Atlas of Genetics and Cytogenetics in Oncology and Haematology


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EGLN1 (egl nine homolog 1 (C. elegans))

Identity

Other namesC1orf12
DKFZp761F179
ECYT3
HIFPH2
HPH-2
PHD2
SM-20
SM20
ZMYND6
HGNC (Hugo) EGLN1
LocusID (NCBI) 54583
Location 1q42.2
Location_base_pair Starts at 231499497 and ends at 231560790 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

Description EGLN1 gene is located on chromosome 1, location 229568054-229627413. Gene spans 61293 bases and has 5 exons.
Transcription PHD2 expression is strongly induced in hypoxia by the HIF-1α transcription factor. Primary transcript length is 5936 bases. On mRNA level two splice variants have been proposed, lacking exons 3 or 4, but these have not been confirmed on protein level.

Protein

Description PHD2 protein is 426 amino acids long and approximately 46 kDa. It has a zf-MYND domain (aa 21-58) and a 2-OG-FeII-oxygenase domain (aa205-391).
Expression Ubiquitous.
Localisation Predominantly cytoplasmic.
Function PHD2 is a member of the 2-oxoglutarate-dependent, non-haem iron binding dioxygenases.
PHD2 post-translationally regulates the levels of hypoxia-inducible factor-α (HIF-α) subunits in normoxic conditions by hydroxylating them in an oxygen-dependant manner on specific proline residues. This enables recognition of HIF by the VHL ubiquitin ligase complex and subsequent degradation of HIF by the proteasome. In hypoxic conditions the hydroxylation is significantly decreased, and the HIF-α subunits are stabilized. PHD2 is considered the main HIF-1α regulator in normoxic and mildly hypoxic conditions.
Homology EGLN1 has two paralogs: EGLN2 and EGLN3 Homologs have been found in all multicellular organisms investigated.

Mutations

Note Homozygous deletion confers embryonic lethality in mouse.
Germinal Heterozygous mutations have been associated with familial erythrocytosis. Currently three point mutations: G1112A ->Arg371His, C950G -> Pro317Arg, C1129T-> Gln377X, one deletion: 606delG -> frameshift, and one insertion: 840_841insA -> frameshift have been reported.

Implicated in

Entity Familial erythrocytosis (ECYT3)
Note ECYT3 is characterized by increased serum hemoglobin and hematocrit, but with normal serum erythropoietin levels.
Disease Characterized EGLN1 mutations result in the loss of catalytic function and thereby aberrant erythropoietin expression.
  
Entity Head and neck squamous cell carcinoma
Note Increased expression levels and nuclear translocation have been associated with the aggressiveness of the carcinoma.
  

