EGLN1

Functionⁱ

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.7 Publications

Caution

It was previously reported that this protein was the ortholog of rat SM-20. However, EGLN3 is now considered the true ortholog of rat SM-20 since it shows substantially greater similarity.Curated

Catalytic activityⁱ

Cofactorⁱ

Protein has several cofactor binding sites:

Activity regulationⁱ

Following exposure to hypoxia, activated in HeLa cells but not in cardiovascular cells.2 Publications

Kineticsⁱ

Sites

Feature key	Position(s)	DescriptionActions	Length
Metal bindingⁱ	313	IronCombined sources3 Publications	1
Metal bindingⁱ	315	IronCombined sources3 Publications	1
Metal bindingⁱ	374	IronCombined sources3 Publications	1
Binding siteⁱ	383	2-oxoglutarate1 Publication	1

Regions

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Zinc fingerⁱ	21 – 58	MYND-typePROSITE-ProRule annotationAdd BLAST		38

GO - Molecular functionⁱ

enzyme binding Source: BHF-UCL
ferrous iron binding
Source: UniProtKB
Inferred from direct assayⁱ
- 28594552
L-ascorbic acid binding Source: UniProtKB-KW
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
Source: MGI
Inferred from direct assayⁱ
- 22955912
peptidyl-proline 4-dioxygenase activity
Source: FlyBase
Inferred from direct assayⁱ
- 11598268
peptidyl-proline dioxygenase activity
Source: HGNC
Traceable author statementⁱ
- 16956324

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

cardiac muscle tissue morphogenesis Source: Ensembl
cellular iron ion homeostasis Source: Ensembl
heart trabecula formation Source: Ensembl
labyrinthine layer development Source: Ensembl
negative regulation of cyclic-nucleotide phosphodiesterase activity Source: BHF-UCL
negative regulation of DNA-binding transcription factor activity
Source: HGNC
Inferred from direct assayⁱ
- 16956324
oxygen homeostasis
Source: HGNC
Inferred from direct assayⁱ
- 16956324
peptidyl-proline hydroxylation to 4-hydroxy-L-proline
Source: FlyBase
Inferred from direct assayⁱ
- 11598268
positive regulation of transcription by RNA polymerase II Source: Ensembl
regulation of angiogenesis Source: UniProtKB
regulation of neuron death Source: Ensembl
regulation of postsynapse organization Source: Ensembl
regulation of protein catabolic process at postsynapse, modulating synaptic transmission Source: Ensembl
regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: Reactome
response to hypoxia
Source: HGNC
Inferred from direct assayⁱ
- 16956324
response to nitric oxide
Source: UniProtKB
Inferred from direct assayⁱ
- 21601578
ventricular septum morphogenesis Source: Ensembl

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Dioxygenase, Oxidoreductase
Ligand	Iron, Metal-binding, Vitamin C, Zinc

Enzyme and pathway databases

BRENDAⁱ	1.14.11.2 2681 1.14.11.29 2681
Reactomeⁱ	R-HSA-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Egl nine homolog 1 (EC:1.14.11.291 Publication) Alternative name(s): Hypoxia-inducible factor prolyl hydroxylase 2 Short name: HIF-PH2 Short name: HIF-prolyl hydroxylase 2 Short name: HPH-2 Prolyl hydroxylase domain-containing protein 2 Short name: PHD2 SM-20
Gene namesⁱ	Name:EGLN1Imported Synonyms:C1orf12 ORF Names:PNAS-118, PNAS-137
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 1

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000135766.8
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:1232 EGLN1
MIMⁱ	606425 gene
neXtProtⁱ	NX_Q9GZT9

Keywords - Cellular componentⁱ

Cytoplasm, Nucleus

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Erythrocytosis, familial, 3 (ECYT3)2 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAn autosomal dominant disorder characterized by increased serum red blood cell mass, elevated serum hemoglobin and hematocrit, and normal serum erythropoietin levels.

