InnateDB Protein
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IDBP-159888.6
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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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Egln2
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Protein Name
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EGL nine homolog 2 (C. elegans)
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Synonyms
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0610011A13Rik; C85656; Hif-p4h-1; Ier4; Phd1; SM-20;
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Species
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Mus musculus
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Ensembl Protein
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ENSMUSP00000078966
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InnateDB Gene
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IDBG-159886 (Egln2)
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Protein Structure
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Function |
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. 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. EGLN2 is involved in regulating hypoxia tolerance and apoptosis in cardiac and skeletal muscle. Also regulates susceptibility to normoxic oxidative neuronal death. Links oxygen sensing to cell cycle and primary cilia formation by hydroxylating the critical centrosome component CEP192 which promotes its ubiquitination and subsequent proteasomal degradation. Hydroxylates IKBKB, mediating NF-kappaB activation in hypoxic conditions. Target proteins are preferencially recognized via a LXXLAP motif. {ECO:0000269PubMed:18176562, ECO:0000269PubMed:19587290, ECO:0000269PubMed:21083501}.
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Subcellular Localization |
Nucleus {ECO:0000269PubMed:12360397}.
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Disease Associations |
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Tissue Specificity |
Highly expressed in testis, expression was also detected in the heart brain, liver kidney and lung. Expression was lowest in spleen and skeletal muscle. Constitutively expressed during differentiation of C2C12 skeletal myocytes. {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 1 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.
Experimentally validated |
Total |
1
[view]
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Protein-Protein |
1
[view]
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Protein-DNA |
0
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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 |
2 [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:0019826
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oxygen sensor activity
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GO:0031418
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L-ascorbic acid binding
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GO:0031543
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peptidyl-proline dioxygenase activity
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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:1932287
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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 |
Q91YE2
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PhosphoSite |
PhosphoSite-Q91YE2
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TrEMBL |
Q80X29
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UniProt Splice Variant |
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Entrez Gene |
112406
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UniGene |
Mm.29978
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RefSeq |
NP_444438
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MGI ID |
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MGI Symbol |
Egln2
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OMIM |
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CCDS |
CCDS21011
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HPRD |
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IMGT |
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EMBL |
AF340231
AF453879
AJ310547
AK075582
AK152223
BC023299
BC051436
BC086764
CH466593
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GenPept |
AAH23299
AAH51436
AAH86764
AAK37525
AAL65166
BAC35835
BAE31050
CAC42516
EDL24202
EDL24203
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