TARGETID

T32880

FORMERID

TTDI02433

UNIPROID

EGLN1_HUMAN

TARGNAME

HIF-prolyl hydroxylase 2 (HPH-2)

GENENAME

EGLN1

TARGTYPE

Patented-recorded target

SYNONYMS

SM-20; Prolyl hydroxylase domain-containing protein 2; PHD2; Hypoxia-inducible factor prolyl hydroxylase 2; HPH-2; HIF-PH2; Egl nine homolog 1; C1orf12

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.

PDBSTRUC

6NMQ; 5V18; 5OX6; 5OX5; 5LBF

BIOCLASS

Paired donor oxygen oxidoreductase

ECNUMBER

EC 1.14.11.29

SEQUENCE

MANDSGGPGGPSPSERDRQYCELCGKMENLLRCSRCRSSFYCCKEHQRQDWKKHKLVCQGSEGALGHGVGPHQHSGPAPPAAVPPPRAGAREPRKAAARRDNASGDAAKGKVKAKPPADPAAAASPCRAAAGGQGSAVAAEAEPGKEEPPARSSLFQEKANLYPPSNTPGDALSPGGGLRPNGQTKPLPALKLALEYIVPCMNKHGICVVDDFLGKETGQQIGDEVRALHDTGKFTDGQLVSQKSDSSKDIRGDKITWIEGKEPGCETIGLLMSSMDDLIRHCNGKLGSYKINGRTKAMVACYPGNGTGYVRHVDNPNGDGRCVTCIYYLNKDWDAKVSGGILRIFPEGKAQFADIEPKFDRLLFFWSDRRNPHEVQPAYATRYAITVWYFDADERARAKVKYLTGEKGVRVELNKPSDSVGKDVF

DRUGINFO

FG-4592

DRUGINFO

US10100051, Compound 1

DRUGINFO

US10100051, Compound 10

DRUGINFO

US10100051, Compound 11

DRUGINFO

US10100051, Compound 2

DRUGINFO

US10149841, Compound 1

DRUGINFO

US10149841, Compound 19

DRUGINFO

US10149841, Compound 5