description
In the presence of oxygen members of the transcription factor family HIF-alpha, comprising HIF1A, HIF2A (EPAS1), and HIF3A, are hydroxylated on proline residues by PHD1 (EGLN2), PHD2 (EGLN1), and PHD3 (EGLN3) and on asparagine residues by HIF1AN (FIH) (reviewed in Pouyssegur et al. 2006, Semenza 2007, Kaelin and Ratcliffe 2008, Nizet and Johnson 2009, Brahimi-Horn and Pouyssegur 2009, Majmundar et al. 2010, Loenarz and Schofield 2011). Both types of reaction require molecular oxygen as a substrate and it is probable that at least some HIF-alpha molecules carry both hydroxylated asparagine and hydroxylated proline (Tian et al. 2011).Hydroxylated asparagine interferes with the ability of HIF-alpha to interact with p300 and CBP while hydroxylated proline facilitates the interaction of HIF-alpha with the E3 ubiquitin ligase VHL, causing ubiquitination and proteolysis of HIF-alpha. Hypoxia inhibits both types of hydroxylation, resulting in the stabilization of HIF-alpha, which then enters the nucleus, binds HIF-beta, and recruits p300 and CBP to activate target genes such as EPO and VEGF

external resources
NCBI:1270416
REACTOME:R-HSA-1234174
PUBMED:19704417
PUBMED:20728359
PUBMED:21335549
PUBMED:19339544
PUBMED:17916722
PUBMED:18498744
PUBMED:16724055
PUBMED:20965423

genes
ARNT , CA9 , CREBBP , EP300 , EPAS1 , EPO , 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 , VEGFA , VHL , SEM1 , CUL2 , LIMD1 , PSMF1 , PSMD6 , RBX1 , PSME3 , PSMD14 , CITED2 , PSME4 , HIGD1A , EGLN1 , HIF1AN , HIF3A , AJUBA , EGLN2 , EGLN3 , PSMB11 , WTIP , PSMA8 , C7orf76 , MIR1281 , LOC100506136 ,