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

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

Written	2008-01	Terhi Jokilehto, Panu M Jaakkola
		Hypoxia group, Turku centre for Biotechnology, Tykistokatu 6, 20520 Turku, Finland

(Note : for Links provided by Atlas : click)

Identity

Alias (NCBI)	C1orf12
	DKFZp761F179
	ECYT3
	HIFPH2
	HPH-2
	PHD2
	SM-20
	SM20
	ZMYND6
HGNC (Hugo)	EGLN1
HGNC Alias symb	SM-20
	PHD2
	ZMYND6
	HIFPH2
HGNC Alias name	HIF prolyl hydroxylase 2
HGNC Previous name	C1orf12
HGNC Previous name	EGL nine (C.elegans) homolog 1
	egl nine homolog 1 (C. elegans)
	egl-9 family hypoxia-inducible factor 1
LocusID (NCBI)	54583
Atlas_Id	44140
Location	1q42.2 [Link to chromosome band 1q42]
Location_base_pair	Starts at 231363757 and ends at 231422287 bp from pter ( according to GRCh38/hg38-Dec_2013) [Mapping EGLN1.png]

Fusion genes
(updated 2017)

Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)

	EGLN1 (1q42.2) / EGLN1 (1q42.2)	EGLN1 (1q42.2) / NRP1 (10p11.22)	EGLN1 (1q42.2) / PGBD5 (1q42.13)
	PPP1R15A (19q13.33) / EGLN1 (1q42.2)

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

Note

Entity	Head and neck squamous cell carcinoma
Note	Increased expression levels and nuclear translocation have been associated with the aggressiveness of the carcinoma.

Bibliography

Disturbance in the HIF-1alpha pathway associated with erythrocytosis: further evidences brought by frameshift and nonsense mutations in the prolyl hydroxylase domain protein 2 (PHD2) gene.

Al-Sheikh M, Moradkhani K, Lopez M, Wajcman H, Préhu C

Blood cells, molecules & diseases. 2008 ; 40 (2) : 160-165.

PMID 17933562

Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor.

Appelhoff RJ, Tian YM, Raval RR, Turley H, Harris AL, Pugh CW, Ratcliffe PJ, Gleadle JM

The Journal of biological chemistry. 2004 ; 279 (37) : 38458-38465.

PMID 15247232

HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia.

Berra E, Benizri E, Ginouvès A, Volmat V, Roux D, Pouysségur J

The EMBO journal. 2003 ; 22 (16) : 4082-4090.

PMID 12912907

Mapping, characterization, and expression analysis of the SM-20 human homologue, c1orf12, and identification of a novel related gene, SCAND2.

Dupuy D, Aubert I, Dupérat VG, Petit J, Taine L, Stef M, Bloch B, Arveiler B

Genomics. 2000 ; 69 (3) : 348-354.

PMID 11056053

C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation.

Epstein AC, Gleadle JM, McNeill LA, Hewitson KS, O'Rourke J, Mole DR, Mukherji M, Metzen E, Wilson MI, Dhanda A, Tian YM, Masson N, Hamilton DL, Jaakkola P, Barstead R, Hodgkin J, Maxwell PH, Pugh CW, Schofield CJ, Ratcliffe PJ

Cell. 2001 ; 107 (1) : 43-54.

PMID 11595184

Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor.

Hirsilä M, Koivunen P, Günzler V, Kivirikko KI, Myllyharju J

The Journal of biological chemistry. 2003 ; 278 (33) : 30772-30780.

PMID 12788921

HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing.

Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS, Kaelin WG Jr

Science (New York, N.Y.). 2001 ; 292 (5516) : 464-468.

PMID 11292862

Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation.

Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ, Kriegsheim Av, Hebestreit HF, Mukherji M, Schofield CJ, Maxwell PH, Pugh CW, Ratcliffe PJ

Science (New York, N.Y.). 2001 ; 292 (5516) : 468-472.

PMID 11292861

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

Clinical cancer research : an official journal of the American Association for Cancer Research. 2006 ; 12 (4) : 1080-1087.

PMID 16489060

Intracellular localisation of human HIF-1 alpha hydroxylases: implications for oxygen sensing.

Metzen E, Berchner-Pfannschmidt U, Stengel P, Marxsen JH, Stolze I, Klinger M, Huang WQ, Wotzlaw C, Hellwig-Bürgel T, Jelkmann W, Acker H, Fandrey J

Journal of cell science. 2003 ; 116 (Pt 7) : 1319-1326.

PMID 12615973

Regulation of the prolyl hydroxylase domain protein 2 (phd2/egln-1) gene: identification of a functional hypoxia-responsive element.

Metzen E, Stiehl DP, Doege K, Marxsen JH, Hellwig-Bürgel T, Jelkmann W

The Biochemical journal. 2005 ; 387 (Pt 3) : 711-717.