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_027371	317	P → R in ECYT3; marked decrease in enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs80358193EnsemblClinVar.		1
Natural variantⁱVAR_045902	371	R → H in ECYT3; decreased interaction with HIF1A and EPAS1 and decreased enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs119476044EnsemblClinVar.		1

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	201	C → A: Little change in enzyme activity. 1 Publication	1
Mutagenesisⁱ	208	C → A: Little change in enzyme activity. 1 Publication	1
Mutagenesisⁱ	252	R → A: Reduced C-terminal ODD domain (CODD) hydroxylation of HIF1A.	1
Mutagenesisⁱ	254	D → A or K: Reduced C-terminal ODD domain (CODD) hxdroxylation of HIF1A.	1
Mutagenesisⁱ	266	C → A: Little change in enzyme activity. 1 Publication	1
Mutagenesisⁱ	283	C → A: Little change in enzyme activity. 1 Publication	1
Mutagenesisⁱ	302	C → A: Slight increase in enzyme activity. 1 Publication	1
Mutagenesisⁱ	303	Y → F: No effect. 1 Publication	1
Mutagenesisⁱ	323	C → A: Little change in enzyme activity. 1 Publication	1
Mutagenesisⁱ	326	C → A: Slight increase in enzyme activity. 1 Publication	1
Mutagenesisⁱ	383	R → A: Reduces enzyme activity by 95%. 1 Publication	1

Keywords - Diseaseⁱ

Congenital erythrocytosis, Disease mutation

Organism-specific databases

DisGeNET More...DisGeNETⁱ	54583
MalaCards human disease database More...MalaCardsⁱ	EGLN1
MIMⁱ	609820 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000135766
Orphanetⁱ	247511 Autosomal dominant secondary polycythemia
PharmGKBⁱ	PA27670

Chemistry databases

ChEMBLⁱ	CHEMBL5697
Drug and drug target database More...DrugBankⁱ	DB04847 FG-4592 DB08687 N-[(1-CHLORO-4-HYDROXYISOQUINOLIN-3-YL)CARBONYL]GLYCINE DB07112 N-[(4-HYDROXY-8-IODOISOQUINOLIN-3-YL)CARBONYL]GLYCINE DB00126 Vitamin C
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	2833

Polymorphism and mutation databases

BioMutaⁱ	EGLN1
DMDMⁱ	32129514

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Initiator methionineⁱ		RemovedCombined sources
ChainⁱPRO_0000206661	2 – 426	Egl nine homolog 1Add BLAST		425

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	2	N-acetylalanineCombined sources	1
Modified residueⁱ	12	PhosphoserineCombined sources	1
Modified residueⁱ	125	PhosphoserineCombined sources	1
Modified residueⁱ	201	S-nitrosocysteine1 Publication	1
Modified residueⁱ	208	S-nitrosocysteine1 Publication	1
Modified residueⁱ	302	S-nitrosocysteine1 Publication	1
Modified residueⁱ	323	S-nitrosocysteine1 Publication	1
Modified residueⁱ	326	S-nitrosocysteine1 Publication	1

Post-translational modificationⁱ

S-nitrosylation inhibits the enzyme activity up to 60% under aerobic conditions. Chelation of Fe²⁺ has no effect on the S-nitrosylation. It is uncertain whether nitrosylation occurs on Cys-323 or Cys-326.1 Publication

Keywords - PTMⁱ

Acetylation, Phosphoprotein, S-nitrosylation

Proteomic databases

EPDⁱ	Q9GZT9
PaxDbⁱ	Q9GZT9
PeptideAtlas More...PeptideAtlasⁱ	Q9GZT9
PRIDEⁱ	Q9GZT9
ProteomicsDBⁱ	80138 80139 [Q9GZT9-2] 80140 [Q9GZT9-3]

