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NameEgl nine homolog 3
Synonyms
  • 1.14.11.29
  • HIF-PH3
  • HIF-prolyl hydroxylase 3
  • HPH-1
  • HPH-3
  • Hypoxia-inducible factor prolyl hydroxylase 3
  • PHD3
  • Prolyl hydroxylase domain-containing protein 3
Gene NameEGLN3
OrganismHuman
Amino acid sequence
>lcl|BSEQ0016716|Egl nine homolog 3
MPLGHIMRLDLEKIALEYIVPCLHEVGFCYLDNFLGEVVGDCVLERVKQLHCTGALRDGQ
LAGPRAGVSKRHLRGDQITWIGGNEEGCEAISFLLSLIDRLVLYCGSRLGKYYVKERSKA
MVACYPGNGTGYVRHVDNPNGDGRCITCIYYLNKNWDAKLHGGILRIFPEGKSFIADVEP
IFDRLLFFWSDRRNPHEVQPSYATRYAMTVWYFDAEERAEAKKKFRNLTRKTESALTED
Number of residues239
Molecular Weight27261.06
Theoretical pI7.7
GO Classification
Functions
  • 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
  • L-ascorbic acid binding
  • peptidyl-proline 4-dioxygenase activity
  • iron ion binding
Processes
  • regulation of transcription from RNA polymerase II promoter in response to hypoxia
  • cellular response to DNA damage stimulus
  • regulation of cell proliferation
  • apoptotic process
  • response to hypoxia
  • regulation of neuron apoptotic process
  • cellular response to hypoxia
  • activation of cysteine-type endopeptidase activity involved in apoptotic process
  • protein hydroxylation
  • peptidyl-proline hydroxylation to 4-hydroxy-L-proline
Components
  • cytoplasm
  • nucleus
  • cytosol
  • nucleoplasm
General FunctionPeptidyl-proline 4-dioxygenase activity
Specific FunctionCellular 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.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID14547150
UniProtKB IDQ9H6Z9
UniProtKB Entry NameEGLN3_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0016717|Egl nine homolog 3 (EGLN3)
ATGCCCCTGGGACACATCATGAGGCTGGACCTGGAGAAAATTGCCCTGGAGTACATCGTG
CCCTGTCTGCACGAGGCAATGGTGGCTTGCTATCCGGGAAATGGAACAGGTTATGTTCGC
CACGTGGACAACCCCAACGGTGATGGTCGCTGCATCACCTGCATCTACTATCTGAACAAG
AATTGGGATGCCAAGCTACATGGTGGGATCCTGCGGATATTTCCAGAGGGGAAATCATTC
ATAGCAGATGTGGAGCCCATTTTTGACAGACTCCTGTTCTTCTGGTCAGATCGTAGGAAC
CCACACGAAGTGCAGCCCTCTTACGCAACCAGATATGCTATGACTGTCTGGTACTTTGAT
GCTGAAGAAAGGGCAGAAGCCAAAAAGAAATTCAGGAATTTAACTAGGAAAACTGAATCT
GCCCTCACTGAAGACTGA
GenBank Gene IDAJ310545
GeneCard IDNot Available
GenAtlas IDEGLN3
HGNC IDHGNC:14661
Chromosome Location14
Locus14q13.1
References
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