Cannabis Compound Database: Showing Protein Egl nine homolog 3 (CDBP04363)

Identification Biological properties Gene properties Protein properties External links References XML Show 5 compounds

Identification

HMDB Protein ID

CDBP04363

Secondary Accession Numbers

Not Available

Name

Egl nine homolog 3

Description

Not Available

Synonyms

HIF-PH3
HIF-prolyl hydroxylase 3
HPH-1
HPH-3
Hypoxia-inducible factor prolyl hydroxylase 3
PHD3
Prolyl hydroxylase domain-containing protein 3

Gene Name

EGLN3

Protein Type

Enzyme

Biological Properties

General Function

Involved in oxidoreductase activity

Specific 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 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.

GO Classification

Biological Process
peptidyl-proline hydroxylation to 4-hydroxy-L-proline
regulation of neuron apoptotic process
protein hydroxylation
regulation of cell proliferation
activation of cysteine-type endopeptidase activity involved in apoptotic process
response to DNA damage stimulus
regulation of transcription from RNA polymerase II promoter in response to hypoxia
Cellular Component
cytosol
nucleoplasm
Function
cation binding
metal ion binding
binding
catalytic activity
transition metal ion binding
l-ascorbic acid binding
iron ion binding
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
vitamin binding
oxidoreductase activity
ion binding
Molecular Function
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
L-ascorbic acid binding
iron ion binding
peptidyl-proline 4-dioxygenase activity
Process
metabolic process
oxidation reduction

Cellular Location

Nucleus
Cytoplasm

Pathways

Name	SMPDB/Pathwhiz	KEGG
HIF-1 signaling pathway	Not Available
Renal cell carcinoma	Not Available
The Oncogenic Action of Succinate		Not Available
The Oncogenic Action of Fumarate		Not Available

Gene Properties

Chromosome Location

Locus

14q13.1

SNPs

EGLN3

Gene Sequence

>720 bp
ATGCCCCTGGGACACATCATGAGGCTGGACCTGGAGAAAATTGCCCTGGAGTACATCGTG
CCCTGTCTGCACGAGGTGGGCTTCTGCTACCTGGACAACTTCCTGGGCGAGGTGGTGGGC
GACTGCGTCCTGGAGCGCGTCAAGCAGCTGCACTGCACCGGGGCCCTGCGGGACGGCCAG
CTGGCGGGGCCGCGCGCCGGCGTCTCCAAGCGACACCTGCGGGGCGACCAGATCACGTGG
ATCGGGGGCAACGAGGAGGGCTGCGAGGCCATCAGCTTCCTCCTGTCCCTCATCGACAGG
CTGGTCCTCTACTGCGGGAGCCGGCTGGGCAAATACTACGTCAAGGAGAGGTCTAAGGCA
ATGGTGGCTTGCTATCCGGGAAATGGAACAGGTTATGTTCGCCACGTGGACAACCCCAAC
GGTGATGGTCGCTGCATCACCTGCATCTACTATCTGAACAAGAATTGGGATGCCAAGCTA
CATGGTGGGATCCTGCGGATATTTCCAGAGGGGAAATCATTCATAGCAGATGTGGAGCCC
ATTTTTGACAGACTCCTGTTCTTCTGGTCAGATCGTAGGAACCCACACGAAGTGCAGCCC
TCTTACGCAACCAGATATGCTATGACTGTCTGGTACTTTGATGCTGAAGAAAGGGCAGAA
GCCAAAAAGAAATTCAGGAATTTAACTAGGAAAACTGAATCTGCCCTCACTGAAGACTGA

Protein Properties

Number of Residues

239

Molecular Weight

27261.06

Theoretical pI

7.636

Pfam Domain Function

2OG-FeII_Oxy (PF03171 )

Signals

Not Available

Transmembrane Regions

Not Available

Protein Sequence

>Egl nine homolog 3
MPLGHIMRLDLEKIALEYIVPCLHEVGFCYLDNFLGEVVGDCVLERVKQLHCTGALRDGQ
LAGPRAGVSKRHLRGDQITWIGGNEEGCEAISFLLSLIDRLVLYCGSRLGKYYVKERSKA
MVACYPGNGTGYVRHVDNPNGDGRCITCIYYLNKNWDAKLHGGILRIFPEGKSFIADVEP
IFDRLLFFWSDRRNPHEVQPSYATRYAMTVWYFDAEERAEAKKKFRNLTRKTESALTED

External Links

GenBank ID Protein

14547150

UniProtKB/Swiss-Prot ID

Q9H6Z9

UniProtKB/Swiss-Prot Entry Name

EGLN3_HUMAN

PDB IDs

Not Available

GenBank Gene ID

AJ310545

GeneCard ID