PTM databases

iPTMnetⁱ	Q9GZT9
PhosphoSitePlusⁱ	Q9GZT9

Expressionⁱ

Tissue specificityⁱ

According to PubMed:11056053, widely expressed with highest levels in skeletal muscle and heart, moderate levels in pancreas, brain (dopaminergic neurons of adult and fetal substantia nigra) and kidney, and lower levels in lung and liver. According to PubMed:12351678 widely expressed with highest levels in brain, kidney and adrenal gland. Expressed in cardiac myocytes, aortic endothelial cells and coronary artery smooth muscle. According to PubMed:12788921; expressed in adult and fetal heart, brain, liver, lung, skeletal muscle and kidney. Also expressed in placenta. Highest levels in adult heart, brain, lung and liver and fetal brain, heart spleen and skeletal muscle.5 Publications

Gene expression databases

Bgeeⁱ	ENSG00000135766 Expressed in 223 organ(s), highest expression level in female gonad
CleanExⁱ	HS_EGLN1
ExpressionAtlasⁱ	Q9GZT9 baseline and differential
Genevisibleⁱ	Q9GZT9 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	HPA022129

HPAⁱ

HPA022129

Interactionⁱ

Subunit structureⁱ

Monomer. Interacts with ING4; the interaction inhibits the hydroxylation of HIF alpha proteins. Interacts with PTGES3 (via PXLE motif); thereby recruiting EGLN1 to the HSP90 pathway to facilitate HIF alpha proteins hydroxylation. Interacts with LIMD1. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2. Interacts with EPAS1. Interacts with CBFA2T3 (PubMed:25974097). Interacts with HIF1A (PubMed:25974097).8 Publications

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
	Q9WMX2	3	EBI-1174818,EBI-6863748	From Hepatitis C virus genotype 1b (isolate Con1).
EPAS1	Q99814	2	EBI-1174818,EBI-447470
FKBP8	Q14318	6	EBI-1174818,EBI-724839
HIF1A	Q16665	4	EBI-1174818,EBI-447269
OS9	Q13438	4	EBI-1174818,EBI-725454

GO - Molecular functionⁱ

enzyme binding Source: BHF-UCL

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	120060, 42 interactors
CORUMⁱ	Q9GZT9
Database of interacting proteins More...DIPⁱ	DIP-37495N
ELMⁱ	Q9GZT9
IntActⁱ	Q9GZT9, 16 interactors
Molecular INTeraction database More...MINTⁱ	Q9GZT9
STRINGⁱ	9606.ENSP00000355601

Chemistry databases

BindingDBⁱ

Q9GZT9

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Helixⁱ	190 – 196	Combined sources	7
Helixⁱ	198 – 205	Combined sources	8
Beta strandⁱ	206 – 214	Combined sources	9
Helixⁱ	216 – 231	Combined sources	16
Beta strandⁱ	240 – 242	Combined sources	3
Helixⁱ	247 – 249	Combined sources	3
Beta strandⁱ	255 – 259	Combined sources	5
Helixⁱ	267 – 283	Combined sources	17
Turnⁱ	284 – 286	Combined sources	3
Beta strandⁱ	287 – 289	Combined sources	3
Beta strandⁱ	292 – 295	Combined sources	4
Beta strandⁱ	298 – 303	Combined sources	6
Beta strandⁱ	305 – 313	Combined sources	9
Beta strandⁱ	315 – 318	Combined sources	4
Beta strandⁱ	321 – 329	Combined sources	9
Beta strandⁱ	331 – 333	Combined sources	3
Helixⁱ	336 – 339	Combined sources	4
Beta strandⁱ	343 – 345	Combined sources	3
Beta strandⁱ	348 – 351	Combined sources	4
Beta strandⁱ	354 – 356	Combined sources	3
Beta strandⁱ	362 – 367	Combined sources	6
Beta strandⁱ	374 – 381	Combined sources	8
Beta strandⁱ	383 – 392	Combined sources	10
Helixⁱ	393 – 402	Combined sources	10
Helixⁱ	407 – 409	Combined sources	3

