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Aliases for EGLN1 Gene

Aliases for EGLN1 Gene

  • Egl-9 Family Hypoxia-Inducible Factor 1 2 3
  • C1orf12 3 4 6
  • PHD2 3 4 6
  • Prolyl Hydroxylase Domain-Containing Protein 2 3 4
  • Hypoxia-Inducible Factor Prolyl Hydroxylase 2 3 4
  • HIF Prolyl Hydroxylase 2 2 3
  • HIF-Prolyl Hydroxylase 2 3 4
  • HIF-PH2 3 4
  • HIFPH2 3 6
  • ZMYND6 3 6
  • ECYT3 3 6
  • HPH-2 3 4
  • SM20 3 6
  • Zinc Finger MYND Domain-Containing Protein 6 3
  • Egl Nine Homolog 1 (C. Elegans) 2
  • EGL Nine (C.Elegans) Homolog 1 2
  • Egl Nine-Like Protein 1 3
  • Egl Nine Homolog 1 3
  • EC 1.14.11.29 4
  • EC 1.14.11 63
  • HALAH 3
  • SM-20 4
  • HPH2 3

External Ids for EGLN1 Gene

Previous HGNC Symbols for EGLN1 Gene

  • C1orf12

Previous GeneCards Identifiers for EGLN1 Gene

  • GC01M229945
  • GC01M227239
  • GC01M227972
  • GC01M228536
  • GC01M228534
  • GC01M227806
  • GC01M229566
  • GC01M231499
  • GC01M201982

Summaries for EGLN1 Gene

Entrez Gene Summary for EGLN1 Gene

  • The protein encoded by this gene catalyzes the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. HIF is a transcriptional complex that plays a central role in mammalian oxygen homeostasis. This protein functions as a cellular oxygen sensor, and under normal oxygen concentration, modification by prolyl hydroxylation is a key regulatory event that targets HIF subunits for proteasomal destruction via the von Hippel-Lindau ubiquitylation complex. Mutations in this gene are associated with erythrocytosis familial type 3 (ECYT3). [provided by RefSeq, Nov 2009]

GeneCards Summary for EGLN1 Gene

EGLN1 (Egl-9 Family Hypoxia-Inducible Factor 1) is a Protein Coding gene. Diseases associated with EGLN1 include erythrocytosis, familial, 3 and autosomal dominant secondary polycythemia. Among its related pathways are Pathways in cancer and Angiogenesis (CST). GO annotations related to this gene include enzyme binding and L-ascorbic acid binding. An important paralog of this gene is EGLN3.

UniProtKB/Swiss-Prot for EGLN1 Gene

  • 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 preferencially recognized via a LXXLAP motif.

Gene Wiki entry for EGLN1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for EGLN1 Gene

Genomics for EGLN1 Gene

Regulatory Elements for EGLN1 Gene

Genomic Location for EGLN1 Gene

Start:
231,363,751 bp from pter
End:
231,425,044 bp from pter
Size:
61,294 bases
Orientation:
Minus strand

Genomic View for EGLN1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for EGLN1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for EGLN1 Gene

Proteins for EGLN1 Gene

  • Protein details for EGLN1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9GZT9-EGLN1_HUMAN
    Recommended name:
    Egl nine homolog 1
    Protein Accession:
    Q9GZT9
    Secondary Accessions:
    • Q8N3M8
    • Q9BZS8
    • Q9BZT0

    Protein attributes for EGLN1 Gene

    Size:
    426 amino acids
    Molecular mass:
    46021 Da
    Cofactor:
    Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Note=Binds 1 Fe(2+) ion per subunit.;
    Cofactor:
    Name=L-ascorbate; Xref=ChEBI:CHEBI:38290;
    Quaternary structure:
    • Monomer. Interacts with ING4; the interaction inhibits the hydroxylation of HIF alpha proteins. Interacts with PTGES3 (via PXLE motif); thereby recruiting EGLN1 to the HSP90 pathway to facilitate HIF alpha proteins hydroxylation. Interacts with LIMD1. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, TCEB2 and CUL2. Interacts with EPAS1.
    SequenceCaution:
    • Sequence=AAK07534.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=AAK07536.1; Type=Frameshift; Positions=239; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for EGLN1 Gene

    Alternative splice isoforms for EGLN1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for EGLN1 Gene

