Zinc homeostasis (Homo sapiens)

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MTs10, 11MTsSynaptic vesicles (neurons)MREsZinc efflux in the extracellular space or into intracellular compartments by ZnT (1-10) transporters belonging to SLC30A family.1, 6Zinc influx into the cytoplasm by ZIP (1-14) transporters, belonging to SLC39A family.5Zinc ++MTF12, 4, 8SLC30A1SLC39A13SLC39A9SLC39A10SLC39A12SLC39A8SLC39A6SLC39A5SLC39A4SLC39A3SLC39A2SLC39A1MT1ASLC30A1SLC30A6SLC30A7SLC30A4MT1BMT1EMT1FMT1GMT1HMT1MMT1XMT2AMT3MT1LMT4SLC39A7SLC39A11SLC39A9SLC30A97SLC30A2SLC30A4SLC39A8SLC30A10SLC30A3SLC30A8SLC30A5SLC30A4SLC30A2SLC39A14Zinc ++Zinc ++Zinc ++Zinc ++Zinc ++Zinc ++Early EndosomesEndosomes / LysosomesInsulin granules(pancreatic beta cells)Vesicles secretory(mammary epithelial cells)


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. 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 Scholia
  2. Jeong J, Eide DJ; ''The SLC39 family of zinc transporters''; Mol Aspects Med. 2013, 2013 PubMed Europe PMC Scholia
  3. Gumulec J, Raudenska M, Adam V, Kizek R, Masarik M; ''Metallothionein - immunohistochemical cancer biomarker: a meta-analysis.''; PLoS One, 2014 PubMed Europe PMC Scholia
  4. ''Role of GAC63 in transcriptional activation mediated by beta-catenin.''; Chen YH; Yang CK; Xia M; Ou CY; Stallcup MR, 2007 PubMed Europe PMC Scholia
  5. 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 Scholia
  6. ''Cellular zinc sensors: MTF-1 regulation of gene expression''; , 2001 PubMed Europe PMC Scholia
  7. 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 Scholia
  8. 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 Scholia
  9. ''The taste of heavy metals: gene regulation by MTF-1''; , 2012 PubMed Europe PMC Scholia
  10. 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 Scholia
  11. ''A conserved cysteine cluster, essential for transcriptional activity, mediates homodimerization of human metal-responsive transcription factor-1 (MTF-1).''; , 2012 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
134312view11:07, 20 July 2024EweitzFix interaction z-index graphical discrepancy between PathVisio and Kaavio / Pvjs
134311view11:03, 20 July 2024EweitzModified description
134310view10:32, 20 July 2024EweitzMitigate graphical discrepancy between PathVisio and Kaavio / Pvjs
134309view10:32, 20 July 2024EweitzMitigate graphical discrepancy between PathVisio and Kaavio / Pvjs
134308view10:31, 20 July 2024EweitzTransform Golgi graphics to mitigate discrepancy between PathVisio and Kaavio / Pvjs
134307view10:29, 20 July 2024EweitzTry new Golgi object to mitigate graphical discrepancy between PathVisio and Kaavio / Pvjs
134306view10:26, 20 July 2024EweitzMitigate graphical discrepancy between PathVisio and Kaavio / Pvjs
134305view10:25, 20 July 2024EweitzMitigate graphical discrepancy between PathVisio and Kaavio / Pvjs
134304view10:24, 20 July 2024EweitzMitigate graphical discrepancy between PathVisio and Kaavio / Pvjs
134303view10:24, 20 July 2024EweitzMitigate graphical discrepancy between PathVisio and Kaavio / Pvjs
134302view10:18, 20 July 2024EweitzEconomize layout
134280view11:37, 19 July 2024EweitzUse ChEBI identifier
134279view11:34, 19 July 2024EweitzVesicles secretory -> Secretory vesicles
134278view11:29, 19 July 2024EweitzChange Zn++ to Zn2+, matching common Ca2+
134277view10:48, 19 July 2024EweitzStandardize case
134276view10:46, 19 July 2024EweitzOntology Term : 'neuron' added !
134275view10:45, 19 July 2024EweitzOntology Term : 'type B pancreatic cell' added !
134274view10:44, 19 July 2024EweitzOntology Term : 'mammary gland epithelial cell' added !
134269view06:44, 19 July 2024EgonwRemoved a template comment
120882view15:56, 27 January 2022EgonwReplaced an old HMDB identifier with the current one
120359view06:46, 29 November 2021EgonwRemoved whitespace in the pubmed id
120272view12:50, 23 November 2021EgonwRemoved whitespace in the pubmed id
120270view12:42, 23 November 2021EgonwRemoved whitespace in the pubmed id
106738view13:22, 17 September 2019MaintBotHMDB identifier normalization
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

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.
MTsProtein
SLC30A10GeneProduct55532 (Entrez Gene)
SLC30A1GeneProduct7779 (Entrez Gene) SLC30A1 (ZnT1) transporter is responsible of zinc efflux
SLC30A2GeneProduct7780 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/169026
SLC30A3GeneProduct7781 (Entrez Gene)
SLC30A4GeneProduct7782 (Entrez Gene) http://www.ncbi.nlm.nih.gov/gene/169026
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)
Zinc ++MetaboliteHMDB01303 (HMDB)

Annotated Interactions

No annotated interactions

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