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Q9GZT9

- EGLN1_HUMAN

UniProt

Q9GZT9 - EGLN1_HUMAN

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Protein

Egl nine homolog 1

Gene

EGLN1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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 preferencially recognized via a LXXLAP motif.7 Publications

Catalytic activityi

Hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 = hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2.1 Publication

Cofactori

Protein has several cofactor binding sites:

Enzyme regulationi

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

Kineticsi

  1. KM=70 nM for HIF2A1 Publication
  2. KM=150 µM for O21 Publication
  3. KM=1.3 µM for 2-oxoglutarate1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi313 – 3131Iron2 Publications
Metal bindingi315 – 3151Iron2 Publications
Metal bindingi374 – 3741Iron2 Publications
Binding sitei383 – 38312-oxoglutarate1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri21 – 5838MYND-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. enzyme binding Source: BHF-UCL
  2. iron ion binding Source: InterPro
  3. L-ascorbic acid binding Source: UniProtKB-KW
  4. peptidyl-proline 4-dioxygenase activity Source: FlyBase
  5. peptidyl-proline dioxygenase activity Source: HGNC

GO - Biological processi

  1. cardiac muscle tissue morphogenesis Source: Ensembl
  2. cellular response to hypoxia Source: Reactome
  3. heart trabecula formation Source: Ensembl
  4. labyrinthine layer development Source: Ensembl
  5. negative regulation of cAMP catabolic process Source: BHF-UCL
  6. negative regulation of cyclic-nucleotide phosphodiesterase activity Source: BHF-UCL
  7. negative regulation of sequence-specific DNA binding transcription factor activity Source: HGNC
  8. oxygen homeostasis Source: HGNC
  9. peptidyl-proline hydroxylation to 4-hydroxy-L-proline Source: FlyBase
  10. regulation of angiogenesis Source: UniProtKB
  11. regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: Reactome
  12. response to hypoxia Source: HGNC
  13. response to nitric oxide Source: UniProtKB
  14. ventricular septum morphogenesis Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Oxidoreductase

Keywords - Ligandi

Iron, Metal-binding, Vitamin C, Zinc

Enzyme and pathway databases

BRENDAi1.14.11.2. 2681.
ReactomeiREACT_120916. 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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:1232. EGLN1.

Subcellular locationi

Cytoplasm 3 Publications. Nucleus 3 Publications
Note: Mainly cytoplasmic. Shuttles between the nucleus and cytoplasm (PubMed:19631610). Nuclear export requires functional XPO1.2 Publications

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytosol Source: Reactome
  3. nucleus Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Erythrocytosis, familial, 3 (ECYT3) [MIM:609820]: An autosomal dominant disorder characterized by increased serum red blood cell mass, elevated serum hemoglobin and hematocrit, and normal serum erythropoietin levels.2 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti317 – 3171P → R in ECYT3; marked decrease in enzyme activity. 1 Publication
VAR_027371
Natural varianti371 – 3711R → H in ECYT3; decreased interaction with HIF1A and HIF2A and decreased enzyme activity. 1 Publication
VAR_045902

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi201 – 2011C → A: Little change in enzyme activity. 1 Publication
Mutagenesisi208 – 2081C → A: Little change in enzyme activity. 1 Publication
Mutagenesisi252 – 2521R → A: Reduced C-terminal ODD domain (CODD) hydroxylation of HIF1A.
Mutagenesisi254 – 2541D → A or K: Reduced C-terminal ODD domain (CODD) hxdroxylation of HIF1A.
Mutagenesisi266 – 2661C → A: Little change in enzyme activity. 1 Publication
Mutagenesisi283 – 2831C → A: Little change in enzyme activity. 1 Publication
Mutagenesisi302 – 3021C → A: Slight increase in enzyme activity. 1 Publication
Mutagenesisi303 – 3031Y → F: No effect. 1 Publication
Mutagenesisi323 – 3231C → A: Little change in enzyme activity. 1 Publication
Mutagenesisi326 – 3261C → A: Slight increase in enzyme activity. 1 Publication
Mutagenesisi383 – 3831R → A: Reduces enzyme activity by 95%. 1 Publication

