Search Results

Overview

Uniprot ID	Q9GZT9
Protein Name	Egl nine homolog 1
Gene Name	EGLN1
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
244	DGQLVSQKSDSSKDI
408	VKYLTGEKGVRVELN

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

Protein Sequence

10 MANDSGGPGG 20 PSPSERDRQY 30 CELCGKMENL 40 LRCSRCRSSF 50 YCCKEHQRQD 60 WKKHKLVCQG 70 SEGALGHGVG 80 PHQHSGPAPP 90 AAVPPPRAGA 100 REPRKAAARR 110 DNASGDAAKG 120 KVKAKPPADP 130 AAAASPCRAA 140 AGGQGSAVAA 150 EAEPGKEEPP 160 ARSSLFQEKA 170 NLYPPSNTPG 180 DALSPGGGLR 190 PNGQTKPLPA 200 LKLALEYIVP 210 CMNKHGICVV 220 DDFLGKETGQ 230 QIGDEVRALH 240 DTGKFTDGQL 250 VSQKSDSSKD 260 IRGDKITWIE 270 GKEPGCETIG 280 LLMSSMDDLI 290 RHCNGKLGSY 300 KINGRTKAMV 310 ACYPGNGTGY 320 VRHVDNPNGD 330 GRCVTCIYYL 340 NKDWDAKVSG 350 GILRIFPEGK 360 AQFADIEPKF 370 DRLLFFWSDR 380 RNPHEVQPAY 390 ATRYAITVWY 400 FDADERARAK 410 VKYLTGEKGV 420 RVELNKPSDS VGKDVF

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0098978	glutamatergic synapse
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0014069	postsynaptic density
Molecular Function	GO:0016706	2-oxoglutarate-dependent dioxygenase activity
Molecular Function	GO:0019899	enzyme binding
Molecular Function	GO:0004857	enzyme inhibitor activity
Molecular Function	GO:0008198	ferrous iron binding
Molecular Function	GO:0160082	hypoxia-inducible factor-proline dioxygenase activity
Molecular Function	GO:0031418	L-ascorbic acid binding
Molecular Function	GO:0031545	peptidyl-proline 4-dioxygenase activity
Molecular Function	GO:0031543	peptidyl-proline dioxygenase activity
Molecular Function	GO:0008270	zinc ion binding
Biological Process	GO:0071456	cellular response to hypoxia
Biological Process	GO:0006879	intracellular iron ion homeostasis
Biological Process	GO:0032364	intracellular oxygen homeostasis
Biological Process	GO:1902072	negative regulation of hypoxia-inducible factor-1alpha signaling pathway
Biological Process	GO:0045944	positive regulation of transcription by RNA polymerase II
Biological Process	GO:0045765	regulation of angiogenesis
Biological Process	GO:0099159	regulation of modification of postsynaptic structure
Biological Process	GO:0043523	regulation of neuron apoptotic process
Biological Process	GO:0140252	regulation protein catabolic process at postsynapse
Biological Process	GO:0001666	response to hypoxia
Biological Process	GO:0071731	response to nitric oxide

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.