P59722
uniprot
P59722
canonical
activity_regulation
ACTIVITY REGULATION: Increased activation in hypoxia. Hydroxylation of the C-terminal ODD domain (CODD) proline of HIF1A is activated by cyclosporin A (CsA). {ECO:0000269|PubMed:12586829, ECO:0000269|PubMed:12876291}.
uniprot
proteins
amino_acid_sequence
PRAQPAPAQPRVAPPPGGAPGAARAGGAARRGDSSTAASRVPGPEDATQAGSGPGPAEPSSEDPPPSRSPGPERASLCPAGGGPGEALSPSGGLRPNGQTKPLPALKLALEYIVPCMNKHGICVVDDFLGRETGQQIGDEVRALHDTGKFTDGQLVSQKSDSSKDIRGDKITWIEGKEPGCETIGLLMSSMDDLIRHCSGKLGNYRINGRTKAMVACYPGNGTGYVRHVDNPNGDGRCVTCIYYLNKDWDAKVSGGILRIFPEGKAQFADIEPKFDRLLFFWSDRRNPHEVQPAYATRYAITVWYFDADERARAKVKYLTGEKGVRVELKPNSVSKDV
uniprot
proteins
ec_number
1.14.11.29
uniprot
proteins
function
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 preferentially recognized via a LXXLAP motif. {ECO:0000250|UniProtKB:Q9GZT9, ECO:0000269|PubMed:12586829}.
uniprot
proteins
mass_dalton
36093
uniprot
proteins
post_translational_modification
PTM: S-nitrosylation inhibits the enzyme activity up to 60% under aerobic conditions. Chelation of Fe(2+) has no effect on the S-nitrosylation. It is uncertain whether nitrosylation occurs on Cys-238 or Cys-241. {ECO:0000250|UniProtKB:Q9GZT9}.
uniprot
proteins
pubmed
12586829
uniprot
proteins
pubmed
12876291
uniprot
proteins
pubmed
15057822
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16765982
uniprot
proteins
sequence_length
338
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16765982}. Nucleus {ECO:0000269|PubMed:16765982}. Note=Mainly cytoplasmic. Shuttles between the nucleus and cytoplasm. Nuclear export requires functional XPO1. {ECO:0000250|UniProtKB:Q9GZT9}.
uniprot
proteins