Tclin EGLN1 Egl nine homolog 1

Protein Summary

Description

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 HIF1B. 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. EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality. Target proteins are preferentially recognized via a LXXLAP motif. 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]

Uniprot Accession IDs

• Q9GZT9
• Q8N3M8
• Q9BZS8
• Q9BZT0

Gene Name

• EGLN1

Ensembl ID

• ENST00000366641
• ENSP00000355601
• ENSG00000135766

Symbol

• C1orf12
• HPH2
• PHD2
• SM20
• ECYT3
• HALAH
• HPH-2
• HIFPH2
• ZMYND6
• C1orf12
• HIF-PH2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
transcription factor perturbation	0.97
kinase perturbation	0.93
biological process	0.9
disease perturbation	0.9
virus perturbation	0.85

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 467.02   (req: < 5)

Gene RIFs: 117   (req: <= 3)

Antibodies: 546   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 467.02   (req: >= 5)

Gene RIFs: 117   (req: > 3)

Antibodies: 546   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 23

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 363

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 4

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (4)

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1 – 4 of 4

roxadustat

EGLN1Tclin

INHIBITOR pIC50 : 4.54

vadadustat

EGLN1Tclin

INHIBITOR pIC50 : 7.81

daprodustat

EGLN1Tclin

INHIBITOR pIC50 : 8.46

enarodustat

EGLN1Tclin

INHIBITOR pKi : 7.8

Active Ligands (363)

Explore Active Ligands

1 – 10 of 363

2,4-pyridine dicarboxylic acid

EGLN1Tclin

pKi : 8.66

IOX1

EGLN1Tclin

pIC50 : 7

CHEMBL2041169

EGLN1Tclin

pIC50 : 9.7

CHEMBL2043004

EGLN1Tclin

pIC50 : 8.89

CHEMBL2041176

EGLN1Tclin

pIC50 : 8.96

CHEMBL2041177

EGLN1Tclin

pIC50 : 9.15

CHEMBL2041172

EGLN1Tclin

pIC50 : 8.7

CHEMBL2040897

EGLN1Tclin

pIC50 : 9.4

CHEMBL2043327

EGLN1Tclin

pIC50 : 8.72

CHEMBL2041185

EGLN1Tclin

pIC50 : 9.7

Protein-Protein Interactions (184)

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1 – 10 of 184

• See Interactions on String-DB

EEF1AKMT1

Tdark

Family:  Enzyme

Novelty:  0.22249584

p_int:  0.93056127

p_ni:  0.06943873

Score:  0.359

Data Source:  BioPlex,STRINGDB

CBWD1

Tbio

Novelty:  0.04321511

p_int:  0.817114935

p_ni:  0.182885064

p_wrong:  1e-9

Score:  0.209

Data Source:  BioPlex,STRINGDB

BTF3

Tbio

Novelty:  0.01198537

p_int:  0.799473653

p_ni:  0.200526347

Data Source:  BioPlex

HIF1A

Tchem

Family:  TF

Novelty:  0.00011503

Score:  0.999

Data Source:  Reactome,STRINGDB

EPAS1

Tchem

Novelty:  0.00307448

Score:  0.997

Data Source:  Reactome,STRINGDB

AKT1

Tchem

Family:  Kinase

Novelty:  0.00003185

Score:  0.995

Data Source:  STRINGDB

AKT2

Tchem

Family:  Kinase

Novelty:  0.00167027

Score:  0.993

Data Source:  STRINGDB

VHL

Tchem

Family:  Enzyme

Novelty:  0.00285782

Score:  0.989

Data Source:  Reactome,STRINGDB

OS9

Tbio

Novelty:  0.01490339

Score:  0.974

Data Source:  STRINGDB

HIF3A

Tbio

Novelty:  0.01505965

Score:  0.973

Data Source:  Reactome,STRINGDB

Nearest Tclin Targets (3)

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Downstream (3)

