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Literature summary for 1.14.11.29 extracted from

  • Taylor, C.T.; Scholz, C.C.
    A PHD in macrophage survival (2014), J. Leukoc. Biol., 96, 365-375 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 1.14.11.29

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
hypoxia-inducible factor-alpha-L-proline + 2-oxoglutarate + O2 Mus musculus
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 hypoxia-inducible factor-alpha-trans-4-hydroxy-L-proline + succinate + CO2
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 ?

Organism

Organism UniProt Comment Textmining
Mus musculus Q91UZ4
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-

Source Tissue

Source Tissue Comment Organism Textmining
macrophage
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 Mus musculus
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
hypoxia-inducible factor-alpha-L-proline + 2-oxoglutarate + O2
-
 Mus musculus hypoxia-inducible factor-alpha-trans-4-hydroxy-L-proline + succinate + CO2
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 ?

Synonyms

Synonyms Comment Organism
EGLN3
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 Mus musculus
PHD3
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 Mus musculus

Expression

Organism Comment Expression
Mus musculus isozyme PHD3 is induced in cells in hypoxia in a HIF-dependent manner and plays a role in a negative-feedback loop up

General Information

General Information Comment Organism
evolution the enzyme belongs to the HIF-PHD family of dioxygenases Mus musculus
malfunction macrophages deficient in PHD3 have decreased levels of stress-induced apoptosis. The antiapoptotic effects of PHD3 knockout are independent of alterations in HIF and instead, appear to occur via reduced expression of Angptl2, an extracellular protein that is structurally similar to angiopoietins. Hypoxia-dependent PHD3 inhibition in macrophages promotes cell survival through the activation of HIF-dependent adaptive pathways and HIF-independent antiapoptotic pathways, including decreased expression of Angptl2, impact of altered PHD3 expression/activity on macrophage function, schematic overview Mus musculus
metabolism PHD isoforms have a differential contribution in controlling hypoxia-inducible factor (HIF)-alpha degradation and activity. Hydroxylases are key oxygen sensors expressed in all cells that regulate the adaptive response to hypoxia and promote a return to oxygen homeostasis. Complex crosstalk exists between inflammatory and hypoxic signaling pathways Mus musculus
physiological function the HIF-PHDs (PHD1, PHD2, and PHD3, also known as EGLN2, EGLN1, and EGLN3, respectively) are a family of dioxygenases that use non-mitochondrial molecular oxygen as a cosubstrate in the hydroxylation of two residues, in what is termed the oxygen-dependent degradation domain of the HIFalpha isoform (Pro402 and Pro564 on HIF-1alpha). Hydroxylation of oxygen-dependent degradation domain of the HIFalpha isoform residues Pro402 and Pro564 renders the HIFalpha subunit as a target for the von Hipple Lindau protein, which recruits an E3 ubiquitin ligase complex that ubiquitinates HIF, leading to its proteasomal degradation. This process is prevented in hypoxia, leading to the rapid stabilization of HIFalpha, which is then free to translocate to the nucleus, to bind to HIF1beta/aryl hydrocarbon receptor nuclear translocator, and to form the transcriptionally active HIF complex. Isozyme PHD3 is proposed to play a role in a negative-feedback loop, curtailing the HIF-dependent response in prolonged hypoxia, presumably, to prevent excessive angiogenesis and other adaptive processes Mus musculus