General Information of the Protein
Protein ID
PT02885
Protein Name
Prolyl hydroxylase EGLN3
Secondarily
Protein Name
Egl nine homolog 3
HPH-1
Hypoxia-inducible factor prolyl hydroxylase 3
Prolyl hydroxylase domain-containing protein 3
Gene Name
EGLN3
Sequence
MPLGHIMRLDLEKIALEYIVPCLHEVGFCYLDNFLGEVVGDCVLERVKQLHCTGALRDGQLAGPRAGVSKRHLRGDQITWIGGNEEGCEAISFLLSLIDRLVLYCGSRLGKYYVKERSKAMVACYPGNGTGYVRHVDNPNGDGRCITCIYYLNKNWDAKLHGGILRIFPEGKSFIADVEPIFDRLLFFWSDRRNPHEVQPSYATRYAMTVWYFDAEERAEAKKKFRNLTRKTESALTED
    Show/Hide
Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Oxidoreductase
Function
Prolyl hydroxylase that mediates hydroxylation of proline residues in target proteins, such as PKM, TELO2, ATF4 and HIF1A (PubMed:19584355, PubMed:21620138, PubMed:21483450, PubMed:22797300, PubMed:20978507, PubMed:21575608). Target proteins are preferentially recognized via a LXXLAP motif. Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins (PubMed:11595184, PubMed:12181324). Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A (PubMed:11595184, PubMed:12181324). Also hydroxylates HIF2A (PubMed:11595184, PubMed:12181324). Has a preference for the CODD site for both HIF1A and HIF2A (PubMed:11595184, PubMed:12181324). Hydroxylation on the NODD site by EGLN3 appears to require prior hydroxylation on the CODD site (PubMed:11595184, PubMed:12181324). Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex (PubMed:11595184, PubMed:12181324). Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes (PubMed:11595184, PubMed:12181324). ELGN3 is the most important isozyme in limiting physiological activation of HIFs (particularly HIF2A) in hypoxia. Also hydroxylates PKM in hypoxia, limiting glycolysis (PubMed:21620138, PubMed:21483450). Under normoxia, hydroxylates and regulates the stability of ADRB2 (PubMed:19584355). Regulator of cardiomyocyte and neuronal apoptosis. In cardiomyocytes, inhibits the anti-apoptotic effect of BCL2 by disrupting the BAX-BCL2 complex (PubMed:20849813). In neurons, has a NGF-induced proapoptotic effect, probably through regulating CASP3 activity (PubMed:16098468). Also essential for hypoxic regulation of neutrophilic inflammation (PubMed:21317538). Plays a crucial role in DNA damage response (DDR) by hydroxylating TELO2, promoting its interaction with ATR which is required for activation of the ATR/CHK1/p53 pathway (PubMed:22797300). Also mediates hydroxylation of ATF4, leading to decreased protein stability of ATF4 (Probable).
    Show/Hide
Uniprot ID
Primary ID:
Q9H6Z9

Secondarily ID:
Q2TA79
Q3B8N4
Q6P1R2
    Show/Hide
HGNC ID
HGNC:14661
Subcellular Location
Nucleus
Cytoplasm
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000013 , Sf9
Compound ID Compound Name Compound Formula
CP0458164
