Metallothioneins bind metals (Homo sapiens)

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2, 3, 5, 15, 21...13, 1411, 22, 26, 28, 30...122710, 188, 16, 24, 38, 3911, 26, 30, 351, 17, 25, 32-349, 19, 29620, 23, 38cytosolZn2+MT1M:7Zn2+Cu1+ As3+Cd2+ Cd2+Cu1+MT4:7Zn2+MT1X:7Cd2+MT3:12Cu1+MT1G Cd2+ MT4Cd2+ Zn2+ MT4:10Cu1+Cd2+MT3:7Cd2+Cd2+ Cd2+Zn2+Zn2+ MT1GZn2+ Cd2+MT2A Cd2+ MT1F:7Zn2+MT1A MT3Cd2+ MT1G:7Zn2+MT1A MT1A Zn2+MT1H:7Zn2+Zn2+ MT1X MT1M MT1E As3+ MT4 Zn2+MT1X MT1H MT1AMT1F MT1MMT1BCd2+ Cd2+ Zn2+MT3 MT1A:7Cd2+Zn2+ MT3 MT1HCd2+Cu1+ Zn2+ MT1M MT1H:7Cd2+MT1B:7Cd2+Zn2+MT1G MT1G:7Cd2+MT4 MT1FCd2+Zn2+MT2A:10Cu1+Cd2+ Cd2+MT2A MT4 MT1F Zn2+MT1B Cd2+MT1XZn2+Cu1+MT1A:6As3+MT1B:7Zn2+MT3:7Zn2+Zn2+ Zn2+ MT4:7Cd2+Zn2+ Zn2+ MT1M:7Cd2+Cu1+ MT1A:7Zn2+Cu2+MT1E MT3 MT3 Zn2+ MT1B MT2AZn2+MT1E:7Zn2+Cu1+ Cd2+Zn2+MT1E:7Cd2+MT2A:7Cd2+Cd2+ Cd2+ MT1X:7Zn2+MT2A:7Zn2+Cd2+Cu1+Cd2+MT1F:7Cd2+MT2A Zn2+ MT1EMT3:4Zn2+:4Cu+MT1H 144, 717, 33, 348, 16, 24, 38, 394, 710, 1826, 304, 720, 23, 384, 79, 19, 2913, 144, 76


Description

Metallothioneins are highly conserved, cysteine-rich proteins that bind metals via thiolate bonds (recent general reviews in Capdevila et al. 2012, Blindauer et al. 2014, reviews of mammalian metallothioneins in Miles et al. 2000, Maret 2011, Vasak and Meloni 2011, Thirumoorthy et al. 2001, Babula et al. 2012). Mammals contain 4 general metallothionein isoforms (MT1,2,3,4). The MT1 isoform has radiated in primates to 8 or 9 functional proteins (depending on classification of MT1L). Each mammalian metallothionein binds a total of 7 divalent metal ions in two clusters, the alpha and beta clusters. Though the functions of metallothioneins have not been fully elucidated, they appear to participate in detoxifying heavy metals (reviewed in Sharma et al. 2013), storing and transporting zinc, and redox biochemistry. Metallothioneins interact with many other cellular proteins, with most interactions involving proteins of the central nervous system (reviewed in Atrian and Capdevila 2013). View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 5661231
Reactome-version 
Reactome version: 66
Reactome Author 
Reactome Author: May, Bruce

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Bibliography

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  1. Luo Y, Xu Y, Bao Q, Ding Z, Zhu C, Huang ZX, Tan X.; ''The molecular mechanism for human metallothionein-3 to protect against the neuronal cytotoxicity of Aβ(1-42) with Cu ions.''; PubMed
  2. Vašák M, Meloni G.; ''Chemistry and biology of mammalian metallothioneins.''; PubMed
  3. Sharma S, Rais A, Sandhu R, Nel W, Ebadi M.; ''Clinical significance of metallothioneins in cell therapy and nanomedicine.''; PubMed
  4. Garrett SH, Sens MA, Todd JH, Somji S, Sens DA.; ''Expression of MT-3 protein in the human kidney.''; PubMed
  5. Thirumoorthy N, Shyam Sunder A, Manisenthil Kumar K, Senthil Kumar M, Ganesh G, Chatterjee M.; ''A review of metallothionein isoforms and their role in pathophysiology.''; PubMed