Keywords - Diseasei

Congenital erythrocytosis, Disease mutation

Organism-specific databases

MIMi609820. phenotype.
Orphaneti247511. Autosomal dominant secondary polycythemia.
PharmGKBiPA27670.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed2 Publications
Chaini2 – 426425Egl nine homolog 1PRO_0000206661Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine2 Publications
Modified residuei125 – 1251Phosphoserine1 Publication
Modified residuei201 – 2011S-nitrosocysteine1 Publication
Modified residuei208 – 2081S-nitrosocysteine1 Publication
Modified residuei302 – 3021S-nitrosocysteine1 Publication
Modified residuei323 – 3231S-nitrosocysteine1 Publication
Modified residuei326 – 3261S-nitrosocysteine1 Publication

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

MaxQBiQ9GZT9.
PaxDbiQ9GZT9.
PRIDEiQ9GZT9.

PTM databases

PhosphoSiteiQ9GZT9.

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

BgeeiQ9GZT9.
CleanExiHS_EGLN1.
ExpressionAtlasiQ9GZT9. baseline and differential.
GenevestigatoriQ9GZT9.

Organism-specific databases

HPAiHPA022129.

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, TCEB2 and CUL2. Interacts with EPAS1.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
EPAS1Q998142EBI-1174818,EBI-447470
FKBP8Q143186EBI-1174818,EBI-724839
HIF1AQ166654EBI-1174818,EBI-447269
OS9Q134384EBI-1174818,EBI-725454

Protein-protein interaction databases

BioGridi120060. 28 interactions.
DIPiDIP-37495N.
IntActiQ9GZT9. 10 interactions.
MINTiMINT-1206232.
STRINGi9606.ENSP00000355601.

Structurei

Secondary structure

1
426
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi190 – 1967Combined sources
Helixi198 – 2058Combined sources
Beta strandi206 – 2149Combined sources
Helixi216 – 23116Combined sources
Beta strandi240 – 2423Combined sources
Helixi247 – 2493Combined sources
Beta strandi255 – 2595Combined sources
Helixi267 – 28317Combined sources
Turni284 – 2863Combined sources
Beta strandi287 – 2893Combined sources
Beta strandi292 – 2954Combined sources
Beta strandi298 – 3036Combined sources
Beta strandi305 – 3139Combined sources
Beta strandi315 – 3184Combined sources
Beta strandi321 – 3299Combined sources
Beta strandi331 – 3333Combined sources
Helixi336 – 3394Combined sources
Beta strandi343 – 3453Combined sources
Beta strandi348 – 3514Combined sources
Beta strandi354 – 3563Combined sources
Beta strandi362 – 3676Combined sources
Beta strandi374 – 3818Combined sources
Beta strandi383 – 39210Combined sources
Helixi393 – 40210Combined sources
Helixi407 – 4093Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2G19X-ray1.70A181-417[»]
2G1MX-ray2.20A181-426[»]
2HBTX-ray1.60A188-426[»]
2HBUX-ray1.85A188-426[»]
2Y33X-ray2.00A181-426[»]
2Y34X-ray2.01A181-426[»]
3HQRX-ray2.00A181-426[»]
3HQUX-ray2.30A181-426[»]
3OUHX-ray2.51A181-416[»]
3OUIX-ray1.70A181-392[»]
3OUJX-ray2.30A181-416[»]
4BQWX-ray1.79A181-426[»]
4BQXX-ray1.79A181-426[»]
4BQYX-ray1.53A181-426[»]
4JZRX-ray2.10A189-399[»]
4KBZX-ray2.15A184-419[»]
4UWDX-ray1.72A181-426[»]
ProteinModelPortaliQ9GZT9.
SMRiQ9GZT9. Positions 20-58, 188-403.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9GZT9.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini291 – 392102Fe2OG dioxygenasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni6 – 2015Required for nuclear exportAdd
BLAST
Regioni241 – 25111Beta(2)beta(3) 'finger-like' loop1 PublicationAdd
BLAST

Domaini

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

Sequence similaritiesi

Contains 1 Fe2OG dioxygenase domain.PROSITE-ProRule annotation
Contains 1 MYND-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri21 – 5838MYND-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiCOG3751.
HOGENOMiHOG000004818.
HOVERGENiHBG051455.
InParanoidiQ9GZT9.
KOiK09592.
OMAiLVCQGSE.
OrthoDBiEOG7TBC2W.
PhylomeDBiQ9GZT9.
TreeFamiTF314595.

