Copper homeostasis (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 (eg. detoxyfication by oxygen free radicals, angiogenesis, pigmentation, peptide hormone production, etc.). However, "free" copper is harmful for cells because 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 (proteins, enzymes, 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-indipendent stimuli (hormone, oxygen, phosphorylation and ubiquination) seem to affect localization and expression of Cu-transporters and chaperones. Potential target of copper ions seem to be crucial signaling pathways, such 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 CPTAC Assay Portal

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  1. Lutsenko S; ''Human copper homeostasis: a network of interconnected pathways.''; Curr Opin Chem Biol, 2010 PubMed Europe PMC Scholia
  2. Ba LA, Doering M, Burkholz T, Jacob C; ''Metal trafficking: from maintaining the metal homeostasis to future drug design.''; Metallomics, 2009 PubMed Europe PMC Scholia
  3. Mufti AR, Burstein E, Duckett CS; ''XIAP: cell death regulation meets copper homeostasis.''; Arch Biochem Biophys, 2007 PubMed Europe PMC Scholia
  4. Nevitt T, Ohrvik H, Thiele DJ; ''Charting the travels of copper in eukaryotes from yeast to mammals.''; Biochim Biophys Acta, 2012 PubMed Europe PMC Scholia
  5. Song IS, Chen HH, Aiba I, Hossain A, Liang ZD, Klomp LW, Kuo MT; ''Transcription factor Sp1 plays an important role in the regulation of copper homeostasis in mammalian cells.''; Mol Pharmacol, 2008 PubMed Europe PMC Scholia
  6. Kim BE, Nevitt T, Thiele DJ; ''Mechanisms for copper acquisition, distribution and regulation.''; Nat Chem Biol, 2008 PubMed Europe PMC Scholia


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106367view23:06, 22 August 2019KhanspersModified description
105561view06:18, 9 August 2019KhanspersModified description
93705view11:20, 11 August 2017Marvin M2Connected unconnected lines, changed lines in graphical lines in legend
89205view04:04, 23 August 2016AriuttaOntology Term : 'copper homeostasis pathway' added !
87382view11:05, 22 July 2016MaintBotadded missing graphids
84312view00:15, 5 February 2016KhanspersMoved pathway to the left and up
84311view00:03, 5 February 2016Khanspersupdated legend and grouped nodes
84179view21:12, 25 January 2016Khanspersconnected one interaction, added anchors and connectors to transporters, grouped some nodes
84178view20:29, 25 January 2016GdannagText label corrected
84177view20:28, 25 January 2016GdannagConnections and Bibliography
82352view15:52, 26 September 2015EgonwConverted the copper nodes to metabolites with ChEBI identifiers.
82270view15:56, 21 September 2015GiorgiaModified title
82192view16:27, 12 September 2015EgonwAdded GraphIDs to DataNodes that had none.
81938view00:20, 6 September 2015MaintBotManually added missing graphIDs
81937view00:18, 6 September 2015MaintBotAttempting to generate missing graphIDs
80955view23:20, 1 July 2015GdannagModified description
80954view22:54, 1 July 2015GdannagModified description
80953view21:28, 1 July 2015GdannagNew pathway

External references


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NameTypeDatabase referenceComment
ADAM10GeneProductENSG00000137845 (Ensembl)
ADAM17GeneProductENSG00000151694 (Ensembl)
ADAM9GeneProductENSG00000168615 (Ensembl)
AKTGeneProductENSG00000142208 (Ensembl)
APCGeneProductENSG00000134982 (Ensembl)
APPGeneProductENSG00000142192 (Ensembl)
ATOX1GeneProductENSG00000177556 (Ensembl)
ATP7AGeneProductENSG00000165240 (Ensembl)
ATP7BGeneProductENSG00000123191 (Ensembl)
BACE1GeneProductENSG00000186318 (Ensembl)
CASP3GeneProductENSG00000164305 (Ensembl)
CCND1GeneProductENSG00000110092 (Ensembl)
CCSGeneProductENSG00000173992 (Ensembl)
COMMD1GeneProductENSG00000173163 (Ensembl)
COX11GeneProductENSG00000166260 (Ensembl)
COX17GeneProductENSG00000138495 (Ensembl)
CPHL1PGeneProductENSG00000240216 (Ensembl)
Cu(I)MetaboliteCHEBI:49552 (ChEBI)
Cu(II)MetaboliteCHEBI:29036 (ChEBI)
FOXO1GeneProductENSG00000150907 (Ensembl)
FOXO3GeneProductENSG00000118689 (Ensembl)
GSK3BGeneProductENSG00000082701 (Ensembl)
JUNGeneProductENSG00000177606 (Ensembl)
MAPTGeneProductENSG00000186868 (Ensembl)
MDM2GeneProductENSG00000135679 (Ensembl)
MT1AGeneProductENSG00000205362 (Ensembl)
MT1BGeneProductENSG00000169688 (Ensembl)
MT1EGeneProductENSG00000169715 (Ensembl)
MT1FGeneProductENSG00000198417 (Ensembl)
MT1GGeneProductENSG00000125144 (Ensembl)
MT1HGeneProductENSG00000205358 (Ensembl)
MT1JPGeneProductENSG00000255986 (Ensembl)
MT1LGeneProductENSG00000260549 (Ensembl)
MT1XGeneProductENSG00000187193 (Ensembl)
MT2AGeneProductENSG00000125148 (Ensembl)
MT3GeneProductENSG00000087250 (Ensembl)
MT4GeneProductENSG00000102891 (Ensembl)
MTF1GeneProductENSG00000188786 (Ensembl)
MTF2GeneProductENSG00000143033 (Ensembl)
PIK3CAGeneProductENSG00000121879 (Ensembl)
PRNPGeneProductENSG00000171867 (Ensembl)
PTENGeneProductENSG00000171862 (Ensembl)
SCO1GeneProductENSG00000133028 (Ensembl)
SCO2GeneProductENSG00000130489 (Ensembl)
SLC11A2GeneProductENSG00000110911 (Ensembl)
SLC31A1GeneProductENSG00000136868 (Ensembl)
SLC31A2GeneProductENSG00000136867 (Ensembl)
SOD1GeneProductENSG00000142168 (Ensembl)
SOD3GeneProductENSG00000109610 (Ensembl)
SP1GeneProductENSG00000185591 (Ensembl)
STEAP1GeneProductENSG00000164647 (Ensembl)
STEAP2GeneProductENSG00000157214 (Ensembl)
STEAP3GeneProductENSG00000115107 (Ensembl)
STEAP4GeneProductENSG00000127954 (Ensembl)
TP53GeneProductENSG00000141510 (Ensembl)
XAF1GeneProductENSG00000132530 (Ensembl)
XIAPGeneProductENSG00000101966 (Ensembl)

Annotated Interactions

No annotated interactions

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