Show more details

3D structure databases

ProteinModelPortalⁱ	Q9GZT9
SMRⁱ	Q9GZT9
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	Q9GZT9

EvolutionaryTraceⁱ

Q9GZT9

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	291 – 392	Fe2OG dioxygenasePROSITE-ProRule annotationAdd BLAST		102

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	6 – 20	Required for nuclear exportAdd BLAST		15
Regionⁱ	241 – 251	Beta(2)beta(3) 'finger-like' loop1 PublicationAdd BLAST		11

Domainⁱ

The beta₂beta₃ 'finger-like' loop domain is important for substrate (HIFs' CODD/NODD) selectivity.1 Publication

Zinc finger

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Zinc fingerⁱ	21 – 58	MYND-typePROSITE-ProRule annotationAdd BLAST		38

Keywords - Domainⁱ

Zinc-finger

Phylogenomic databases

eggNOGⁱ	KOG3710 Eukaryota ENOG410ZHZN LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00390000001936
HOGENOMⁱ	HOG000004818
HOVERGENⁱ	HBG051455
InParanoidⁱ	Q9GZT9
KEGG Orthology (KO) More...KOⁱ	K09592
OMAⁱ	KANLYPP
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G03SP
PhylomeDBⁱ	Q9GZT9
TreeFamⁱ	TF314595

Family and domain databases

InterProⁱ	View protein in InterPro IPR005123 Oxoglu/Fe-dep_dioxygenase IPR006620 Pro_4_hyd_alph IPR002893 Znf_MYND
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF13640 2OG-FeII_Oxy_3, 1 hit PF01753 zf-MYND, 1 hit
SMARTⁱ	View protein in SMART SM00702 P4Hc, 1 hit
PROSITEⁱ	View protein in PROSITE PS51471 FE2OG_OXY, 1 hit PS01360 ZF_MYND_1, 1 hit PS50865 ZF_MYND_2, 1 hit

Sequences (3)ⁱ

Sequence statusⁱ: Complete.

Sequence processingⁱ: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsⁱ produced by alternative splicing. Align Add to basket

Isoform 1 (identifier: Q9GZT9-1) [UniParc]FASTA Add to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MANDSGGPGG PSPSERDRQY CELCGKMENL LRCSRCRSSF YCCKEHQRQD 
        60         70         80         90        100
WKKHKLVCQG SEGALGHGVG PHQHSGPAPP AAVPPPRAGA REPRKAAARR 
       110        120        130        140        150
DNASGDAAKG KVKAKPPADP AAAASPCRAA AGGQGSAVAA EAEPGKEEPP 
       160        170        180        190        200
ARSSLFQEKA NLYPPSNTPG DALSPGGGLR PNGQTKPLPA LKLALEYIVP 
       210        220        230        240        250
CMNKHGICVV DDFLGKETGQ QIGDEVRALH DTGKFTDGQL VSQKSDSSKD 
       260        270        280        290        300
IRGDKITWIE GKEPGCETIG LLMSSMDDLI RHCNGKLGSY KINGRTKAMV 
       310        320        330        340        350
ACYPGNGTGY VRHVDNPNGD GRCVTCIYYL NKDWDAKVSG GILRIFPEGK 
       360        370        380        390        400
AQFADIEPKF DRLLFFWSDR RNPHEVQPAY ATRYAITVWY FDADERARAK 
       410        420 
VKYLTGEKGV RVELNKPSDS VGKDVF

Length:426

Mass (Da):46,021

Last modified:March 1, 2001 - v1

Checksum:ⁱ81A97FF772CAA14C

GO

Isoform 2 (identifier: Q9GZT9-2) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
338-359: Missing.

