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Aliases for EGLN2 Gene

Aliases for EGLN2 Gene

  • Egl-9 Family Hypoxia Inducible Factor 2 2 3 5
  • Prolyl Hydroxylase Domain-Containing Protein 1 3 4
  • Hypoxia-Inducible Factor Prolyl Hydroxylase 1 3 4
  • HIF-Prolyl Hydroxylase 1 3 4
  • Estrogen-Induced Tag 6 3 4
  • HIF-PH1 3 4
  • HPH-1 3 4
  • HPH-3 3 4
  • EIT6 3 4
  • PHD1 3 4
  • Egl Nine Homolog 2 (C. Elegans) 2
  • HIF Prolyl Hydroxylase 1 2
  • Egl Nine Homolog 2 3
  • EC 1.14.11.29 4
  • EC 1.14.11 61
  • HIFPH1 3

External Ids for EGLN2 Gene

Previous GeneCards Identifiers for EGLN2 Gene

  • GC19P041944
  • GC19P041696
  • GC19P045981
  • GC19P045996
  • GC19P041305
  • GC19P037738
  • GC19P041304

Summaries for EGLN2 Gene

Entrez Gene Summary for EGLN2 Gene

  • The hypoxia inducible factor (HIF) is a transcriptional complex that is involved in oxygen homeostasis. At normal oxygen levels, the alpha subunit of HIF is targeted for degration by prolyl hydroxylation. This gene encodes an enzyme responsible for this post-translational modification. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the upstream RAB4B (RAB4B, member RAS oncogene family) gene. [provided by RefSeq, Feb 2011]

GeneCards Summary for EGLN2 Gene

EGLN2 (Egl-9 Family Hypoxia Inducible Factor 2) is a Protein Coding gene. Diseases associated with EGLN2 include Hypoxia and Renal Oncocytoma. Among its related pathways are CDK-mediated phosphorylation and removal of Cdc6 and Development HGF signaling pathway. GO annotations related to this gene include oxidoreductase activity and oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen. An important paralog of this gene is EGLN1.

UniProtKB/Swiss-Prot for EGLN2 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 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.

Gene Wiki entry for EGLN2 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for EGLN2 Gene

Genomics for EGLN2 Gene

Regulatory Elements for EGLN2 Gene

Enhancers for EGLN2 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH19G040796 2.1 FANTOM5 Ensembl ENCODE dbSUPER 14.8 +3.3 3342 11.8 CREB3L1 MLX AGO1 ZFP64 DMAP1 YBX1 FEZF1 YY1 ZNF416 ZNF143 ENSG00000205041 SNRPA ENSG00000269843 ENSG00000269069 NUMBL ITPKC FBL COQ8B CCDC97 EGLN2
GH19G040747 1.8 FANTOM5 ENCODE dbSUPER 12.1 -46.2 -46235 9.8 MLX CREB3L1 ZFP64 DMAP1 YBX1 FEZF1 YY1 ZNF416 ZNF143 ZNF263 ENSG00000269843 SNRPA ENSG00000205041 FBL COQ8B ITPKC CCDC97 NUMBL C19orf54 SERTAD3
GH19G040662 1.4 Ensembl ENCODE 11.3 -135.3 -135250 2.8 HDGF PKNOX1 MLX CREB3L1 AGO1 ZFP64 ARID4B SIN3A FEZF1 DMAP1 SNRPA NUMBL ENSG00000205041 FBL RAB4B C19orf54 ITPKC ENSG00000269843 RNU6-195P ZNF546
GH19G040665 1.3 Ensembl ENCODE 11.1 -132.5 -132510 1.7 ATF1 ARNT SIN3A TCF12 GATA2 FOS YY2 JUNB NCOA1 ZNF592 C19orf54 RNU6-195P RAB4B RAB4B-EGLN2 SNRPA EGLN2 COQ8B ITPKC PIR47829 NUMBL
GH19G040818 1.6 Ensembl ENCODE dbSUPER 8.7 +20.1 20141 2.2 PKNOX1 AGO1 ARID4B SIN3A DMAP1 ZNF2 ZNF766 ZNF416 ZNF143 FOS ENSG00000205041 SNRPA ENSG00000269069 COQ8B NUMBL EGLN2 C19orf54 ITPKC BLVRB PIR36050
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around EGLN2 on UCSC Golden Path with GeneCards custom track