2-[[3-(4-cyanophenyl)-10-hydroxy-12-oxo-7-(trifluoromethoxy)-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5,7,9(13),10-tetraene-11-carbonyl]amino]acetic acid
   Show/Hide
C22H14F3N3O7
 1
1
IC50 = 5.1 nM
   TI
   LI
   LO
   TS
CP0437857
2-[[4-hydroxy-2-oxo-1-[[4-(trifluoromethoxy)phenyl]methyl]-5,7-dihydrofuro[3,4-b]pyridine-3-carbonyl]amino]acetic acid
   Show/Hide
C18H15F3N2O7
 1
1
IC50 = 5.8 nM
   TI
   LI
   LO
   TS
CP0517636
2-[[4-hydroxy-2-oxo-1-[(1-phenylpyrazol-3-yl)methyl]-5,7-dihydrofuro[3,4-b]pyridine-3-carbonyl]amino]acetic acid
   Show/Hide
C20H18N4O6
 1
1
IC50 = 6 nM
   TI
   LI
   LO
   TS
CP0439910
2-[[4-hydroxy-2-oxo-1-[[2-(trifluoromethyl)-1,3-thiazol-5-yl]methyl]-5,7-dihydrofuro[3,4-b]pyridine-3-carbonyl]amino]acetic acid
   Show/Hide
C15H12F3N3O6S
 1
1
IC50 = 6.4 nM
   TI
   LI
   LO
   TS
CP0521144
2-[[1-[(4-chlorophenyl)methyl]-4-hydroxy-2-oxo-5,7-dihydrofuro[3,4-b]pyridine-3-carbonyl]amino]acetic acid
   Show/Hide
C17H15ClN2O6
 1
1
IC50 = 6.4 nM
   TI
   LI
   LO
   TS
CP0426003
2-[[4-hydroxy-2-oxo-1-[(2,4,5-trifluorophenyl)methyl]-5,7-dihydrofuro[3,4-b]pyridine-3-carbonyl]amino]acetic acid
   Show/Hide
C17H13F3N2O6
 1
1
IC50 = 6.6 nM
   TI
   LI
   LO
   TS
CP0533783
2-[[1-(1,3-benzoxazol-2-ylmethyl)-4-hydroxy-2-oxo-5,7-dihydrofuro[3,4-b]pyridine-3-carbonyl]amino]acetic acid
   Show/Hide
C18H15N3O7
 1
1
IC50 = 6.6 nM
   TI
   LI
   LO
   TS
CP0533798
2-[[10-hydroxy-12-oxo-3-[6-(trifluoromethyl)pyridin-3-yl]-1,4-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13),10-tetraene-11-carbonyl]amino]acetic acid
   Show/Hide
C20H15F3N4O5
 1
1
IC50 = 6.6 nM
   TI
   LI
   LO
   TS
CP0492051
2-[[4-hydroxy-2-oxo-1-[[4-(trifluoromethyl)-1,3-thiazol-2-yl]methyl]-5,7-dihydrofuro[3,4-b]pyridine-3-carbonyl]amino]acetic acid
   Show/Hide
C15H12F3N3O6S
 1
1
IC50 = 7.8 nM
   TI
   LI
   LO
   TS
CP0142820
2-[[4-hydroxy-2-oxo-1-[[4-(trifluoromethyl)phenyl]methyl]-5,7-dihydrofuro[3,4-b]pyridine-3-carbonyl]amino]acetic acid
   Show/Hide
C18H15F3N2O6
 1
1
IC50 = 8.2 nM
   TI
   LI
   LO
   TS
CP0434449
2-[[1-[(2,4-difluorophenyl)methyl]-4-hydroxy-2-oxo-5,7-dihydrofuro[3,4-b]pyridine-3-carbonyl]amino]acetic acid
   Show/Hide
C17H14F2N2O6
 1
1
IC50 = 8.8 nM
   TI
   LI
   LO
   TS
CP0559017
2-[[10-hydroxy-12-oxo-2-[6-(trifluoromethyl)pyridin-3-yl]-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5,7,9(13),10-tetraene-11-carbonyl]amino]acetic acid
   Show/Hide
C20H14F3N3O6
 1
1
IC50 = 8.9 nM
   TI
   LI
   LO
   TS
CP0426000
2-[[4-hydroxy-2-oxo-1-[[6-(trifluoromethyl)pyridin-3-yl]methyl]-5,7-dihydrofuro[3,4-b]pyridine-3-carbonyl]amino]acetic acid
   Show/Hide
C17H14F3N3O6
 1
1
IC50 = 13 nM
   TI
   LI
   LO
   TS
CP0426002
2-[[4-hydroxy-2-oxo-1-[[5-(trifluoromethyl)pyrazin-2-yl]methyl]-5,7-dihydrofuro[3,4-b]pyridine-3-carbonyl]amino]acetic acid
   Show/Hide
C16H13F3N4O6
 1
1
IC50 = 13 nM
   TI
   LI
   LO
   TS
