Zinc homeostasis (Homo sapiens)

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2, 3MTsMREsSynaptic vesicles(neurons)Zinc efflux in the extracellular space or into intracellular compartments by ZnT (1-10) transporters belonging to SLC30A family.4, 5Zinc influx into the cytoplasm by ZIP (1-14) transporters, belonging to SLC39A family.8MTF11, 9, 11SLC30A1SLC39A13SLC39A9SLC39A10SLC39A12SLC39A8SLC39A5SLC39A4SLC39A3SLC39A2SLC39A1MT1ASLC30A1MT1BMT1EMT1FMT1GMT1HMT1MMT1XMT2AMT3MT1LMT4SLC39A7SLC39A11SLC39A9SLC30A96SLC30A4SLC39A8SLC30A10SLC30A3SLC30A4SLC30A2SLC39A14Zn++Zn++Zn++Zn++Zn++Early EndosomesEndosomes / LysosomesInsulin granules(pancreatic beta cells)Vesicles secretory(mammary epithelial cells)MTsZn++Zn++Zn++Zn++Zn++Zn++Zn++Zn++Zn++Zn++Zn++Zn++SLC30A5Zn++Zn++Zn++Zn++Zn++Zn++Zn++Zn++Zn++Zn++Zn++Zn++Zn++Zn++Zn++Zn++Zn++Zn++Zn++Zn++Zn++Zn++Zn++SLC30A2Zn++SLC30A7SLC30A4SLC30A6SLC39A6SLC30A8


Description

Zinc is a transition metal and catalytic cofactor involved in many biological processes such as proliferation, development and differentiation, regulation of DNA synthesis, genomic stability, cell activation, RNA transcription, immune function. Zinc homeostasis in cells is ensured by various protein families including zinc transporters, zinc-binding proteins (Metallothioneins, MTs), transcription factors (MTF1-2). ZnT (1-10) transporters are responsible of zinc efflux and are assigned to the SLC30A family while ZIP (1-14) transporters are responsible for the influx of zinc into the cytoplasm and are assigned to the SLC39A family. Zn2+ enters into the cell by the ZIP transporters, and once inside the cell is available to bind metalloproteins (MT) which deliver to ZnT, or the zinc can bind to directly ZnTs and then deliver in the organelles / vesicles or lead outside the cell. Elevated zinc levels have been reported in different tumour tissue, such as breast and lung cancer

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Bibliography

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  1. ''Cellular zinc sensors: MTF-1 regulation of gene expression''; , 2001 PubMed Europe PMC
  2. Miles AT, Hawksworth GM, Beattie JH, Rodilla V; ''Induction, regulation, degradation, and biological significance of mammalian metallothioneins.''; Crit Rev Biochem Mol Biol, 2000 PubMed Europe PMC
  3. Gumulec J, Raudenska M, Adam V, Kizek R, Masarik M; ''Metallothionein - immunohistochemical cancer biomarker: a meta-analysis.''; PLoS One, 2014 PubMed Europe PMC
  4. Huang L, Tepaamorndech S.; ''The SLC30 family of zinc transporters - a review of current understanding of their biological and pathophysiological roles''; , 2013 PubMed Europe PMC
  5. Kambe T, Hashimoto A, Fujimoto S.; ''Current understanding of ZIP and ZnT zinc transporters in human health and diseases.''; Cell Mol Life Sci. , 2014 PubMed Europe PMC
  6. ''Role of GAC63 in transcriptional activation mediated by beta-catenin.''; Chen YH; Yang CK; Xia M; Ou CY; Stallcup MR, 2007 PubMed Europe PMC
  7. Gumulec J, Raudenska M, Adam V, Kizek R, Masarik M.; ''Metallothionein - immunohistochemical cancer biomarker: a meta-analysis.''; PLoS One. 2014 Jan 8;9(1):e85346, 2014 PubMed Europe PMC
  8. Jeong J, Eide DJ; ''The SLC39 family of zinc transporters''; Mol Aspects Med. 2013, 2013 PubMed Europe PMC
  9. ''A conserved cysteine cluster, essential for transcriptional activity, mediates homodimerization of human metal-responsive transcription factor-1 (MTF-1).''; , 2012 PubMed Europe PMC
  10. Miles AT, Hawksworth GM, Beattie JH, Rodilla V.; ''Induction, regulation, degradation, and biological significance of mammalian metallothioneins''; Crit Rev Biochem Mol Biol. 2000;35(1):35-70., 2000 PubMed Europe PMC
  11. ''The taste of heavy metals: gene regulation by MTF-1''; , 2012 PubMed Europe PMC