Family and domain databases

InterProiIPR005123. Oxoglu/Fe-dep_dioxygenase.
IPR006620. Pro_4_hyd_alph.
IPR002893. Znf_MYND.
[Graphical view]
PfamiPF13640. 2OG-FeII_Oxy_3. 1 hit.
PF01753. zf-MYND. 1 hit.
[Graphical view]
SMARTiSM00702. P4Hc. 1 hit.
[Graphical view]
PROSITEiPS51471. FE2OG_OXY. 1 hit.
PS01360. ZF_MYND_1. 1 hit.
PS50865. ZF_MYND_2. 1 hit.
[Graphical view]

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

Isoform 1 (identifier: Q9GZT9-1) [UniParc]FASTAAdd 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]FASTAAdd to Basket

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

Note: Inactive isoform.

Show »
Length:404
Mass (Da):43,666
Checksum:i32B08D27CD89A8B9
GO
Isoform 3 (identifier: Q9GZT9-3) [UniParc]FASTAAdd to Basket

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

Note: No experimental confirmation available.

Show »
Length:325
Mass (Da):36,486
Checksum:i116F684A91222E6A
GO

Sequence cautioni

The sequence AAK07534.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAK07536.1 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 to 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).4 PublicationsCurated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti4 – 41D → E Polymorphism present in the majority of Tibetans; increased protection from polycythemia at high altitude; when associated with S-127. 1 Publication
VAR_071858
Natural varianti127 – 1271C → S Polymorphism present in the majority of Tibetans; increased protection from polycythemia at high altitude; when associated with E-4. 1 Publication
VAR_071859
Natural varianti317 – 3171P → R in ECYT3; marked decrease in enzyme activity. 1 Publication
VAR_027371
Natural varianti371 – 3711R → H in ECYT3; decreased interaction with HIF1A and HIF2A and decreased enzyme activity. 1 Publication
VAR_045902

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei58 – 175118CQGSE…DALSP → LLGGYRFAFSWNSDERA in isoform 3. 1 PublicationVSP_042191Add
BLAST
Alternative sequencei338 – 35922Missing in isoform 2. 1 PublicationVSP_007569Add
BLAST

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, AL445524 Genomic DNA. Translation: CAI23092.1.
AL445524, AL117352 Genomic DNA. Translation: CAH72105.1.
CCDSiCCDS1595.1. [Q9GZT9-1]
RefSeqiNP_071334.1. NM_022051.2. [Q9GZT9-1]
UniGeneiHs.444450.

Genome annotation databases

EnsembliENST00000366641; ENSP00000355601; ENSG00000135766. [Q9GZT9-1]
GeneIDi54583.
KEGGihsa:54583.
UCSCiuc001huv.2. human. [Q9GZT9-1]

Polymorphism databases

DMDMi32129514.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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 , AL445524 Genomic DNA. Translation: CAI23092.1 .
AL445524 , AL117352 Genomic DNA. Translation: CAH72105.1 .
CCDSi CCDS1595.1. [Q9GZT9-1 ]
RefSeqi NP_071334.1. NM_022051.2. [Q9GZT9-1 ]
UniGenei Hs.444450.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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 [» ]
ProteinModelPortali Q9GZT9.
SMRi Q9GZT9. Positions 20-58, 188-403.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 120060. 28 interactions.
DIPi DIP-37495N.
IntActi Q9GZT9. 10 interactions.
MINTi MINT-1206232.
STRINGi 9606.ENSP00000355601.

