EGLN1 egl nine homolog 1 (C. elegans) [Homo sapiens (human)] - Gene

Summary

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Official Symbol: EGLN1provided by HGNC
Official Full Name: egl nine homolog 1 (C. elegans)provided by HGNC
Primary source: HGNC:1232
Locus tag: PNAS-118
See related: Ensembl:ENSG00000135766; HPRD:06971; MIM:606425; Vega:OTTHUMG00000038027
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HPH2; PHD2; SM20; ECYT3; HPH-2; HIFPH2; ZMYND6; C1orf12; HIF-PH2
Summary: 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]

Genomic context

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Location :: 1q42.1

Sequence :: Chromosome: 1; NC_000001.10 (231499497..231560790, complement)

See EGLN1 in Epigenomics, MapViewer

Chromosome 1 - NC_000001.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Knockdown of prolyl-4-hydroxylase domain 2 inhibits tumor growth of human breast cancer MDA-MB-231 cells by affecting TGF-beta1 processing.
Title: Knockdown of prolyl-4-hydroxylase domain 2 inhibits tumor growth of human breast cancer MDA-MB-231 cells by affecting TGF-β1 processing.
PHD2-mediated hydroxylation of HIF-1alpha predominantly occurs in the cell nucleus and is dependent on very dynamic subcellular trafficking of PHD2.
Title: Oxygen sensing by the prolyl-4-hydroxylase PHD2 within the nuclear compartment and the influence of compartmentalisation on HIF-1 signalling.
p23 recruits PHD2 to the HSP90 machinery to facilitate HIF-1alpha hydroxylation
Title: Prolyl hydroxylase domain protein 2 (PHD2) binds a Pro-Xaa-Leu-Glu motif, linking it to the heat shock protein 90 pathway.
a unique mechanism for the regulation of HIF-1alpha stability that involves ERbeta-mediated transcriptional regulation of PHD2 and they highlight an unexpected role for PHD2 in maintaining epithelial differentiation.
Title: Estrogen receptor β sustains epithelial differentiation by regulating prolyl hydroxylase 2 transcription.
The study scrutinizes the unfolding pathways of the PHD2 catalytic domain's possible species and demonstrates the properties of their unfolding states by computational approaches.
Title: Thermal unfolding pathway of PHD2 catalytic domain in three different PHD2 species: computational approaches.
PHD2 may directly interact with PDE4D to function as a novel regulator of the intracellular cAMP levels in cardiomyocytes.
Title: Prolyl hydroxylase domain protein 2 regulates the intracellular cyclic AMP level in cardiomyocytes through its interaction with phosphodiesterase 4D.
prevalence of the risk alleles in high altitude pulmonary edema and the protective alleles in healthy Lakakhi highland natives have provided us with allelic variants at the same locus that are involved in disease and adaptation
Title: EGLN1 variants influence expression and SaO2 levels to associate with high-altitude pulmonary oedema and adaptation.
Heart rate and oxygen saturation level of hemoglobin were found to be significantly associated with the EGLN1 (rs480902) SNP in the Han patients with acute mountain sickness.
Title: EPAS1 and EGLN1 associations with high altitude sickness in Han and Tibetan Chinese at the Qinghai-Tibetan Plateau.
Our data suggest that PHD-2 is the major hydroxylase regulating HIF levels and the expression of angiogenic genes in arthritic cells.
Title: Prolyl hydroxylase domain enzyme 2 is the major player in regulating hypoxic responses in rheumatoid arthritis.
The unusual kinetic pK(a) further suggested that PHD2 might function physiologically to sense both intracellular pO(2) as well as pH, which could provide for feedback between anaerobic metabolism and hypoxia sensing.
Title: Inverse solvent isotope effects demonstrate slow aquo release from hypoxia inducible factor-prolyl hydroxylase (PHD2).

