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

Identity

Other names	C1orf12
	DKFZp761F179
	ECYT3
	HIFPH2
	HPH-2
	PHD2
	SM-20
	SM20
	ZMYND6
HGNC	EGLN1
Location	1q42.2
Location_base_pair	Starts at 229568054 and ends at 229627413 bp from pter ( according to hg18-Mar_2006).

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	EGLN1   1232
Entrez_Gene	EGLN1  54583  egl nine homolog 1 (C. elegans)
	Cards
Atlas	EGLN1ID44140ch1q42
GeneCards	EGLN1
Ensembl	EGLN1 [Search_View]   ENSG00000135766 [Gene_View]
Genatlas	EGLN1
GeneLynx	EGLN1
eGenome	EGLN1
euGene	54583
	Genomic and cartography
GoldenPath	EGLN1  -  1q42.2   chr1:229568054-229627413 -  1q42.1   [Description]    (hg18-Mar_2006)
Ensembl	EGLN1 - 1q42.1 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	EGLN1
	Gene and transcription
Genbank	AF229245 [ ENTREZ ]
Genbank	AF277174 [ ENTREZ ]
Genbank	AF277176 [ ENTREZ ]
Genbank	AF334711 [ ENTREZ ]
Genbank	AJ227859 [ ENTREZ ]
RefSeq	NM_022051 [ SRS ]    NM_022051 [ ENTREZ ]
RefSeq	AC_000044 [ SRS ]    AC_000044 [ ENTREZ ]
RefSeq	AC_000133 [ SRS ]    AC_000133 [ ENTREZ ]
RefSeq	NC_000001 [ SRS ]    NC_000001 [ ENTREZ ]
RefSeq	NT_004559 [ SRS ]    NT_004559 [ ENTREZ ]
RefSeq	NW_001838549 [ SRS ]    NW_001838549 [ ENTREZ ]
RefSeq	NW_927128 [ SRS ]    NW_927128 [ ENTREZ ]
AceView	EGLN1 AceView - NCBI
Unigene	Hs.444450 [ SRS ]    Hs.444450 [ NCBI ]     HS444450 [ spliceNest ]
Fast-db	17924 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q9GZT9 [ SRS]    Q9GZT9 [ EXPASY ]     Q9GZT9 [ INTERPRO ]     Q9GZT9 [ UNIPROT ]
Prosite	PS01360 ZF_MYND_1 [ SRS ]    PS01360 ZF_MYND_1 [ Expasy ]
Prosite	PS50865 ZF_MYND_2 [ SRS ]    PS50865 ZF_MYND_2 [ Expasy ]
Interpro	IPR005123 2OG-FeII_Oase [ SRS ]    IPR005123 2OG-FeII_Oase [ EBI ]
Interpro	IPR006620 Pro_4_hyd_alph [ SRS ]    IPR006620 Pro_4_hyd_alph [ EBI ]
Interpro	IPR002893 Znf_MYND [ SRS ]    IPR002893 Znf_MYND [ EBI ]
CluSTr	Q9GZT9
Pfam	PF03171 2OG-FeII_Oxy [ SRS ]    PF03171 2OG-FeII_Oxy [ Sanger ]    pfam03171 [ NCBI-CDD ]
Pfam	PF01753 zf-MYND [ SRS ]    PF01753 zf-MYND [ Sanger ]    pfam01753 [ NCBI-CDD ]
Smart	SM00702 P4Hc [EMBL]
Blocks	Q9GZT9
PDB	2G19 [ SRS ]    2G19 [ PdbSum ],   2G19 [ IMB ]   2G19 [ RSDB ]
PDB	2G1M [ SRS ]    2G1M [ PdbSum ],   2G1M [ IMB ]   2G1M [ RSDB ]
PDB	2HBT [ SRS ]    2HBT [ PdbSum ],   2HBT [ IMB ]   2HBT [ RSDB ]
PDB	2HBU [ SRS ]    2HBU [ PdbSum ],   2HBU [ IMB ]   2HBU [ RSDB ]
HPRD	06971
	Protein Interaction databases
DIP	Q9GZT9
IntAct	Q9GZT9
	Polymorphism : SNP, mutations, diseases
OMIM	606425;609820    [ map ]
GENECLINICS	606425;609820
SNP	EGLN1 [dbSNP-NCBI]
SNP	NM_022051 [SNP-NCI]
SNP	EGLN1 [GeneSNPs - Utah]  EGLN1] [HGBASE - SRS]
HAPMAP	EGLN1 [HAPMAP]
COSMIC	EGLN1 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	EGLN1
	General knowledge
Family Browser	EGLN1 [UCSC Family Browser]
SOURCE	NM_022051
SMD	Hs.444450
SAGE	Hs.444450
Enzyme	1.14.11.- [ Enzyme-Expasy ]   1.14.11.- [ Enzyme-SRS ]   1.14.11.- [ IntEnz-EBI ]   1.14.11.- [ BRENDA ]   1.14.11.- [ KEGG ]   1.14.11.- [ WIT ]
GO	response to hypoxia [Amigo]  response to hypoxia
GO	embryonic placenta development [Amigo]  embryonic placenta development
GO	iron ion binding [Amigo]  iron ion binding
GO	protein binding [Amigo]  protein binding
GO	cytosol [Amigo]  cytosol
GO	heart development [Amigo]  heart development
GO	zinc ion binding [Amigo]  zinc ion binding
GO	oxidoreductase activity [Amigo]  oxidoreductase activity
GO	oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen [Amigo]  oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
GO	protein metabolic process [Amigo]  protein metabolic process
GO	L-ascorbic acid binding [Amigo]  L-ascorbic acid binding
GO	peptidyl-proline dioxygenase activity [Amigo]  peptidyl-proline dioxygenase activity
GO	oxygen homeostasis [Amigo]  oxygen homeostasis
GO	negative regulation of transcription factor activity [Amigo]  negative regulation of transcription factor activity
GO	metal ion binding [Amigo]  metal ion binding
GO	oxidation reduction [Amigo]  oxidation reduction
KEGG	Diterpenoid biosynthesis
PubGene	EGLN1
TreeFam	EGLN1
CTD	54583 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	EGLN1 Related clones (RZPD - Berlin)
	PubMed
PubMed	34 Pubmed reference(s) in Entrez

Bibliography

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

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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

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

PMID 16489060

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.

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

PMID 16966370

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, Prˆ©hu C

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

PMID 17933562

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

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Contributor(s)

Written	01-2008	Terhi 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. January 2008 . URL : http://AtlasGeneticsOncology.org/Genes/EGLN1ID44140ch1q42.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Tue Oct 14 21:18:17 2008