Zinc homeostasis (Homo sapiens)
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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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- 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
- Jeong J, Eide DJ; ''The SLC39 family of zinc transporters''; Mol Aspects Med. 2013, 2013 PubMed Europe PMC Scholia
- Gumulec J, Raudenska M, Adam V, Kizek R, Masarik M; ''Metallothionein - immunohistochemical cancer biomarker: a meta-analysis.''; PLoS One, 2014 PubMed Europe PMC Scholia
- ''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
- 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
- ''Cellular zinc sensors: MTF-1 regulation of gene expression''; , 2001 PubMed Europe PMC Scholia
- 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
- 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
- ''The taste of heavy metals: gene regulation by MTF-1''; , 2012 PubMed Europe PMC Scholia
- 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
- ''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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External references
DataNodes
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Name | Type | Database reference | Comment |
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MT1A | GeneProduct | 4489 (Entrez Gene) | zinc is chelated by cytoplasmic proteins, such as MTs |
MT1B | GeneProduct | 4490 (Entrez Gene) | zinc is chelated by cytoplasmic proteins, such as MTs |
MT1E | GeneProduct | 4493 (Entrez Gene) | zinc is chelated by cytoplasmic proteins, such as MTs |
MT1F | GeneProduct | 4494 (Entrez Gene) | zinc is chelated by cytoplasmic proteins, such as MTs |
MT1G | GeneProduct | 4495 (Entrez Gene) | zinc is chelated by cytoplasmic proteins, such as MTs |
MT1H | GeneProduct | 4496 (Entrez Gene) | zinc is chelated by cytoplasmic proteins, such as MTs |
MT1L | GeneProduct | 4500 (Entrez Gene) | zinc is chelated by cytoplasmic proteins, such as MTs |
MT1M | GeneProduct | 4499 (Entrez Gene) | zinc is chelated by cytoplasmic proteins, such as MTs |
MT1X | GeneProduct | 4501 (Entrez Gene) | zinc is chelated by cytoplasmic proteins, such as MTs |
MT2A | GeneProduct | 4502 (Entrez Gene) | zinc is chelated by cytoplasmic proteins, such as MTs |
MT3 | GeneProduct | 4504 (Entrez Gene) | zinc is chelated by cytoplasmic proteins, such as MTs |
MT4 | GeneProduct | 84560 (Entrez Gene) | zinc is chelated by cytoplasmic proteins, such as MTs |
MTF1 | GeneProduct | ENSG00000188786 (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. |
SLC30A10 | GeneProduct | 55532 (Entrez Gene) | |
SLC30A1 | GeneProduct | 7779 (Entrez Gene) | SLC30A1 (ZnT1) transporter is responsible of zinc efflux |
SLC30A2 | GeneProduct | 7780 (Entrez Gene) | |
SLC30A3 | GeneProduct | 7781 (Entrez Gene) | |
SLC30A4 | GeneProduct | 7782 (Entrez Gene) | |
SLC30A5 | GeneProduct | 64924 (Entrez Gene) | |
SLC30A6 | GeneProduct | 55676 (Entrez Gene) | |
SLC30A7 | GeneProduct | 148867 (Entrez Gene) | |
SLC30A8 | GeneProduct | 169026 (Entrez Gene) | http://www.ncbi.nlm.nih.gov/gene/169026 |
SLC30A9 | GeneProduct | 10463 (Entrez Gene) | |
SLC39A10 | GeneProduct | 57181 (Entrez Gene) | |
SLC39A11 | GeneProduct | 201266 (Entrez Gene) | |
SLC39A12 | GeneProduct | 221074 (Entrez Gene) | |
SLC39A1 | GeneProduct | 27173 (Entrez Gene) | SLC39A1 (ZIP1) transporter is responsible for the influx of zinc into the cytoplasm |
SLC39A13 | GeneProduct | 91252 (Entrez Gene) | |
SLC39A14 | GeneProduct | 23516 (Entrez Gene) | |
SLC39A2 | GeneProduct | 29986 (Entrez Gene) | |
SLC39A3 | GeneProduct | 29985 (Entrez Gene) | |
SLC39A4 | GeneProduct | 55630 (Entrez Gene) | |
SLC39A5 | GeneProduct | 283375 (Entrez Gene) | |
SLC39A6 | GeneProduct | 25800 (Entrez Gene) | |
SLC39A7 | GeneProduct | 7922 (Entrez Gene) | |
SLC39A8 | GeneProduct | 64116 (Entrez Gene) | |
SLC39A9 | GeneProduct | 55334 (Entrez Gene) | |
Zn++ | Metabolite | HMDB01303 (HMDB) |
Annotated Interactions
No annotated interactions