  6. Pan PK, Zheng ZF, Lyu PC, Huang PC.; ''Why reversing the sequence of the alpha domain of human metallothionein-2 does not change its metal-binding and folding characteristics.''; PubMed
  7. Pountney DL, Dickson TC, Power JH, Vickers JC, West AJ, Gai WP.; ''Association of metallothionein-III with oligodendroglial cytoplasmic inclusions in multiple system atrophy.''; PubMed
  8. Rigby Duncan KE, Stillman MJ.; ''Evidence for noncooperative metal binding to the alpha domain of human metallothionein.''; PubMed
  9. Stillman MJ, Thomas D, Trevithick C, Guo X, Siu M.; ''Circular dichroism, kinetic and mass spectrometric studies of copper(I) and mercury(II) binding to metallothionein.''; PubMed
  10. Irvine GW, Summers KL, Stillman MJ.; ''Cysteine accessibility during As3+ metalation of the α- and β-domains of recombinant human MT1a.''; PubMed
  11. Wu Q, Li B, Wu F, Yang L, Li S, Li H, Wu D, Cui T, Tang D.; ''High level expression, efficient purification, and bioactivity of recombinant human metallothionein 3 (rhMT3) from methylotrophic yeast Pichia pastoris.''; PubMed
  12. Tío L, Villarreal L, Atrian S, Capdevila M.; ''Functional differentiation in the mammalian metallothionein gene family: metal binding features of mouse MT4 and comparison with its paralog MT1.''; PubMed
  13. Banci L, Bertini I, Ciofi-Baffoni S, Kozyreva T, Zovo K, Palumaa P.; ''Affinity gradients drive copper to cellular destinations.''; PubMed
  14. Chung RS, Howells C, Eaton ED, Shabala L, Zovo K, Palumaa P, Sillard R, Woodhouse A, Bennett WR, Ray S, Vickers JC, West AK.; ''The native copper- and zinc-binding protein metallothionein blocks copper-mediated Abeta aggregation and toxicity in rat cortical neurons.''; PubMed
  15. Atrian S, Capdevila M.; ''Metallothionein-protein interactions.''; PubMed
  16. Sutherland DE, Willans MJ, Stillman MJ.; ''Single domain metallothioneins: supermetalation of human MT 1a.''; PubMed
  17. Roschitzki B, Vasák M.; ''Redox labile site in a Zn4 cluster of Cu4,Zn4-metallothionein-3.''; PubMed
  18. Ngu TT, Stillman MJ.; ''Arsenic binding to human metallothionein.''; PubMed
  19. Jiang LJ, Vasák M, Vallee BL, Maret W.; ''Zinc transfer potentials of the alpha - and beta-clusters of metallothionein are affected by domain interactions in the whole molecule.''; PubMed
  20. Sutherland DE, Summers KL, Stillman MJ.; ''Noncooperative metalation of metallothionein 1a and its isolated domains with zinc.''; PubMed
  21. Miles AT, Hawksworth GM, Beattie JH, Rodilla V.; ''Induction, regulation, degradation, and biological significance of mammalian metallothioneins.''; PubMed
  22. Knipp M, Meloni G, Roschitzki B, Vasák M.; ''Zn7metallothionein-3 and the synaptic vesicle cycle: interaction of metallothionein-3 with the small GTPase Rab3A.''; PubMed
  23. Summers KL, Sutherland DE, Stillman MJ.; ''Single-domain metallothioneins: evidence of the onset of clustered metal binding domains in Zn-rhMT 1a.''; PubMed
  24. Rigby Duncan KE, Kirby CW, Stillman MJ.; ''Metal exchange in metallothioneins: a novel structurally significant Cd(5) species in the alpha domain of human metallothionein 1a.''; PubMed
