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.  
6
  • CuratedUniProtKB
GO molecular function 
Enzyme bindingdefinition[GO:0019899]  
  • ISSOrtholog Curator
Iron ion bindingdefinition[GO:0005506] silver  
  • IEAInterPro 2 GO
L-ascorbic acid bindingdefinition[GO:0031418]  
  • IEAUniProtKB KW
Peptidyl-proline 4-dioxygenase activitydefinition[GO:0031545]  
1
  • IDAFlyBase
Peptidyl-proline dioxygenase activitydefinition[GO:0031543]  
1
  • TASHGNC
Protein bindingdefinition[GO:0005515]  
5
  • IPIUniProtKB
  • IPIIntAct
GO biological process 
Cardiac muscle tissue morphogenesisdefinition[GO:0055008] silver  
  • IEAOrtholog Compara
Heart trabecula formationdefinition[GO:0060347] silver  
  • IEAOrtholog Compara
Labyrinthine layer developmentdefinition[GO:0060711] silver  
  • IEAOrtholog Compara
Negative regulation of cAMP catabolic processdefinition[GO:0030821]  
  • ISSOrtholog Curator
Negative regulation of cyclic-nucleotide phosphodiesterase activitydefinition[GO:0051344]  
  • ISSOrtholog Curator
Negative regulation of sequence-specific DNA binding transcription factor activitydefinition[GO:0043433]  
1
  • IDAHGNC
Oxygen homeostasisdefinition[GO:0032364]  
1
  • IDAHGNC
Peptidyl-proline hydroxylation to 4-hydroxy-L-prolinedefinition[GO:0018401]  
1
  • IDAFlyBase
Regulation of angiogenesisdefinition[GO:0045765]  
  • ISSOrtholog Curator
Response to hypoxiadefinition[GO:0001666]  
1
  • IDAHGNC
Response to nitric oxidedefinition[GO:0071731]  
1
  • IDAUniProtKB
Ventricular septum morphogenesisdefinition[GO:0060412] silver  
  • IEAOrtholog 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).  
  • CuratedUniProtKB
It requires the following cofactors
Binds 1 Fe(2+) ion per subunit.  
  • CuratedUniProtKB
Ascorbate.  
  • CuratedUniProtKB
It is regulated in the following manner
Following exposure to hypoxia, activated in HeLa cells but not in cardiovascular cells.  
2
  • CuratedUniProtKB
 
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:
Cellular responses to stress  REACT_120956  
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.  
  • CuratedUniProtKB
 

Keywords

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

Further external links

GeneWiki: EGLN1
GenomeRNAi: 54583
PRO: PR:Q9GZT9