Names & Taxonomy

Uniprot ID:
Q96KS0
Entry Name:
EGLN2_HUMAN
Status:
reviewed
Protein Names:
Egl nine homolog 2 (EC 1.14.11.29) (Estrogen-induced tag 6) (HPH-3) (Hypoxia-inducible factor prolyl hydroxylase 1) (HIF-PH1) (HIF-prolyl hydroxylase 1) (HPH-1) (Prolyl hydroxylase domain-containing protein 1) (PHD1)
Gene Names:
EGLN2 EIT6
Gene Names Primary:
EGLN2
Organism:
Homo sapiens (Human)

Structure

Length:
407
Sequence:
MDSPCQPQPLSQALPQLPGSSSEPLEPEPGRARMGVESYLPCPLLPSYHCPGVPSEASAGSGTPRATATSTTASPLRDGFGGQDGGELRPLQSEGAAALVTKGCQRLAAQGARPEAPKRKWAEDGGDAPSPSKRPWARQENQEAEREGGMSCSCSSGSGEASAGLMEEALPSAPERLALDYIVPCMRYYGICVKDSFLGAALGGRVLAEVEALKRGGRLRDGQLVSQRAIPPRSIRGDQIAWVEGHEPGCRSIGALMAHVDAVIRHCAGRLGSYVINGRTKAMVACYPGNGLGYVRHVDNPHGDGRCITCIYYLNQNWDVKVHGGLLQIFPEGRPVVANIEPLFDRLLIFWSDRRNPHEVKPAYATRYAITVWYFDAKERAAAKDKYQLASGQKGVQVPVSQPPTPT
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Nucleus

Function

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 preferentially recognized via a LXXLAP motif.
Catalytic Activity:
Hypoxia-inducible factor-L-proline + 2-oxoglutarate + O(2) = hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO(2).
Cofactor:
COFACTOR: Name=Fe(2+); Xref=ChEBI:CHEBI:29033; ; Note=Binds 1 Fe(2+) ion per subunit.;; COFACTOR: Name=L-ascorbate; Xref=ChEBI:CHEBI:38290;
Cross Reference Drug Bank:
DB00126
Gene Ontology Go:
nucleoplasm
nucleus
ferrous iron binding
L-ascorbic acid binding
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
oxygen sensor activity
peptidyl-proline 4-dioxygenase activity
cell redox homeostasis
cellular response to hypoxia
intracellular estrogen receptor signaling pathway
peptidyl-proline hydroxylation to 4-hydroxy-L-proline
positive regulation of protein catabolic process
regulation of cell growth
regulation of neuron apoptotic process
regulation of transcription from RNA polymerase II promoter in response to hypoxia
response to hypoxia
Gene Ontology Biological Process:
cell redox homeostasis
cellular response to hypoxia
intracellular estrogen receptor signaling pathway
peptidyl-proline hydroxylation to 4-hydroxy-L-proline
positive regulation of protein catabolic process
regulation of cell growth
regulation of neuron apoptotic process
regulation of transcription from RNA polymerase II promoter in response to hypoxia
response to hypoxia
Gene Ontology Molecular Function:
ferrous iron binding
L-ascorbic acid binding
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
oxygen sensor activity
peptidyl-proline 4-dioxygenase activity
Gene Ontology Cellular Component:
nucleoplasm
nucleus
Keywords:
Alternative initiation
Complete proteome
Dioxygenase
Iron
Metal-binding
Nucleus
Oxidoreductase
Reference proteome
Vitamin C
Interacts With:
Q16665

Publication

PubMed ID:
11574160 11850811 14702039 17974005 15057824 15489334 11595178 11595184 12163023 12039559 12181324 12615973 15247232 16509823 17114296 19631610 19339211 21410436 22286099 23932902