  25. Meloni G, Vašák M.; ''Redox activity of α-synuclein-Cu is silenced by Zn₇-metallothionein-3.''; PubMed
  26. Palumaa P, Eriste E, Njunkova O, Pokras L, Jörnvall H, Sillard R.; ''Brain-specific metallothionein-3 has higher metal-binding capacity than ubiquitous metallothioneins and binds metals noncooperatively.''; PubMed
  27. Roschitzki B, Vasák M.; ''A distinct Cu(4)-thiolate cluster of human metallothionein-3 is located in the N-terminal domain.''; PubMed
  28. Meloni G, Polanski T, Braun O, Vasák M.; ''Effects of Zn(2+), Ca(2+), and Mg(2+) on the structure of Zn(7)metallothionein-3: evidence for an additional zinc binding site.''; PubMed
  29. Yang F, Zhou M, He Z, Liu X, Sun L, Sun Y, Chen Z.; ''High-yield expression in Escherichia coli of soluble human MT2A with native functions.''; PubMed
  30. Palumaa P, Tammiste I, Kruusel K, Kangur L, Jörnvall H, Sillard R.; ''Metal binding of metallothionein-3 versus metallothionein-2: lower affinity and higher plasticity.''; PubMed
  31. Eriste E, Kruusel K, Palumaa P, Jörnvall H, Sillard R.; ''Purification of recombinant human apometallothionein-3 and reconstitution with zinc.''; PubMed
  32. Pedersen JT, Hureau C, Hemmingsen L, Heegaard NH, Østergaard J, Vašák M, Faller P.; ''Rapid exchange of metal between Zn(7)-metallothionein-3 and amyloid-β peptide promotes amyloid-related structural changes.''; PubMed
  33. Meloni G, Sonois V, Delaine T, Guilloreau L, Gillet A, Teissié J, Faller P, Vasák M.; ''Metal swap between Zn7-metallothionein-3 and amyloid-beta-Cu protects against amyloid-beta toxicity.''; PubMed
  34. Meloni G, Faller P, Vasák M.; ''Redox silencing of copper in metal-linked neurodegenerative disorders: reaction of Zn7metallothionein-3 with Cu2+ ions.''; PubMed
  35. Wang H, Li H, Cai B, Huang ZX, Sun H.; ''The effect of nitric oxide on metal release from metallothionein-3: gradual unfolding of the protein.''; PubMed
  36. Maret W.; ''Redox biochemistry of mammalian metallothioneins.''; PubMed
  37. Babula P, Masarik M, Adam V, Eckschlager T, Stiborova M, Trnkova L, Skutkova H, Provaznik I, Hubalek J, Kizek R.; ''Mammalian metallothioneins: properties and functions.''; PubMed
  38. Sutherland DE, Summers KL, Stillman MJ.; ''Modeling the Zn(2+) and Cd(2+) metalation mechanism in mammalian metallothionein 1a.''; PubMed
  39. Sutherland DE, Stillman MJ.; ''Noncooperative cadmium(II) binding to human metallothionein 1a.''; PubMed

History

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CompareRevisionActionTimeUserComment
101377view11:26, 1 November 2018ReactomeTeamreactome version 66
100915view21:01, 31 October 2018ReactomeTeamreactome version 65
100456view19:36, 31 October 2018ReactomeTeamreactome version 64
100003view16:19, 31 October 2018ReactomeTeamreactome version 63
99556view14:53, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99185view12:42, 31 October 2018ReactomeTeamreactome version 62
93884view13:42, 16 August 2017ReactomeTeamreactome version 61
93452view11:24, 9 August 2017ReactomeTeamreactome version 61
87923view13:00, 25 July 2016RyanmillerOntology Term : 'classic metabolic pathway' added !
