Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

EGLN1 (Q9GZT9) - Overview - Molecular Target Synopsis

Protein


EGLN1, Egl nine homolog 1
Enzyme Classification 1.14.11.29
UniProt Q9GZT9

Also Known as EGLN1_HUMAN, EGLN1, C1orf12

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. Monomer. Interacts with ING4; the interaction inhibits the hydroxylation of HIF alpha proteins. Interacts with PTGES3 (via PXLE motif); thereby recruiting EGLN1 to the HSP90 pathway to facilitate HIF alpha proteins hydroxylation. Interacts with LIMD1. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2. Interacts with EPAS1. Interacts with CBFA2T3 (PubMed:25974097). Interacts with HIF1A (PubMed:25974097).

5OX5
HIF PROLYL HYDROXYLASE 2 (PHD2/ EGLN1) IN COMPLEX WITH CCT6, A GSK1278863-RELATED COMPOUND
RCSB/PDB
Inspect Structure
See all 3D Structures for EGLN1

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
426ENSG00000135766ENST00000366641ENSP00000355601Q9GZT9-1
404Q9GZT9-2
325Q9GZT9-3

Sub-cellular localization


UniProt: EGLN1 is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: EGLN1 is active in the following subcellular-locations: cytoplasm, cytosol, glutamatergic synapse, nucleus, postsynaptic density.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project EGLN1 has gain in 4 cell-lines, loss in 0 cell-lines and no signal in 1000 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MALME_3M, BT_549, SF_268

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: OVISE, MOR, 888

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: A549, NHLF, HSMM

(see details)

3D Structures


For EGLN1 there are:
32 structures (38 chains) solved
32 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


EGLN1 has been screened with 701 compounds (881 bioactivities), 196 compounds have bioactivities that show binding affinity of <= 500nM (214 bioactivities). (see details)