Promoters for EGLN2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000109588 304 2201 MLX CREB3L1 ZFP64 FEZF1 DMAP1 YY1 ZNF416 ZNF143 ZNF263 SP3

Transcription factor binding sites by QIAGEN in the EGLN2 gene promoter:

Genomic Location for EGLN2 Gene

Chromosome:
19
Start:
40,798,996 bp from pter
End:
40,808,441 bp from pter
Size:
9,446 bases
Orientation:
Plus strand

Genomic View for EGLN2 Gene

Genes around EGLN2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
EGLN2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for EGLN2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for EGLN2 Gene

Proteins for EGLN2 Gene

  • Protein details for EGLN2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96KS0-EGLN2_HUMAN
    Recommended name:
    Egl nine homolog 2
    Protein Accession:
    Q96KS0
    Secondary Accessions:
    • A8K5S0
    • Q8WWY4
    • Q9BV14

    Protein attributes for EGLN2 Gene

    Size:
    407 amino acids
    Molecular mass:
    43650 Da
    Cofactor:
    Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
    Cofactor:
    Name=L-ascorbate; Xref=ChEBI:CHEBI:38290;
    Quaternary structure:
    • Interacts (preferably isoform p40) with SIAH2; the interaction targets both SIAH2 isoforms for proteasomal degradation in vitro. Interacts with LIMD1, WTIP and AJUBA.
    SequenceCaution:
    • Sequence=AAH01723.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Alternative splice isoforms for EGLN2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for EGLN2 Gene

Selected DME Specific Peptides for EGLN2 Gene

Q96KS0:
  • GYVRHVDNP
  • TVWYFDA
  • INGRTKAMVACYPGNG
  • GDGRCITCIYYLN

Post-translational modifications for EGLN2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for EGLN2 Gene

Protein Domains for EGLN2 Gene

Suggested Antigen Peptide Sequences for EGLN2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q96KS0

UniProtKB/Swiss-Prot:

EGLN2_HUMAN :
  • The Beta(2)beta(3) finger-like loop domain is important for substrate (HIFs CODD/NODD) selectivity.
Domain:
  • The Beta(2)beta(3) finger-like loop domain is important for substrate (HIFs CODD/NODD) selectivity.
genes like me logo Genes that share domains with EGLN2: view

No data available for Gene Families for EGLN2 Gene

Function for EGLN2 Gene

Molecular function for EGLN2 Gene

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 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 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.
UniProtKB/Swiss-Prot Induction:
By estrogen. Isoform p43 is induced by hypoxia leading to protein stability. Isoform p40 repressed by hypoxia. Both isoforms are induced by proteasomal inhibitor MG132 (at protein level).

Enzyme Numbers (IUBMB) for EGLN2 Gene

Gene Ontology (GO) - Molecular Function for EGLN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005506 iron ion binding IEA --
GO:0005515 protein binding IPI 16511565
GO:0008198 ferrous iron binding NAS 12039559
GO:0016491 oxidoreductase activity IEA --
GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen IEA --
genes like me logo Genes that share ontologies with EGLN2: view
genes like me logo Genes that share phenotypes with EGLN2: view

Animal Models for EGLN2 Gene

MGI Knock Outs for EGLN2:

Animal Model Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for EGLN2

Flow Cytometry Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for EGLN2 Gene

Localization for EGLN2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for EGLN2 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for EGLN2 gene
Compartment Confidence
nucleus 5
mitochondrion 1

