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Tclin
EGLN3
Egl nine homolog 3

Protein Summary
Description
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. Hydroxylation on the NODD site by EGLN3 appears to require prior hydroxylation on the CODD site. 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. EGLN3 is the most important isozyme in limiting physiological activation of HIFs (particularly HIF2A) in hypoxia. Also hydroxylates PKM in hypoxia, limi ...more
Uniprot Accession IDs
Gene Name
Ensembl ID
  • ENST00000250457
  • ENSP00000250457
  • ENSG00000129521

Symbol
  • PHD3
  • HIFPH3
  • HIFP4H3
Illumination Graph
Knowledge Table
Most Knowledge About
Knowledge Value (0 to 1 scale)
gene perturbation
0.96
PubMedID
0.95
kinase perturbation
0.91
microRNA
0.83
biological process
0.79


IDG Development Level Summary
Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 126.64   (req: < 5)
Gene RIFs: 68   (req: <= 3)
Antibodies: 440   (req: <= 50)
Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 126.64   (req: >= 5)
Gene RIFs: 68   (req: > 3)
Antibodies: 440   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 13
Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 82
Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 1
Approved Drugs (1)
1 – 1 of 1
roxadustat
chemical structure image
Pathways (31)
Cellular response to hypoxia (R-HSA-1234174)

Click on a row in the table to change the structure displayed.

Items per page:
1 – 4 of 4
Data Source
Name
Explore in Pharos
Explore in Source
Reactome
Cellular response to hypoxia
Reactome
Cellular responses to external stimuli
Reactome
Cellular responses to stress
Reactome
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
Name
Explore in Pharos
Explore in Source
Cellular response to hypoxia
Cellular responses to external stimuli
Cellular responses to stress
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
Gene Ontology Terms (17)
Items per page:
10
1 – 4 of 4
GO Term
Evidence
Assigned by
Inferred from Direct Assay (IDA)
MGI
Inferred from Direct Assay (IDA)
FlyBase
Inferred from Electronic Annotation (IEA)
InterPro
Inferred from Electronic Annotation (IEA)
UniProtKB-KW
Protein-Protein Interactions (158)
1 – 10 of 158
SBDS
Tbio
Novelty: 0.00526647
p_int: 0.999984597
p_ni: 0.000015403
Data Source: BioPlex
CCT6B
Tdark
Novelty: 0.35608309
p_int: 0.993218455
p_ni: 0.006781544
p_wrong: 1e-9
Data Source: BioPlex
ACACA
Tchem
Family: Enzyme
Novelty: 0.00198949
p_int: 0.984992108
p_ni: 0.015007892
Data Source: BioPlex
HIF1A
Tchem
Family: TF
Novelty: 0.00031917
Score: 0.991
Data Source: Reactome,STRINGDB
EPAS1
Tchem
Novelty: 0.00460751
Score: 0.983
Data Source: Reactome,STRINGDB
VHL
Tchem
Family: Enzyme
Novelty: 0.00323188
Score: 0.982
Data Source: Reactome,STRINGDB
HIF3A
Tbio
Novelty: 0.00260684
Score: 0.976
Data Source: Reactome,STRINGDB
ELOC
Tbio
Novelty: 0.0146568
Score: 0.954
Data Source: Reactome,STRINGDB
OS9
Tbio
Novelty: 0.01598375
Score: 0.952
Data Source: STRINGDB
CUL2
Tbio
Novelty: 0.00892549
Score: 0.946
Data Source: Reactome,STRINGDB
Publication Statistics
PubMed Score  126.64

PubMed score by year
PubTator Score  110.98

PubTator score by year
Amino Acid Sequence
Residue Counts
Sequence
MPLGHIMRLDLEKIALEYIVPCLHEVGFCYLDNFLGEVVGDCVLERVKQLHCTGALRDGQLAGPRAGVSK
1-70
RHLRGDQITWIGGNEEGCEAISFLLSLIDRLVLYCGSRLGKYYVKERSKAMVACYPGNGTGYVRHVDNPN
70-140
GDGRCITCIYYLNKNWDAKLHGGILRIFPEGKSFIADVEPIFDRLLFFWSDRRNPHEVQPSYATRYAMTV
140-210
WYFDAEERAEAKKKFRNLTRKTESALTED
210-239
MPLGHIMRLDLEKIALEYIVPCLHEVGFCYLDNFLGEVVGDCVLERVKQLHCTGALRDGQLAGPRAGVSKRHLRGDQITWIGGNEEGCEAISFLLSLIDRLVLYCGSRLGKYYVKERSKAMVACYPGNGTGYVRHVDNPNGDGRCITCIYYLNKNWDAKLHGGILRIFPEGKSFIADVEPIFDRLLFFWSDRRNPHEVQPSYATRYAMTVWYFDAEERAEAKKKFRNLTRKTESALTED