EGLN1 - Egl nine homolog 1 - human protein (Function)
 
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Protein
Gene
References

 
EGLN1 »  Egl nine homolog 1   [ EC 1.14.11.29 ]
 
Protein also known as:  Prolyl hydroxylase domain-containing protein 2 (PHD2).
Gene name:  EGLN1
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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 preferencially recognized via a LXXLAP motif.  
8
  • UniProtKB
GO molecular function 
Enzyme bindingdefinition[GO:0019899]  
1
  • Ortholog Curator
Iron ion bindingdefinition[GO:0005506] silver  
1
  • InterPro 2 GO
L-ascorbic acid bindingdefinition[GO:0031418]  
1
  • UniProtKB KW
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 donorsdefinition[GO:0016706]  
1
  • MGI
Peptidyl-proline 4-dioxygenase activitydefinition[GO:0031545]  
1
  • FlyBase
Peptidyl-proline dioxygenase activitydefinition[GO:0031543]  
1
  • HGNC
Protein bindingdefinition[GO:0005515]  
7
  • UniProtKB
  • IntAct
GO biological process 
Cardiac muscle tissue morphogenesisdefinition[GO:0055008] silver  
1
  • Ortholog Compara
Heart trabecula formationdefinition[GO:0060347] silver  
1
  • Ortholog Compara
Labyrinthine layer developmentdefinition[GO:0060711] silver  
1
  • Ortholog Compara
Negative regulation of cAMP catabolic processdefinition[GO:0030821]  
1
  • Ortholog Curator
Negative regulation of cyclic-nucleotide phosphodiesterase activitydefinition[GO:0051344]  
1
  • Ortholog Curator
Negative regulation of sequence-specific DNA binding transcription factor activitydefinition[GO:0043433]  
1
  • HGNC
Oxidation-reduction processdefinition[GO:0055114]  
1
  • UniProtKB KW
Oxygen homeostasisdefinition[GO:0032364]  
1
  • HGNC
Peptidyl-proline hydroxylation to 4-hydroxy-L-prolinedefinition[GO:0018401]  
1
  • FlyBase
Regulation of angiogenesisdefinition[GO:0045765]  
1
  • Ortholog Curator
Response to hypoxiadefinition[GO:0001666]  
1
  • HGNC
Response to nitric oxidedefinition[GO:0071731]  
1
  • UniProtKB
Ventricular septum morphogenesisdefinition[GO:0060412] silver  
1
  • Ortholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 1.14.11.29: Hypoxia-inducible factor-L-proline + 2-oxoglutarate + O(2) hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO(2).  
2
  • UniProtKB
It requires the following cofactors
 Fe(2+) : Binds 1 Fe(2+) ion per subunit.  
4
  • UniProtKB
  • PROSITE-ProRule
 L-ascorbate  
2
  • UniProtKB
It is regulated in the following manner
Following exposure to hypoxia, activated in HeLa cells but not in cardiovascular cells.  
3
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Pathways in cancer  hsa05200+54583  
Renal cell carcinoma  hsa05211+54583  
According to Reactome, this protein belongs to the following pathway:
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha  REACT_120916  
Caution 
It was previously reported that this protein was the ortholog of rat SM-20. However, EGLN3 is now considered the true ortholog of rat SM-20 since it shows substantially greater similarity.  
1
  • UniProtKB
 

Biophysicochemical properties

Kinetic parameters
KM 1.3 uM for 2-oxoglutarate
KM 70 nM for HIF2A
KM 150 uM for O(2)

Keywords

Molecular function 
Dioxygenase  definition   [KW-0223]
Oxidoreductase  definition   [KW-0560]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: EGLN1
GenomeRNAi: 54583
PRO: PR:Q9GZT9
Chemistry
GuidetoPHARMACOLOGY: 2833