Hmdb loader
Identification
HMDB Protein ID HMDBP09211
Secondary Accession Numbers
  • 14993
Name Egl nine homolog 2
Synonyms
  1. Estrogen-induced tag 6
  2. HIF-PH1
  3. HIF-prolyl hydroxylase 1
  4. HPH-1
  5. HPH-3
  6. Hypoxia-inducible factor prolyl hydroxylase 1
  7. PHD1
  8. Prolyl hydroxylase domain-containing protein 1
Gene Name EGLN2
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. 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. EGLN2 is involved in regulating hypoxia tolerance and apoptosis in cardiac and skeletal muscle. Also regulates susceptibility to normoxic oxidative neuronal death.
Pathways
  • HIF-1 signaling pathway
  • Renal cell carcinoma
  • The Oncogenic Action of Fumarate
  • The Oncogenic Action of Succinate
Reactions
Hypoxia-inducible factor-L-proline + Oxoglutaric acid + Oxygen → hypoxia-inducible factor-trans-4-hydroxy-L-proline + Succinic acid + CO(2) details
GO Classification
Biological Process
cell redox homeostasis
peptidyl-proline hydroxylation to 4-hydroxy-L-proline
regulation of cell growth
positive regulation of protein catabolic process
regulation of neuron apoptotic process
intracellular estrogen receptor signaling pathway
regulation of transcription from RNA polymerase II promoter in response to hypoxia
Cellular Component
nucleoplasm
Function
ion binding
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
Molecular Function
oxygen sensor activity
ferrous iron binding
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
L-ascorbic acid binding
peptidyl-proline 4-dioxygenase activity
Process
metabolic process
oxidation reduction
Cellular Location
  1. Nucleus
  2. Cytoplasm
Gene Properties
Chromosome Location 19
Locus 19q13.2
SNPs EGLN2
Gene Sequence
>1224 bp
ATGGACAGCCCGTGCCAGCCGCAGCCCCTAAGTCAGGCTCTCCCTCAGTTACCAGGGTCT
TCGTCAGAGCCCTTGGAGCCTGAGCCTGGCCGGGCCAGGATGGGAGTGGAGAGTTACCTG
CCCTGTCCCCTGCTCCCCTCCTACCACTGTCCAGGAGTGCCTAGTGAGGCCTCGGCAGGG
AGTGGGACCCCCAGAGCCACAGCCACCTCTACCACTGCCAGCCCTCTTCGGGACGGTTTT
GGCGGGCAGGATGGTGGTGAGCTGCGGCCGCTGCAGAGTGAAGGCGCTGCAGCGCTGGTC
ACCAAGGGGTGCCAGCGATTGGCAGCCCAGGGCGCACGGCCTGAGGCCCCCAAACGGAAA
TGGGCCGAGGATGGTGGGGATGCCCCTTCACCCAGCAAACGGCCCTGGGCCAGGCAAGAG
AACCAGGAGGCAGAGCGGGAGGGTGGCATGAGCTGCAGCTGCAGCAGTGGCAGTGGTGAG
GCCAGTGCTGGGCTGATGGAGGAGGCGCTGCCCTCTGCGCCCGAGCGCCTGGCCCTGGAC
TATATCGTGCCCTGCATGCGGTACTACGGCATCTGCGTCAAGGACAGCTTCCTGGGGGCA
GCACTGGGCGGTCGCGTGCTGGCCGAGGTGGAGGCCCTCAAACGGGGTGGGCGCCTGCGA
GACGGGCAGCTAGTGAGCCAGAGGGCGATCCCGCCGCGCAGCATCCGTGGGGACCAGATT
GCCTGGGTGGAAGGCCATGAACCAGGCTGTCGAAGCATTGGTGCCCTCATGGCCCATGTG
GACGCCGTCATCCGCCACTGCGCAGGGCGGCTGGGCAGCTATGTCATCAACGGGCGCACC
AAGGCCATGGTGGCGTGTTACCCAGGCAACGGGCTCGGGTACGTAAGGCACGTTGACAAT
CCCCACGGCGATGGGCGCTGCATCACCTGTATCTATTACCTGAATCAGAACTGGGACGTT
AAGGTGCATGGCGGCCTGCTGCAGATCTTCCCTGAGGGCCGGCCCGTGGTAGCCAACATC
GAGCCACTCTTTGACCGGTTGCTCATTTTCTGGTCTGACCGGCGGAACCCCCACGAGGTG
AAGCCAGCCTATGCCACCAGGTACGCCATCACTGTCTGGTATTTTGATGCCAAGGAGCGG
GCAGCAGCCAAAGACAAGTATCAGCTAGCATCAGGACAGAAAGGTGTCCAAGTACCTGTA
TCACAGCCGCCTACGCCCACCTAG
Protein Properties
Number of Residues 407
Molecular Weight 43650.03
Theoretical pI 7.908
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Egl nine homolog 2
MDSPCQPQPLSQALPQLPGSSSEPLEPEPGRARMGVESYLPCPLLPSYHCPGVPSEASAG
SGTPRATATSTTASPLRDGFGGQDGGELRPLQSEGAAALVTKGCQRLAAQGARPEAPKRK
WAEDGGDAPSPSKRPWARQENQEAEREGGMSCSCSSGSGEASAGLMEEALPSAPERLALD
YIVPCMRYYGICVKDSFLGAALGGRVLAEVEALKRGGRLRDGQLVSQRAIPPRSIRGDQI
AWVEGHEPGCRSIGALMAHVDAVIRHCAGRLGSYVINGRTKAMVACYPGNGLGYVRHVDN
PHGDGRCITCIYYLNQNWDVKVHGGLLQIFPEGRPVVANIEPLFDRLLIFWSDRRNPHEV
KPAYATRYAITVWYFDAKERAAAKDKYQLASGQKGVQVPVSQPPTPT
GenBank ID Protein 14547148
UniProtKB/Swiss-Prot ID Q96KS0
UniProtKB/Swiss-Prot Entry Name EGLN2_HUMAN
PDB IDs Not Available
GenBank Gene ID AJ310544
GeneCard ID EGLN2
GenAtlas ID EGLN2
HGNC ID HGNC:14660
References
General References
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