InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: EGLN1

Summary

InnateDB Protein

IDBP-107433.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

EGLN1

Protein Name

egl nine homolog 1 (C. elegans)

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000355601

InnateDB Gene

IDBG-107429 (EGLN1)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:11595184, ECO:0000269PubMed:12181324, ECO:0000269PubMed:12351678, ECO:0000269PubMed:15897452, ECO:0000269PubMed:19339211, ECO:0000269PubMed:21792862}.

Subcellular Localization

Cytoplasm. Nucleus. Note=Mainly cytoplasmic. Shuttles between the nucleus and cytoplasm. Nuclear export requires functional XPO1.

Disease Associations

Erythrocytosis, familial, 3 (ECYT3) [MIM:609820]: An autosomal dominant disorder characterized by increased serum red blood cell mass, elevated serum hemoglobin and hematocrit, and normal serum erythropoietin levels. {ECO:0000269PubMed:16407130, ECO:0000269PubMed:17579185}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

According to PubMed:11056053, widely expressed with highest levels in skeletal muscle and heart, moderate levels in pancreas, brain (dopaminergic neurons of adult and fetal substantia nigra) and kidney, and lower levels in lung and liver. According to PubMed:12351678 widely expressed with highest levels in brain, kidney and adrenal gland. Expressed in cardiac myocytes, aortic endothelial cells and coronary artery smooth muscle. According to PubMed:12788921; expressed in adult and fetal heart, brain, liver, lung, skeletal muscle and kidney. Also expressed in placenta. Highest levels in adult heart, brain, lung and liver and fetal brain, heart spleen and skeletal muscle. {ECO:0000269PubMed:11056053, ECO:0000269PubMed:12163023, ECO:0000269PubMed:12670503, ECO:0000269PubMed:12788921}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 41 experimentally validated interaction(s) in this database.

Experimentally validated
Total	41 [view]
Protein-Protein	41 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005506	iron ion binding
GO:0005515	protein binding
GO:0016491	oxidoreductase activity
GO:0016705	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
GO:0016706	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 donors
GO:0019899	enzyme binding
GO:0031418	L-ascorbic acid binding
GO:0031543	peptidyl-proline dioxygenase activity
GO:0031545	peptidyl-proline 4-dioxygenase activity

Biological Process

GO:0001666	response to hypoxia
GO:0018401	peptidyl-proline hydroxylation to 4-hydroxy-L-proline
GO:0030821	negative regulation of cAMP catabolic process
GO:0032364	oxygen homeostasis
GO:0043433	negative regulation of sequence-specific DNA binding transcription factor activity
GO:0045765	regulation of angiogenesis
GO:0051344	negative regulation of cyclic-nucleotide phosphodiesterase activity
GO:0055008	cardiac muscle tissue morphogenesis
GO:0055114	oxidation-reduction process
GO:0060347	heart trabecula formation
GO:0060412	ventricular septum morphogenesis
GO:0060711	labyrinthine layer development
GO:0061418	regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:0071456	cellular response to hypoxia
GO:0071731	response to nitric oxide