Zinc homeostasis (WP3529)

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
last edited

Authors

GIOVANNA VALENTI, Trovato angela, Egonw, Khanspers, Mkutmon, and MaintBot

Cited In

Organism

Homo sapiens

Communities

Annotations

Pathway Ontology: homeostasis pathway

Participants

Label Type Compact Identifier
MTF1 GeneProduct ensembl:ENSG00000188786
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
MT1A GeneProduct ncbigene:4489
SLC30A1 GeneProduct ncbigene:7779
MT1B GeneProduct ncbigene:4490
MT1E GeneProduct ncbigene:4493
MT1F GeneProduct ncbigene:4494
MT1G GeneProduct ncbigene:4495
MT1H GeneProduct ncbigene:4496
MT1M GeneProduct ncbigene:4499
MT1X GeneProduct ncbigene:4501
MT2A GeneProduct ncbigene:4502
MT3 GeneProduct ncbigene:4504
MT1L GeneProduct ncbigene:4500
MT4 GeneProduct ncbigene:84560
SLC39A7 GeneProduct ncbigene:7922
SLC39A11 GeneProduct ncbigene:201266
SLC39A9 GeneProduct ncbigene:55334
SLC30A9 GeneProduct ncbigene:10463
SLC30A4 GeneProduct ncbigene:7782
SLC39A8 GeneProduct ncbigene:64116
SLC30A10 GeneProduct ncbigene:55532
SLC30A3 GeneProduct ncbigene:7781
SLC30A4 GeneProduct ncbigene:7782
SLC30A2 GeneProduct ncbigene:7780
SLC39A14 GeneProduct ncbigene:23516
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
SLC30A5 GeneProduct ncbigene:64924
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
Zn++ Metabolite hmdb:HMDB0015532
SLC30A2 GeneProduct ncbigene:7780
Zn++ Metabolite hmdb:HMDB0015532
SLC30A7 GeneProduct ncbigene:148867
SLC30A4 GeneProduct ncbigene:7782
SLC30A6 GeneProduct ncbigene:55676
SLC39A6 GeneProduct ncbigene:25800
SLC30A8 GeneProduct ncbigene:169026

References

  1. 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. PubMed Europe PMC Scholia
  2. Andrews GK. Cellular zinc sensors: MTF-1 regulation of gene expression. Biometals. 2001;14(3–4):223–37. PubMed Europe PMC Scholia
  3. Chen Y-H, Yang CK, Xia M, Ou C-Y, Stallcup MR. Role of GAC63 in transcriptional activation mediated by beta-catenin. Nucleic Acids Res. 2007;35(6):2084–92. PubMed Europe PMC Scholia
  4. 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). Biochim Biophys Acta. 2012 Feb;1823(2):476–83. PubMed Europe PMC Scholia
  5. Günther V, Lindert U, Schaffner W. The taste of heavy metals: gene regulation by MTF-1. Biochim Biophys Acta. 2012 Sep;1823(9):1416–25. PubMed Europe PMC Scholia
  6. Huang L, Tepaamorndech S. The SLC30 family of zinc transporters - a review of current understanding of their biological and pathophysiological roles. Mol Aspects Med. 2013;34(2–3):548–60. PubMed Europe PMC Scholia
  7. Jeong J, Eide DJ. The SLC39 family of zinc transporters. Mol Aspects Med. 2013;34(2–3):612–9. PubMed Europe PMC Scholia
  8. 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. PubMed Europe PMC Scholia
  9. Kambe T, Hashimoto A, Fujimoto S. Current understanding of ZIP and ZnT zinc transporters in human health and diseases. Cell Mol Life Sci. 2014 Sep;71(17):3281–95. PubMed Europe PMC Scholia