Gene Ontology (GO) - Cellular Components for EGLN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA,IEA 11850811
GO:0005654 nucleoplasm TAS,IDA --
genes like me logo Genes that share ontologies with EGLN2: view

Pathways & Interactions for EGLN2 Gene

genes like me logo Genes that share pathways with EGLN2: view

SIGNOR curated interactions for EGLN2 Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for EGLN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001558 regulation of cell growth NAS 11850811
GO:0001666 response to hypoxia IDA 11595184
GO:0018401 peptidyl-proline hydroxylation to 4-hydroxy-L-proline IDA 11598268
GO:0030520 intracellular estrogen receptor signaling pathway NAS 11850811
GO:0043523 regulation of neuron apoptotic process IMP 19587290
genes like me logo Genes that share ontologies with EGLN2: view

Drugs & Compounds for EGLN2 Gene

(11) Drugs for EGLN2 Gene - From: DrugBank, ApexBio, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Vitamin C Approved Nutra Target 531,531
Oxygen Approved, Vet_approved Pharma 0
hydroxyproline Approved, Experimental Pharma 0
L-Proline Approved Nutra 0
Succinic acid Approved Nutra Full agonist, Agonist 0

(3) Additional Compounds for EGLN2 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Oxoglutaric acid
  • 2-Ketoglutarate
  • 2-Ketoglutaric acid
  • 2-Oxo-1,5-pentanedioate
  • 2-Oxo-1,5-pentanedioic acid
  • 2-Oxoglutarate
328-50-7

(1) ApexBio Compounds for EGLN2 Gene

Compound Action Cas Number
FG2216 HIF-prolyl hydroxylase inhibitor 223387-75-5
genes like me logo Genes that share compounds with EGLN2: view

Transcripts for EGLN2 Gene

Unigene Clusters for EGLN2 Gene

Egl nine homolog 2 (C. elegans):
Representative Sequences:

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for EGLN2

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for EGLN2 Gene

No ASD Table

Relevant External Links for EGLN2 Gene

GeneLoc Exon Structure for
EGLN2
ECgene alternative splicing isoforms for
EGLN2

Expression for EGLN2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for EGLN2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for EGLN2 Gene

This gene is overexpressed in Whole Blood (x5.8).

Protein differential expression in normal tissues from HIPED for EGLN2 Gene

This gene is overexpressed in Liver (57.8) and Heart (11.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for EGLN2 Gene



Protein tissue co-expression partners for EGLN2 Gene

NURSA nuclear receptor signaling pathways regulating expression of EGLN2 Gene:

EGLN2

SOURCE GeneReport for Unigene cluster for EGLN2 Gene:

Hs.515417

mRNA Expression by UniProt/SwissProt for EGLN2 Gene:

Q96KS0-EGLN2_HUMAN
Tissue specificity: Expressed in adult and fetal heart, brain, liver, lung, skeletal muscle, and kidney. Also expressed in testis and placenta. Highest levels in adult brain, placenta, lung, kidney, and testis. Expressed in hormone responsive tissues, including normal and cancerous mammary, ovarian and prostate epithelium.

Evidence on tissue expression from TISSUES for EGLN2 Gene

  • Lung(4.2)
  • Nervous system(4.1)
genes like me logo Genes that share expression patterns with EGLN2: view

Primer Products

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for EGLN2 Gene

Orthologs for EGLN2 Gene

This gene was present in the common ancestor of animals.