Proteomics data for EGLN1 Gene at MOPED

Selected DME Specific Peptides for EGLN1 Gene

Post-translational modifications for EGLN1 Gene

  • 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-323 or Cys-326.
  • Ubiquitination at Lys234
  • Modification sites at PhosphoSitePlus

Other Protein References for EGLN1 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Domains for EGLN1 Gene

Gene Families for EGLN1 Gene

HGNC:
  • ZMYND :Zinc fingers, MYND-type

Protein Domains for EGLN1 Gene

Suggested Antigen Peptide Sequences for EGLN1 Gene

Graphical View of Domain Structure for InterPro Entry

Q9GZT9

UniProtKB/Swiss-Prot:

EGLN1_HUMAN :
  • Q9GZT9
Domain:
  • The beta(2)beta(3) finger-like loop domain is important for substrate (HIFs CODD/NODD) selectivity.
  • Contains 1 Fe2OG dioxygenase domain.
Similarity:
  • Contains 1 MYND-type zinc finger.
genes like me logo Genes that share domains with EGLN1: view

Function for EGLN1 Gene

Molecular function for EGLN1 Gene

UniProtKB/Swiss-Prot BiophysicochemicalProperties: Kinetic parameters: KM=70 nM for HIF2A {ECO:0000269 PubMed:25129147}; KM=150 uM for O(2) {ECO:0000269 PubMed:25129147}; KM=1.3 uM for 2-oxoglutarate {ECO:0000269 PubMed:25129147};
UniProtKB/Swiss-Prot CatalyticActivity: Hypoxia-inducible factor-L-proline + 2-oxoglutarate + O(2) = hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO(2).
UniProtKB/Swiss-Prot EnzymeRegulation: Following exposure to hypoxia, activated in HeLa cells but not in cardiovascular cells.
UniProtKB/Swiss-Prot 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 preferencially recognized via a LXXLAP motif.

Enzyme Numbers (IUBMB) for EGLN1 Gene

Gene Ontology (GO) - Molecular Function for EGLN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005506 iron ion binding IEA --
GO:0005515 protein binding IPI 15721254
GO:0016491 oxidoreductase activity --
GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen --
GO:0016706 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors IDA 22955912
genes like me logo Genes that share ontologies with EGLN1: view
genes like me logo Genes that share phenotypes with EGLN1: view

Animal Models for EGLN1 Gene

MGI Knock Outs for EGLN1:

miRNA for EGLN1 Gene

miRTarBase miRNAs that target EGLN1

No data available for Transcription Factor Targeting and HOMER Transcription for EGLN1 Gene

Localization for EGLN1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for EGLN1 Gene

Cytoplasm. Nucleus. Note=Mainly cytoplasmic. Shuttles between the nucleus and cytoplasm (PubMed:19631610). Nuclear export requires functional XPO1. {ECO:0000269 PubMed:19339211, ECO:0000269 PubMed:19631610}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for EGLN1 Gene COMPARTMENTS Subcellular localization image for EGLN1 gene
Compartment Confidence
nucleus 5
cytosol 4
cytoskeleton 1
mitochondrion 1

Gene Ontology (GO) - Cellular Components for EGLN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005737 cytoplasm IDA 12615973
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with EGLN1: view

Pathways for EGLN1 Gene

genes like me logo Genes that share pathways with EGLN1: view

Gene Ontology (GO) - Biological Process for EGLN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001666 response to hypoxia IDA 16956324
GO:0018401 peptidyl-proline hydroxylation to 4-hydroxy-L-proline IDA 11598268
GO:0030821 negative regulation of cAMP catabolic process ISS --
GO:0032364 oxygen homeostasis IDA 16956324
GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity IDA 16956324
genes like me logo Genes that share ontologies with EGLN1: view

Compounds for EGLN1 Gene

(3) HMDB Compounds for EGLN1 Gene

Compound Synonyms Cas Number PubMed IDs
Ascorbic acid
  • (+)-ascorbate
50-81-7
Hydroxyproline
  • (2S,4R)-4-hydroxy-2-pyrrolidinecarboxylic acid
51-35-4
L-Proline
  • (-)-(S)-Proline
147-85-3

