Copper homeostasis (WP3286)

Homo sapiens

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Copper is a redox-active transition metal and an essential trace element for life. It is a catalytic cofactor for numerous enzymes involved in critical biological processes (e.g. detoxification by oxygen free radicals, angiogenesis, pigmentation, peptide hormone production, etc.). However, "free" copper is harmful for cells because it can generate ROS that leads to cellular damage. Thus, all organisms and cells maintain a tight control of its uptake, trafficking and export. This process is rather intricate and requires an interplay between numerous biomolecules (e.g. proteins, metabolites) that act as copper ions importers (CTR1, CTR2, DMT1, Prp, APP), chaperones (CCS, ATOX1, COX17, COMMD1) and exporters (ATP7A, ATP7B). Copper ions and Cu-independent stimuli (hormone, oxygen, phosphorylation and ubiquination) seem to affect localization and expression of Cu-transporters and chaperones. Potential targets of copper ions seem to be crucial signaling pathways, such as PI3K/Akt, in which copper induces insulin-like effects. Copper dyshomeostasis could be implicated in cancer and a number of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, prion disease and ALS. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP3286 CPTAC Assay Portal]

Authors

Giuseppe D'Anna , Egon Willighagen , Giorgia Spampinato , Kristina Hanspers , Anders Riutta , Marvin Martens , and Eric Weitz

Activity

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

copper homeostasis pathway

Participants
Query Drugst.One

Label Type Compact URI Comment
Cu+ Metabolite chebi:49552
Cu2+ Metabolite chebi:29036
Cu(I) Metabolite chebi:49552
MTF2 GeneProduct ensembl:ENSG00000143033
STEAP2 GeneProduct ensembl:ENSG00000157214
APP GeneProduct ensembl:ENSG00000142192
STEAP1 GeneProduct ensembl:ENSG00000164647
SP1 GeneProduct ensembl:ENSG00000185591
STEAP4 GeneProduct ensembl:ENSG00000127954
ADAM9 GeneProduct ensembl:ENSG00000168615
ADAM10 GeneProduct ensembl:ENSG00000137845
ADAM17 GeneProduct ensembl:ENSG00000151694
STEAP3 GeneProduct ensembl:ENSG00000115107
FOXO1 GeneProduct ensembl:ENSG00000150907
CCS GeneProduct ensembl:ENSG00000173992
SLC31A1 GeneProduct ensembl:ENSG00000136868
COMMD1 GeneProduct ensembl:ENSG00000173163
SLC31A2 GeneProduct ensembl:ENSG00000136867
MT1A GeneProduct ensembl:ENSG00000205362
MT1B GeneProduct ensembl:ENSG00000169688
MT1E GeneProduct ensembl:ENSG00000169715
MT1F GeneProduct ensembl:ENSG00000198417
MT1G GeneProduct ensembl:ENSG00000125144
MT1H GeneProduct ensembl:ENSG00000205358
MT1JP GeneProduct ensembl:ENSG00000255986
MT1L GeneProduct ensembl:ENSG00000260549
MT1X GeneProduct ensembl:ENSG00000187193
MT2A GeneProduct ensembl:ENSG00000125148
MT3 GeneProduct ensembl:ENSG00000087250
MT4 GeneProduct ensembl:ENSG00000102891
PRNP GeneProduct ensembl:ENSG00000171867
ATP7B GeneProduct ensembl:ENSG00000123191
XAF1 GeneProduct ensembl:ENSG00000132530
ATOX1 GeneProduct ensembl:ENSG00000177556
MDM2 GeneProduct ensembl:ENSG00000135679
TP53 GeneProduct ensembl:ENSG00000141510
MAPT GeneProduct ensembl:ENSG00000186868
PIK3CA GeneProduct ensembl:ENSG00000121879
MTF1 GeneProduct ensembl:ENSG00000188786
CPHL1P GeneProduct ensembl:ENSG00000240216
ATP7A GeneProduct ensembl:ENSG00000165240
CASP3 GeneProduct ensembl:ENSG00000164305
CCND1 GeneProduct ensembl:ENSG00000110092
JUN GeneProduct ensembl:ENSG00000177606
AKT GeneProduct ensembl:ENSG00000142208
SOD3 GeneProduct ensembl:ENSG00000109610
BACE1 GeneProduct ensembl:ENSG00000186318
COX11 GeneProduct ensembl:ENSG00000166260
COX17 GeneProduct ensembl:ENSG00000138495
XIAP GeneProduct ensembl:ENSG00000101966
FOXO3 GeneProduct ensembl:ENSG00000118689
APC GeneProduct ensembl:ENSG00000134982
SOD1 GeneProduct ensembl:ENSG00000142168
PTEN GeneProduct ensembl:ENSG00000171862
GSK3B GeneProduct ensembl:ENSG00000082701
SLC11A2 GeneProduct ensembl:ENSG00000110911
SCO1 GeneProduct ensembl:ENSG00000133028
SCO2 GeneProduct ensembl:ENSG00000130489

References

  1. XIAP: cell death regulation meets copper homeostasis. Mufti AR, Burstein E, Duckett CS. Arch Biochem Biophys. 2007 Jul 15;463(2):168–74. PubMed Europe PMC Scholia
  2. Mechanisms for copper acquisition, distribution and regulation. Kim BE, Nevitt T, Thiele DJ. Nat Chem Biol. 2008 Mar;4(3):176–85. PubMed Europe PMC Scholia
  3. Transcription factor Sp1 plays an important role in the regulation of copper homeostasis in mammalian cells. Song IS, Chen HHW, Aiba I, Hossain A, Liang ZD, Klomp LWJ, et al. Mol Pharmacol. 2008 Sep;74(3):705–13. PubMed Europe PMC Scholia
  4. Human copper homeostasis: a network of interconnected pathways. Lutsenko S. Curr Opin Chem Biol. 2010 Apr;14(2):211–7. PubMed Europe PMC Scholia
  5. Metal trafficking: from maintaining the metal homeostasis to future drug design. Ba LA, Doering M, Burkholz T, Jacob C. Metallomics. 2009;1(4):292–311. PubMed Europe PMC Scholia
  6. Charting the travels of copper in eukaryotes from yeast to mammals. Nevitt T, Ohrvik H, Thiele DJ. Biochim Biophys Acta. 2012 Sep;1823(9):1580–93. PubMed Europe PMC Scholia