Chemistry

BindingDBi Q9GZT9.
ChEMBLi CHEMBL5697.
DrugBanki DB00126. Vitamin C.

PTM databases

PhosphoSitei Q9GZT9.

Polymorphism databases

DMDMi 32129514.

Proteomic databases

MaxQBi Q9GZT9.
PaxDbi Q9GZT9.
PRIDEi Q9GZT9.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000366641 ; ENSP00000355601 ; ENSG00000135766 . [Q9GZT9-1 ]
GeneIDi 54583.
KEGGi hsa:54583.
UCSCi uc001huv.2. human. [Q9GZT9-1 ]

Organism-specific databases

CTDi 54583.
GeneCardsi GC01M231499.
H-InvDB HIX0159985.
HGNCi HGNC:1232. EGLN1.
HPAi HPA022129.
MIMi 606425. gene.
609820. phenotype.
neXtProti NX_Q9GZT9.
Orphaneti 247511. Autosomal dominant secondary polycythemia.
PharmGKBi PA27670.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG3751.
HOGENOMi HOG000004818.
HOVERGENi HBG051455.
InParanoidi Q9GZT9.
KOi K09592.
OMAi LVCQGSE.
OrthoDBi EOG7TBC2W.
PhylomeDBi Q9GZT9.
TreeFami TF314595.

Enzyme and pathway databases

BRENDAi 1.14.11.2. 2681.
Reactomei REACT_120916. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.

Miscellaneous databases

ChiTaRSi EGLN1. human.
EvolutionaryTracei Q9GZT9.
GeneWikii EGLN1.
GenomeRNAii 54583.
NextBioi 57101.
PROi Q9GZT9.
SOURCEi Search...

Gene expression databases

Bgeei Q9GZT9.
CleanExi HS_EGLN1.
ExpressionAtlasi Q9GZT9. baseline and differential.
Genevestigatori Q9GZT9.