PMID 15563275

A novel erythrocytosis-associated PHD2 mutation suggests the location of a HIF binding groove.

Percy MJ, Furlow PW, Beer PA, Lappin TR, McMullin MF, Lee FS

Blood. 2007 ; 110 (6) : 2193-2196.

PMID 17579185

A family with erythrocytosis establishes a role for prolyl hydroxylase domain protein 2 in oxygen homeostasis.

Percy MJ, Zhao Q, Flores A, Harrison C, Lappin TR, Maxwell PH, McMullin MF, Lee FS

Proceedings of the National Academy of Sciences of the United States of America. 2006 ; 103 (3) : 654-659.

PMID 16407130

Placental but not heart defects are associated with elevated hypoxia-inducible factor alpha levels in mice lacking prolyl hydroxylase domain protein 2.

Takeda K, Ho VC, Takeda H, Duan LJ, Nagy A, Fong GH

Molecular and cellular biology. 2006 ; 26 (22) : 8336-8346.

PMID 16966370

Characterization and comparative analysis of the EGLN gene family.

Taylor MS

Gene. 2001 ; 275 (1) : 125-132.

PMID 11574160

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 journal version : [ pdf ] [ DOI ]

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 2 ]

Head and Neck: Paraganglioma: an overview
EGLN1/PGBD5 (1q42)