External links

Nomenclature
HGNC (Hugo)EGLN1   1232
Cards
AtlasEGLN1ID44140ch1q42
Entrez_Gene (NCBI)EGLN1  54583  egl-9 family hypoxia-inducible factor 1
GeneCards (Weizmann)EGLN1
Ensembl (Hinxton)ENSG00000135766 [Gene_View]  chr1:231499497-231560790 [Contig_View]  EGLN1 [Vega]
ICGC DataPortalENSG00000135766
cBioPortalEGLN1
AceView (NCBI)EGLN1
Genatlas (Paris)EGLN1
WikiGenes54583
SOURCE (Princeton)NM_022051
Genomic and cartography
GoldenPath (UCSC)EGLN1  -  1q42.2   chr1:231499497-231560790 -  1q42.1   [Description]    (hg19-Feb_2009)
EnsemblEGLN1 - 1q42.1 [CytoView]
Mapping of homologs : NCBIEGLN1 [Mapview]
OMIM606425   609820   
Gene and transcription
Genbank (Entrez)AF229245 AF277174 AF277176 AF334711 AI017372
RefSeq transcript (Entrez)NM_022051
RefSeq genomic (Entrez)AC_000133 NC_000001 NC_018912 NG_015865 NT_167186 NW_001838549 NW_004929294
Consensus coding sequences : CCDS (NCBI)EGLN1
Cluster EST : UnigeneHs.444450 [ NCBI ]
CGAP (NCI)Hs.444450
Alternative Splicing : Fast-db (Paris)GSHG0003043
Alternative Splicing GalleryENSG00000135766
Gene ExpressionEGLN1 [ NCBI-GEO ]     EGLN1 [ SEEK ]   EGLN1 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9GZT9 (Uniprot)
NextProtQ9GZT9  [Medical]
With graphics : InterProQ9GZT9
Splice isoforms : SwissVarQ9GZT9 (Swissvar)
Catalytic activity : Enzyme1.14.11.29 [ Enzyme-Expasy ]   1.14.11.291.14.11.29 [ IntEnz-EBI ]   1.14.11.29 [ BRENDA ]   1.14.11.29 [ KEGG ]   
Domaine pattern : Prosite (Expaxy)FE2OG_OXY (PS51471)    ZF_MYND_1 (PS01360)    ZF_MYND_2 (PS50865)   
Domains : Interpro (EBI)Oxoglu/Fe-dep_dioxygenase [organisation]   Pro_4_hyd_alph [organisation]   Znf_MYND [organisation]  
Related proteins : CluSTrQ9GZT9
Domain families : Pfam (Sanger)2OG-FeII_Oxy_3 (PF13640)    zf-MYND (PF01753)   
Domain families : Pfam (NCBI)pfam13640    pfam01753   
Domain families : Smart (EMBL)P4Hc (SM00702)  
DMDM Disease mutations54583
Blocks (Seattle)Q9GZT9
PDB (SRS)2G19    2G1M    2HBT    2HBU    2Y33    2Y34    3HQR    3HQU    3OUH    3OUI    3OUJ    4BQW    4BQX    4BQY    4JZR    4KBZ   
PDB (PDBSum)2G19    2G1M    2HBT    2HBU    2Y33    2Y34    3HQR    3HQU    3OUH    3OUI    3OUJ    4BQW    4BQX    4BQY    4JZR    4KBZ   
PDB (IMB)2G19    2G1M    2HBT    2HBU    2Y33    2Y34    3HQR    3HQU    3OUH    3OUI    3OUJ    4BQW    4BQX    4BQY    4JZR    4KBZ   
PDB (RSDB)2G19    2G1M    2HBT    2HBU    2Y33    2Y34    3HQR    3HQU    3OUH    3OUI    3OUJ    4BQW    4BQX    4BQY    4JZR    4KBZ   
Human Protein AtlasENSG00000135766 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ9GZT9
HPRD06971
IPIIPI00004928   IPI00328822   IPI01013261   IPI00984285   
Protein Interaction databases
DIP (DOE-UCLA)Q9GZT9
IntAct (EBI)Q9GZT9
FunCoupENSG00000135766
BioGRIDEGLN1
InParanoidQ9GZT9
Interologous Interaction database Q9GZT9
IntegromeDBEGLN1
STRING (EMBL)EGLN1
Ontologies - Pathways
Ontology : AmiGOresponse to hypoxia  iron ion binding  protein binding  nucleus  cytoplasm  cytosol  peptidyl-proline hydroxylation to 4-hydroxy-L-proline  enzyme binding  negative regulation of cAMP catabolic process  L-ascorbic acid binding  peptidyl-proline dioxygenase activity  peptidyl-proline 4-dioxygenase activity  oxygen homeostasis  negative regulation of sequence-specific DNA binding transcription factor activity  regulation of angiogenesis  negative regulation of cyclic-nucleotide phosphodiesterase activity  cardiac muscle tissue morphogenesis  oxidation-reduction process  heart trabecula formation  ventricular septum morphogenesis  labyrinthine layer development  regulation of transcription from RNA polymerase II promoter in response to hypoxia  cellular response to hypoxia  response to nitric oxide  
Ontology : EGO-EBIresponse to hypoxia  iron ion binding  protein binding  nucleus  cytoplasm  cytosol  peptidyl-proline hydroxylation to 4-hydroxy-L-proline  enzyme binding  negative regulation of cAMP catabolic process  L-ascorbic acid binding  peptidyl-proline dioxygenase activity  peptidyl-proline 4-dioxygenase activity  oxygen homeostasis  negative regulation of sequence-specific DNA binding transcription factor activity  regulation of angiogenesis  negative regulation of cyclic-nucleotide phosphodiesterase activity  cardiac muscle tissue morphogenesis  oxidation-reduction process  heart trabecula formation  ventricular septum morphogenesis  labyrinthine layer development  regulation of transcription from RNA polymerase II promoter in response to hypoxia  cellular response to hypoxia  response to nitric oxide  
Pathways : KEGGHIF-1 signaling pathway    Pathways in cancer    Renal cell carcinoma   
Protein Interaction DatabaseEGLN1
Wikipedia pathwaysEGLN1
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)EGLN1
snp3D : Map Gene to Disease54583
SNP (GeneSNP Utah)EGLN1
SNP : HGBaseEGLN1
Genetic variants : HAPMAPEGLN1
Exome VariantEGLN1
1000_GenomesEGLN1 
ICGC programENSG00000135766 
Somatic Mutations in Cancer : COSMICEGLN1 
CONAN: Copy Number AnalysisEGLN1 
Mutations and Diseases : HGMDEGLN1
Mutations and Diseases : intOGenEGLN1
Genomic VariantsEGLN1  EGLN1 [DGVbeta]
dbVarEGLN1
ClinVarEGLN1
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM606425    609820   
MedgenEGLN1
GENETestsEGLN1
Disease Genetic AssociationEGLN1
Huge Navigator EGLN1 [HugePedia]  EGLN1 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneEGLN1
Homology/Alignments : Family Browser (UCSC)EGLN1
Phylogenetic Trees/Animal Genes : TreeFamEGLN1
Chemical/Protein Interactions : CTD54583
Chemical/Pharm GKB GenePA27670
Clinical trialEGLN1
Cancer Resource (Charite)ENSG00000135766
Other databases
Probes
Litterature
PubMed120 Pubmed reference(s) in Entrez
CoreMineEGLN1
iHOPEGLN1
OncoSearchEGLN1

