EGLN2
entrez
112398
canonical
uniprot
Q96KS0
canonical
ensembl
ENSG00000269858
resolver
ensp
ENSP00000307080
resolver
ensp
ENSP00000385253
resolver
genesymbol
EGLN2
resolver
genesymbol_syn
EIT6
resolver
hgnc
HGNC:14660
resolver
uniprot
A8K5S0
resolver
uniprot
Q8WWY4
resolver
uniprot
Q9BV14
resolver
uniprot_entry
EGLN2_HUMAN
resolver
uniprot_sec
A8K5S0
resolver
uniprot_sec
Q8WWY4
resolver
uniprot_sec
Q9BV14
resolver
amino_acid_sequence
MDSPCQPQPLSQALPQLPGSSSEPLEPEPGRARMGVESYLPCPLLPSYHCPGVPSEASAGSGTPRATATSTTASPLRDGFGGQDGGELRPLQSEGAAALVTKGCQRLAAQGARPEAPKRKWAEDGGDAPSPSKRPWARQENQEAEREGGMSCSCSSGSGEASAGLMEEALPSAPERLALDYIVPCMRYYGICVKDSFLGAALGGRVLAEVEALKRGGRLRDGQLVSQRAIPPRSIRGDQIAWVEGHEPGCRSIGALMAHVDAVIRHCAGRLGSYVINGRTKAMVACYPGNGLGYVRHVDNPHGDGRCITCIYYLNQNWDVKVHGGLLQIFPEGRPVVANIEPLFDRLLIFWSDRRNPHEVKPAYATRYAITVWYFDAKERAAAKDKYQLASGQKGVQVPVSQPPTPT
uniprot
proteins
ec_number
1.14.11.-
uniprot
proteins
ec_number
1.14.11.29
uniprot
proteins
function
FUNCTION: Prolyl hydroxylase that mediates hydroxylation of proline residues in target proteins, such as ATF4, IKBKB, CEP192 and HIF1A (PubMed:11595184, PubMed:12039559, PubMed:15925519, PubMed:16509823, PubMed:17114296, PubMed:23932902). Target proteins are preferentially recognized via a LXXLAP motif (PubMed:11595184, PubMed:12039559, PubMed:15925519). Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins (PubMed:11595184, PubMed:12039559, PubMed:12181324, PubMed:15925519, PubMed:19339211). Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A (PubMed:11595184, PubMed:12039559, PubMed:12181324, PubMed:15925519). Also hydroxylates HIF2A (PubMed:11595184, PubMed:12039559, PubMed:15925519). Has a preference for the CODD site for both HIF1A and HIF2A (PubMed:11595184, PubMed:12039559, PubMed:15925519). Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex (PubMed:11595184, PubMed:12039559, PubMed:15925519). 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 (PubMed:11595184, PubMed:12039559, PubMed:15925519). EGLN2 is involved in regulating hypoxia tolerance and apoptosis in cardiac and skeletal muscle (PubMed:11595184, PubMed:12039559, PubMed:15925519). Also regulates susceptibility to normoxic oxidative neuronal death (PubMed:11595184, PubMed:12039559, PubMed:15925519). 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 (PubMed:23932902). Hydroxylates IKBKB, mediating NF-kappa-B activation in hypoxic conditions (PubMed:17114296). Also mediates hydroxylation of ATF4, leading to decreased protein stability of ATF4 (By similarity). {ECO:0000250|UniProtKB:Q91YE2, ECO:0000269|PubMed:11595184, ECO:0000269|PubMed:12039559, ECO:0000269|PubMed:12181324, ECO:0000269|PubMed:15925519, ECO:0000269|PubMed:16509823, ECO:0000269|PubMed:17114296, ECO:0000269|PubMed:19339211, ECO:0000269|PubMed:23932902}.
uniprot
proteins
mass_dalton
43650
uniprot
proteins
mutagenesis
MUTAGEN 1; /note="M->A: Leads to expression of isoform p40 only."; /evidence="ECO:0000269|PubMed:16509823"; MUTAGEN 34; /note="M->A: Leads to expression of isoform p43 only."; /evidence="ECO:0000269|PubMed:16509823"; MUTAGEN 102; /note="K->A: Retained in the nucleus."; /evidence="ECO:0000269|PubMed:19339211"; MUTAGEN 106; /note="R->A: Retained in the nucleus."; /evidence="ECO:0000269|PubMed:19339211"; MUTAGEN 113; /note="R->A: Retained in the nucleus."; /evidence="ECO:0000269|PubMed:19339211"; MUTAGEN 119; /note="R->A: Cytoplasmic and nuclear localization. Reduced transcriptional activity of HIF1A as for wild type."; /evidence="ECO:0000269|PubMed:19339211"; MUTAGEN 134; /note="R->A: Retained in the nucleus."; /evidence="ECO:0000269|PubMed:19339211"; MUTAGEN 297; /note="H->A: Eliminates hydroxylase activity."; /evidence="ECO:0000269|PubMed:12039559"; MUTAGEN 299; /note="D->A: Eliminates hydroxylase activity."; /evidence="ECO:0000269|PubMed:12039559"; MUTAGEN 358; /note="H->A: Eliminates hydroxylase activity."; /evidence="ECO:0000269|PubMed:11595184, ECO:0000269|PubMed:12039559"; MUTAGEN 367; /note="R->A: Eliminates hydroxylase activity."; /evidence="ECO:0000269|PubMed:12039559"; MUTAGEN 367; /note="R->K: Eliminates hydroxylase activity on a HIF1A peptide."; /evidence="ECO:0000269|PubMed:12039559
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated by SIAH1 and/or SIAH2 in response to the unfolded protein response (UPR), leading to its degradation. {ECO:0000250|UniProtKB:Q91YE2}.
uniprot
proteins
pubmed
11574160
uniprot
proteins
pubmed
11595178
uniprot
proteins
pubmed
11595184
uniprot
proteins
pubmed
11850811
uniprot
proteins
pubmed
12039559
uniprot
proteins
pubmed
12163023
uniprot
proteins
pubmed
12181324
uniprot
proteins
pubmed
12615973
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15057824
uniprot
proteins
pubmed
15247232
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15925519
uniprot
proteins
pubmed
16509823
uniprot
proteins
pubmed
17114296
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
19339211
uniprot
proteins
pubmed
19631610
uniprot
proteins
pubmed
21410436
uniprot
proteins
pubmed
22286099
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23932902
uniprot
proteins
pubmed
28594552
uniprot
proteins
sequence_length
407
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12163023, ECO:0000269|PubMed:12615973, ECO:0000269|PubMed:19339211, ECO:0000269|PubMed:19631610}.
uniprot
proteins