTDIVLTITKHLRQVGVVGKFVEFFGPGVAQLSIADRATIANMC
PEYGATAAFFPVDEVSITYLVQTGRDEEKLKYIKKYLQAVGMFRDFNDPSQDPDFTQVVE
LDLKTVVPCCSGPKRPQDKVAVSDMKKDFESCLGAKQGFKGFQVAPEHHNDHKTFIYDNT
EFTLAHGSVVIAAITSCTNTSNPSVMLGAGLLAKKAVDAGLNVMPYIKTSLSPGSGVVTY
YLQESGVMPYLSQLGFDVVGYGCMTCIGNSGPLPEPVVEAITQGDLVAVGVLSGNRNFEG
RVHPNTRANYLASPPLVIAYAIAGTIRIDFEKEPLGVNAKGQQVFLKDIWPTRDEIQAVE
RQYVIPGMFKEVYQKIETVNESWNALATPSDKLFFWNSKSTYIKSPPFFENLTLDLQPPK
SIVDAYVLLNLGDSVTTDHISPAGNIARNSPAARYLTNRGLTPREFNSYGSRRGNDAVMA
RGTFANIRLLNRFLNKQAPQTIHLPSGEILDVFDAAERYQQAGLPLIVLAGKEYGAGSSR
DWAAKGPFLLGIKAVLAESYERIHRSNLVGMGVIPLEYLPGENADALGLTGQERYTIIIP
ENLKPQMKVQVKLDTGKTFQAVMRFDTDVELTYFLNGGILNYMIRKMAK
Target 4 Number of Residues 889
Target 4 Molecular Weight 98398.1
Target 4 Theoretical pI 6.66
Target 4 GO Classification
Function
ion binding
cation binding
transition metal ion binding
iron ion binding
carbon-oxygen lyase activity
hydro-lyase activity
aconitate hydratase activity
binding
nucleic acid binding
RNA binding
catalytic activity
lyase activity
Process
physiological process
metabolism
Component
Not Available
Target 4 General Function Energy production and conversion
Target 4 Pathways Not Available
Target 4 Reactions Not Available
Target 4 Signals
  • None
Target 4 Transmembrane Regions
  • None
Target 4 Essentiality Non Essential
Target 4 Domain Function PF00330:Aconitase PF00694:Aconitase_C
Target 4 GenBank ID Protein Not Available
Target 4 UniProtKB ID P21399 Link Image
Target 4 Cellular Location Cytoplasm
Target 4 Gene Sequence >2670 bp 
ATGAGCAACCCATTCGCACACCTTGCTGAGCCATTGGATCCTGTACAACCAGGAAAGAAA
TTCTTCAATTTGAATAAATTGGAGGATTCAAGATATGGGCGCTTACCATTTTCGATCAGA
GTTCTTCTGGAAGCAGCCATTCGGAATTGTGATGAGTTTTTGGTGAAGAAACAGGATATT
GAAAATATTCTACATTGGAATGTCACTCAGCACAAGAACATAGAAGTGCCATTTAAGCCT
GCTCGTGTCATCCTGCAGGACTTTACGGGTGTGCCCGCTGTGGTTGACTTTGCTGCAATG
CGTGATGCTGTGAAAAAGTTAGGAGGAGATCCAGAGAAAATAAACCCTGTCTGCCCTGCT
GATCTTGTAATAGATCATTCCATCCAGGTTGATTTCAACAGAAGGGCAGACAGTTTACAG
AAGAATCAAGACCTGGAATTTGAAAGAAATAGAGAGCGATTTGAATTTTTAAAGTGGGGT
TCCCAGGCTTTTCACAACATGCGGATTATTCCCCCTGGCTCAGGAATCATCCACCAGGTG
AATTTGGAATATTTGGCAAGAGTGGTATTTGATCAGGATGGATATTATTACCCAGACAGC
CTCGTGGGCACAGACTCGCACACTACCATGATTGATGGCTTGGGCATTCTTGGTTGGGGT
GTCGGTGGTATTGAAGCAGAAGCTGTCATGCTGGGTCAGCCAATCAGTATGGTGCTTCCT
CAGGTGATTGGCTACAGGCTGATGGGGAAGCCCCACCCTCTGGTAACATCCACTGACATC
GTGCTCACCATTACCAAGCACCTCCGCCAGGTTGGGGTAGTGGGCAAATTTGTCGAGTTC
TTCGGGCCTGGAGTAGCCCAGTTGTCCATTGCTGACCGAGCTACGATTGCTAACATGTGT
CCAGAGTACGGAGCAACTGCTGCCTTTTTCCCAGTTGATGAAGTTAGTATCACGTACCTG
GTGCAAACAGGTCGTGATGAAGAAAAATTAAAGTATATTAAAAAATATCTTCAGGCTGTA
GGAATGTTTCGAGATTTCAATGACCCTTCTCAAGACCCAGACTTCACCCAGGTTGTGGAA
TTAGATTTGAAAACAGTAGTGCCTTGCTGTAGTGGACCCAAAAGGCCTCAGGACAAAGTT
GCTGTGTCCGACATGAAAAAGGACTTTGAGAGCTGCCTTGGAGCCAAGCAAGGATTTAAA
GGATTCCAAGTTGCTCCTGAACATCATAATGACCATAAGACCTTTATCTATGATAACACT