History

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CompareRevisionActionTimeUserComment
101992view19:18, 22 November 2018EgonwRemoved whitespace in PubMed identifiers.
86971view14:28, 15 July 2016MkutmonOntology Term : 'homeostasis pathway' added !
84285view08:57, 3 February 2016GIOVANNA VALENTIconnected interaction
84284view08:54, 3 February 2016GIOVANNA VALENTIconnected interaction
84283view08:30, 3 February 2016GIOVANNA VALENTISpecify description
84282view08:26, 3 February 2016GIOVANNA VALENTIconnected interaction
84281view08:25, 3 February 2016GIOVANNA VALENTIconnected interaction
84280view08:23, 3 February 2016GIOVANNA VALENTIPeriodical save, work in progress
84279view08:13, 3 February 2016GIOVANNA VALENTIPeriodical save, work in progress
84278view21:45, 2 February 2016Khanspersupdated transcription/translation
84277view21:44, 2 February 2016Khanspersreplaced unconnected interactions with graphical lines
84274view20:57, 2 February 2016KhanspersChanged Zinc++ to Zn++
84273view19:27, 2 February 2016Khansperssimplify layout
84266view12:59, 2 February 2016GIOVANNA VALENTIconnected interaction
84265view12:59, 2 February 2016GIOVANNA VALENTIconnected interaction
84264view12:56, 2 February 2016GIOVANNA VALENTIReverted to version '12:54, 2 February 2016' by GIOVANNA VALENTI
84263view12:54, 2 February 2016GIOVANNA VALENTISpecify description
84262view12:54, 2 February 2016GIOVANNA VALENTISpecify description
84261view12:52, 2 February 2016GIOVANNA VALENTISpecify description
84260view12:51, 2 February 2016GIOVANNA VALENTISpecify description
84259view12:46, 2 February 2016GIOVANNA VALENTIPeriodical save, work in progress
84258view12:36, 2 February 2016GIOVANNA VALENTIPeriodical save, work in progress
84257view12:26, 2 February 2016GIOVANNA VALENTIPeriodical save, work in progress
84256view12:18, 2 February 2016GIOVANNA VALENTIconnected interaction
84255view12:15, 2 February 2016GIOVANNA VALENTIPeriodical save, work in progress
84254view12:05, 2 February 2016GIOVANNA VALENTIPeriodical save, work in progress
84253view11:55, 2 February 2016GIOVANNA VALENTIPeriodical save, work in progress
84252view11:45, 2 February 2016GIOVANNA VALENTIPeriodical save, work in progress
84251view11:35, 2 February 2016GIOVANNA VALENTIPeriodical save, work in progress
84250view10:17, 2 February 2016GIOVANNA VALENTIconnected interaction
84249view10:09, 2 February 2016GIOVANNA VALENTIPeriodical save, work in progress
84248view09:59, 2 February 2016GIOVANNA VALENTIPeriodical save, work in progress
84247view09:48, 2 February 2016GIOVANNA VALENTIPeriodical save, work in progress
84246view09:38, 2 February 2016GIOVANNA VALENTIPeriodical save, work in progress
84245view09:28, 2 February 2016GIOVANNA VALENTIPeriodical save, work in progress
84244view09:27, 2 February 2016GIOVANNA VALENTIconnected interaction
84243view09:18, 2 February 2016GIOVANNA VALENTIPeriodical save, work in progress
84242view09:08, 2 February 2016GIOVANNA VALENTIPeriodical save, work in progress
84241view08:58, 2 February 2016GIOVANNA VALENTIPeriodical save, work in progress
84240view08:50, 2 February 2016GIOVANNA VALENTIconnected interaction
84239view08:48, 2 February 2016GIOVANNA VALENTIPeriodical save, work in progress
84238view08:38, 2 February 2016GIOVANNA VALENTISpecify description
84149view07:25, 20 January 2016GIOVANNA VALENTISpecify description
84148view20:27, 19 January 2016Khanspersconnected interaction
84147view20:25, 19 January 2016Khansperschanged one final unannotated data node to label
84146view20:03, 19 January 2016Khanspersconnected interactions, switched unannotated data nodes to labels, added Zn metabolites
84122view16:35, 17 January 2016GIOVANNA VALENTIPeriodical save, work in progress
84121view16:29, 17 January 2016GIOVANNA VALENTIGene ID, Data Node properties
84120view16:15, 17 January 2016GIOVANNA VALENTIPeriodical save, work in progress
84119view16:05, 17 January 2016GIOVANNA VALENTIPeriodical save, work in progress