External links

	Nomenclature
HGNC (Hugo)	EGLN1 1232
	Cards
Atlas	EGLN1ID44140ch1q42
Entrez_Gene (NCBI)	EGLN1 egl-9 family hypoxia inducible factor 1
Aliases	C1orf12; ECYT3; HALAH; HIF-PH2;
	HIFPH2; HPH-2; HPH2; PHD2; SM20; ZMYND6
GeneCards (Weizmann)	EGLN1
Ensembl hg19 (Hinxton)	ENSG00000135766 [Gene_View]
Ensembl hg38 (Hinxton)	ENSG00000135766 [Gene_View] ENSG00000135766 [Sequence] chr1:231363757-231422287 [Contig_View] EGLN1 [Vega]
ICGC DataPortal	ENSG00000135766
TCGA cBioPortal	EGLN1
AceView (NCBI)	EGLN1
Genatlas (Paris)	EGLN1
SOURCE (Princeton)	EGLN1
Genetics Home Reference (NIH)	EGLN1
	Genomic and cartography
GoldenPath hg38 (UCSC)	EGLN1 - chr1:231363757-231422287 - 1q42.2 [Description] (hg38-Dec_2013)
GoldenPath hg19 (UCSC)	EGLN1 - 1q42.2 [Description] (hg19-Feb_2009)
GoldenPath	EGLN1 - 1q42.2 [CytoView hg19] EGLN1 - 1q42.2 [CytoView hg38]
ImmunoBase	ENSG00000135766
genome Data Viewer NCBI	EGLN1 [Mapview hg19]
OMIM	606425 609070 609820
	Gene and transcription
Genbank (Entrez)	AF229245 AF277174 AF277176 AF334711 AI017372
RefSeq transcript (Entrez)	NM_001377260 NM_001377261 NM_022051
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)	EGLN1
Alternative Splicing Gallery	ENSG00000135766
Gene Expression	EGLN1 [ NCBI-GEO ] EGLN1 [ EBI - ARRAY_EXPRESS ] EGLN1 [ SEEK ] EGLN1 [ MEM ]
Gene Expression Viewer (FireBrowse)	EGLN1 [ Firebrowse - Broad ]
Genevisible	Expression of EGLN1 in : [tissues] [cell-lines] [cancer] [perturbations]
BioGPS (Tissue expression)	54583
GTEX Portal (Tissue expression)	EGLN1
Human Protein Atlas	ENSG00000135766-EGLN1 [pathology] [cell] [tissue]
	Protein : pattern, domain, 3D structure
UniProt/SwissProt	Q9GZT9 [function] [subcellular_location] [family_and_domains] [pathology_and_biotech] [ptm_processing] [expression] [interaction]
NextProt	Q9GZT9 [Sequence] [Exons] [Medical] [Publications]
With graphics : InterPro	Q9GZT9
Splice isoforms : SwissVar	Q9GZT9
PhosPhoSitePlus	Q9GZT9
Domaine pattern : Prosite (Expaxy)	FE2OG_OXY (PS51471) ZF_MYND_1 (PS01360) ZF_MYND_2 (PS50865)
Domains : Interpro (EBI)	Oxoglu/Fe-dep_dioxygenase Pro_4_hyd_alph Znf_MYND
Domain families : Pfam (Sanger)	2OG-FeII_Oxy_3 (PF13640) zf-MYND (PF01753)
Domain families : Pfam (NCBI)	pfam13640 pfam01753
Domain families : Smart (EMBL)	P4Hc (SM00702)
Conserved Domain (NCBI)	EGLN1
Blocks (Seattle)	EGLN1
PDB (RSDB)	2G19 2G1M 2HBT 2HBU 2Y33 2Y34 3HQR 3HQU 3OUH 3OUI 3OUJ 4BQW 4BQX 4BQY 4JZR 4KBZ 4UWD 5A3U 5L9B 5L9R 5L9V 5LA9 5LAS 5LAT 5LB6 5LBB 5LBC 5LBE 5LBF 5OX5 5OX6 5V18 6NMQ 6ST3
PDB Europe	2G19 2G1M 2HBT 2HBU 2Y33 2Y34 3HQR 3HQU 3OUH 3OUI 3OUJ 4BQW 4BQX 4BQY 4JZR 4KBZ 4UWD 5A3U 5L9B 5L9R 5L9V 5LA9 5LAS 5LAT 5LB6 5LBB 5LBC 5LBE 5LBF 5OX5 5OX6 5V18 6NMQ 6ST3
PDB (PDBSum)	2G19 2G1M 2HBT 2HBU 2Y33 2Y34 3HQR 3HQU 3OUH 3OUI 3OUJ 4BQW 4BQX 4BQY 4JZR 4KBZ 4UWD 5A3U 5L9B 5L9R 5L9V 5LA9 5LAS 5LAT 5LB6 5LBB 5LBC 5LBE 5LBF 5OX5 5OX6 5V18 6NMQ 6ST3
PDB (IMB)	2G19 2G1M 2HBT 2HBU 2Y33 2Y34 3HQR 3HQU 3OUH 3OUI 3OUJ 4BQW 4BQX 4BQY 4JZR 4KBZ 4UWD 5A3U 5L9B 5L9R 5L9V 5LA9 5LAS 5LAT 5LB6 5LBB 5LBC 5LBE 5LBF 5OX5 5OX6 5V18 6NMQ 6ST3
Structural Biology KnowledgeBase	2G19 2G1M 2HBT 2HBU 2Y33 2Y34 3HQR 3HQU 3OUH 3OUI 3OUJ 4BQW 4BQX 4BQY 4JZR 4KBZ 4UWD 5A3U 5L9B 5L9R 5L9V 5LA9 5LAS 5LAT 5LB6 5LBB 5LBC 5LBE 5LBF 5OX5 5OX6 5V18 6NMQ 6ST3
SCOP (Structural Classification of Proteins)	2G19 2G1M 2HBT 2HBU 2Y33 2Y34 3HQR 3HQU 3OUH 3OUI 3OUJ 4BQW 4BQX 4BQY 4JZR 4KBZ 4UWD 5A3U 5L9B 5L9R 5L9V 5LA9 5LAS 5LAT 5LB6 5LBB 5LBC 5LBE 5LBF 5OX5 5OX6 5V18 6NMQ 6ST3
CATH (Classification of proteins structures)	2G19 2G1M 2HBT 2HBU 2Y33 2Y34 3HQR 3HQU 3OUH 3OUI 3OUJ 4BQW 4BQX 4BQY 4JZR 4KBZ 4UWD 5A3U 5L9B 5L9R 5L9V 5LA9 5LAS 5LAT 5LB6 5LBB 5LBC 5LBE 5LBF 5OX5 5OX6 5V18 6NMQ 6ST3
Superfamily	Q9GZT9
Human Protein Atlas [tissue]	ENSG00000135766-EGLN1 [tissue]
Peptide Atlas	Q9GZT9
HPRD	06971
IPI	IPI00004928 IPI00328822 IPI01013261 IPI00984285
	Protein Interaction databases
DIP (DOE-UCLA)	Q9GZT9
IntAct (EBI)	Q9GZT9
BioGRID	EGLN1
STRING (EMBL)	EGLN1
ZODIAC	EGLN1
	Ontologies - Pathways
QuickGO	Q9GZT9
