InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: EGLN2

Summary

InnateDB Protein

IDBP-52266.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

EGLN2

Protein Name

egl nine homolog 2 (C. elegans)

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000307080

InnateDB Gene

IDBG-728297 (EGLN2)

Protein Structure

UniProt Annotation

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}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:12163023, ECO:0000269PubMed:12615973, ECO:0000269PubMed:19339211, ECO:0000269PubMed:19631610}.

Disease Associations

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}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 27 experimentally validated interaction(s) in this database.

Experimentally validated
Total	27 [view]
Protein-Protein	26 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005506	iron ion binding
GO:0005515	protein binding
GO:0008198	ferrous iron binding
GO:0016491	oxidoreductase activity
GO:0016705	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
GO:0016706	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
GO:0019826	oxygen sensor activity
GO:0031418	L-ascorbic acid binding
GO:0031545	peptidyl-proline 4-dioxygenase activity

Biological Process

GO:0001558	regulation of cell growth
GO:0001666	response to hypoxia
GO:0018401	peptidyl-proline hydroxylation to 4-hydroxy-L-proline
GO:0030520	intracellular estrogen receptor signaling pathway
GO:0043523	regulation of neuron apoptotic process
GO:0045087	innate immune response (InnateDB)
GO:0045454	cell redox homeostasis
GO:0045732	positive regulation of protein catabolic process
GO:0055114	oxidation-reduction process
GO:0061418	regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:0071456	cellular response to hypoxia