CP0470792
2-[[10-hydroxy-12-oxo-3-[4-(trifluoromethyl)phenyl]-4-thia-1-azatricyclo[7.3.1.05,13]trideca-5,7,9(13),10-tetraene-11-carbonyl]amino]acetic acid
   Show/Hide
C21H15F3N2O5S
 1
1
IC50 = 13 nM
   TI
   LI
   LO
   TS
CP0458167
2-[[1-(1,3-benzothiazol-2-ylmethyl)-4-hydroxy-2-oxo-7,8-dihydro-5H-pyrano[4,3-b]pyridine-3-carbonyl]amino]acetic acid
   Show/Hide
C19H17N3O6S
 1
1
IC50 = 14 nM
   TI
   LI
   LO
   TS
CP0136665
N-[bis(4-methoxyphenyl)methyl]-6-oxo-2-pyridazin-3-yl-1H-pyrimidine-5-carboxamide
   Show/Hide
C24H21N5O4
 1
1
IC50 = 14 nM
   TI
   LI
   LO
   TS
CP0470796
2-[[7-chloro-4-hydroxy-2-oxo-1-[[4-(trifluoromethyl)phenyl]methyl]quinoline-3-carbonyl]amino]acetic acid
   Show/Hide
C20H14ClF3N2O5
 1
1
IC50 = 16 nM
   TI
   LI
   LO
   TS
CP0519246
2-[[4-hydroxy-1-[[4-(2-hydroxypropan-2-yl)phenyl]methyl]-2-oxo-5,7-dihydrofuro[3,4-b]pyridine-3-carbonyl]amino]acetic acid
   Show/Hide
C20H22N2O7
 1
1
IC50 = 16 nM
   TI
   LI
   LO
   TS
CP0426423
2-[[4-hydroxy-2-oxo-1-[[2-(trifluoromethyl)pyrimidin-5-yl]methyl]-5,7-dihydrofuro[3,4-b]pyridine-3-carbonyl]amino]acetic acid
   Show/Hide
C16H13F3N4O6
 1
1
IC50 = 18 nM
   TI
   LI
   LO
   TS
CP0533799
2-[[1-[(4-cyano-2-fluorophenyl)methyl]-4-hydroxy-2-oxo-7,8-dihydro-5H-pyrano[4,3-b]pyridine-3-carbonyl]amino]acetic acid
   Show/Hide
C19H16FN3O6
 1
1
IC50 = 18 nM
   TI
   LI
   LO
   TS
CP0425999
2-[[10-hydroxy-2-(4-methoxyphenyl)-12-oxo-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5,7,9(13),10-tetraene-11-carbonyl]amino]acetic acid
   Show/Hide
C21H18N2O7
 1
1
IC50 = 21 nM
   TI
   LI
   LO
   TS
CP0426422
2-[[4-hydroxy-2-oxo-1-[[5-(trifluoromethyl)pyrimidin-2-yl]methyl]-5,7-dihydrofuro[3,4-b]pyridine-3-carbonyl]amino]acetic acid
   Show/Hide
C16H13F3N4O6
 1
1
IC50 = 22 nM
   TI
   LI
   LO
   TS
CP0533800
2-[[1-[(4-chlorophenyl)methyl]-4-hydroxy-2-oxo-7,8-dihydro-5H-pyrano[4,3-b]pyridine-3-carbonyl]amino]acetic acid
   Show/Hide
C18H17ClN2O6
 1
1
IC50 = 33 nM
   TI
   LI
   LO
   TS
CP0437858
2-[[4-hydroxy-2-oxo-1-[[4-(trifluoromethyl)phenyl]methyl]-6,8-dihydro-5H-pyrano[3,4-b]pyridine-3-carbonyl]amino]acetic acid
   Show/Hide
C19H17F3N2O6
 1
1
IC50 = 40 nM
   TI
   LI
   LO
   TS
CP0492050
2-[[4-hydroxy-2-oxo-1-[[6-(trifluoromethyl)pyridin-3-yl]methyl]-7,8-dihydro-5H-pyrano[4,3-b]pyridine-3-carbonyl]amino]acetic acid
   Show/Hide
C18H16F3N3O6
 1
1
IC50 = 41 nM
   TI
   LI
   LO
   TS
CP0492049
2-[[4-hydroxy-2-oxo-1-[[4-(trifluoromethyl)phenyl]methyl]-7,8-dihydro-5H-pyrano[4,3-b]pyridine-3-carbonyl]amino]acetic acid
   Show/Hide
C19H17F3N2O6
 1
1
IC50 = 51 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0138757
3-methyl-4-[4-[8-[(3-methylpyridin-2-yl)methyl]-2,4-dioxo-1-pyrimidin-4-yl-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]benzoic acid
   Show/Hide
C32H30N6O4
 1
1 IC50 = 1.6 nM