InnateDB Protein
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IDBP-294795.4
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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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Species
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Homo sapiens
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Ensembl Protein
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ENSP00000385253
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InnateDB Gene
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IDBG-728297 (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:11595184, ECO:0000269PubMed:12181324, ECO:0000269PubMed:16509823, ECO:0000269PubMed:17114296, ECO:0000269PubMed:19339211, ECO:0000269PubMed:23932902}.
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Subcellular Localization |
Nucleus {ECO:0000269PubMed:12163023, ECO:0000269PubMed:12615973, ECO:0000269PubMed:19339211, ECO:0000269PubMed:19631610}.
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Disease Associations |
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Tissue Specificity |
Expressed in adult and fetal heart, brain, liver, lung, skeletal muscle, and kidney. Also expressed in testis and placenta. Highest levels in adult brain, placenta, lung, kidney, and testis. Expressed in hormone responsive tissues, including normal and cancerous mammary, ovarian and prostate epithelium. {ECO:0000269PubMed:12163023}.
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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 27 experimentally validated interaction(s) in this database.
Experimentally validated |
Total |
27
[view]
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Protein-Protein |
26
[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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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:0008198
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ferrous iron 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:0031545
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peptidyl-proline 4-dioxygenase activity
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Biological Process |
GO:0001558
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regulation of cell growth
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GO:0001666
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response to hypoxia
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GO:0018401
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peptidyl-proline hydroxylation to 4-hydroxy-L-proline
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GO:0030520
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intracellular estrogen receptor signaling pathway
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GO:0043523
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regulation of neuron apoptotic process
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GO:0045454
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cell redox homeostasis
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GO:0045732
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positive regulation of protein catabolic process
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GO:0055114
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oxidation-reduction process
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GO:0061418
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regulation of transcription from RNA polymerase II promoter in response to hypoxia
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GO:0071456
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cellular response to hypoxia
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Cellular Component |
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PDB ID |
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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 |
Q96KS0
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PhosphoSite |
PhosphoSite-Q96KS0
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TrEMBL |
M0R2X9
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UniProt Splice Variant |
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Entrez Gene |
112398
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UniGene |
Hs.515417
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RefSeq |
NP_444274
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HUGO |
HGNC:14660
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OMIM |
606424
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CCDS |
CCDS12567
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HPRD |
06970
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IMGT |
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EMBL |
AC008537
AJ310544
AK291385
AL832506
AY040565
BC001723
BC036051
CH471126
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GenPept |
AAH01723
AAH36051
AAK82943
BAF84074
CAC42510
EAW57008
EAW57009
EAW57010
EAW57011
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