86546view09:20, 11 July 2016ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
As3+ MetaboliteCHEBI:35828 (ChEBI)
As3+MetaboliteCHEBI:35828 (ChEBI)
Cd2+ MetaboliteCHEBI:48775 (ChEBI)
Cd2+MetaboliteCHEBI:48775 (ChEBI)
Cu1+ MetaboliteCHEBI:49552 (ChEBI)
Cu1+MetaboliteCHEBI:49552 (ChEBI)
Cu2+MetaboliteCHEBI:29036 (ChEBI)
MT1A ProteinP04731 (Uniprot-TrEMBL)
MT1A:6As3+ComplexR-HSA-5661211 (Reactome)
MT1A:7Cd2+ComplexR-HSA-5661235 (Reactome)
MT1A:7Zn2+ComplexR-HSA-5661213 (Reactome)
MT1AProteinP04731 (Uniprot-TrEMBL)
MT1B ProteinP07438 (Uniprot-TrEMBL)
MT1B:7Cd2+ComplexR-HSA-5662575 (Reactome)
MT1B:7Zn2+ComplexR-HSA-5662583 (Reactome)
MT1BProteinP07438 (Uniprot-TrEMBL)
MT1E ProteinP04732 (Uniprot-TrEMBL)
MT1E:7Cd2+ComplexR-HSA-5662590 (Reactome)
MT1E:7Zn2+ComplexR-HSA-5662567 (Reactome)
MT1EProteinP04732 (Uniprot-TrEMBL)
MT1F ProteinP04733 (Uniprot-TrEMBL)
MT1F:7Cd2+ComplexR-HSA-5662561 (Reactome)
MT1F:7Zn2+ComplexR-HSA-5662578 (Reactome)
MT1FProteinP04733 (Uniprot-TrEMBL)
MT1G ProteinP13640 (Uniprot-TrEMBL)
MT1G:7Cd2+ComplexR-HSA-5662582 (Reactome)
MT1G:7Zn2+ComplexR-HSA-5662585 (Reactome)
MT1GProteinP13640 (Uniprot-TrEMBL)
MT1H ProteinP80294 (Uniprot-TrEMBL)
MT1H:7Cd2+ComplexR-HSA-5662589 (Reactome)
MT1H:7Zn2+ComplexR-HSA-5662579 (Reactome)
MT1HProteinP80294 (Uniprot-TrEMBL)
MT1M ProteinQ8N339 (Uniprot-TrEMBL)
MT1M:7Cd2+ComplexR-HSA-5662581 (Reactome)
MT1M:7Zn2+ComplexR-HSA-5662570 (Reactome)
MT1MProteinQ8N339 (Uniprot-TrEMBL)
MT1X ProteinP80297 (Uniprot-TrEMBL)
MT1X:7Cd2+ComplexR-HSA-5662568 (Reactome)
MT1X:7Zn2+ComplexR-HSA-5662591 (Reactome)
MT1XProteinP80297 (Uniprot-TrEMBL)
MT2A ProteinP02795 (Uniprot-TrEMBL)
MT2A:10Cu1+ComplexR-HSA-5662969 (Reactome)
MT2A:7Cd2+ComplexR-HSA-5662574 (Reactome)
MT2A:7Zn2+ComplexR-HSA-5662577 (Reactome)
MT2AProteinP02795 (Uniprot-TrEMBL)
MT3 ProteinP25713 (Uniprot-TrEMBL)
MT3:12Cu1+ComplexR-HSA-5662992 (Reactome)
MT3:4Zn2+:4Cu+ComplexR-HSA-5662563 (Reactome)
MT3:7Cd2+ComplexR-HSA-5662584 (Reactome)
MT3:7Zn2+ComplexR-HSA-5662573 (Reactome)
MT3ProteinP25713 (Uniprot-TrEMBL)
MT4 ProteinP47944 (Uniprot-TrEMBL)
MT4:10Cu1+ComplexR-HSA-5662637 (Reactome)
MT4:7Cd2+ComplexR-HSA-5662648 (Reactome)
MT4:7Zn2+ComplexR-HSA-5662640 (Reactome)
MT4ProteinP47944 (Uniprot-TrEMBL)
Zn2+ MetaboliteCHEBI:29105 (ChEBI)
Zn2+MetaboliteCHEBI:29105 (ChEBI)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
As3+R-HSA-5661230 (Reactome)
Cd2+R-HSA-5661219 (Reactome)
Cd2+R-HSA-5662595 (Reactome)
Cd2+R-HSA-5662596 (Reactome)
Cd2+R-HSA-5662597 (Reactome)
Cd2+R-HSA-5662599 (Reactome)
Cd2+R-HSA-5662608 (Reactome)
Cd2+R-HSA-5662610 (Reactome)