« Hide

        10         20         30         40         50
MANDSGGPGG PSPSERDRQY CELCGKMENL LRCSRCRSSF YCCKEHQRQD 
        60         70         80         90        100
WKKHKLVCQG SEGALGHGVG PHQHSGPAPP AAVPPPRAGA REPRKAAARR 
       110        120        130        140        150
DNASGDAAKG KVKAKPPADP AAAASPCRAA AGGQGSAVAA EAEPGKEEPP 
       160        170        180        190        200
ARSSLFQEKA NLYPPSNTPG DALSPGGGLR PNGQTKPLPA LKLALEYIVP 
       210        220        230        240        250
CMNKHGICVV DDFLGKETGQ QIGDEVRALH DTGKFTDGQL VSQKSDSSKD 
       260        270        280        290        300
IRGDKITWIE GKEPGCETIG LLMSSMDDLI RHCNGKLGSY KINGRTKAMV 
       310        320        330        340        350
ACYPGNGTGY VRHVDNPNGD GRCVTCIYYL NKDWDAKFDR LLFFWSDRRN 
       360        370        380        390        400
PHEVQPAYAT RYAITVWYFD ADERARAKVK YLTGEKGVRV ELNKPSDSVG 

KDVF

Note: Inactive isoform.

Show »

Length:404

Mass (Da):43,666

Checksum:ⁱ32B08D27CD89A8B9

GO

Isoform 3 (identifier: Q9GZT9-3) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
58-175: CQGSEGALGH...SNTPGDALSP → LLGGYRFAFSWNSDERA

« Hide

        10         20         30         40         50
MANDSGGPGG PSPSERDRQY CELCGKMENL LRCSRCRSSF YCCKEHQRQD 
        60         70         80         90        100
WKKHKLVLLG GYRFAFSWNS DERAGGGLRP NGQTKPLPAL KLALEYIVPC 
       110        120        130        140        150
MNKHGICVVD DFLGKETGQQ IGDEVRALHD TGKFTDGQLV SQKSDSSKDI 
       160        170        180        190        200
RGDKITWIEG KEPGCETIGL LMSSMDDLIR HCNGKLGSYK INGRTKAMVA 
       210        220        230        240        250
CYPGNGTGYV RHVDNPNGDG RCVTCIYYLN KDWDAKVSGG ILRIFPEGKA 
       260        270        280        290        300
QFADIEPKFD RLLFFWSDRR NPHEVQPAYA TRYAITVWYF DADERARAKV 
       310        320 
KYLTGEKGVR VELNKPSDSV GKDVF

Note: No experimental confirmation available.

Show »

Length:325

Mass (Da):36,486

Checksum:ⁱ116F684A91222E6A

GO

Sequence cautionⁱ

The sequence AAK07534 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

The sequence AAK07536 differs from that shown. Reason: Frameshift at position 239.Curated

Polymorphismⁱ

Variations in EGLN1 are associated with adaptation to high altitude (PubMed:20838600, PubMed:20466884, PubMed:24711448, PubMed:25129147). High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body and leads to an elevation of hematocrit levels and an increased number of erythrocytes (polycythemia) in non-adapted individuals. Genetic variations in EGLN1 contribute to adaptation to high altitute by maintaining hematocrit levels comparable to those for populations living at sea level and are present in two high-altitude regions where humans have lived for millennia, the Andean Altiplano and the Tibetan Plateau (PubMed:20838600, PubMed:20466884). Variants Glu-4 and Ser-127, which are frequently associated together and are present in the majority of Tibetan populations, participate in adaptation to high altitude (PubMed:24711448, PubMed:25129147). Molecular mechanisms explaining this adaptation are however unclear. According to a report, variants Glu-4 and Ser-127 lead to decreased interaction with PTGES3 and subsequent decrease of HIF alpha proteins degradation (PubMed:24711448). According to a second report, Glu-4 and Ser-127 haplotype enhances the catalytic activity under hypoxic conditions, promoting increased HIF alpha proteins degradation, thereby abrogating hypoxia-induced and HIF alpha-mediated augmentation of erythropoiesis and protecting Tibetans from polycythemia at high altitude (PubMed:25129147).Curated4 Publications

