EGLN3
entrez
112399
canonical
uniprot
Q9H6Z9
canonical
ensembl
ENSG00000129521
resolver
ensp
ENSP00000250457
resolver
ensp
ENSP00000447470
resolver
enst
ENST00000250457
resolver
enst
ENST00000553215
resolver
genesymbol
EGLN3
resolver
hgnc
HGNC:14661
resolver
uniprot
B3KVT0
resolver
uniprot
F8W1G2
resolver
uniprot
Q2TA79
resolver
uniprot
Q3B8N4
resolver
uniprot
Q3T1B0
resolver
uniprot
Q6P1R2
resolver
uniprot_entry
B3KVT0_HUMAN
resolver
uniprot_entry
EGLN3_HUMAN
resolver
uniprot_entry
F8W1G2_HUMAN
resolver
uniprot_entry
Q3T1B0_HUMAN
resolver
uniprot_sec
Q2TA79
resolver
uniprot_sec
Q3B8N4
resolver
uniprot_sec
Q6P1R2
resolver
activity_regulation
ACTIVITY REGULATION: Activated in cardiovascular cells and Hela cells following exposure to hypoxia. Inhibited by polynitrogen compounds probably by chelation to Fe(2+) ions. {ECO:0000269|PubMed:11595184, ECO:0000269|PubMed:12670503, ECO:0000269|PubMed:21421125}.
uniprot
proteins
amino_acid_sequence
MPLGHIMRLDLEKIALEYIVPCLHEVGFCYLDNFLGEVVGDCVLERVKQLHCTGALRDGQLAGPRAGVSKRHLRGDQITWIGGNEEGCEAISFLLSLIDRLVLYCGSRLGKYYVKERSKAMVACYPGNGTGYVRHVDNPNGDGRCITCIYYLNKNWDAKLHGGILRIFPEGKSFIADVEPIFDRLLFFWSDRRNPHEVQPSYATRYAMTVWYFDAEERAEAKKKFRNLTRKTESALTED
uniprot
proteins
ec_number
1.14.11.-
uniprot
proteins
ec_number
1.14.11.29
uniprot
proteins
function
FUNCTION: Prolyl hydroxylase that mediates hydroxylation of proline residues in target proteins, such as PKM, TELO2, ATF4, GPX4 and HIF1A (PubMed:19584355, PubMed:20978507, PubMed:21483450, PubMed:21575608, PubMed:21620138, PubMed:22797300, PubMed:40281343). 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). Acts as an inhibitor of ferroptosis by mediating hydroxylation of GPX4, thereby preventing GPX4 degradation via chaperone-mediated autophagy (PubMed:40281343). GPX4 hydroxylation is promoted by PSAT1, which provides 2-oxoglutarate substrate to EGLN3 (PubMed:40281343). ELGN3 is the most important isozyme in limiting physiological activation of HIFs (particularly HIF2A) in hypoxia. Also hydroxylates PKM in hypoxia, limiting glycolysis (PubMed:21483450, PubMed:21620138). 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). {ECO:0000269|PubMed:11595184, ECO:0000269|PubMed:12181324, ECO:0000269|PubMed:16098468, ECO:0000269|PubMed:19584355, ECO:0000269|PubMed:20849813, ECO:0000269|PubMed:20978507, ECO:0000269|PubMed:21317538, ECO:0000269|PubMed:21483450, ECO:0000269|PubMed:21575608, ECO:0000269|PubMed:21620138, ECO:0000269|PubMed:22797300, ECO:0000269|PubMed:40281343, ECO:0000305|PubMed:17684156}.
uniprot
proteins
mass_dalton
27261
uniprot
proteins
mutagenesis
MUTAGEN 91..102; /note="ISFLLSLIDRLV->RSFLRSLIRRLR: Abolishes interaction with ADRB2 and no increase in cellular abundance of ADRB2."; /evidence="ECO:0000269|PubMed:19584355"; MUTAGEN 135; /note="H->A: Eliminates hydroxylase activity."; /evidence="ECO:0000269|PubMed:11598268"; MUTAGEN 137; /note="D->A: Eliminates hydroxylase activity."; /evidence="ECO:0000269|PubMed:11598268"; MUTAGEN 196; /note="H->A: Eliminates hydroxylase activity."; /evidence="ECO:0000269|PubMed:11598268, ECO:0000269|PubMed:40281343
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated by SIAH1 and/or SIAH2 in response to the unfolded protein response (UPR), leading to its degradation. {ECO:0000250|UniProtKB:Q91UZ4}.
uniprot
proteins
pubmed
11574160
uniprot
proteins
pubmed
11595178
uniprot
proteins
pubmed
11595184
uniprot
proteins
pubmed
11598268
uniprot
proteins
pubmed
12163023
uniprot
proteins
pubmed
12181324
uniprot
proteins
pubmed
12615973
uniprot
proteins
pubmed
12670503
uniprot
proteins
pubmed
12788921
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15247232
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16098468
uniprot
proteins
pubmed
17684156
uniprot
proteins
pubmed
19584355
uniprot
proteins
pubmed
20849813
uniprot
proteins
pubmed
20978507
uniprot
proteins
pubmed
21317538
uniprot
proteins
pubmed
21410436
uniprot
proteins
pubmed
21421125
uniprot
proteins
pubmed
21483450
uniprot
proteins
pubmed
21575608
uniprot
proteins
pubmed
21620138
uniprot
proteins
pubmed
22286099
uniprot
proteins
pubmed
22797300
uniprot
proteins
pubmed
40281343
uniprot
proteins
sequence_length
239
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12163023, ECO:0000269|PubMed:12615973}. Cytoplasm {ECO:0000269|PubMed:12615973}. Note=Colocalizes with WDR83 in the cytoplasm. {ECO:0000250|UniProtKB:Q62630}.
uniprot
proteins