Cd2+R-HSA-5662617 (Reactome)
Cd2+R-HSA-5662620 (Reactome)
Cd2+R-HSA-5662622 (Reactome)
Cd2+R-HSA-5662649 (Reactome)
Cu1+R-HSA-5662647 (Reactome)
Cu1+R-HSA-5662986 (Reactome)
Cu1+R-HSA-5663002 (Reactome)
Cu2+R-HSA-5662613 (Reactome)
MT1A:6As3+ArrowR-HSA-5661230 (Reactome)
MT1A:7Cd2+ArrowR-HSA-5661219 (Reactome)
MT1A:7Zn2+ArrowR-HSA-5661217 (Reactome)
MT1AR-HSA-5661217 (Reactome)
MT1AR-HSA-5661219 (Reactome)
MT1AR-HSA-5661230 (Reactome)
MT1B:7Cd2+ArrowR-HSA-5662610 (Reactome)
MT1B:7Zn2+ArrowR-HSA-5662603 (Reactome)
MT1BR-HSA-5662603 (Reactome)
MT1BR-HSA-5662610 (Reactome)
MT1E:7Cd2+ArrowR-HSA-5662595 (Reactome)
MT1E:7Zn2+ArrowR-HSA-5662614 (Reactome)
MT1ER-HSA-5662595 (Reactome)
MT1ER-HSA-5662614 (Reactome)
MT1F:7Cd2+ArrowR-HSA-5662596 (Reactome)
MT1F:7Zn2+ArrowR-HSA-5662623 (Reactome)
MT1FR-HSA-5662596 (Reactome)
MT1FR-HSA-5662623 (Reactome)
MT1G:7Cd2+ArrowR-HSA-5662617 (Reactome)
MT1G:7Zn2+ArrowR-HSA-5662618 (Reactome)
MT1GR-HSA-5662617 (Reactome)
MT1GR-HSA-5662618 (Reactome)
MT1H:7Cd2+ArrowR-HSA-5662597 (Reactome)
MT1H:7Zn2+ArrowR-HSA-5662619 (Reactome)
MT1HR-HSA-5662597 (Reactome)
MT1HR-HSA-5662619 (Reactome)
MT1M:7Cd2+ArrowR-HSA-5662599 (Reactome)
MT1M:7Zn2+ArrowR-HSA-5662621 (Reactome)
MT1MR-HSA-5662599 (Reactome)
MT1MR-HSA-5662621 (Reactome)
MT1X:7Cd2+ArrowR-HSA-5662622 (Reactome)
MT1X:7Zn2+ArrowR-HSA-5662615 (Reactome)
MT1XR-HSA-5662615 (Reactome)
MT1XR-HSA-5662622 (Reactome)
MT2A:10Cu1+ArrowR-HSA-5662986 (Reactome)
MT2A:7Cd2+ArrowR-HSA-5662608 (Reactome)
MT2A:7Zn2+ArrowR-HSA-5662598 (Reactome)
MT2AR-HSA-5662598 (Reactome)
MT2AR-HSA-5662608 (Reactome)
MT2AR-HSA-5662986 (Reactome)
MT3:12Cu1+ArrowR-HSA-5663002 (Reactome)
MT3:4Zn2+:4Cu+ArrowR-HSA-5662613 (Reactome)
MT3:7Cd2+ArrowR-HSA-5662620 (Reactome)
MT3:7Zn2+ArrowR-HSA-5662606 (Reactome)
MT3:7Zn2+R-HSA-5662613 (Reactome)
MT3R-HSA-5662606 (Reactome)
MT3R-HSA-5662620 (Reactome)
MT3R-HSA-5663002 (Reactome)
MT4:10Cu1+ArrowR-HSA-5662647 (Reactome)
MT4:7Cd2+ArrowR-HSA-5662649 (Reactome)
MT4:7Zn2+ArrowR-HSA-5662653 (Reactome)
MT4R-HSA-5662647 (Reactome)
MT4R-HSA-5662649 (Reactome)
MT4R-HSA-5662653 (Reactome)
R-HSA-5661217 (Reactome) The MT1A metallothionein binds 7 zinc(II) atoms, 3 at the N-terminal beta domain and 4 at the C-terminal alpha domain (Sunderland et al. 2012). Binding is non-cooperative (Sunderland et al. 2012) and occurs via thiolate bonds between zinc and cysteine residues of the protein. MT1A binds 5 atoms of zinc before clustering of the zinc occurs (Summers et al. 2013). The 2 remaining zinc atoms bind MT1A with significantly less affinity (Summers et al. 2013).
