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Protein

Egl nine homolog 1

Gene

Egln1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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 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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi290 – 2901IronPROSITE-ProRule annotation
Metal bindingi292 – 2921IronPROSITE-ProRule annotation
Metal bindingi351 – 3511IronPROSITE-ProRule annotation
Binding sitei360 – 36012-oxoglutaratePROSITE-ProRule annotation

Regions

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

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 sequence-specific 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 from RNA polymerase II promoter 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
Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Oxidoreductase

Keywords - Ligandi

Iron, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:1932286. Egln1.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity

  • Note: Mainly cytoplasmic. Shuttles between the nucleus and cytoplasm. Nuclear export requires functional XPO1.By similarity

GO - Cellular componenti

Complete GO annotation...

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)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 400399Egl nine homolog 1PRO_0000206662Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei12 – 121PhosphoserineBy similarity
Modified residuei114 – 1141PhosphoserineBy similarity
Modified residuei178 – 1781S-nitrosocysteineBy similarity
Modified residuei185 – 1851S-nitrosocysteineBy similarity
Modified residuei279 – 2791S-nitrosocysteineBy similarity
Modified residuei300 – 3001S-nitrosocysteineBy similarity
Modified residuei303 – 3031S-nitrosocysteineBy similarity

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.
PhosphoSiteiQ91YE3.

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, TCEB2 and CUL2. Interacts with EPAS1. Interacts with CBFA2T3 and HIF1A.By similarity

Protein-protein interaction databases

BioGridi227481. 3 interactions.
STRINGi10090.ENSMUSP00000034469.

Structurei

3D structure databases

ProteinModelPortaliQ91YE3.
SMRiQ91YE3. Positions 10-58, 165-380.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini271 – 36999Fe2OG dioxygenasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni6 – 2015Required for nuclear exportAdd
BLAST
Regioni218 – 22811Beta(2)beta(3) 'finger-like' loopBy similarityAdd
BLAST

Domaini

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

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

eggNOGiKOG3710. Eukaryota.
ENOG410ZHZN. LUCA.
GeneTreeiENSGT00390000001936.
HOGENOMiHOG000004818.
HOVERGENiHBG051455.
InParanoidiQ91YE3.
KOiK09592.
OMAiKMENLMK.
OrthoDBiEOG091G03SP.
PhylomeDBiQ91YE3.
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]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti205 – 2095ALHDT → RIRHE in AAL65165 (PubMed:12234095).Curated

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ91YE3.
SMRiQ91YE3. Positions 10-58, 165-380.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi227481. 3 interactions.
STRINGi10090.ENSMUSP00000034469.

PTM databases

iPTMnetiQ91YE3.
PhosphoSiteiQ91YE3.

Proteomic databases

EPDiQ91YE3.
MaxQBiQ91YE3.
PaxDbiQ91YE3.
PeptideAtlasiQ91YE3.
PRIDEiQ91YE3.

Protocols and materials databases

DNASUi112405.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi54583.
MGIiMGI:1932286. Egln1.

Phylogenomic databases

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

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiEgln1. mouse.
PROiQ91YE3.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031987.
CleanExiMM_EGLN1.
GenevisibleiQ91YE3. MM.

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]
ProtoNetiSearch...

Entry informationi

Entry nameiEGLN1_MOUSE
AccessioniPrimary (citable) accession number: Q91YE3
Secondary accession number(s): Q8VHJ2, Q922P3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 16, 2003
Last sequence update: June 16, 2003
Last modified: September 7, 2016
This is version 123 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.