InnateDB Protein
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IDBP-139440.6
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Last Modified
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2014-10-13 [Report errors or provide feedback]
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Gene Symbol
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Egln3
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Protein Name
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EGL nine homolog 3 (C. elegans)
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Synonyms
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2610021G09Rik; AI505553; AI648162; Hif-p4h-3; Phd3; SM-20;
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Species
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Mus musculus
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Ensembl Protein
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ENSMUSP00000041874
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InnateDB Gene
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IDBG-139438 (Egln3)
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Protein Structure
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Function |
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). Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF2A. Hydroxylation on the NODD site by EGLN3 appears to require prior hydroxylation on the CODD site. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. 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. ELGN3 is the most important isozyme in limiting physiological activation of HIFs (particularly HIF2A) in hypoxia. Also hydroxylates PKM in hypoxia, limiting glycolysis. Under normoxia, hydroxylates and regulates the stability of ADRB2. Regulator of cardiomyocyte and neuronal apoptosis. In cardiomyocytes, inhibits the anti-apoptotic effect of BCL2 by disrupting the BAX-BCL2 complex. In neurons, has a NGF-induced proapoptotic effect, probably through regulating CASP3 activity. Also essential for hypoxic regulation of neutrophilic inflammation. Target proteins are preferencially recognized via a LXXLAP motif. {ECO:0000250, ECO:0000269PubMed:21317538}.
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Subcellular Localization |
Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}. Note=Colocalizes with WDR83 in the cytoplasm. {ECO:0000250}.
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Disease Associations |
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Tissue Specificity |
Highly expressed in cardiac and smooth muscle. Also high expression in brain, skeletal muscle and kidney. Low levels in lung. {ECO:0000269PubMed:12234095}.
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Comments |
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Number of Interactions
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This gene and/or its encoded proteins are associated with 6 experimentally validated interaction(s) in this database.
They are also associated with 22 interaction(s) predicted by orthology.
Experimentally validated |
Total |
6
[view]
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Protein-Protein |
5
[view]
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Protein-DNA |
1
[view]
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Protein-RNA |
0
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DNA-DNA |
0
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RNA-RNA |
0
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DNA-RNA |
0
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Predicted by orthology |
Total |
22 [view]
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Molecular Function |
Accession |
GO Term |
GO:0005506
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iron ion binding
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GO:0005515
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protein binding
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GO:0016491
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oxidoreductase activity
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GO:0016705
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oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
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GO:0016706
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oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors
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GO:0031418
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L-ascorbic acid binding
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GO:0031545
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peptidyl-proline 4-dioxygenase activity
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Biological Process |
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Cellular Component |
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PDB ID |
MGI:1932288
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InterPro |
IPR005123
Oxoglutarate/iron-dependent dioxygenase
IPR006620
Prolyl 4-hydroxylase, alpha subunit
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PFAM |
PF03171
PF13640
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PRINTS |
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PIRSF |
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SMART |
SM00702
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TIGRFAMs |
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Modification |
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SwissProt |
Q91UZ4
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PhosphoSite |
PhosphoSite-
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TrEMBL |
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UniProt Splice Variant |
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Entrez Gene |
112407
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UniGene |
Mm.472562
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RefSeq |
NP_082409
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MGI ID |
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MGI Symbol |
Egln3
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OMIM |
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CCDS |
CCDS25908
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HPRD |
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IMGT |
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EMBL |
AF421882
AJ310548
AK044787
AK165972
AK170732
BC022961
BC044926
BC058278
BC069893
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GenPept |
AAH22961
AAH44926
AAH58278
AAH69893
AAL17824
BAC32092
BAE38492
BAE41988
CAC42517
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