InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Egln1

Summary

InnateDB Protein

IDBP-200542.6

Last Modified

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

Gene Symbol

Egln1

Protein Name

EGL nine homolog 1 (C. elegans)

Synonyms

AI503754; C1orf12; Hif-p4h-2; HIF-PH2; HPH-2; ORF13; Phd2; SM-20;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000034469

InnateDB Gene

IDBG-200540 (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:18096761, ECO:0000269PubMed:18500250, ECO:0000269PubMed:21435465}.

Subcellular Localization

Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. Note=Mainly cytoplasmic. Shuttles between the nucleus and cytoplasm. Nuclear export requires functional XPO1 (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

Expressed in heart, brain liver, skeletal muscle and kidney. Low levels were detected in the lung. Constitutively expressed during differentiation of C2C12 skeletal myocytes. {ECO:0000269PubMed:12234095}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 1 experimentally validated interaction(s) in this database.
They are also associated with 18 interaction(s) predicted by orthology.

Experimentally validated
Total	1 [view]
Protein-Protein	1 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	18 [view]

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:0071731	response to nitric oxide