Family and domain databases

InterProi IPR005123. Oxoglu/Fe-dep_dioxygenase.
IPR006620. Pro_4_hyd_alph.
IPR002893. Znf_MYND.
[Graphical view ]
Pfami PF13640. 2OG-FeII_Oxy_3. 1 hit.
PF01753. zf-MYND. 1 hit.
[Graphical view ]
SMARTi SM00702. P4Hc. 1 hit.
[Graphical view ]
PROSITEi PS51471. FE2OG_OXY. 1 hit.
PS01360. ZF_MYND_1. 1 hit.
PS50865. ZF_MYND_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Mapping, characterization, and expression analysis of the SM-20 human homologue, C1orf12, and identification of a novel related gene, SCAND2."
    Dupuy D., Aubert I., Duperat V.G., Petit J., Taine L., Stef M., Bloch B., Arveiler B.
    Genomics 69:348-354(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
  2. "Characterization and comparative analysis of the EGLN gene family."
    Taylor M.S.
    Gene 275:125-132(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1).
  3. "Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor."
    Hirsila M., Koivunen P., Gunzler V., Kivirikko K.I., Myllyharju J.
    J. Biol. Chem. 278:30772-30780(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY, SUBSTRATE SPECIFICITY.
    Tissue: Aorta, Colon and Lung.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 160-426 (ISOFORM 1).
    Tissue: Amygdala.
  5. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "Human acute promyelocytic leukemia cell line NB4's apoptosis related genes."
    Yu W.-Q., Sun B.-Z., Chai Y.-B., Zhu F., Liu X.-S., Li Z., Lu F., Yan W., Yang H., Zhao Z.-L.
    Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 136-426 (ISOFORM 2).
    Tissue: Promyelocytic leukemia.
  7. "HIF-1, O(2), and the 3 PHDs: how animal cells signal hypoxia to the nucleus."
    Semenza G.L.
    Cell 107:1-3(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  8. Cited for: FUNCTION.
  9. "Sequence determinants in hypoxia-inducible factor-1alpha for hydroxylation by the prolyl hydroxylases PHD1, PHD2, and PHD3."
    Huang J., Zhao Q., Mooney S.M., Lee F.S.
    J. Biol. Chem. 277:39792-39800(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBSTRATE RECOGNITION MOTIF.
  10. "Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor."
    Ivan M., Haberberger T., Gervasi D.C., Michelson K.S., Guenzler V., Kondo K., Yang H., Sorokina I., Conaway R.C., Conaway J.W., Kaelin W.G. Jr.
    Proc. Natl. Acad. Sci. U.S.A. 99:13459-13464(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  11. "Overexpression of PH-4, a novel putative proline 4-hydroxylase, modulates activity of hypoxia-inducible transcription factors."
    Oehme F., Ellinghaus P., Kolkhof P., Smith T.J., Ramakrishnan S., Huetter J., Schramm M., Flamme I.
    Biochem. Biophys. Res. Commun. 296:343-349(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  12. "Differential regulation of HIF-1alpha prolyl-4-hydroxylase genes by hypoxia in human cardiovascular cells."
    Cioffi C.L., Qin Liu X., Kosinski P.A., Garay M., Bowen B.R.
    Biochem. Biophys. Res. Commun. 303:947-953(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, ENZYME REGULATION.
  13. Cited for: SUBCELLULAR LOCATION, INDUCTION.
  14. "Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor."
    Appelhoff R.J., Tian Y.M., Raval R.R., Turley H., Harris A.L., Pugh C.W., Ratcliffe P.J., Gleadle J.M.
    J. Biol. Chem. 279:38458-38465(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION, SUBSTRATE SPECIFICITY.
  15. "The candidate tumor suppressor ING4 represses activation of the hypoxia inducible factor (HIF)."
    Ozer A., Wu L.C., Bruick R.K.
    Proc. Natl. Acad. Sci. U.S.A. 102:7481-7486(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ING4, FUNCTION.
  16. "Kinetic rationale for selectivity toward N- and C-terminal oxygen-dependent degradation domain substrates mediated by a loop region of hypoxia-inducible factor prolyl hydroxylases."
    Flashman E., Bagg E.A., Chowdhury R., Mecinovic J., Loenarz C., McDonough M.A., Hewitson K.S., Schofield C.J.
    J. Biol. Chem. 283:3808-3815(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBSTRATE SPECIFICITY, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF 237-ASP--ILE-251, DOMAIN.
  17. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
    Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
    Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
  18. "Cellular oxygen sensing: Importins and exportins are mediators of intracellular localisation of prolyl-4-hydroxylases PHD1 and PHD2."
    Steinhoff A., Pientka F.K., Mockel S., Kettelhake A., Hartmann E., Kohler M., Depping R.
    Biochem. Biophys. Res. Commun. 387:705-711(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  19. "Role of the intracellular localization of HIF-prolyl hydroxylases."
