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Protein

Egl nine homolog 1

Gene

Egln1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 preferentially recognized via a LXXLAP motif.3 Publications

Catalytic activityi

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

Cofactori

Protein has several cofactor binding sites:
  • Fe2+PROSITE-ProRule annotationNote: Binds 1 Fe2+ ion per subunit.PROSITE-ProRule annotation
  • L-ascorbateBy similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi290IronPROSITE-ProRule annotation1
Metal bindingi292IronPROSITE-ProRule annotation1
Metal bindingi351IronPROSITE-ProRule annotation1
Binding sitei3602-oxoglutaratePROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri21 – 58MYND-typePROSITE-ProRule annotationAdd BLAST38

GO - Molecular functioni

GO - Biological processi

  • cardiac muscle tissue morphogenesis Source: MGI
  • cellular iron ion homeostasis Source: ParkinsonsUK-UCL
  • heart trabecula formation Source: MGI
  • labyrinthine layer development Source: MGI
  • negative regulation of DNA binding transcription factor activity Source: MGI
  • oxygen homeostasis Source: MGI
  • peptidyl-proline hydroxylation to 4-hydroxy-L-proline Source: MGI
  • positive regulation of transcription by RNA polymerase II Source: ParkinsonsUK-UCL
  • regulation of angiogenesis Source: UniProtKB
  • regulation of neuron death Source: ParkinsonsUK-UCL
  • response to hypoxia Source: MGI
  • response to nitric oxide Source: UniProtKB
  • ventricular septum morphogenesis Source: MGI

Keywordsi

Molecular functionDioxygenase, Oxidoreductase
LigandIron, Metal-binding, Vitamin C, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha

Names & Taxonomyi

Protein namesi
Recommended name:
Egl nine homolog 1 (EC:1.14.11.29By similarity)
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:Egln1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:1932286 Egln1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Null mice are smaller than wild type and are erythematous with some animals having evidence of retroperitoneal hemorrhage. The resulting polycythemia can cause thrombosis and cardiac failure and animals die off after 10 weeks. Erythropoietin levels are increased in kidneys but not in livers. In neonatal null mice exposed to 75% oxygen, there are high levels of HIF1A nuclear abundance in retinal tissues accompanied by well-preserved retinal microvessels compared to wild type where oxygen-treated retinas exhibit reverse effects with increased risks of retinopathy.3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00002066622 – 400Egl nine homolog 1Add BLAST399

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei12PhosphoserineBy similarity1
Modified residuei114PhosphoserineBy similarity1
Modified residuei178S-nitrosocysteineBy similarity1
Modified residuei185S-nitrosocysteineBy similarity1
Modified residuei279S-nitrosocysteineBy similarity1
Modified residuei300S-nitrosocysteineBy similarity1
Modified residuei303S-nitrosocysteineBy similarity1

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-300 or Cys-303.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, S-nitrosylation

Proteomic databases

EPDiQ91YE3
MaxQBiQ91YE3
PaxDbiQ91YE3
PeptideAtlasiQ91YE3
PRIDEiQ91YE3

PTM databases

iPTMnetiQ91YE3
PhosphoSitePlusiQ91YE3

Expressioni

Tissue specificityi

Expressed in heart, brain liver, skeletal muscle and kidney. Low levels were detected in the lung. Constitutively expressed during differentiation of C2C12 skeletal myocytes.1 Publication

Inductioni

Induced by growth factors in cultured vascular smooth muscle. Up-regulated in proliferating myoblasts induced to form differentiated myotubes.1 Publication

Gene expression databases

BgeeiENSMUSG00000031987
CleanExiMM_EGLN1
GenevisibleiQ91YE3 MM

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 and HIF1A.By similarity

Protein-protein interaction databases

BioGridi227481, 3 interactors
STRINGi10090.ENSMUSP00000034469

Structurei

3D structure databases

ProteinModelPortaliQ91YE3
SMRiQ91YE3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini271 – 369Fe2OG dioxygenasePROSITE-ProRule annotationAdd BLAST99

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni6 – 20Required for nuclear exportAdd BLAST15
Regioni218 – 228Beta(2)beta(3) 'finger-like' loopBy similarityAdd BLAST11

Domaini

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri21 – 58MYND-typePROSITE-ProRule annotationAdd BLAST38

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3710 Eukaryota
ENOG410ZHZN LUCA
GeneTreeiENSGT00390000001936
HOGENOMiHOG000004818
HOVERGENiHBG051455
InParanoidiQ91YE3
KOiK09592
OMAiKANLYPP
OrthoDBiEOG091G03SP
PhylomeDBiQ91YE3
TreeFamiTF314595

Family and domain databases

InterProiView protein in InterPro
IPR005123 Oxoglu/Fe-dep_dioxygenase
IPR006620 Pro_4_hyd_alph
IPR002893 Znf_MYND
PfamiView protein in Pfam
PF13640 2OG-FeII_Oxy_3, 1 hit
PF01753 zf-MYND, 1 hit
SMARTiView protein in SMART
SM00702 P4Hc, 1 hit
PROSITEiView protein in PROSITE
PS51471 FE2OG_OXY, 1 hit
PS01360 ZF_MYND_1, 1 hit
PS50865 ZF_MYND_2, 1 hit

Sequencei

Sequence statusi: Complete.

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

Q91YE3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASDSGGPGV LSASERDRQY CELCGKMENL LRCGRCRSSF YCCKEHQRQD
60 70 80 90 100
WKKHKLVCQG GEAPRAQPAP AQPRVAPPPG GAPGAARAGG AARRGDSAAA
110 120 130 140 150
SRVPGPEDAA QARSGPGPAE PGSEDPPLSR SPGPERASLC PAGGGPGEAL
160 170 180 190 200
SPGGGLRPNG QTKPLPALKL ALEYIVPCMN KHGICVVDDF LGRETGQQIG
210 220 230 240 250
DEVRALHDTG KFTDGQLVSQ KSDSSKDIRG DQITWIEGKE PGCETIGLLM
260 270 280 290 300
SSMDDLIRHC SGKLGNYRIN GRTKAMVACY PGNGTGYVRH VDNPNGDGRC
310 320 330 340 350
VTCIYYLNKD WDAKVSGGIL RIFPEGKAQF ADIEPKFDRL LFFWSDRRNP
360 370 380 390 400
HEVQPAYATR YAITVWYFDA DERARAKVKY LTGEKGVRVE LKPNSVSKDV
Length:400
Mass (Da):43,111
Last modified:June 16, 2003 - v2
Checksum:iA7EBC2BF6E22CDB9
GO

Sequence cautioni

The sequence AAH06903 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti205 – 209ALHDT → RIRHE in AAL65165 (PubMed:12234095).Curated5

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL672234 Genomic DNA No translation available.
AJ310546 mRNA Translation: CAC42515.1
AF453878 mRNA Translation: AAL65165.1
BC006903 mRNA Translation: AAH06903.1 Different initiation.
CCDSiCCDS52706.1
RefSeqiNP_444437.2, NM_053207.2
UniGeneiMm.140619

Genome annotation databases

EnsembliENSMUST00000034469; ENSMUSP00000034469; ENSMUSG00000031987
GeneIDi112405
KEGGimmu:112405
UCSCiuc012gna.1 mouse

Similar proteinsi

Entry informationi

Entry nameiEGLN1_MOUSE
AccessioniPrimary (citable) accession number: Q91YE3
Secondary accession number(s): Q8VHJ2, Q922P3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 16, 2003
Last sequence update: June 16, 2003
Last modified: March 28, 2018
This is version 131 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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