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, limiting glycolysis. Under normoxia, hydroxylates and regulates the stability of ADRB2. Regulator of cardiomyocyte and neuronal apoptosis. In cardiomyocytes, inhibits the anti-apoptotic effect of BCL2 by disrupting the BAX-BCL2 complex. In neurons, has a NGF-induced proapoptotic effect, probably through regulating CASP3 activity. Also essential for hypoxic regulation of neutrophilic inflammation. Plays a crucial role in DNA damage response (DDR) by hydroxylating TELO2, promoting its interaction with ATR which is required for activation of the ATR/CHK1/p53 pathway. Target proteins are preferentially recognized via a LXXLAP motif.

Uniprot Accession IDs

• Q9H6Z9
• Q2TA79
• Q3B8N4
• Q6P1R2

Gene Name

• EGLN3

Ensembl ID

• ENST00000250457
• ENSP00000250457
• ENSG00000129521

Symbol

• PHD3
• HIFPH3
• HIFP4H3

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

Protein Classes

No PANTHER Classes or DTO Classes found

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: 192.75   (req: < 5)

Gene RIFs: 84   (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: 192.75   (req: >= 5)

Gene RIFs: 84   (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: 112

Tclin

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

Active Drugs: 5