Submit: New GeneRIF Correction See all (72)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_071334.1	NP_001521.1	HIF1A	BIND	PubMed	HIF-1 alpha interacts with PHD2.
NP_071334.1	NP_006803.1	OS9	BIND	PubMed	OS-9 interacts with PHD2.
Q9GZT9	Q99814	EPAS1	HPRD	PubMed
Q9GZT9	Q16665	HIF1A	HPRD	PubMed
Q9GZT9	Hypoxia inducible factor 3 alpha subunit	HIF3A	HPRD	PubMed
Q9GZT9	Q9UNL4	ING4	HPRD	PubMed
Q9GZT9	Q13438	OS9	HPRD	PubMed
BioGRID:120060	BioGRID:120060	EGLN1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:120060	BioGRID:125185	EGLN3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:120060	BioGRID:108348	EPAS1	BioGRID	PubMed	Affinity Capture-MS; Reconstituted Complex; Two-hybrid
BioGRID:120060	BioGRID:117270	FKBP8	BioGRID	PubMed	FRET; Protein-peptide; Reconstituted Complex; Two-hybrid
BioGRID:120060	BioGRID:109338	HIF1A	BioGRID	PubMed	Affinity Capture-Western; Co-crystal Structure; Reconstituted Complex
BioGRID:120060	BioGRID:113946	HIST1H3A	BioGRID	PubMed	Co-crystal Structure; Reconstituted Complex
BioGRID:120060	BioGRID:119331	ING4	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:120060	BioGRID:110043	KRAS	BioGRID	PubMed	Two-hybrid
BioGRID:120060	BioGRID:114475	LIMD1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:120060	BioGRID:110284	MAGEA11	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:120060	BioGRID:110282	MAGEA9	BioGRID	PubMed	Affinity Capture-Western
BioGRID:120060	BioGRID:116156	OS9	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:120060	BioGRID:126234	OSR1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:120060	BioGRID:111332	PKM	BioGRID	PubMed	Affinity Capture-Western
BioGRID:120060	BioGRID:111426	POLR2A	BioGRID	PubMed	Affinity Capture-Western
BioGRID:120060	BioGRID:112373	SIAH2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:120060	BioGRID:115547	SPRY2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:120060	BioGRID:112592	SRC	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Reconstituted Complex
BioGRID:120060	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:120060	BioGRID:113269	VHL	BioGRID	PubMed	Affinity Capture-Western
BioGRID:120060	BioGRID:117074	ZNF281	BioGRID	PubMed	Two-hybrid

Pathways from BioSystems

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Cellular response to hypoxia, organism-specific biosystem (from REACTOME)
Cellular response to hypoxia, organism-specific biosystemOxygen plays a central role in the functioning of human cells: it is both essential for normal metabolism and toxic. To begin the annotation of stress responses in Reactome, we have annotated one asp...
Cellular responses to stress, organism-specific biosystem (from REACTOME)
Cellular responses to stress, organism-specific biosystemCells are subject to external molecular and physical stresses such as foreign molecules that perturb metabolic or signaling processes, and changes in temperature or pH. The ability of cells and tissu...
HIF-1 signaling pathway, organism-specific biosystem (from KEGG)
HIF-1 signaling pathway, organism-specific biosystemHypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis. It consists of two subunits: an inducibly-expressed HIF-1alpha subunit and a c...
HIF-1-alpha transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
HIF-1-alpha transcription factor network, organism-specific biosystem
HIF-1-alpha transcription factor network
HIF-2-alpha transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
HIF-2-alpha transcription factor network, organism-specific biosystem
HIF-2-alpha transcription factor network
Oxygen-dependent Proline Hydroxylation of Hypoxia-inducible Factor Alpha, organism-specific biosystem (from REACTOME)
Oxygen-dependent Proline Hydroxylation of Hypoxia-inducible Factor Alpha, organism-specific biosystemHIF-alpha subunits, comprising HIF1A (Bruick and McKnight 2001, Ivan et al. 2001, Jaakkola et al. 2001), HIF2A (Percy et al. 2008, Furlow et al. 2009), and HIF3A (Maynard et al. 2003), are hydroxylat...
Pathways in cancer, organism-specific biosystem (from KEGG)
Pathways in cancer, organism-specific biosystem
Pathways in cancer
Regulation of Hypoxia-inducible Factor (HIF) by Oxygen, organism-specific biosystem (from REACTOME)
Regulation of Hypoxia-inducible Factor (HIF) by Oxygen, organism-specific biosystemIn the presence of oxygen members of the transcription factor family HIF-alpha, comprising HIF1A, HIF2A (EPAS1), and HIF3A, are hydroxylated on proline residues by PHD1 (EGLN2), PHD2 (EGLN1), and PHD...
Renal cell carcinoma, organism-specific biosystem (from KEGG)
Renal cell carcinoma, organism-specific biosystemRenal cell cancer (RCC) accounts for ~3% of human malignancies and its incidence appears to be rising. Although most cases of RCC seem to occur sporadically, an inherited predisposition to renal canc...
Renal cell carcinoma, conserved biosystem (from KEGG)
Renal cell carcinoma, conserved biosystemRenal cell cancer (RCC) accounts for ~3% of human malignancies and its incidence appears to be rising. Although most cases of RCC seem to occur sporadically, an inherited predisposition to renal canc...