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_071858	4	D → E Polymorphism present in the majority of Tibetans; increased protection from polycythemia at high altitude; when associated with S-127. 2 PublicationsCorresponds to variant dbSNP:rs186996510EnsemblClinVar.	1
Natural variantⁱVAR_071859	127	C → S Polymorphism present in the majority of Tibetans; increased protection from polycythemia at high altitude; when associated with E-4. 2 PublicationsCorresponds to variant dbSNP:rs12097901EnsemblClinVar.	1
Natural variantⁱVAR_027371	317	P → R in ECYT3; marked decrease in enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs80358193EnsemblClinVar.	1
Natural variantⁱVAR_045902	371	R → H in ECYT3; decreased interaction with HIF1A and EPAS1 and decreased enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs119476044EnsemblClinVar.	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_042191	58 – 175	CQGSE…DALSP → LLGGYRFAFSWNSDERA in isoform 3. 1 PublicationAdd BLAST		118
Alternative sequenceⁱVSP_007569	338 – 359	Missing in isoform 2. 1 PublicationAdd BLAST		22

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AF246631, AF246630 Genomic DNA Translation: AAG34568.1 AF229245 mRNA Translation: AAG33965.1 AJ310543 mRNA Translation: CAC42509.1 AL833885 mRNA Translation: CAD38741.2 AF277174 mRNA Translation: AAK07534.1 Different initiation. AF277176 mRNA Translation: AAK07536.1 Frameshift. AL117352 Genomic DNA No translation available. AL445524 Genomic DNA No translation available.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS1595.1 [Q9GZT9-1]
NCBI Reference Sequences More...RefSeqⁱ	NP_071334.1, NM_022051.2 [Q9GZT9-1]
UniGeneⁱ	Hs.444450

Genome annotation databases

Ensemblⁱ	ENST00000366641; ENSP00000355601; ENSG00000135766 [Q9GZT9-1]
GeneIDⁱ	54583
KEGGⁱ	hsa:54583

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q9GZT9	Egl nine homolog 1 (C. elegans)		HUMAN		426	UniRef100_Q9GZT9
UPI0000E062A8		HUMAN		383

Protein	Similar proteins		Species	Score	Length	Source
Q9GZT9	Egl nine homolog 1 (C. elegans)		HUMAN		426	UniRef90_Q9GZT9
egl nine homolog 1 isoform X1		TURTR		440
egl nine homolog 1		Yangtze finless porpoise		225
egl nine homolog 1		DELLE		439
egl nine homolog 1 isoform X1		PHYCD		437
+67
Q9GZT9-3	Egl nine-like protein 1 (Fragment)		HETGA		260	UniRef90_Q9GZT9-3
UPI000C8117B4		LOXAF		265

Protein	Similar proteins		Species	Score	Length	Source
Q9GZT9	Egl nine homolog 1 (C. elegans)		HUMAN		426	UniRef50_Q9GZT9
egl nine homolog 1 isoform X1		TURTR		440
egl nine homolog 1		Yangtze finless porpoise		225
egl nine homolog 1		DELLE		439
egl nine homolog 1 isoform X1		PHYCD		437
+150
Q9GZT9-2	Egl-9 family hypoxia inducible factor 1		CANLF		360	UniRef50_Q9GZT9-2
Egl-9 family hypoxia inducible factor 1		MUSPF		296
Egl nine homolog 1 (Fragment)		NEOVI		166
egl nine homolog 1 isoform X3		TURTR		355
egl nine homolog 1		BALAS		273
+37
Q9GZT9-3	Isoform 2 of Egl nine homolog 1		HUMAN		404	UniRef50_Q9GZT9-2
Egl-9 family hypoxia inducible factor 1		CANLF		360
Egl-9 family hypoxia inducible factor 1		MUSPF		296
Egl nine homolog 1 (Fragment)		NEOVI		166
egl nine homolog 1 isoform X3		TURTR		355
+37