(3) Drugbank Compounds for EGLN1 Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
N-[(1-CHLORO-4-HYDROXYISOQUINOLIN-3-YL)CARBONYL]GLYCINE
target
N-[(4-HYDROXY-8-IODOISOQUINOLIN-3-YL)CARBONYL]GLYCINE
target
Vitamin C
  • Ascorbate
50-81-7 target

(9) Novoseek inferred chemical compound relationships for EGLN1 Gene

Compound -log(P) Hits PubMed IDs
alpha-ketoglutarate 78 6
proline 61.7 7
oxygen 53.8 17
asparagine 47.3 2
vegf 37.2 7
genes like me logo Genes that share compounds with EGLN1: view

Transcripts for EGLN1 Gene

mRNA/cDNA for EGLN1 Gene

Unigene Clusters for EGLN1 Gene

Egl nine homolog 1 (C. elegans):
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for EGLN1 Gene

No ASD Table

Relevant External Links for EGLN1 Gene

GeneLoc Exon Structure for
EGLN1
ECgene alternative splicing isoforms for
EGLN1

Expression for EGLN1 Gene

mRNA expression in normal human tissues for EGLN1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for EGLN1 Gene

This gene is overexpressed in Muscle - Skeletal (11.9).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for EGLN1 Gene

SOURCE GeneReport for Unigene cluster for EGLN1 Gene Hs.444450

mRNA Expression by UniProt/SwissProt for EGLN1 Gene

Q9GZT9-EGLN1_HUMAN
Tissue specificity: According to PubMed:11056053, widely expressed with highest levels in skeletal muscle and heart, moderate levels in pancreas, brain (dopaminergic neurons of adult and fetal substantia nigra) and kidney, and lower levels in lung and liver. According to PubMed:12351678 widely expressed with highest levels in brain, kidney and adrenal gland. Expressed in cardiac myocytes, aortic endothelial cells and coronary artery smooth muscle. According to PubMed:12788921; expressed in adult and fetal heart, brain, liver, lung, skeletal muscle and kidney. Also expressed in placenta. Highest levels in adult heart, brain, lung and liver and fetal brain, heart spleen and skeletal muscle.
genes like me logo Genes that share expressions with EGLN1: view

Orthologs for EGLN1 Gene

This gene was present in the common ancestor of animals.

Orthologs for EGLN1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia EGLN1 35
  • 99.66 (n)
  • 99.32 (a)
EGLN1 36
  • 96 (a)
OneToOne
cow
(Bos Taurus)
Mammalia EGLN1 36
  • 75 (a)
OneToOne
dog
(Canis familiaris)
Mammalia EGLN1 35
  • 87.18 (n)
  • 82.97 (a)
EGLN1 36
  • 76 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Egln1 35
  • 83.58 (n)
  • 82.41 (a)
Egln1 16
Egln1 36
  • 79 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia EGLN1 36
  • 72 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia EGLN1 36
  • 91 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Egln1 35
  • 85.86 (n)
  • 89.31 (a)
chicken
(Gallus gallus)
Aves EGLN1 36
  • 73 (a)
OneToOne
LOC768374 35
  • 86.09 (n)
  • 87.59 (a)
lizard
(Anolis carolinensis)
Reptilia EGLN1 36
  • 63 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia egln1 35
  • 75.39 (n)
  • 80.79 (a)
zebrafish
(Danio rerio)
Actinopterygii egln1 36
  • 70 (a)
OneToMany
EGLN1 (2 of 2) 36
  • 70 (a)
OneToMany
si:ch1073-423n4.1 35
  • 75.06 (n)
  • 83.58 (a)
fruit fly
(Drosophila melanogaster)
Insecta Hph 36
  • 31 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea egl-9 36
  • 17 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 37 (a)
OneToMany
Species with no ortholog for EGLN1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for EGLN1 Gene

ENSEMBL:
Gene Tree for EGLN1 (if available)
TreeFam:
Gene Tree for EGLN1 (if available)

Paralogs for EGLN1 Gene

Paralogs for EGLN1 Gene

genes like me logo Genes that share paralogs with EGLN1: view

Variants for EGLN1 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for EGLN1 Gene