R-HSA-5661219 (Reactome) MT1A binds 7 atoms of cadmium(II), 3 atoms at the N-terminal beta domain and 4 atoms at the C-terminal alpha domain (Rigby Duncan et al. 2008, Sunderland and Stillman 2008, Sutherland et al. 2012). A fifth cadmium atom bound to the alpha domain may be an intermediate formed during metal exchange (Rigby Duncan et al. 2008). Binding of cadmium is non-cooperative (Rigby Duncan and Stillman 2007, Sunderland and Stillman 2008). As inferred from mouse Mt1, MT1A may show less preference for zinc compared with cadmium and may therefore serve more than other metallothionein isoforms to detoxify cadmium.
R-HSA-5661230 (Reactome) Metallothionein MT1A binds 6 atoms of arsenic(III), 3 atoms at the N-terminal beta domain and 3 atoms at the C-terminal alpha domain (Ngu and Stillman 2006, Irvine et al. 2013). Each arsenic atom binds 3 cysteine thiols (Ngu and Stillman 2006, Irvine et al. 2013).
R-HSA-5662595 (Reactome) As inferred from MT1A, the metallothionein MT1E binds 7 atoms of cadmium(II) non-cooperatively.
R-HSA-5662596 (Reactome) As inferred from MT1A, the metallothionein MT1F binds 7 atoms of cadmium(II) non-cooperatively.
R-HSA-5662597 (Reactome) As inferred from MT1A, the metallothionein MT1H binds 7 atoms of cadmium(II) non-cooperatively.
R-HSA-5662598 (Reactome) The metallothionein MT2A binds 7 atoms of zinc(II) in two clusters, one at the N-terminal beta domain and one at the C-terminal alpha domain (Stillman et al. 2000, Yang et al. 2007). The cluster at the alpha domain is more stable than the cluster at the beta domain, making the beta domain a better zinc donor (Jiang et al. 2000). Each cluster assembles independently (Jiang et al. 2000).
R-HSA-5662599 (Reactome) As inferred from MT1A, the metallothionein MT1M binds 7 atoms of cadmium(II) non-cooperatively.
R-HSA-5662603 (Reactome) As inferred from MT1A, the metallothionein MT1B binds 7 atoms of zinc(II) non-cooperatively.
R-HSA-5662606 (Reactome) The metallothionein MT3 binds 7 zinc(II) atoms in 2 clusters, one cluster of 4 atoms at the C-terminal alpha domain and one cluster of 3 atoms at the N-terminal beta domain (Eriste et al. 2003, Knipp et al. 2005, Meloni et al. 2007, Meloni et al. 2008, Meloni et al. 2009, Wu et al. 2014). Though MT3 has a lower overall affinity for zinc than MT2A does (Palumaa et al. 2005), MT3 is capable of binding an additional zinc atom with a binding constant of 100 micromolar (Eriste et al. 2003, Palumaa et al. 2005, Meloni et al. 2009). Stoichiometries up to MT3:11Zn2+ have been observed but the MT3:7Zn2+ form is more stable and predominates (Palumaa et al. 2002, Eriste et al. 2003, Palumaa et al.).
R-HSA-5662608 (Reactome) The metallothionein MT2A binds 7 atoms of cadmium(II), a cluster of 4 atoms at the alpha domain at the C-terminus and a cluster of 3 atoms at the beta domain at the N-terminus (Pan et al. 1999).
R-HSA-5662610 (Reactome) As inferred from MT1A, the metallothionein MT1B binds 7 atoms of cadmium(II) non-cooperatively.