GAATTCACCCTTGCTCATGGTTCTGTGGTCATTGCTGCCATTACTAGCTGCACAAACACC
AGTAATCCGTCTGTGATGTTAGGGGCAGGATTGTTAGCAAAGAAAGCTGTGGATGCTGGC
CTGAACGTGATGCCTTACATCAAAACTAGCCTGTCTCCTGGGAGTGGCGTGGTCACCTAC
TACCTACAAGAAAGCGGAGTCATGCCTTATCTGTCTCAGCTTGGGTTTGACGTGGTGGGC
TATGGCTGCATGACCTGCATTGGCAACAGTGGGCCTTTACCTGAACCTGTGGTAGAAGCC
ATCACACAGGGAGACCTTGTAGCTGTTGGAGTACTATCTGGAAACAGGAATTTTGAAGGT
CGAGTTCACCCCAACACCCGGGCCAACTATTTAGCCTCTCCCCCCTTAGTAATAGCATAT
GCAATTGCTGGAACCATCAGAATCGACTTTGAGAAAGAGCCATTGGGAGTAAATGCAAAG
GGACAGCAGGTATTTCTGAAAGATATCTGGCCGACTAGAGACGAGATCCAGGCAGTGGAG
CGTCAGTATGTCATCCCGGGGATGTTTAAGGAAGTCTATCAGAAAATAGAGACTGTGAAT
GAAAGCTGGAATGCCTTAGCAACCCCATCAGATAAGCTGTTTTTCTGGAATTCCAAATCT
ACGTATATCAAATCACCACCATTCTTTGAAAACCTGACTTTGGATCTTCAGCCCCCTAAA
TCTATAGTGGATGCCTATGTGCTGCTAAATTTGGGAGATTCGGTAACAACTGACCACATC
TCCCCAGCTGGAAATATTGCAAGAAACAGTCCTGCTGCTCGCTACTTAACTAACAGAGGC
CTAACTCCACGAGAATTCAACTCCTATGGCTCCCGCCGAGGTAATGACGCCGTCATGGCA
CGGGGAACATTTGCCAACATTCGCTTGTTAAACAGATTTTTGAACAAGCAGGCACCACAG
ACTATCCATCTGCCTTCTGGGGAAATCCTTGATGTGTTTGATGCTGCTGAGCGGTACCAG
CAGGCAGGCCTTCCCCTGATCGTTCTGGCTGGCAAAGAGTACGGTGCAGGCAGCTCCCGA
GACTGGGCAGCTAAGGGCCCTTTCCTGCTGGGAATCAAAGCCGTCCTGGCCGAGAGCTAC
GAGCGCATTCACCGCAGTAACCTGGTTGGGATGGGTGTGATCCCACTTGAATATCTCCCT
GGTGAGAATGCAGATGCCCTGGGGCTCACAGGGCAAGAACGATACACTATCATTATTCCA
GAAAACCTCAAACCACAAATGAAAGTCCAGGTCAAGCTGGATACTGGCAAGACCTTCCAG
GCTGTCATGAGGTTTGACACTGATGTGGAGCTCACTTATTTCCTCAACGGGGGCATCCTC
AACTACATGATCCGCAAGATGGCCAAGTAG
Target 4 GenBank Gene ID Not Available
Target 4 GeneCard ID ACO1 Link Image
Target 4 GenAtlas ID ACO1 Link Image
Target 4 HGNC ID HGNC:117 Link Image
Target 4 Chromosome Location Not Available
Target 4 Locus 9p22-q32|9p21.1
Target 4 SNPs SNPJam Report Link Image
Target 4 Toxin References
  • R444 - Crooks DR, Ghosh MC, Braun-Sommargren M, Rouault TA, Smith DR: Manganese targets m-aconitase and activates iron regulatory protein 2 in AF5 GABAergic cells. J Neurosci Res. 2007 Jun;85(8):1797-809. [PubMed Link Image]
Target 4 General References 1738601; 15489334; 2172968; 1903202; 1946430
Target 5 [top]
Target 5 ID 637
Target 5 Name Iron-responsive element-binding protein 2
Target 5 Mechanism of Action Manganese alters cellular iron homeostasis by stabilizing iron regulatory protein 2. This may occur by manganese competing directly for an iron-binding site on the iron binding protein, disrupting the cellular mechanisms responsible for its iron-dependent degradation. (R444)
Target 5 Description Binds to iron-responsive elements (IRES), which are stem-loop structures found in the 5'-UTR of ferritin, and delta aminolevulinic acid synthase mRNAs, and in the 3'-UTR of transferrin receptor mRNA. Binding to the IRE element in ferritin results in the repression of its mRNA translation. Binding of the protein to the transferrin receptor mRNA inhibits the degradation of this otherwise rapidly degraded mRNA
