LMPD Database

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LMP001120

UniProt Annotations

Entry Information
Gene Nameegl-9 family hypoxia-inducible factor 2
Protein EntryEGLN2_HUMAN
UniProt IDQ96KS0
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative initiation; Named isoforms=2; Name=p43; Synonyms=PHD1p43; IsoId=Q96KS0-1; Sequence=Displayed; Name=p40; Synonyms=PHD1p40; IsoId=Q96KS0-2; Sequence=VSP_038836;
Catalytic ActivityHypoxia-inducible factor-L-proline + 2- oxoglutarate + O(2) = hypoxia-inducible factor-trans-4-hydroxy-L- proline + succinate + CO(2).
CofactorName=Fe(2+); Xref=ChEBI
CofactorName=L-ascorbate; Xref=ChEBI
DomainThe Beta(2)beta(3) 'finger-like' loop domain is important for substrate (HIFs' CODD/NODD) selectivity.
FunctionCellular 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
InductionBy estrogen. Isoform p43 is induced by hypoxia leading to protein stability. Isoform p40 repressed by hypoxia. Both isoforms are induced by proteasomal inhibitor MG132 (at protein level). {ECO
InteractionQ16665:HIF1A; NbExp=2; IntAct=EBI-726614, EBI-447269;
Sequence CautionSequence=AAH01723.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence= ;
SimilarityContains 1 Fe2OG dioxygenase domain.
Subcellular LocationNucleus {ECO
SubunitInteracts (preferably isoform p40) with SIAH2; the interaction targets both SIAH2 isoforms for proteasomal degradation in vitro. Interacts with LIMD1, WTIP and AJUBA.
Tissue SpecificityExpressed 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.