Cytosolic PHD2,3 hydroxylates proline residues on HIF1A

Stable Identifier
Homo sapiens
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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).

Literature References
PubMed ID Title Journal Year
11292861 Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation

Jaakkola, P, Mole, DR, Tian, YM, Wilson, MI, Gielbert, J, Gaskell, SJ, Kriegsheim, Av, Hebestreit, HF, Mukherji, M, Schofield, CJ, Maxwell, PH, Pugh, CW, Ratcliffe, PJ

Science 2001
17434750 Expression and purification of catalytically active human PHD3 in Escherichia coli

Fedulova, N, Hanrieder, J, Bergquist, J, Emrén, LO

Protein Expr Purif 2007
22286099 The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF-1 activity

Foxler, DE, Bridge, KS, James, V, Webb, TM, Mee, M, Wong, SC, Feng, Y, Constantin-Teodosiu, D, Petursdottir, TE, Bjornsson, J, Ingvarsson, S, Ratcliffe, PJ, Longmore, GD, Sharp, TV

Nat. Cell Biol. 2012
15474027 Determination and comparison of specific activity of the HIF-prolyl hydroxylases

Tuckerman, JR, Zhao, Y, Hewitson, KS, Tian, YM, Pugh, CW, Ratcliffe, PJ, Mole, DR

FEBS Lett 2004
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
12351678 Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor

Ivan, M, Haberberger, T, Gervasi, DC, Michelson, KS, Günzler, V, Kondo, K, Yang, H, Sorokina, I, Conaway, RC, Conaway, JW, Kaelin WG, Jr

Proc Natl Acad Sci U S A 2002
15247232 Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor

Appelhoff, RJ, Tian, YM, Raval, RR, Turley, H, Harris, AL, Pugh, CW, Ratcliffe, PJ, Gleadle, JM

J Biol Chem 2004
11292862 HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing

Ivan, M, Kondo, K, Yang, H, Kim, W, Valiando, J, Ohh, M, Salic, A, Asara, JM, Lane, WS, Kaelin WG, Jr

Science 2001
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
12912907 HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia

Berra, E, Benizri, E, Ginouvès, A, Volmat, V, Roux, D, Pouysségur, J

EMBO J 2003
11598268 A conserved family of prolyl-4-hydroxylases that modify HIF

Bruick, RK, McKnight, SL

Science 2001
21335549 Differential sensitivity of HIF hydroxylation sites to hypoxia and hydroxylase inhibitors

Tian, YM, Yeoh, KK, Lee, MK, Eriksson, T, Kessler, BM, Kramer, HB, Edelmann, MJ, Willam, C, Pugh, CW, Schofield, CJ, Ratcliffe, PJ

J Biol Chem 2011
Participant Of
Catalyst Activity
Catalyst Activity
peptidyl-proline 4-dioxygenase activity of PHD2,3:LIMD1,AJUBA,WTIP:VHL:EloB:EloC:CUL2:RBX1 [cytosol]
Physical Entity
Orthologous Events
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