Names & Taxonomy

Uniprot ID:
Q9GZT9
Entry Name:
EGLN1_HUMAN
Status:
reviewed
Protein Names:
Egl nine homolog 1 (EC 1.14.11.29) (Hypoxia-inducible factor prolyl hydroxylase 2) (HIF-PH2) (HIF-prolyl hydroxylase 2) (HPH-2) (Prolyl hydroxylase domain-containing protein 2) (PHD2) (SM-20)
Gene Names:
EGLN1 C1orf12 PNAS-118 PNAS-137
Gene Names Orf:
PNAS-118 PNAS-137
Gene Names Primary:
EGLN1
Organism:
Homo sapiens (Human)

Structure

Length:
426
Sequence:
MANDSGGPGGPSPSERDRQYCELCGKMENLLRCSRCRSSFYCCKEHQRQDWKKHKLVCQGSEGALGHGVGPHQHSGPAPPAAVPPPRAGAREPRKAAARRDNASGDAAKGKVKAKPPADPAAAASPCRAAAGGQGSAVAAEAEPGKEEPPARSSLFQEKANLYPPSNTPGDALSPGGGLRPNGQTKPLPALKLALEYIVPCMNKHGICVVDDFLGKETGQQIGDEVRALHDTGKFTDGQLVSQKSDSSKDIRGDKITWIEGKEPGCETIGLLMSSMDDLIRHCNGKLGSYKINGRTKAMVACYPGNGTGYVRHVDNPNGDGRCVTCIYYLNKDWDAKVSGGILRIFPEGKAQFADIEPKFDRLLFFWSDRRNPHEVQPAYATRYAITVWYFDADERARAKVKYLTGEKGVRVELNKPSDSVGKDVF
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cytoplasm

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 HIF1B. 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. EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality. 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;
Kinetics:
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=70 nM for HIF2A
Enzyme Regulation:
ENZYME REGULATION: Following exposure to hypoxia, activated in HeLa cells but not in cardiovascular cells.
Cross Reference Drug Bank:
DB00126
Gene Ontology Go:
cytoplasm
cytosol
nucleus
enzyme binding
iron ion 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
peptidyl-proline 4-dioxygenase activity
peptidyl-proline dioxygenase activity
cardiac muscle tissue morphogenesis
cellular response to hypoxia
heart trabecula formation
labyrinthine layer development
negative regulation of cAMP catabolic process
negative regulation of cyclic-nucleotide phosphodiesterase activity
negative regulation of sequence-specific DNA binding transcription factor activity
oxygen homeostasis
peptidyl-proline hydroxylation to 4-hydroxy-L-proline
regulation of angiogenesis
regulation of transcription from RNA polymerase II promoter in response to hypoxia
response to hypoxia
response to nitric oxide
ventricular septum morphogenesis
Gene Ontology Biological Process:
cardiac muscle tissue morphogenesis
cellular response to hypoxia
heart trabecula formation
labyrinthine layer development
negative regulation of cAMP catabolic process
negative regulation of cyclic-nucleotide phosphodiesterase activity
negative regulation of sequence-specific DNA binding transcription factor activity
oxygen homeostasis
peptidyl-proline hydroxylation to 4-hydroxy-L-proline
regulation of angiogenesis
regulation of transcription from RNA polymerase II promoter in response to hypoxia
response to hypoxia
response to nitric oxide
ventricular septum morphogenesis
Gene Ontology Molecular Function:
enzyme binding
iron ion 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
peptidyl-proline 4-dioxygenase activity
peptidyl-proline dioxygenase activity
Gene Ontology Cellular Component:
cytoplasm
cytosol
nucleus
Keywords:
3D-structure
Acetylation
Alternative splicing
Complete proteome
Congenital erythrocytosis
Cytoplasm
Dioxygenase
Disease mutation
Iron
Metal-binding
Nucleus
Oxidoreductase
Phosphoprotein
Polymorphism
Reference proteome
S-nitrosylation
Vitamin C
Zinc
Zinc-finger
Interacts With:
Q9WMX2; Q99814; Q14318; Q16665; Q13438

Publication

PubMed ID:
11056053 11574160 12788921 17974005 16710414 11595178 11595184 12181324 12351678 12163023 12670503 12615973 15247232 15897452 18063574 19413330 19631610 19339211 19208626 20840591 20838600 20068231 20466884 21269460 21792862 22286099 22814378 24681946 25974097 16782814 19604478 21601578 16407130 17579185 24711448 25129147