Bibliography

Mapping, characterization, and expression analysis of the SM-20 human homologue, c1orf12, and identification of a novel related gene, SCAND2.
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Characterization and comparative analysis of the EGLN gene family.
Taylor MS
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HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia.
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Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor.
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Regulation of the prolyl hydroxylase domain protein 2 (phd2/egln-1) gene: identification of a functional hypoxia-responsive element.
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The Biochemical journal. 2005 ; 387 (Pt 3) : 711-717.
PMID 15563275
 
Overexpression and nuclear translocation of hypoxia-inducible factor prolyl hydroxylase PHD2 in head and neck squamous cell carcinoma is associated with tumor aggressiveness.
Jokilehto T, Rantanen K, Luukkaa M, Heikkinen P, Grenman R, Minn H, Kronqvist P, Jaakkola PM
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A family with erythrocytosis establishes a role for prolyl hydroxylase domain protein 2 in oxygen homeostasis.
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Placental but not heart defects are associated with elevated hypoxia-inducible factor alpha levels in mice lacking prolyl hydroxylase domain protein 2.
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A novel erythrocytosis-associated PHD2 mutation suggests the location of a HIF binding groove.
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Contributor(s)

Written01-2008Terhi Jokilehto, Panu M Jaakkola
Hypoxia group, Turku centre for Biotechnology, Tykistokatu 6, 20520 Turku, Finland

Citation

This paper should be referenced as such :
Jokilehto, T ; Jaakkola, PM. EGLN1 (egl nine homolog 1 (C
elegans))
Atlas Genet Cytogenet Oncol Haematol. 2008;12(5):365-366.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/EGLN1ID44140ch1q42.html

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indexed on : Sat Oct 4 13:02:40 CEST 2014

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