Ontology : AmiGO	"response to hypoxia protein binding nucleus nucleus cytoplasm cytoplasm cytosol cellular iron ion homeostasis ferrous iron binding ferrous iron binding postsynaptic density 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 peptidyl-proline hydroxylation to 4-hydroxy-L-proline peptidyl-proline hydroxylation to 4-hydroxy-L-proline enzyme binding L-ascorbic acid binding peptidyl-proline dioxygenase activity peptidyl-proline dioxygenase activity peptidyl-proline 4-dioxygenase activity peptidyl-proline 4-dioxygenase activity peptidyl-proline 4-dioxygenase activity oxygen homeostasis negative regulation of DNA-binding transcription factor activity regulation of angiogenesis positive regulation of transcription by RNA polymerase II 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 glutamatergic synapse regulation of postsynapse organization regulation of protein catabolic process at postsynapse, modulating synaptic transmission regulation of neuron death"
Ontology : EGO-EBI	"response to hypoxia protein binding nucleus nucleus cytoplasm cytoplasm cytosol cellular iron ion homeostasis ferrous iron binding ferrous iron binding postsynaptic density 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 peptidyl-proline hydroxylation to 4-hydroxy-L-proline peptidyl-proline hydroxylation to 4-hydroxy-L-proline enzyme binding L-ascorbic acid binding peptidyl-proline dioxygenase activity peptidyl-proline dioxygenase activity peptidyl-proline 4-dioxygenase activity peptidyl-proline 4-dioxygenase activity peptidyl-proline 4-dioxygenase activity oxygen homeostasis negative regulation of DNA-binding transcription factor activity regulation of angiogenesis positive regulation of transcription by RNA polymerase II 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 glutamatergic synapse regulation of postsynapse organization regulation of protein catabolic process at postsynapse, modulating synaptic transmission regulation of neuron death"
Pathways : KEGG	HIF-1 signaling pathway Pathways in cancer Renal cell carcinoma
NDEx Network	EGLN1
Atlas of Cancer Signalling Network	EGLN1
Wikipedia pathways	EGLN1
	Orthology - Evolution
OrthoDB	54583
GeneTree (enSembl)	ENSG00000135766
Phylogenetic Trees/Animal Genes : TreeFam	EGLN1
HOGENOM	Q9GZT9
Homologs : HomoloGene	EGLN1
Homology/Alignments : Family Browser (UCSC)	EGLN1
	Gene fusions - Rearrangements
Fusion : Mitelman	EGLN1/PGBD5 [1q42.2/1q42.13]
Fusion Portal	EGLN1 1q42.2 PGBD5 1q42.13 BRCA
Fusion : Fusion_Hub	AKT3--EGLN1 C1S--EGLN1 CRISPLD2--EGLN1 EGLN1--DISC1 EGLN1--EGLN1 EGLN1--HP1BP3 EGLN1--ILF2 EGLN1--NRP1 EGLN1--PGBD5 EGLN1--PTPRF EGLN1--RBBP9 EGLN1--RYR2 EGLN1--SCAND2P EGLN1--SEC23B EGLN1--SFTPB
	EGLN1--SIL1 FAM175A--EGLN1 GALNT2--EGLN1 PPP1R15A--EGLN1 TCF12--EGLN1
Fusion : Quiver	EGLN1
	Polymorphisms : SNP and Copy number variants
NCBI Variation Viewer	EGLN1 [hg38]
dbVar	EGLN1
ClinVar	EGLN1
Monarch	EGLN1
1000_Genomes	EGLN1
Exome Variant Server	EGLN1
GNOMAD Browser	ENSG00000135766
Varsome Browser	EGLN1
Genomic Variants (DGV)	EGLN1 [DGVbeta]
DECIPHER	EGLN1 [patients] [syndromes] [variants] [genes]
CONAN: Copy Number Analysis	EGLN1
	Mutations
ICGC Data Portal	EGLN1
TCGA Data Portal	EGLN1
Broad Tumor Portal	EGLN1
OASIS Portal	EGLN1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMIC	EGLN1 [overview] [genome browser] [tissue] [distribution]
Somatic Mutations in Cancer : COSMIC3D	EGLN1
Mutations and Diseases : HGMD	EGLN1
LOVD (Leiden Open Variation Database)	Whole genome datasets
LOVD (Leiden Open Variation Database)	LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)	LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)	Mendelian genes
BioMuta	search EGLN1
DgiDB (Drug Gene Interaction Database)	EGLN1
DoCM (Curated mutations)	EGLN1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)	EGLN1 (select a term)
intoGen	EGLN1
NCG6 (London)	select EGLN1
Cancer3D	EGLN1(select the gene name)
Impact of mutations	[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
	Diseases
OMIM	606425 609070 609820
Orphanet	19522
DisGeNET	EGLN1
Medgen	EGLN1
Genetic Testing Registry	EGLN1
NextProt	Q9GZT9 [Medical]
GENETests	EGLN1
Target Validation	EGLN1
Huge Navigator	EGLN1 [HugePedia]
ClinGen	EGLN1
	Clinical trials, drugs, therapy
MyCancerGenome	EGLN1
Protein Interactions : CTD
Pharm GKB Gene	PA27670
Pharos	Q9GZT9
Clinical trial	EGLN1
	Miscellaneous
canSAR (ICR)	EGLN1 (select the gene name)
Harmonizome	EGLN1
DataMed Index	EGLN1
	Probes
	Litterature
PubMed	189 Pubmed reference(s) in Entrez
GeneRIFs	Gene References Into Functions (Entrez)
EVEX	EGLN1

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Search in all EBI NCBI

indexed on : Fri Feb 19 17:49:42 CET 2021

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