Meta-Biol

• Pathways

Proline hydroxylases PHD2 (EGLN1) and PHD3 (EGLN3) located in the cytosol (Metzen et al. 2003) hydroxylate HIF1A at proline-402 and proline-564 (Bruick and McKnight 2001, Jaakkola et al. 2001, Ivan et al. 2001, Ivan et al. 2002, Berra et al. 2003, Hirsila et al. 2003, Appelhoff et al. 2004, Tuckerman et al. 2004, Fedulova et al. 2007, Tian et al. 2011). A portion of PHD3 (EGLN3) is also located in the nucleus (Rantanen et al. 2008). PHD1, PHD2, and PHD3 are each contained in a complex with LIMD1 and VHL (Foxler et al. 2012).
PHD activity is competitively inhibited by succinate (Selak et al, 2005; Pollard et al, 2005; Koivunen et al, 2007).