R-HSA-5662613 (Reactome) MT3:7Zn2+ releases 3 zinc ions and binds 4 copper ions at the N-terminal beta domain (Roschitszi et al. 2003, Meloni et al. 2007, Meloni et al. 2008). By this mechanism MT3 is able to scavenge free copper ions and swap metal with an aggregated amyloid beta:copper(II) complex and a alpha-synuclein:copper(II) complex and thereby abolish production of reactive oxygen species (Meloni et al. 2008, Meloni and Vasak 2011, Pedersen et al. 2012, Luo et al. 2013). The copper ions are divalent (copper(II), Cu2+) before binding but univalent (copper(I), Cu1+) after binding (Meloni et al. 2008).
R-HSA-5662614 (Reactome) As inferred from MT1A, the metallothionein MT1E binds 7 atoms of zinc(II) non-cooperatively.
R-HSA-5662615 (Reactome) As inferred from MT1A, the metallothionein MT1X binds 7 atoms of zinc(II) non-cooperatively.
R-HSA-5662617 (Reactome) As inferred from MT1A, the metallothionein MT1G binds 7 atoms of cadmium(II) non-cooperatively.
R-HSA-5662618 (Reactome) As inferred from MT1A, the metallothionein MT1G binds 7 atoms of zinc(II) non-cooperatively.
R-HSA-5662619 (Reactome) As inferred from MT1A, the metallothionein MT1H binds 7 atoms of zinc(II) non-cooperatively.
R-HSA-5662620 (Reactome) The metallothionein binds 7 atoms of cadmium(II) in 2 clusters, 4 atoms at the C-terminal alpha domain and 3 atoms at the N-terminal beta domain (Palumaa et al. 2002, Palumaa et al. 2005, Wu et al. 2014). MT3 binds cadmium with a lower affinity than MT2A does (Palumaa et al. 2005). MT3 can bind more than 7 cadmium atoms, however the MT3:7Cd2+ complex is most prevalent (Palumaa et al. 2002, Palumaa et al. 2005). Exposure of MT3:7Cd2+ to nitric oxide causes release of cadmium (Wang et al. 2008).
R-HSA-5662621 (Reactome) As inferred from MT1A, the metallothionein MT1M binds 7 atoms of zinc(II) non-cooperatively.
R-HSA-5662622 (Reactome) As inferred from MT1A, metallothionein MT1X binds 7 atoms of cadmium(II) non-cooperatively.
R-HSA-5662623 (Reactome) As inferred from MT1A, the metallothionein MT1F binds 7 atoms of zinc(II) non-cooperatively.
R-HSA-5662647 (Reactome) As inferred from the mouse homolog, MT4 binds 10 atoms of copper(I).
R-HSA-5662649 (Reactome) As inferred from the mouse homolog, MT4 binds 7 atoms of cadmium(II).
R-HSA-5662653 (Reactome) As inferred from the mouse homolog, MT4 binds 7 atoms of zinc(II).
R-HSA-5662986 (Reactome) The metallothionein MT2A binds 10 atoms of copper(I). Complexes with up to 12 atoms of Cu+ are observed, however the predominant form appears to be MT2A:10Cu+ (Banci et al. 2010, Chung et al. 2010). Metallothioneins and CuZn-SOD have the highest affinities of cellular proteins for copper(I), but metallothioneins are incapable of removing copper from other cellular enzymes (Banci et al. 2010).
R-HSA-5663002 (Reactome) The metallothionein MT3 is able to bind 12 copper(I) atoms when fully saturated (Roschitzki et al. 2002). Initially, 4 copper(I) atoms bind to each of the alpha and beta domains followed by the binding of 4 more copper(I) atoms. As inferred from the mouse homolog, MT3 exhibits a Cu-thionein character stronger than that of the MT1 and MT2 isoforms and it displays a high capacity to bind Cu+ provided that this occurs in a non-oxidative milieux.
Zn2+ArrowR-HSA-5662613 (Reactome)
Zn2+R-HSA-5661217 (Reactome)
Zn2+R-HSA-5662598 (Reactome)
Zn2+R-HSA-5662603 (Reactome)
Zn2+R-HSA-5662606 (Reactome)
Zn2+R-HSA-5662614 (Reactome)
Zn2+R-HSA-5662615 (Reactome)
Zn2+R-HSA-5662618 (Reactome)
Zn2+R-HSA-5662619 (Reactome)
Zn2+R-HSA-5662621 (Reactome)
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