1 – 3 of 3

VEGFA

Tclin

Family:  Other

KEGG Distance:  2

Common Pathways:  3

1: HIF-1 signaling pathway

2: Renal cell carcinoma

3: Pathways in cancer

VEGFB

Tclin

Family:  Other

KEGG Distance:  2

Common Pathways:  1

1: Pathways in cancer

PGF

Tclin

Family:  Other

KEGG Distance:  2

Common Pathways:  1

1: Pathways in cancer

Pathways (35)

Reactome (4)

KEGG (3)

PathwayCommons (4)

WikiPathways (24)

Cellular response to hypoxia (R-HSA-1234174)

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1 – 4 of 4

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Cellular response to hypoxia	76 targets	R-HSA-1234174
Reactome	Cellular responses to external stimuli	487 targets	R-HSA-8953897
Reactome	Cellular responses to stress	392 targets	R-HSA-2262752
Reactome	Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	67 targets	R-HSA-1234176

Name	Explore in Pharos	Explore in Source
Cellular response to hypoxia	76 targets	R-HSA-1234174
Cellular responses to external stimuli	487 targets	R-HSA-8953897
Cellular responses to stress	392 targets	R-HSA-2262752
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	67 targets	R-HSA-1234176

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (28)

Functions (6)

Components (5)

Processes (17)

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1 – 6 of 6

GO Term	Evidence	Assigned by
ferrous iron binding	Inferred from Direct Assay (IDA)	UniProtKB
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	Inferred from Direct Assay (IDA)	MGI
peptidyl-proline 4-dioxygenase activity	Inferred from Direct Assay (IDA)	FlyBase
enzyme binding	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
peptidyl-proline dioxygenase activity	Traceable Author Statement (TAS)	HGNC
L-ascorbic acid binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Disease Associations ()

No disease associations found

GWAS Traits (4)

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1 – 4 of 4

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
hematocrit	EFO_0004348	4	5	6		98
hemoglobin measurement	EFO_0004509	4	5	6		97.9
red blood cell density measurement	EFO_0007978	2	2	2		93.2
erythrocyte count	EFO_0004305	1	2	2		83.8

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 4 of 4

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
hematocrit	EFO_0004348	6		98
hemoglobin measurement	EFO_0004509	6		97.9
red blood cell density measurement	EFO_0007978	2		93.2
erythrocyte count	EFO_0004305	2		83.8

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Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Alternative splicing
Complete proteome
Congenital erythrocytosis
Cytoplasm
Dioxygenase
Disease mutation
Iron
Metal-binding

GWAS Trait Find Similar Targets

No Header	No Header
erythrocyte count
hematocrit
hemoglobin measurement
red blood cell density measurement

MGI Phenotype Find Similar Targets

No Header	No Header
cardiovascular system phenotype
cellular phenotype
embryo phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
integument phenotype
liver/biliary system phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (11)

1 – 5 of 11

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	egl-9 family hypoxia inducible factor 1	VGNC:9857	469708
Macaque	egl-9 family hypoxia inducible factor 1		713410
Mouse	egl-9 family hypoxia-inducible factor 1	MGI:1932286	112405
Dog	egl-9 family hypoxia inducible factor 1	VGNC:40240	488971
Horse	egl-9 family hypoxia inducible factor 1	VGNC:51494	100060551

Species	Name	OMA	EggNOG	Inparanoid
Chimp	egl-9 family hypoxia inducible factor 1
Macaque	egl-9 family hypoxia inducible factor 1
Mouse	egl-9 family hypoxia-inducible factor 1
Dog	egl-9 family hypoxia inducible factor 1
Horse	egl-9 family hypoxia inducible factor 1

Publication Statistics

PubMed Score 467.02

PubMed score by year

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PubTator Score 257.47

PubTator score by year

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Related Publications

Text Mined References (142)

GeneRif Annotations (117)

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PMID	Year	Title