Q9GZT9-EGLN1_HUMAN
Variations in EGLN1 are associated with adaptation to high altitude (PubMed:20838600, PubMed:20466884, PubMed:24711448, PubMed:25129147). High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body and leads to an elevation of hematocrit levels and an increased number of erythrocytes (polycythemia) in non-adapted individuals. Genetic variations in EGLN1 contribute to adaptation to high altitute by maintaining hematocrit levels comparable to those for populations living at sea level and are present in two high-altitude regions where humans have lived for millennia, the Andean Altiplano and the Tibetan Plateau (PubMed:20838600, PubMed:20466884). Variants Glu-4 and Ser-127, which are frequently associated together and are present in the majority of Tibetan populations, participate to adaptation to high altitude (PubMed:24711448, PubMed:25129147). Molecular mechanisms explaining this adaptation are however unclear. According to a report, variants Glu-4 and Ser-127 lead to decreased interaction with PTGES3 and subsequent decrease of HIF alpha proteins degradation (PubMed:24711448). According to a second report, Glu-4 and Ser-127 haplotype enhances the catalytic activity under hypoxic conditions, promoting increased HIF alpha proteins degradation, thereby abrogating hypoxia-induced and HIF alpha-mediated augmentation of erythropoiesis and protecting Tibetans from polycythemia at high altitude (PubMed:25129147).

Sequence variations from dbSNP and Humsavar for EGLN1 Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type MAF
rs182197 -- 231,381,692(+) GTTAT(A/G)CTTTA intron-variant
rs203747 -- 231,380,133(+) aagcc(A/G)tgtgc intron-variant
rs474517 -- 231,408,555(-) ACACA(A/C)TTTTT intron-variant
rs479200 -- 231,408,034(-) TGTTA(C/T)GTACA intron-variant
rs479311 -- 231,407,996(-) GTGAA(C/T)TGCCC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for EGLN1 Gene

Variant ID Type Subtype PubMed ID
esv2724861 CNV Deletion 23290073
esv2661110 CNV Deletion 23128226
nsv827208 CNV Loss 20364138
nsv441741 CNV CNV 18776908
esv2421419 CNV Deletion 20811451

Relevant External Links for EGLN1 Gene

HapMap Linkage Disequilibrium report
EGLN1
Human Gene Mutation Database (HGMD)
EGLN1

Disorders for EGLN1 Gene

MalaCards: The human disease database

MalaCards: The human disease database. (3) Diseases for EGLN1 Gene including...

Search for EGLN1 Gene in MalaCards »

(1) OMIM Diseases for EGLN1 Gene (606425)

UniProtKB/Swiss-Prot

EGLN1_HUMAN
  • Erythrocytosis, familial, 3 (ECYT3) [MIM:609820]: An autosomal dominant disorder characterized by increased serum red blood cell mass, elevated serum hemoglobin and hematocrit, and normal serum erythropoietin levels. {ECO:0000269 PubMed:16407130, ECO:0000269 PubMed:17579185}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(3) Novoseek inferred disease relationships for EGLN1 Gene

Disease -log(P) Hits PubMed IDs
erythrocytosis, familial 89.3 4
osteosarcoma 30.5 1
tumors 29.7 12

Relevant External Links for EGLN1

Genetic Association Database (GAD)
EGLN1
Human Genome Epidemiology (HuGE) Navigator
EGLN1
genes like me logo Genes that share disorders with EGLN1: view

Publications for EGLN1 Gene

  1. Mapping, characterization, and expression analysis of the SM-20 human homologue, C1orf12, and identification of a novel related gene, SCAND2. (PMID: 11056053) Dupuy D. … Arveiler B. (Genomics 2000) 2 3 4 23
  2. Characterization and comparative analysis of the EGLN gene family. (PMID: 11574160) Taylor M.S. (Gene 2001) 3 4 23
  3. Intracellular localisation of human HIF-1 alpha hydroxylases: implications for oxygen sensing. (PMID: 12615973) Metzen E. … Fandrey J. (J. Cell Sci. 2003) 3 4 23
  4. Differential regulation of HIF-1alpha prolyl-4-hydroxylase genes by hypoxia in human cardiovascular cells. (PMID: 12670503) Cioffi C.L. … Bowen B.R. (Biochem. Biophys. Res. Commun. 2003) 3 4 23
  5. Cellular oxygen sensing: crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2). (PMID: 16782814) McDonough M.A. … Schofield C.J. (Proc. Natl. Acad. Sci. U.S.A. 2006) 3 4 23

Products for EGLN1 Gene

  • Addgene plasmids for EGLN1

Sources for EGLN1 Gene

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