MTF1 activates gene expression (Homo sapiens)

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1-3, 6-8, 114, 123, 512endoplasmic reticulum lumencytosolnucleoplasmendosomeMTF1 Zn2+ MTF1 CSRP1 gene SNCBSNCB geneMTF1dimer:12Zn2+:CSRP1geneSNCB gene CSRP1 geneMTF1 dimer:12Zn2+Zn2+ CSRP1Zn2+ MTF1dimer:12Zn2+:SNCBgeneMTF1 91012


Description

The MTF1:zinc complex in the nucleus binds Metal Response Elements (MREs), DNA containing the core consensus sequence 5'-TGCRCNC-3', and activates or represses transcription depending on the context of the MRE (reviewed in Laity and Andrews 2007, Jackson et al. 2008, Gunther et al. 2012, Grzywacz et al. 2015). The 6 zinc fingers of each MTF1 monomer have different affinities for zinc and evidence from the mouse homolog indicates that different concentrations of zinc, and hence different metal loads in MTF1, activate different subsets of target genes (Wang et al. 2004, Dong et al. 2015). Genes activated by MTF1 include those encoding metallothioneins, zinc transporters, and stress-response proteins (Hardyman et al. 2016). View original pathway at Reactome.

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Reactome-Converter 
Pathway is converted from Reactome ID: 5660489
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Reactome version: 75
Reactome Author 
Reactome Author: May, Bruce

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Bibliography

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  1. Grzywacz A, Gdula-Argasińska J, Muszyńska B, Tyszka-Czochara M, Librowski T, Opoka W.; ''Metal responsive transcription factor 1 (MTF-1) regulates zinc dependent cellular processes at the molecular level.''; PubMed Europe PMC Scholia
  2. Laity JH, Andrews GK.; ''Understanding the mechanisms of zinc-sensing by metal-response element binding transcription factor-1 (MTF-1).''; PubMed Europe PMC Scholia
  3. Hardyman JE, Tyson J, Jackson KA, Aldridge C, Cockell SJ, Wakeling LA, Valentine RA, Ford D.; ''Zinc sensing by metal-responsive transcription factor 1 (MTF1) controls metallothionein and ZnT1 expression to buffer the sensitivity of the transcriptome response to zinc.''; PubMed Europe PMC Scholia
  4. Lavedan C, Leroy E, Torres R, Dehejia A, Dutra A, Buchholtz S, Nussbaum RL, Polymeropoulos MH.; ''Genomic organization and expression of the human beta-synuclein gene (SNCB).''; PubMed Europe PMC Scholia
  5. Wang X, Lee G, Liebhaber SA, Cooke NE.; ''Human cysteine-rich protein. A member of the LIM/double-finger family displaying coordinate serum induction with c-myc.''; PubMed Europe PMC Scholia
  6. Günther V, Lindert U, Schaffner W.; ''The taste of heavy metals: gene regulation by MTF-1.''; PubMed Europe PMC Scholia
  7. Wang Y, Lorenzi I, Georgiev O, Schaffner W.; ''Metal-responsive transcription factor-1 (MTF-1) selects different types of metal response elements at low vs. high zinc concentration.''; PubMed Europe PMC Scholia
  8. Dong G, Chen H, Qi M, Dou Y, Wang Q.; ''Balance between metallothionein and metal response element binding transcription factor 1 is mediated by zinc ions (review).''; PubMed Europe PMC Scholia
  9. Günther V, Davis AM, Georgiev O, Schaffner W.; ''A conserved cysteine cluster, essential for transcriptional activity, mediates homodimerization of human metal-responsive transcription factor-1 (MTF-1).''; PubMed Europe PMC Scholia
  10. Jakes R, Spillantini MG, Goedert M.; ''Identification of two distinct synucleins from human brain.''; PubMed Europe PMC Scholia
  11. Jackson KA, Valentine RA, Coneyworth LJ, Mathers JC, Ford D.; ''Mechanisms of mammalian zinc-regulated gene expression.''; PubMed Europe PMC Scholia
  12. McHugh PC, Wright JA, Brown DR.; ''Transcriptional regulation of the beta-synuclein 5'-promoter metal response element by metal transcription factor-1.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114838view16:34, 25 January 2021ReactomeTeamReactome version 75
113284view11:35, 2 November 2020ReactomeTeamReactome version 74
112495view15:45, 9 October 2020ReactomeTeamReactome version 73
101407view11:29, 1 November 2018ReactomeTeamreactome version 66
100945view21:05, 31 October 2018ReactomeTeamreactome version 65
100482view19:39, 31 October 2018ReactomeTeamreactome version 64
100027view16:23, 31 October 2018ReactomeTeamreactome version 63
99580view14:55, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99202view12:43, 31 October 2018ReactomeTeamreactome version 62
93263view11:18, 9 August 2017ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
CSRP1 gene ProteinENSG00000159176 (Ensembl)
CSRP1 geneGeneProductENSG00000159176 (Ensembl)
CSRP1ProteinP21291 (Uniprot-TrEMBL)
MTF1

