Egl nine homolog 2

NameEgl nine homolog 2
Synonyms
  • 1.14.11.29
  • EIT6
  • Estrogen-induced tag 6
  • HIF-PH1
  • HIF-prolyl hydroxylase 1
  • HPH-1
  • HPH-3
  • Hypoxia-inducible factor prolyl hydroxylase 1
  • PHD1
  • Prolyl hydroxylase domain-containing protein 1
Gene NameEGLN2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0004339|Egl nine homolog 2
MDSPCQPQPLSQALPQLPGSSSEPLEPEPGRARMGVESYLPCPLLPSYHCPGVPSEASAG
SGTPRATATSTTASPLRDGFGGQDGGELRPLQSEGAAALVTKGCQRLAAQGARPEAPKRK
WAEDGGDAPSPSKRPWARQENQEAEREGGMSCSCSSGSGEASAGLMEEALPSAPERLALD
YIVPCMRYYGICVKDSFLGAALGGRVLAEVEALKRGGRLRDGQLVSQRAIPPRSIRGDQI
AWVEGHEPGCRSIGALMAHVDAVIRHCAGRLGSYVINGRTKAMVACYPGNGLGYVRHVDN
PHGDGRCITCIYYLNQNWDVKVHGGLLQIFPEGRPVVANIEPLFDRLLIFWSDRRNPHEV
KPAYATRYAITVWYFDAKERAAAKDKYQLASGQKGVQVPVSQPPTPT
Number of residues407
Molecular Weight43650.03
Theoretical pI7.97
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
  • oxygen sensor activity
  • ferrous iron binding
  • L-ascorbic acid binding
  • peptidyl-proline 4-dioxygenase activity
Processes
  • intracellular estrogen receptor signaling pathway
  • regulation of cell growth
  • cell redox homeostasis
  • response to hypoxia
  • regulation of neuron apoptotic process
  • cellular response to hypoxia
  • positive regulation of protein catabolic process
  • peptidyl-proline hydroxylation to 4-hydroxy-L-proline
  • regulation of transcription from RNA polymerase II promoter in response to hypoxia
Components
  • 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. 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. Links oxygen sensing to cell cycle and primary cilia formation by hydroxylating the critical centrosome component CEP192 which promotes its ubiquitination and subsequent proteasomal degradation. Hydroxylates IKBKB, mediating NF-kappaB activation in hypoxic conditions. Target proteins are preferentially recognized via a LXXLAP motif.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID14547148
UniProtKB IDQ96KS0
UniProtKB Entry NameEGLN2_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0016715|Egl nine homolog 2 (EGLN2)
ATGGACAGCCCGTGCCAGCCGCAGCCCCTAAGTCAGGCTCTCCCTCAGTTACCAGGGTCT
TCGTCAGAGCCCTTGGAGCCTGAGCCTGGCCGGGCCAGGATGGGAGTGGAGAGTTACCTG
CCCTGTCCCCTGCTCCCCTCCTACCACTGTCCAGGAGTGCCTAGTGAGGCCTCGGCAGGG
AGTGGGACCCCCAGAGCCACAGCCACCTCTACCACTGCCAGCCCTCTTCGGGACGGTTTT
GGCGGGCAGGATGGTGGTGAGCTGCGGCCGCTGCAGAGTGAAGGCGCTGCAGCGCTGGTC
ACCAAGGGGTGCCAGCGATTGGCAGCCCAGGGCGCACGGCCTGAGGCCCCCAAACGGAAA
TGGGCCGAGGATGGTGGGGATGCCCCTTCACCCAGCAAACGGCCCTGGGCCAGGCAAGAG
AACCAGGAGGCAGAGCGGGAGGGTGGCATGAGCTGCAGCTGCAGCAGTGGCAGTGGTGAG
GCCAGTGCTGGGCTGATGGAGGAGGCGCTGCCCTCTGCGCCCGAGCGCCTGGCCCTGGAC
TATATCGTGCCCTGCATGCGGTACTACGGCATCTGCGTCAAGGACAGCTTCCTGGGGGCA
GCACTGGGCGGTCGCGTGCTGGCCGAGGTGGAGGCCCTCAAACGGGGTGGGCGCCTGCGA
GACGGGCAGCTAGTGAGCCAGAGGGCGATCCCGCCGCGCAGCATCCGTGGGGACCAGATT
GCCTGGGTGGAAGGCCATGAACCAGGCTGTCGAAGCATTGGTGCCCTCATGGCCCATGTG
GACGCCGTCATCCGCCACTGCGCAGGGCGGCTGGGCAGCTATGTCATCAACGGGCGCACC
AAGGCCATGGTGGCGTGTTACCCAGGCAACGGGCTCGGGTACGTAAGGCACGTTGACAAT
CCCCACGGCGATGGGCGCTGCATCACCTGTATCTATTACCTGAATCAGAACTGGGACGTT
AAGGTGCATGGCGGCCTGCTGCAGATCTTCCCTGAGGGCCGGCCCGTGGTAGCCAACATC
GAGCCACTCTTTGACCGGTTGCTCATTTTCTGGTCTGACCGGCGGAACCCCCACGAGGTG
AAGCCAGCCTATGCCACCAGGTACGCCATCACTGTCTGGTATTTTGATGCCAAGGAGCGG
GCAGCAGCCAAAGACAAGTATCAGCTAGCATCAGGACAGAAAGGTGTCCAAGTACCTGTA
TCACAGCCGCCTACGCCCACCTAG
GenBank Gene IDAJ310544
GeneCard IDNot Available
GenAtlas IDEGLN2
HGNC IDHGNC:14660
Chromosome Location19
Locus19q13.2
References
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