Egln3
entrez
112407
canonical
uniprot
Q91UZ4
canonical
ensembl
ENSMUSG00000035105
resolver
ensp
ENSMUSP00000041874
resolver
enst
ENSMUST00000039516
resolver
genesymbol
Egln3
resolver
uniprot
A0A0R4J0H9
resolver
uniprot
Q3TCG8
resolver
uniprot
Q8C8M6
resolver
uniprot
Q8CCA8
resolver
uniprot
Q8R5C7
resolver
uniprot_entry
A0A0R4J0H9_MOUSE
resolver
uniprot_entry
EGLN3_MOUSE
resolver
uniprot_sec
Q3TCG8
resolver
uniprot_sec
Q8C8M6
resolver
uniprot_sec
Q8CCA8
resolver
uniprot_sec
Q8R5C7
resolver
amino_acid_sequence
MPLGHIMRLDLEKIALEYIVPCLHEVGFCYLDNFLGEVVGDCVLERVKQLHYNGALRDGQLAGPRAGVSKRHLRGDQITWIGGNEEGCEAINFLLSLIDRLVLYCGSRLGKYYVKERSKAMVACYPGNGTGYVRHVDNPNGDGRCITCIYYLNKNWDAKLHGGVLRIFPEGKSFVADVEPIFDRLLFFWSDRRNPHEVQPSYATRYAMTVWYFDAEERAEAKKKFRNLTRKTESALAKD
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:24809345). Target proteins are preferentially recognized via a LXXLAP motif (By similarity). Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins (By similarity). Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A (By similarity). Also hydroxylates HIF2A (By similarity). Has a preference for the CODD site for both HIF1A and HIF2A (By similarity). Hydroxylation on the NODD site by EGLN3 appears to require prior hydroxylation on the CODD site (By similarity). Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex (By similarity). 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 (By similarity). Acts as an inhibitor of ferroptosis by mediating hydroxylation of GPX4, thereby preventing GPX4 degradation via chaperone-mediated autophagy (By similarity). GPX4 hydroxylation is promoted by PSAT1, which provides 2-oxoglutarate substrate to EGLN3 (By similarity). ELGN3 is the most important isozyme in limiting physiological activation of HIFs (particularly HIF2A) in hypoxia (By similarity). Also hydroxylates PKM in hypoxia, limiting glycolysis (By similarity). Under normoxia, hydroxylates and regulates the stability of ADRB2. Regulator of cardiomyocyte and neuronal apoptosis (By similarity). In cardiomyocytes, inhibits the anti-apoptotic effect of BCL2 by disrupting the BAX-BCL2 complex (By similarity). In neurons, has a NGF-induced proapoptotic effect, probably through regulating CASP3 activity (By similarity). 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 (By similarity). Also mediates hydroxylation of ATF4, leading to decreased protein stability of ATF4 (PubMed:24809345). {ECO:0000250|UniProtKB:Q9H6Z9, ECO:0000269|PubMed:21317538, ECO:0000269|PubMed:24809345}.
uniprot
proteins
mass_dalton
27302
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:0000269|PubMed:24809345}.
uniprot
proteins
pubmed
10543731
uniprot
proteins
pubmed
11574160
uniprot
proteins
pubmed
12234095
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
18332118
uniprot
proteins
pubmed
19584355
uniprot
proteins
pubmed
19720742
uniprot
proteins
pubmed
21317538
uniprot
proteins
pubmed
24809345
uniprot
proteins
sequence_length
239
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9H6Z9}. Cytoplasm {ECO:0000250|UniProtKB:Q9H6Z9}. Note=Colocalizes with WDR83 in the cytoplasm. {ECO:0000250|UniProtKB:Q62630}.
uniprot
proteins