Cross-referencesⁱ

Web resourcesⁱ

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AF246631, AF246630 Genomic DNA Translation: AAG34568.1 AF229245 mRNA Translation: AAG33965.1 AJ310543 mRNA Translation: CAC42509.1 AL833885 mRNA Translation: CAD38741.2 AF277174 mRNA Translation: AAK07534.1 Different initiation. AF277176 mRNA Translation: AAK07536.1 Frameshift. AL117352 Genomic DNA No translation available. AL445524 Genomic DNA No translation available.
CCDSⁱ	CCDS1595.1 [Q9GZT9-1]
RefSeqⁱ	NP_071334.1, NM_022051.2 [Q9GZT9-1]
UniGeneⁱ	Hs.444450

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	2G19	X-ray	1.70	A	181-417	[»]
	2G1M	X-ray	2.20	A	181-426	[»]
	2HBT	X-ray	1.60	A	188-426	[»]
	2HBU	X-ray	1.85	A	188-426	[»]
	2Y33	X-ray	2.00	A	181-426	[»]
	2Y34	X-ray	2.01	A	181-426	[»]
	3HQR	X-ray	2.00	A	181-426	[»]
	3HQU	X-ray	2.30	A	181-426	[»]
	3OUH	X-ray	2.51	A	181-416	[»]
	3OUI	X-ray	1.70	A	181-392	[»]
	3OUJ	X-ray	2.30	A	181-416	[»]
	4BQW	X-ray	1.79	A	181-426	[»]
	4BQX	X-ray	1.79	A	181-426	[»]
	4BQY	X-ray	1.53	A	181-426	[»]
	4JZR	X-ray	2.10	A	189-399	[»]
	4KBZ	X-ray	2.15	A	184-419	[»]
	4UWD	X-ray	1.72	A	181-426	[»]
	5A3U	X-ray	3.30	A/B/C	181-426	[»]
	5L9B	X-ray	1.95	A/B	181-426	[»]
	5L9R	X-ray	1.81	A	181-426	[»]
	5L9V	X-ray	1.83	A/B	181-426	[»]
	5LA9	X-ray	2.81	A/B	181-426	[»]
	5LAS	X-ray	2.10	A/B	181-426	[»]
	5LAT	X-ray	1.90	A	181-426	[»]
	5LB6	X-ray	1.70	A	181-426	[»]
	5LBB	X-ray	1.70	A	181-426	[»]
	5LBC	X-ray	1.82	A	181-426	[»]
	5LBE	X-ray	1.75	A	181-426	[»]
	5LBF	X-ray	1.90	A	181-426	[»]
	5OX5	X-ray	2.25	A	181-426	[»]
	5OX6	X-ray	1.99	A	181-426	[»]
	5V18	X-ray	2.15	A	181-416	[»]
ProteinModelPortalⁱ	Q9GZT9
SMRⁱ	Q9GZT9
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	120060, 42 interactors
CORUMⁱ	Q9GZT9
DIPⁱ	DIP-37495N
ELMⁱ	Q9GZT9
IntActⁱ	Q9GZT9, 16 interactors
MINTⁱ	Q9GZT9
STRINGⁱ	9606.ENSP00000355601

Chemistry databases

BindingDBⁱ	Q9GZT9
ChEMBLⁱ	CHEMBL5697
DrugBankⁱ	DB04847 FG-4592 DB08687 N-[(1-CHLORO-4-HYDROXYISOQUINOLIN-3-YL)CARBONYL]GLYCINE DB07112 N-[(4-HYDROXY-8-IODOISOQUINOLIN-3-YL)CARBONYL]GLYCINE DB00126 Vitamin C
GuidetoPHARMACOLOGYⁱ	2833

PTM databases

iPTMnetⁱ	Q9GZT9
PhosphoSitePlusⁱ	Q9GZT9

Polymorphism and mutation databases

BioMutaⁱ	EGLN1
DMDMⁱ	32129514

Proteomic databases

EPDⁱ	Q9GZT9
PaxDbⁱ	Q9GZT9
PeptideAtlasⁱ	Q9GZT9
PRIDEⁱ	Q9GZT9
ProteomicsDBⁱ	80138 80139 [Q9GZT9-2] 80140 [Q9GZT9-3]

