Zinc homeostasis (WP3529)
Homo sapiens
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 directly to ZnTs and then deliver in the organelles / vesicles or lead outside the cell. Elevated zinc levels have been reported in different tumor tissue, such as breast and lung cancer.
Authors
Giovanna Valenti , Trovato Angela , Egon Willighagen , Kristina Hanspers , Martina Summer-Kutmon , and Eric WeitzActivity
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Cited In
- Transcriptome Profiling of Human Follicle Dermal Papilla Cells in response to Porphyra-334 Treatment by RNA-Seq (2021).
- In silico transcriptional analysis of asymptomatic and severe COVID-19 patients reveals the susceptibility of severe patients to other comorbidities and non-viral pathological conditions (2023).
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Organisms
Homo sapiensCommunities
Annotations
Cell Type Ontology
neuron type B pancreatic cell mammary gland epithelial cellPathway Ontology
homeostasis pathwayLabel | Type | Compact URI | Comment |
---|---|---|---|
Zn2+ | Metabolite | chebi:29105 | |
MTF1 | GeneProduct | ensembl:ENSG00000188786 | 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. |
SLC30A1 | GeneProduct | ncbigene:7779 | |
SLC39A13 | GeneProduct | ncbigene:91252 | |
SLC39A9 | GeneProduct | ncbigene:55334 | |
SLC39A10 | GeneProduct | ncbigene:57181 | |
SLC39A12 | GeneProduct | ncbigene:221074 | |
SLC39A8 | GeneProduct | ncbigene:64116 | |
SLC39A5 | GeneProduct | ncbigene:283375 | |
SLC39A4 | GeneProduct | ncbigene:55630 | |
SLC39A3 | GeneProduct | ncbigene:29985 | |
SLC39A2 | GeneProduct | ncbigene:29986 | |
SLC39A1 | GeneProduct | ncbigene:27173 | SLC39A1 (ZIP1) transporter is responsible for the influx of zinc into the cytoplasm |
MT1A | GeneProduct | ncbigene:4489 | zinc is chelated by cytoplasmic proteins, such as MTs |
SLC30A1 | GeneProduct | ncbigene:7779 | SLC30A1 (ZnT1) transporter is responsible of zinc efflux |
MT1B | GeneProduct | ncbigene:4490 | zinc is chelated by cytoplasmic proteins, such as MTs |
MT1E | GeneProduct | ncbigene:4493 | zinc is chelated by cytoplasmic proteins, such as MTs |
MT1F | GeneProduct | ncbigene:4494 | zinc is chelated by cytoplasmic proteins, such as MTs |
MT1G | GeneProduct | ncbigene:4495 | zinc is chelated by cytoplasmic proteins, such as MTs |
MT1H | GeneProduct | ncbigene:4496 | zinc is chelated by cytoplasmic proteins, such as MTs |
MT1M | GeneProduct | ncbigene:4499 | zinc is chelated by cytoplasmic proteins, such as MTs |
MT1X | GeneProduct | ncbigene:4501 | zinc is chelated by cytoplasmic proteins, such as MTs |
MT2A | GeneProduct | ncbigene:4502 | zinc is chelated by cytoplasmic proteins, such as MTs |
MT3 | GeneProduct | ncbigene:4504 | zinc is chelated by cytoplasmic proteins, such as MTs |
MT1L | GeneProduct | ncbigene:4500 | zinc is chelated by cytoplasmic proteins, such as MTs |
MT4 | GeneProduct | ncbigene:84560 | zinc is chelated by cytoplasmic proteins, such as MTs |
SLC39A7 | GeneProduct | ncbigene:7922 | |
SLC39A11 | GeneProduct | ncbigene:201266 | |
SLC30A9 | GeneProduct | ncbigene:10463 | |
SLC30A4 | GeneProduct | ncbigene:7782 | |
SLC30A10 | GeneProduct | ncbigene:55532 | |
SLC30A3 | GeneProduct | ncbigene:7781 | |
SLC30A4 | GeneProduct | ncbigene:7782 | http://www.ncbi.nlm.nih.gov/gene/169026 |
SLC30A2 | GeneProduct | ncbigene:7780 | http://www.ncbi.nlm.nih.gov/gene/169026 |
SLC39A14 | GeneProduct | ncbigene:23516 | |
SLC30A5 | GeneProduct | ncbigene:64924 | |
SLC30A2 | GeneProduct | ncbigene:7780 | |
SLC30A7 | GeneProduct | ncbigene:148867 | |
SLC30A6 | GeneProduct | ncbigene:55676 | |
SLC39A6 | GeneProduct | ncbigene:25800 | |
SLC30A8 | GeneProduct | ncbigene:169026 | http://www.ncbi.nlm.nih.gov/gene/169026 |
References
- Induction, regulation, degradation, and biological significance of mammalian metallothioneins. Miles AT, Hawksworth GM, Beattie JH, Rodilla V. Crit Rev Biochem Mol Biol. 2000;35(1):35–70. PubMed Europe PMC Scholia
- Cellular zinc sensors: MTF-1 regulation of gene expression. Andrews GK. Biometals. 2001;14(3–4):223–37. PubMed Europe PMC Scholia
- Role of GAC63 in transcriptional activation mediated by beta-catenin. Chen YH, Yang CK, Xia M, Ou CY, Stallcup MR. Nucleic Acids Res. 2007;35(6):2084–92. PubMed Europe PMC Scholia
- A conserved cysteine cluster, essential for transcriptional activity, mediates homodimerization of human metal-responsive transcription factor-1 (MTF-1). Günther V, Davis AM, Georgiev O, Schaffner W. Biochim Biophys Acta. 2012 Feb;1823(2):476–83. PubMed Europe PMC Scholia
- The taste of heavy metals: gene regulation by MTF-1. Günther V, Lindert U, Schaffner W. Biochim Biophys Acta. 2012 Sep;1823(9):1416–25. PubMed Europe PMC Scholia
- The SLC30 family of zinc transporters - a review of current understanding of their biological and pathophysiological roles. Huang L, Tepaamorndech S. Mol Aspects Med. 2013;34(2–3):548–60. PubMed Europe PMC Scholia
- The SLC39 family of zinc transporters. Jeong J, Eide DJ. Mol Aspects Med. 2013;34(2–3):612–9. PubMed Europe PMC Scholia
- Metallothionein - immunohistochemical cancer biomarker: a meta-analysis. Gumulec J, Raudenska M, Adam V, Kizek R, Masarik M. PLoS One. 2014 Jan 8;9(1):e85346. PubMed Europe PMC Scholia
- Current understanding of ZIP and ZnT zinc transporters in human health and diseases. Kambe T, Hashimoto A, Fujimoto S. Cell Mol Life Sci. 2014 Sep;71(17):3281–95. PubMed Europe PMC Scholia