Zinc homeostasis (WP3529)

Homo sapiens

Open in new tab Open in NDEx
Download PNG Download SVG Download JSON Download GPML Learn more about Downloads
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

Authors

Giovanna Valenti , Trovato Angela , Egon Willighagen , Kristina Hanspers , and Martina Summer-Kutmon

Activity

last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited By

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.

Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

homeostasis pathway

Participants
Query Drugst.One

Label Type Compact Identifier Comment
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
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
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 Type your comment here
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
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 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
SLC30A4 GeneProduct ncbigene:7782
SLC30A6 GeneProduct ncbigene:55676
SLC39A6 GeneProduct ncbigene:25800
SLC30A8 GeneProduct ncbigene:169026 http://www.ncbi.nlm.nih.gov/gene/169026

References

  1. 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
  2. Cellular zinc sensors: MTF-1 regulation of gene expression. Andrews GK. Biometals. 2001;14(3–4):223–37. PubMed Europe PMC Scholia
  3. 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
  4. 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
  5. 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
  6. 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
  7. The SLC39 family of zinc transporters. Jeong J, Eide DJ. Mol Aspects Med. 2013;34(2–3):612–9. PubMed Europe PMC Scholia
  8. 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
  9. 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