Cytosolic PHD2,3 hydroxylates proline residues on EPAS1 (HIF2A)

Stable Identifier
R-HSA-1234179
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

Proline hydroxylases PHD2 (EGLN1) and PHD3 (EGLN3) located in the cytosol (Metzen et al. 2003) hydroxylate EPAS1 (HIF2A) at proline-405 and proline-531 (Hirsila et al. 2003, Percy et al. 2008, Furlow et al. 2009). A portion of PHD3 (EGLN3) is also located in the nucleus (Rantanen et al. 2008).

Literature References
PubMed ID Title Journal Year
18184961 A gain-of-function mutation in the HIF2A gene in familial erythrocytosis

Percy, MJ, Furlow, PW, Lucas, GS, Li, X, Lappin, TR, McMullin, MF

N Engl J Med 2008
19208626 Erythrocytosis-associated HIF-2alpha mutations demonstrate a critical role for residues C-terminal to the hydroxylacceptor proline

Furlow, PW, Percy, MJ, Sutherland, S, Bierl, C, McMullin, MF, Master, SR, Lappin, TR

J Biol Chem 2009
18337469 Prolyl hydroxylase PHD3 activates oxygen-dependent protein aggregation

Rantanen, K, Pursiheimo, J, Högel, H, Himanen, V, Metzen, E, Jaakkola, PM

Mol. Biol. Cell 2008
12615973 Intracellular localisation of human HIF-1 alpha hydroxylases: implications for oxygen sensing

Metzen, E, Berchner-Pfannschmidt, U, Stengel, P, Marxsen, JH, Stolze, I, Klinger, M, Huang, WQ, Wotzlaw, C, Hellwig-Bürgel, T, Jelkmann, W, Acker, H, Fandrey, J

J Cell Sci 2003
12788921 Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor

Hirsilä, M, Koivunen, P, Günzler, V, Kivirikko, KI, Myllyharju, J

J Biol Chem 2003
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
peptidyl-proline 4-dioxygenase activity of PHD2,3:LIMD1,AJUBA,WTIP:VHL:EloB:EloC:CUL2:RBX1 [cytosol]
Physical Entity
Activity
Inferred From
Authored
Reviewed
Created