description
HIF-alpha subunits, comprising HIF1A (Bruick and McKnight 2001, Ivan et al. 2001, Jaakkola et al. 2001), HIF2A (Percy et al. 2008, Furlow et al. 2009), and HIF3A (Maynard et al. 2003), are hydroxylated at proline residues by the prolyl hydroxylases PHD1 (EGLN2), PHD2 (EGLN1), and PHD3 (EGLN3) (Bruick and McKnight 2001, Berra et al. 2003, Hirsila et al. 2003, Metzen et al. 2003, Tuckerman et al. 2004, Appelhoff et al. 2004, Fedulova et al. 2007, Tian et al. 2011). The reaction requires molecular oxygen as a substrate and so it is inhibited by hypoxia. PHD2 (EGLN1) is predominantly cytosolic (Metzen et al. 2003) and is the key determinant in the regulation of HIF-alpha subunits by oxygen (Berra et al. 2003).HIF-alpha subunits hydroxylated at proline residues are bound by VHL, an E3 ubiquitin ligase in a complex containing ElonginB, Elongin C, CUL2, and RBX1. VHL ubiquitinates HIF-alpha, resulting in destruction of HIF-alpha by proteolysis. Hypoxia inhibits proline hydroxylation and interaction with VHL, stabilizing HIF-alpha, which transits to the nucleus and activates gene expression

external resources
NCBI:1270418
REACTOME:R-HSA-1234176
PUBMED:15247232
PUBMED:15474027
PUBMED:12788921
PUBMED:18184961
PUBMED:12351678
PUBMED:11292861
PUBMED:17434750
PUBMED:19208626
PUBMED:12538644
PUBMED:12615973
PUBMED:11598268
PUBMED:21335549
PUBMED:12912907
PUBMED:11292862

genes
EPAS1 , HIF1A , PSMA1 , PSMA2 , PSMA3 , PSMA4 , PSMA5 , PSMA6 , PSMA7 , PSMB1 , PSMB2 , PSMB3 , PSMB4 , PSMB5 , PSMB6 , PSMB7 , PSMB8 , PSMB9 , PSMB10 , PSMC1 , PSMC2 , PSMC3 , PSMC4 , PSMC5 , PSMC6 , PSMD1 , PSMD2 , PSMD3 , PSMD4 , PSMD5 , PSMD7 , PSMD8 , PSMD9 , PSMD10 , PSMD11 , PSMD12 , PSMD13 , PSME1 , PSME2 , RPS27A , ELOC , ELOB , UBA52 , UBB , UBC , UBE2D1 , UBE2D2 , UBE2D3 , VHL , SEM1 , CUL2 , LIMD1 , PSMF1 , PSMD6 , RBX1 , PSME3 , PSMD14 , PSME4 , EGLN1 , HIF3A , AJUBA , EGLN2 , EGLN3 , PSMB11 , WTIP , PSMA8 , C7orf76 , LOC100506136 ,