General gene information

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Markers

RH64701 (e-PCR)
- UniSTS:57089

G19709 (e-PCR)
- UniSTS:57360

A001W16 (e-PCR)
- UniSTS:57361

RH36231 (e-PCR)
- UniSTS:80951

RH48299 (e-PCR)
- UniSTS:44871

STS-T77466 (e-PCR)
- UniSTS:15498

WI-11258 (e-PCR)
- UniSTS:62354

RH15809 (e-PCR)
- UniSTS:50882

SHGC-76521 (e-PCR)
- UniSTS:46787

RH79614 (e-PCR)
- UniSTS:84195

Genotypes

See EGLN1 SNP Geneview Report
See EGLN1 SNP Genotype Report
See EGLN1 SNP Variation Viewer Report

Homology

Homologs of the EGLN1 gene: The EGLN1 gene is conserved in Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, and mosquito.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
L-ascorbic acid binding	IEA Inferred from Electronic Annotation more info
iron ion binding	IEA Inferred from Electronic Annotation more info
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen	IEA Inferred from Electronic Annotation more info
peptidyl-proline 4-dioxygenase activity	IDA Inferred from Direct Assay more info	PubMed
peptidyl-proline dioxygenase activity	TAS Traceable Author Statement more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
cardiac muscle tissue morphogenesis	IEA Inferred from Electronic Annotation more info
cellular response to hypoxia	TAS Traceable Author Statement more info
heart trabecula formation	IEA Inferred from Electronic Annotation more info
labyrinthine layer development	IEA Inferred from Electronic Annotation more info
negative regulation of sequence-specific DNA binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
oxygen homeostasis	IDA Inferred from Direct Assay more info	PubMed
peptidyl-proline hydroxylation to 4-hydroxy-L-proline	IDA Inferred from Direct Assay more info	PubMed
regulation of angiogenesis	ISS Inferred from Sequence or Structural Similarity more info
regulation of transcription from RNA polymerase II promoter in response to hypoxia	TAS Traceable Author Statement more info
response to hypoxia	IDA Inferred from Direct Assay more info	PubMed
response to nitric oxide	IDA Inferred from Direct Assay more info
ventricular septum morphogenesis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytosol	TAS Traceable Author Statement more info
nucleus	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: egl nine homolog 1

Names: egl nine homolog 1; egl nine-like protein 1; HIF prolyl hydroxylase 2; HIF-prolyl hydroxylase 2; zinc finger MYND domain-containing protein 6; hypoxia-inducible factor prolyl hydroxylase 2; prolyl hydroxylase domain-containing protein 2

NP_071334.1

EC 1.14.11.29

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_015865.1 RefSeqGene

Range

5001..66294

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_022051.2 → NP_071334.1 egl nine homolog 1

Status: REVIEWED

Source sequence(s)

AF229245, AI017372, AL117352

Consensus CDS

CCDS1595.1

UniProtKB/Swiss-Prot

Q9GZT9

Related

ENSP00000355601, OTTHUMP00000036152, ENST00000366641, OTTHUMT00000092879

Conserved Domains (2) summary

pfam01753
Location:21 – 58
Blast Score: 82

zf-MYND; MYND finger

smart00702
Location:220 – 391
Blast Score: 325

P4Hc; Prolyl 4-hydroxylase alpha subunit homologues

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000001.10 Reference GRCh37.p10 Primary Assembly

Range

231499497..231560790, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000133.1 Alternate HuRef

Range

201982787..202043989, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018912.1 Alternate CHM1_1.0

Range

238283974..238345380, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01033038.1 (7178..65276)	None
genomic	ABBA01033039.1	None
genomic	AF246630.1	AAG34568.1
genomic	AF246631.1	AAG34568.1
genomic	AL117352.12 (92486..137957)	None
genomic	AL445524.28	None
genomic	AMYH01001819.1 (201663..263069)	None
genomic	CH471098.1	EAW69959.1
genomic	CS681768.1	CAP11376.1
genomic	KC554048.1	AGL94925.1
mRNA	AF229245.1	AAG33965.1
mRNA	AF277174.1	AAK07534.1
mRNA	AF277176.1	AAK07536.1
mRNA	AF334711.1	None
mRNA	AI017372.1	None
mRNA	AJ227859.1	None
mRNA	AJ310543.1	CAC42509.1
mRNA	AL833885.1	CAD38741.2
mRNA	BC005369.1	AAH05369.1
mRNA	DQ975380.1	ABM44413.1