Orthologs for EGLN2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia EGLN2 34 35
  • 99.84 (n)
cow
(Bos Taurus)
Mammalia EGLN2 35
  • 95 (a)
OneToOne
dog
(Canis familiaris)
Mammalia EGLN2 34 35
  • 89.47 (n)
rat
(Rattus norvegicus)
Mammalia Egln2 34
  • 88.89 (n)
mouse
(Mus musculus)
Mammalia Egln2 34 16 35
  • 88.48 (n)
oppossum
(Monodelphis domestica)
Mammalia EGLN2 35
  • 74 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia EGLN2 35
  • 59 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia EGLN2 35
  • 72 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia egln2 34
  • 64.94 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.32075 34
zebrafish
(Danio rerio)
Actinopterygii egln2 35
  • 41 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Hph 35
  • 27 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea egl-9 35
  • 14 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 31 (a)
OneToMany
Species where no ortholog for EGLN2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • chicken (Gallus gallus)
  • 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 EGLN2 Gene

ENSEMBL:
Gene Tree for EGLN2 (if available)
TreeFam:
Gene Tree for EGLN2 (if available)

Paralogs for EGLN2 Gene

Paralogs for EGLN2 Gene

genes like me logo Genes that share paralogs with EGLN2: view

Variants for EGLN2 Gene

Sequence variations from dbSNP and Humsavar for EGLN2 Gene

SNP ID Clin Chr 19 pos Sequence Context AA Info Type
rs1000058022 -- 40,800,666(+) GCCGG(A/G)CCAGG nc-transcript-variant, reference, missense
rs1000181343 -- 40,804,791(+) GCCCC(C/T)TCCTG intron-variant
rs1000260619 -- 40,801,208(+) GAGGC(C/T)CTCAA nc-transcript-variant, reference, synonymous-codon
rs1000528182 -- 40,805,987(+) GAGGT(C/G)TATGG intron-variant
rs1000763607 -- 40,804,955(+) GTGCA(C/T)ATGGT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for EGLN2 Gene

Variant ID Type Subtype PubMed ID
esv2758762 CNV gain+loss 17122850
nsv1066637 CNV gain 25217958
nsv1118831 CNV deletion 24896259
nsv521459 CNV loss 19592680
nsv833832 CNV loss 17160897

Variation tolerance for EGLN2 Gene

Residual Variation Intolerance Score: 8.87% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.99; 36.81% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for EGLN2 Gene

Human Gene Mutation Database (HGMD)
EGLN2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
EGLN2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for EGLN2 Gene

Disorders for EGLN2 Gene

MalaCards: The human disease database

(3) MalaCards diseases for EGLN2 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
hypoxia
renal oncocytoma
  • oncocytoma of kidney
renal cell carcinoma
  • renal cell carcinoma, clear cell, somatic
- elite association - COSMIC cancer census association via MalaCards
Search EGLN2 in MalaCards View complete list of genes associated with diseases

Relevant External Links for EGLN2

Genetic Association Database (GAD)
EGLN2
Human Genome Epidemiology (HuGE) Navigator
EGLN2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
EGLN2
genes like me logo Genes that share disorders with EGLN2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for EGLN2 Gene

Publications for EGLN2 Gene

  1. Role of the intracellular localization of HIF-prolyl hydroxylases. (PMID: 19339211) Yasumoto K. … Sogawa K. (Biochim. Biophys. Acta 2009) 3 4 22 64
  2. Cellular oxygen sensing: Importins and exportins are mediators of intracellular localisation of prolyl-4-hydroxylases PHD1 and PHD2. (PMID: 19631610) Steinhoff A. … Depping R. (Biochem. Biophys. Res. Commun. 2009) 3 4 22 64
  3. Characterization of different isoforms of the HIF prolyl hydroxylase PHD1 generated by alternative initiation. (PMID: 16509823) Tian Y.M. … Gleadle J.M. (Biochem. J. 2006) 3 4 22 64
  4. Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkappaB activity. (PMID: 17114296) Cummins E.P. … Taylor C.T. (Proc. Natl. Acad. Sci. U.S.A. 2006) 3 4 22 64
  5. Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor. (PMID: 15247232) Appelhoff R.J. … Gleadle J.M. (J. Biol. Chem. 2004) 3 4 22 64

Products for EGLN2 Gene

Sources for EGLN2 Gene

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