Hypoxia-inducible factor 1-alpha inhibitor (FIH) is a protein that in humans is encoded by the HIF1AN gene. [5] [6]
FIH has been shown to interact with HIF1A [5] and Von Hippel-Lindau tumor suppressor. [5] Additionally, asparaginyl hydroxylation of HIF1α by FIH-1 (HIF1AN) at N803 impairs its interaction with CBP/P300. [7]
Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular environment, or hypoxia. They also respond to instances of pseudohypoxia, such as thiamine deficiency. Both hypoxia and pseudohypoxia leads to impairment of adenosine triphosphate (ATP) production by the mitochondria.
Histone acetyltransferase p300 also known as p300 HAT or E1A-associated protein p300 also known as EP300 or p300 is an enzyme that, in humans, is encoded by the EP300 gene. It functions as histone acetyltransferase that regulates transcription of genes via chromatin remodeling by allowing histone proteins to wrap DNA less tightly. This enzyme plays an essential role in regulating cell growth and division, prompting cells to mature and assume specialized functions (differentiate), and preventing the growth of cancerous tumors. The p300 protein appears to be critical for normal development before and after birth.
The Von Hippel–Lindau tumor suppressor also known as pVHL is a protein that, in humans, is encoded by the VHL gene. Mutations of the VHL gene are associated with Von Hippel–Lindau disease, which is characterized by hemangioblastomas of the brain, spinal cord and retina. It is also associated with kidney and pancreatic lesions.
Hypoxia-inducible factor 1-alpha, also known as HIF-1-alpha, is a subunit of a heterodimeric transcription factor hypoxia-inducible factor 1 (HIF-1) that is encoded by the HIF1A gene. The Nobel Prize in Physiology or Medicine 2019 was awarded for the discovery of HIF.
Procollagen-proline dioxygenase, commonly known as prolyl hydroxylase, is a member of the class of enzymes known as alpha-ketoglutarate-dependent hydroxylases. These enzymes catalyze the incorporation of oxygen into organic substrates through a mechanism that requires alpha-Ketoglutaric acid, Fe2+, and ascorbate. This particular enzyme catalyzes the formation of (2S, 4R)-4-hydroxyproline, a compound that represents the most prevalent post-translational modification in the human proteome.
Endothelial PAS domain-containing protein 1 is a protein that is encoded by the EPAS1 gene in mammals. It is a type of hypoxia-inducible factor, a group of transcription factors involved in the physiological response to oxygen concentration. The gene is active under hypoxic conditions. It is also important in the development of the heart, and for maintaining the catecholamine balance required for protection of the heart. Mutation often leads to neuroendocrine tumors.
Hypoxia-inducible factor 3 alpha is a protein that in humans is encoded by the HIF3A gene.
Egl nine homolog 2 is a protein that in humans is encoded by the EGLN2 gene. ELGN2 is an alpha-ketoglutarate-dependent hydroxylase, a superfamily of non-haem iron-containing proteins.
Hypoxia-inducible factor prolyl hydroxylase 2 (HIF-PH2), or prolyl hydroxylase domain-containing protein 2 (PHD2), is an enzyme encoded by the EGLN1 gene. It is also known as Egl nine homolog 1. PHD2 is a α-ketoglutarate/2-oxoglutarate-dependent hydroxylase, a superfamily non-haem iron-containing proteins. In humans, PHD2 is one of the three isoforms of hypoxia-inducible factor-proline dioxygenase, which is also known as HIF prolyl-hydroxylase.
Aspartyl/asparaginyl beta-hydroxylase (HAAH) is an enzyme that in humans is encoded by the ASPH gene. ASPH is an alpha-ketoglutarate-dependent hydroxylase, a superfamily non-haem iron-containing proteins.
Egl nine homolog 3 is a protein that in humans is encoded by the EGLN3 gene. ELGN3 is a member of the superfamily of alpha-ketoglutarate-dependent hydroxylases, which are non-haem iron-containing proteins.
Ras Related Glycolysis Inhibitor and Calcium Channel Regulator (RRAD) is a protein that in humans is encoded by the RRAD gene. RRAD is a Ras-related small GTPase that is regulated by p53 and plays a role in the regulation of aerobic glycolysis.
Prolyl 4-hydroxylase subunit alpha-1 is an enzyme that in humans is encoded by the P4HA1 gene.
Prolyl 4-hydroxylase subunit alpha-2 is an enzyme that in humans is encoded by the P4HA2 gene.
Hypoxia-inducible factor-proline dioxygenase (EC 1.14.11.29, HIF hydroxylase) is an enzyme with systematic name hypoxia-inducible factor-L-proline, 2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating). This enzyme catalyses the following chemical reaction
Hypoxia-inducible factor-asparagine dioxygenase (EC 1.14.11.30, HIF hydroxylase) is an enzyme with systematic name hypoxia-inducible factor-L-asparagine, 2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating). This enzyme catalyses the following chemical reaction:
hypoxia-inducible factor-L-asparagine + 2-oxoglutarate + O2 hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + succinate + CO2
Alpha-ketoglutarate-dependent hydroxylases are a major class of non-heme iron proteins that catalyse a wide range of reactions. These reactions include hydroxylation reactions, demethylations, ring expansions, ring closures, and desaturations. Functionally, the αKG-dependent hydroxylases are comparable to cytochrome P450 enzymes. Both use O2 and reducing equivalents as cosubstrates and both generate water.
Christopher Joseph Schofield is a Professor of Chemistry at the University of Oxford and a Fellow of the Royal Society. Chris Schofield is a professor of organic chemistry at the University of Oxford, Department of Chemistry and a Fellow of Hertford College. Schofield studied functional, structural and mechanistic understanding of enzymes that employ oxygen and 2-oxoglutarate as a co-substrate. His work has opened up new possibilities in antibiotic research, oxygen sensing, and gene regulation.
RNA demethylase ALKBH5 is a protein that in humans is encoded by the ALKBH5 gene.
Prolyl 4-hydroxylase, transmembrane is a protein that in humans is encoded by the P4HTM gene.