    Yasumoto K., Kowata Y., Yoshida A., Torii S., Sogawa K.
    Biochim. Biophys. Acta 1793:792-797(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, FUNCTION.
  20. "Erythrocytosis-associated HIF-2alpha mutations demonstrate a critical role for residues C-terminal to the hydroxylacceptor proline."
    Furlow P.W., Percy M.J., Sutherland S., Bierl C., McMullin M.F., Master S.R., Lappin T.R., Lee F.S.
    J. Biol. Chem. 284:9050-9058(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH EPAS1.
  21. "Evidence for the slow reaction of hypoxia-inducible factor prolyl hydroxylase 2 with oxygen."
    Flashman E., Hoffart L.M., Hamed R.B., Bollinger J.M. Jr., Krebs C., Schofield C.J.
    FEBS J. 277:4089-4099(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: ENZYME REGULATION.
  22. "Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data."
    Bigham A., Bauchet M., Pinto D., Mao X., Akey J.M., Mei R., Scherer S.W., Julian C.G., Wilson M.J., Lopez Herraez D., Brutsaert T., Parra E.J., Moore L.G., Shriver M.D.
    PLoS Genet. 6:E1001116-E1001116(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: POLYMORPHISM.
  23. Cited for: POLYMORPHISM.
  24. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  25. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  26. "Prolyl hydroxylase-2 (PHD2) exerts tumor-suppressive activity in pancreatic cancer."
    Su Y., Loos M., Giese N., Metzen E., Buchler M.W., Friess H., Kornberg A., Buchler P.
    Cancer 118:960-972(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION.
  27. Cited for: INTERACTION WITH LIMD1, IDENTIFICATION IN A COMPLEX WITH LIMD1; VHL; TCEB2 AND CUL2.
  28. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  29. "SIRT2 regulates tumour hypoxia response by promoting HIF-1alpha hydroxylation."
    Seo K.S., Park J.H., Heo J.Y., Jing K., Han J., Min K.N., Kim C., Koh G.Y., Lim K., Kang G.Y., Uee Lee J., Yim Y.H., Shong M., Kwak T.H., Kweon G.R.
    Oncogene 0:0-0(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HIF1A.
  30. Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 181-417 IN COMPLEXES WITH IRON AND COMPETITIVE INHIBITOR, METAL-BINDING SITES, MUTAGENESIS OF TYR-303 AND ARG-383, SUBUNIT, COFACTOR.
  31. "Structural basis for binding of hypoxia-inducible factor to the oxygen-sensing prolyl hydroxylases."
    Chowdhury R., McDonough M.A., Mecinovic J., Loenarz C., Flashman E., Hewitson K.S., Domene C., Schofield C.J.
    Structure 17:981-989(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 181-426 OF WILD TYPE AND MUTANTS ALA-252; ALA-254; LYS-254 AND ALA-398 IN COMPLEX WITH HIF1A, IRON, N-OXALYGLYCINE AND MANGANESE, METAL-BINDING SITES, COFACTOR.
  32. "Studies on the reaction of nitric oxide with the hypoxia-inducible factor prolyl hydroxylase domain 2 (EGLN1)."
    Chowdhury R., Flashman E., Mecinovic J., Kramer H.B., Kessler B.M., Frapart Y.M., Boucher J.L., Clifton I.J., McDonough M.A., Schofield C.J.
    J. Mol. Biol. 410:268-279(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 181-426 IN COMPLEX WITH NITRIC OXIDE OR A NITRIC OXIDE TRANSFER REAGENT, IDENTIFICATION BY MASS SPECTROMETRY, S-NITROSYLATION AT CYS-201; CYS-208; CYS-302; CYS-323 AND CYS-326, MUTAGENESIS OF CYS-201; CYS-208; CYS-266; CYS-283; CYS-302; CYS-323 AND CYS-326.
  33. "A family with erythrocytosis establishes a role for prolyl hydroxylase domain protein 2 in oxygen homeostasis."
    Percy M.J., Zhao Q., Flores A., Harrison C., Lappin T.R., Maxwell P.H., McMullin M.F., Lee F.S.
    Proc. Natl. Acad. Sci. U.S.A. 103:654-659(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT ECYT3 ARG-317, CHARACTERIZATION OF VARIANT ECYT3 ARG-317.
  34. "A novel erythrocytosis-associated PHD2 mutation suggests the location of a HIF binding groove."
    Percy M.J., Furlow P.W., Beer P.A., Lappin T.R.J., McMullin M.F., Lee F.S.
    Blood 110:2193-2196(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT ECYT3 HIS-371, CHARACTERIZATION OF VARIANT EXCYT3 HIS-371.
  35. "Defective Tibetan PHD2 binding to p23 links high altitude adaption to altered oxygen sensing."
    Song D., Li L.S., Arsenault P.R., Tan Q., Bigham A.W., Heaton-Johnson K.J., Master S.R., Lee F.S.
    J. Biol. Chem. 289:14656-14665(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS GLU-4 AND SER-127, POLYMORPHISM, INTERACTION WITH PTGES3, CHARACTERIZATION OF VARIANTS GLU-4 AND SER-127.
  36. Cited for: VARIANTS GLU-4 AND SER-127, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, POLYMORPHISM, CHARACTERIZATION OF VARIANTS GLU-4 AND SER-127.

Entry informationi

Entry nameiEGLN1_HUMAN
AccessioniPrimary (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 26, 2014
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3