dimer:12Zn2+:CSRP1

gene
ComplexR-HSA-5660435 (Reactome)
MTF1

dimer:12Zn2+:SNCB

gene
ComplexR-HSA-5660451 (Reactome)
MTF1 ProteinQ14872 (Uniprot-TrEMBL)
MTF1 dimer:12Zn2+ComplexR-HSA-5660456 (Reactome)
SNCB gene ProteinENSG00000074317 (Ensembl)
SNCB geneGeneProductENSG00000074317 (Ensembl)
SNCBProteinQ16143 (Uniprot-TrEMBL)
Zn2+ MetaboliteCHEBI:29105 (ChEBI)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
CSRP1 geneR-HSA-5660503 (Reactome)
CSRP1 geneR-HSA-5660514 (Reactome)
CSRP1ArrowR-HSA-5660503 (Reactome)
MTF1

dimer:12Zn2+:CSRP1

gene
ArrowR-HSA-5660503 (Reactome)
MTF1

dimer:12Zn2+:CSRP1

gene
ArrowR-HSA-5660514 (Reactome)
MTF1

dimer:12Zn2+:SNCB

gene
ArrowR-HSA-5660479 (Reactome)
MTF1

dimer:12Zn2+:SNCB

gene
ArrowR-HSA-5660530 (Reactome)
MTF1 dimer:12Zn2+R-HSA-5660479 (Reactome)
MTF1 dimer:12Zn2+R-HSA-5660514 (Reactome)
R-HSA-5660479 (Reactome) The MTF1:zinc complex binds a metal response element in the promoter of the beta-synuclein (SNCB) gene and activates transcription in response to zinc (McHugh et al. 2011).
R-HSA-5660503 (Reactome) The CSRP1 gene is transcribed to yield mRNA which is translated to yield protein. Expression of CSRP1 is activated by zinc via MTF1 (Hardyman et al. 2016). As inferred from the mouse homolog, expression of CSRP1 is activated by cadmium via MTF1.
R-HSA-5660514 (Reactome) As inferred from the mouse homolog, the promoter of the CSRP1 gene contains 3 consensus metal response elements, at least one of which binds MTF1. Expression of CSRP1 is activated by cadmium via MTF1.
R-HSA-5660530 (Reactome) The SNCB (beta-synuclein) gene is transcribed to yield mRNA which is translated to yield protein (Lavedan et al. 1998). Transcription of SNCB is up-regulated by copper via a metal response binding element in the 5' promoter that binds MTF1 (McHugh et al. 2011).
SNCB geneR-HSA-5660479 (Reactome)
SNCB geneR-HSA-5660530 (Reactome)
SNCBArrowR-HSA-5660530 (Reactome)
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