TARGETID

T53904

FORMERID

TTDC00054

UNIPROID

EGLN2_HUMAN

TARGNAME

HIF-prolyl hydroxylase 1 (HPH-1)

GENENAME

EGLN2

TARGTYPE

Clinical trial target

SYNONYMS

Prolyl hydroxylase domain-containing protein 1; PHD1; Hypoxia-inducible factor prolyl hydroxylase 1; HPH-3; HIF-PH1; HIF-PH; Estrogen-induced tag6; Estrogen-induced tag 6; Egl nine homolog 2; EIT6; EIT-6

FUNCTION

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. Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins.

PDBSTRUC

5V1B

BIOCLASS

Paired donor oxygen oxidoreductase

ECNUMBER

EC 1.14.11.29

SEQUENCE

MDSPCQPQPLSQALPQLPGSSSEPLEPEPGRARMGVESYLPCPLLPSYHCPGVPSEASAGSGTPRATATSTTASPLRDGFGGQDGGELRPLQSEGAAALVTKGCQRLAAQGARPEAPKRKWAEDGGDAPSPSKRPWARQENQEAEREGGMSCSCSSGSGEASAGLMEEALPSAPERLALDYIVPCMRYYGICVKDSFLGAALGGRVLAEVEALKRGGRLRDGQLVSQRAIPPRSIRGDQIAWVEGHEPGCRSIGALMAHVDAVIRHCAGRLGSYVINGRTKAMVACYPGNGLGYVRHVDNPHGDGRCITCIYYLNQNWDVKVHGGLLQIFPEGRPVVANIEPLFDRLLIFWSDRRNPHEVKPAYATRYAITVWYFDAKERAAAKDKYQLASGQKGVQVPVSQPPTPT

DRUGINFO

FG-4592

DRUGINFO

GSK1278863

DRUGINFO

BAY-85-3934

DRUGINFO

2-(carboxymethylamino)-2-oxoacetic acid

DRUGINFO

Pyridine-2,4-dicarboxylic acid

KEGGPATH

hsa04066:HIF-1 signaling pathway

KEGGPATH

hsa05200:Pathways in cancer

KEGGPATH

hsa05211:Renal cell carcinoma