Application | Comment | Organism |
---|---|---|
medicine | PHD2 represents a potential contributing factor for hepatocellular carcinoma-associated erythrocytosis. Selective inhibition of PHD2 in HCC cells might be considered as a way to manage erythrocytosis in hepatocellular carcinoma (HCC) patients | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
gene EGLN1 | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
additional information | the expression of PHD2 gene is silenced via specific siRNA (siPHD2) in the erythropoietin (EPO)-producing human HCC cell line HepG2. PHD2 knockdown causes a marked reduction of erythropoietin (EPO) production. HIF seems not to be involved in this process | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
hypoxia-inducible factor-alpha-L-proline + 2-oxoglutarate + O2 | Homo sapiens | - |
hypoxia-inducible factor-alpha-trans-4-hydroxy-L-proline + succinate + CO2 | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q9GZT9 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
Hep-G2 cell | - |
Homo sapiens | - |
hepatocellular carcinoma cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
hypoxia-inducible factor-alpha-L-proline + 2-oxoglutarate + O2 | - |
Homo sapiens | hypoxia-inducible factor-alpha-trans-4-hydroxy-L-proline + succinate + CO2 | - |
? |
Synonyms | Comment | Organism |
---|---|---|
EGLN1 | - |
Homo sapiens |
PHD2 | - |
Homo sapiens |
prolyl-4-hydroxylase 2 | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | PHD2 knockdown causes a marked reduction of erythropoietin (EPO) production. HIF seems not to be involved in this process | Homo sapiens |
metabolism | PDH2 regulates hypoxia-inducible factor (HIF)-independent pathways, as well as the degradation pathway of HIFalpha. HIF-2alpha does not play a major role in the regulation of erythropoietin (EPO) expression by PHD2 | Homo sapiens |
physiological function | enzyme PHD2 is to mediate the oxygen-dependent degradation of the labile alpha-subunit of hypoxia-inducible factor (HIF). In the erythropoietin (EPO)-producing human HCC cell line HepG2, PHD2 maintains the expression of hepatocyte nuclear factor-4alpha (HNF-4alpha), an important mediator of EPO expression in hepatocytes, by inhibiting the auto-/paracrine signalling of transforming growth factor-beta1. PHD2 also regulates HIF-independent pathways by interacting with other substrates. In HepG2 cells, PHD2 suppresses the activity of TGF-beta1 pathway and consequently maintains the expression of hepatocyte nuclear factor-4alpha (HNF-4alpha), an important transcription factor promoting the erythropoietin (EPO) expression in hepatocytes. PHD2 represents a potential contributing factor for hepatocellular carcinoma-associated erythrocytosis. Erythrocytosis generally leads to elevated blood viscosity and is a significant risk factor for lung artery thromboembolism, a life-threatening condition. The ability of some HCC cells to secrete EPO, a glycoprotein hormone which promotes erythropoiesis, contributes to HCC-associated erythrocytosis | Homo sapiens |