Target 5 Synonyms
  1. IRE-BP 2; Iron regulatory protein 2; IRP2
Target 5 Gene Name IREB2
Target 5 Protein Sequence >Iron-responsive element-binding protein 2 
MDAPKAGYAFEYLIETLNDSSHKKFFDVSKLGTKYDVLPYSIRVLLEAAVRNCDGFLMKK
EDVMNILDWKTKQSNVEVPFFPARVLLQDFTGIPAMVDFAAMREAVKTLGGDPEKVHPAC
PTDLTVDHSLQIDFSKCAIQNAPNPGGGDLQKAGKLSPLKVQPKKLPCRGQTTCRGSCDS
GELGRNSGTFSSQIENTPILCPFHLQPVPEPETVLKNQEVEFGRNRERLQFFKWSSRVFK
NVAVIPPGTGMAHQINLEYLSRVVFEEKDLLFPDSVVGTDSHITMVNGLGILGWGVGGIE
TEAVMLGLPVSLTLPEVVGCELTGSSNPFVTSIDVVLGITKHLRQVGVAGKFVEFFGSGV
SQLSIVDRTTIANMCPEYGAILSFFPVDNVTLKHLEHTGFSKAKLESMETYLKAVKLFRN
DQNSSGEPEYSQVIQINLNSIVPSVSGPKRPQDRVAVTDMKSDFQACLNEKVGFKGFQIA
AEKQKDIVSIHYEGSEYKLSHGSVVIAAVISCTNNCNPSVMLAAGLLAKKAVEAGLRVKP
YIRTSLSPGSGMVTHYLSSSGVLPYLSKLGFEIVGYGCSTCVGNTAPLSDAVLNAVKQGD
LVTCGILSGNKNFEGRLCDCVRANYLASPPLVVAYAIAGTVNIDFQTEPLGTDPTGKNIY
LHDIWPSREEVHRVEEEHVILSMFKALKDKIEMGNKRWNSLEAPDSVLFPWDLKSTYIRC
PSFFDKLTKEPIALQAIENAHVLLYLGDSVTTDHISPAGSIARNSAAAKYLTNRGLTPRE
FNSYGARRGNDAVMTRGTFANIKLFNKFIGKPAPKTIHFPSGQTLDVFEAAELYQKEGIP
LIILAGKKYGSGNSRDWAAKGPYLLGVKAVLAESYEKIHKDHLIGIGIAPLQFLPGENAD
SLGLSGRETFSLTFPEELSPGITLNIQTSTGKVFSVIASFEDDVEITLYKHGGLLNFVAR
KFS
Target 5 Number of Residues 963
Target 5 Molecular Weight 105045.6
Target 5 Theoretical pI 7.05
Target 5 GO Classification
Function
ion binding
cation binding
transition metal ion binding
iron ion binding
carbon-oxygen lyase activity
hydro-lyase activity
aconitate hydratase activity
binding
nucleic acid binding
RNA binding
catalytic activity
lyase activity
Process
physiological process
metabolism
Component
Not Available
Target 5 General Function Energy production and conversion
Target 5 Pathways Not Available
Target 5 Reactions Not Available
Target 5 Signals
  • None
Target 5 Transmembrane Regions
  • None
Target 5 Essentiality Non Essential
Target 5 Domain Function PF00330:Aconitase PF00694:Aconitase_C
Target 5 GenBank ID Protein Not Available
Target 5 UniProtKB ID P48200 Link Image
Target 5 Cellular Location Cytoplasm
Target 5 Gene Sequence Not Available
Target 5 GenBank Gene ID Not Available
Target 5 GeneCard ID IREB2 Link Image
Target 5 GenAtlas ID IREB2 Link Image
Target 5 HGNC ID HGNC:6115 Link Image
Target 5 Chromosome Location Chromosome:15
Target 5 Locus 15q25.1
Target 5 SNPs SNPJam Report Link Image
Target 5 Toxin References
  • R444 - Crooks DR, Ghosh MC, Braun-Sommargren M, Rouault TA, Smith DR: Manganese targets m-aconitase and activates iron regulatory protein 2 in AF5 GABAergic cells. J Neurosci Res. 2007 Jun;85(8):1797-809. [PubMed Link Image]
Target 5 General References 7983023; 14702039; 16572171; 15489334; 2172968; 7622457

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government.