Nuclear PHD1,3 hydroxylates proline residues on HIF1A

Stable Identifier
Reaction [transition]
Homo sapiens
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Proline hydroxylases PHD1 (EGLN2) and PHD3 (EGLN3) located in the nucleus (Metzen et al. 2003) hydroxylate HIF1A at proline-402 and proline-564 (Buick 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). The amount of hydroxylation occurring in the nucleus is controversial. Most hydroxylation is believed to occur in the cytosol.

Literature References
PubMed ID Title Journal Year
17434750 Expression and purification of catalytically active human PHD3 in Escherichia coli

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

Protein Expr Purif 2007
12351678 Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor

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

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

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

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

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

Science 2001
11292861 Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation

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

Science 2001
12615973 Intracellular localisation of human HIF-1 alpha hydroxylases: implications for oxygen sensing

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

J Cell Sci 2003
15474027 Determination and comparison of specific activity of the HIF-prolyl hydroxylases

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

FEBS Lett 2004
12912907 HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia

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

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

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

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

McKnight, SL, Bruick, RK

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

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

J Biol Chem 2011
Catalyst Activity

peptidyl-proline 4-dioxygenase activity of PHD1,3 [nucleoplasm]

Orthologous Events
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