External references

DataNodes

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NameTypeDatabase referenceComment
MT1AGeneProduct4489 (Entrez Gene) zinc is chelated by cytoplasmic proteins, such as MTs
MT1BGeneProduct4490 (Entrez Gene) zinc is chelated by cytoplasmic proteins, such as MTs
MT1EGeneProduct4493 (Entrez Gene) zinc is chelated by cytoplasmic proteins, such as MTs
MT1FGeneProduct4494 (Entrez Gene) zinc is chelated by cytoplasmic proteins, such as MTs
MT1GGeneProduct4495 (Entrez Gene) zinc is chelated by cytoplasmic proteins, such as MTs
MT1HGeneProduct4496 (Entrez Gene) zinc is chelated by cytoplasmic proteins, such as MTs
MT1LGeneProduct4500 (Entrez Gene) zinc is chelated by cytoplasmic proteins, such as MTs
MT1MGeneProduct4499 (Entrez Gene) zinc is chelated by cytoplasmic proteins, such as MTs
MT1XGeneProduct4501 (Entrez Gene) zinc is chelated by cytoplasmic proteins, such as MTs
MT2AGeneProduct4502 (Entrez Gene) zinc is chelated by cytoplasmic proteins, such as MTs
MT3GeneProduct4504 (Entrez Gene) zinc is chelated by cytoplasmic proteins, such as MTs
MT4GeneProduct84560 (Entrez Gene) zinc is chelated by cytoplasmic proteins, such as MTs
MTF1GeneProductENSG00000188786 (Ensembl) Metal-response element-binding transcription factor-1 (MTF-1) functions as a cellular zinc sensor which coordinates the expression of genes involved in zinc homeostasis.
SLC30A10GeneProduct55532 (Entrez Gene)
SLC30A1GeneProduct7779 (Entrez Gene) SLC30A1 (ZnT1) transporter is responsible of zinc efflux
SLC30A2GeneProduct7780 (Entrez Gene)
SLC30A3GeneProduct7781 (Entrez Gene)
SLC30A4GeneProduct7782 (Entrez Gene)
SLC30A5GeneProduct64924 (Entrez Gene)
SLC30A6GeneProduct55676 (Entrez Gene)
SLC30A7GeneProduct148867 (Entrez Gene)
SLC30A8GeneProduct169026 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/169026
SLC30A9GeneProduct10463 (Entrez Gene)
SLC39A10GeneProduct57181 (Entrez Gene)
SLC39A11GeneProduct201266 (Entrez Gene)
SLC39A12GeneProduct221074 (Entrez Gene)
SLC39A1GeneProduct27173 (Entrez Gene) SLC39A1 (ZIP1) transporter is responsible for the influx of zinc into the cytoplasm
SLC39A13GeneProduct91252 (Entrez Gene)
SLC39A14GeneProduct23516 (Entrez Gene)
SLC39A2GeneProduct29986 (Entrez Gene)
SLC39A3GeneProduct29985 (Entrez Gene)
SLC39A4GeneProduct55630 (Entrez Gene)
SLC39A5GeneProduct283375 (Entrez Gene)
SLC39A6GeneProduct25800 (Entrez Gene)
SLC39A7GeneProduct7922 (Entrez Gene)
SLC39A8GeneProduct64116 (Entrez Gene)
SLC39A9GeneProduct55334 (Entrez Gene)
Zn++MetaboliteHMDB01303 (HMDB)

Annotated Interactions

No annotated interactions

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