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENST00000366641; ENSP00000355601; ENSG00000135766 [Q9GZT9-1]
GeneIDⁱ	54583
KEGGⁱ	hsa:54583

Organism-specific databases

CTDⁱ	54583
DisGeNETⁱ	54583
EuPathDBⁱ	HostDB:ENSG00000135766.8
GeneCardsⁱ	EGLN1
H-InvDBⁱ	HIX0159985
HGNCⁱ	HGNC:1232 EGLN1
HPAⁱ	HPA022129
MalaCardsⁱ	EGLN1
MIMⁱ	606425 gene 609820 phenotype
neXtProtⁱ	NX_Q9GZT9
OpenTargetsⁱ	ENSG00000135766
Orphanetⁱ	247511 Autosomal dominant secondary polycythemia
PharmGKBⁱ	PA27670
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG3710 Eukaryota ENOG410ZHZN LUCA
GeneTreeⁱ	ENSGT00390000001936
HOGENOMⁱ	HOG000004818
HOVERGENⁱ	HBG051455
InParanoidⁱ	Q9GZT9
KOⁱ	K09592
OMAⁱ	KANLYPP
OrthoDBⁱ	EOG091G03SP
PhylomeDBⁱ	Q9GZT9
TreeFamⁱ	TF314595

Enzyme and pathway databases

BRENDAⁱ	1.14.11.2 2681 1.14.11.29 2681
Reactomeⁱ	R-HSA-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha

Miscellaneous databases

ChiTaRSⁱ	EGLN1 human
EvolutionaryTraceⁱ	Q9GZT9
GeneWikiⁱ	EGLN1
GenomeRNAiⁱ	54583
Protein Ontology More...PROⁱ	PR:Q9GZT9
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000135766 Expressed in 223 organ(s), highest expression level in female gonad
CleanExⁱ	HS_EGLN1
ExpressionAtlasⁱ	Q9GZT9 baseline and differential
Genevisibleⁱ	Q9GZT9 HS

Family and domain databases

InterProⁱ	View protein in InterPro IPR005123 Oxoglu/Fe-dep_dioxygenase IPR006620 Pro_4_hyd_alph IPR002893 Znf_MYND
Pfamⁱ	View protein in Pfam PF13640 2OG-FeII_Oxy_3, 1 hit PF01753 zf-MYND, 1 hit
SMARTⁱ	View protein in SMART SM00702 P4Hc, 1 hit
PROSITEⁱ	View protein in PROSITE PS51471 FE2OG_OXY, 1 hit PS01360 ZF_MYND_1, 1 hit PS50865 ZF_MYND_2, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	EGLN1_HUMAN
Accessionⁱ	Q9GZT9Primary (citable) accession number: Q9GZT9 Secondary accession number(s): Q8N3M8, Q9BZS8, Q9BZT0
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	June 16, 2003
	Last sequence update:	March 1, 2001
	Last modified:	November 7, 2018
	This is version 176 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Reference proteome

Documents

Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PDB cross-references
Index of Protein Data Bank (PDB) cross-references

UniProtKB

UniParc

Help

UniRef

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Annotation systems

Supporting data

UniProtKB - Q9GZT9 (EGLN1_HUMAN)

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Egl nine homolog 1

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Caution

<p>This subsection of the ‘Function’ section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

Sites

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Nucleus

Other locations

Cytosol

Nucleus

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Keywords - Diseasei

Organism-specific databases

Chemistry databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

Chemistry databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Region

Zinc finger

Keywords - Domaini

Phylogenomic databases

Family and domain databases

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

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Functionⁱ

Kineticsⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Keywords - Domainⁱ

Sequence cautionⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Web resourcesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