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Protein

Egl nine homolog 2

Gene

Egln2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 HIF2A. 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. EGLN2 is involved in regulating hypoxia tolerance and apoptosis in cardiac and skeletal muscle. Also regulates susceptibility to normoxic oxidative neuronal death. Links oxygen sensing to cell cycle and primary cilia formation by hydroxylating the critical centrosome component CEP192 which promotes its ubiquitination and subsequent proteasomal degradation. Hydroxylates IKBKB, mediating NF-kappaB activation in hypoxic conditions. 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.

Cofactori

Protein has several cofactor binding sites:

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi309IronPROSITE-ProRule annotation1
Metal bindingi311IronPROSITE-ProRule annotation1
Metal bindingi370IronPROSITE-ProRule annotation1
Binding sitei3792-oxoglutaratePROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Oxidoreductase

Keywords - Ligandi

Iron, Metal-binding, Vitamin C

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 2 (EC:1.14.11.29)
Alternative name(s):
Falkor
Hypoxia-inducible factor prolyl hydroxylase 1
Short name:
HIF-PH1
Short name:
HIF-prolyl hydroxylase 1
Short name:
HPH-1
Prolyl hydroxylase domain-containing protein 1
Short name:
PHD1
Gene namesi
Name:Egln2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1932287. Egln2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Null mice exhibit a lowering of oxygen consumption in skeletal muscle. Glucose oxidation is reduced to around 35%. Hypoxia tolerance is induced in myofibers.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002066651 – 419Egl nine homolog 2Add BLAST419

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei130PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ91YE2.
PaxDbiQ91YE2.
PRIDEiQ91YE2.

PTM databases

iPTMnetiQ91YE2.
PhosphoSitePlusiQ91YE2.

Expressioni

Tissue specificityi

Highly expressed in testis, expression was also detected in the heart brain, liver kidney and lung. Expression was lowest in spleen and skeletal muscle. Constitutively expressed during differentiation of C2C12 skeletal myocytes.1 Publication

Gene expression databases

BgeeiENSMUSG00000058709.
CleanExiMM_EGLN2.
ExpressionAtlasiQ91YE2. baseline and differential.
GenevisibleiQ91YE2. MM.

Interactioni

Subunit structurei

Interacts with E3 ligase SIAH2. Interacts with LIMD1, WTIP and AJUBA.By similarity

Protein-protein interaction databases

BioGridi227482. 2 interactors.
STRINGi10090.ENSMUSP00000078966.

Structurei

3D structure databases

ProteinModelPortaliQ91YE2.
SMRiQ91YE2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini290 – 388Fe2OG dioxygenasePROSITE-ProRule annotationAdd BLAST99

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni237 – 247Beta(2)beta(3) 'finger-like' loopBy similarityAdd BLAST11

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi89 – 134Bipartite nuclear localization signalBy similarityAdd BLAST46

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi64 – 72Poly-Thr9
Compositional biasi157 – 164Poly-Ser8

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

Phylogenomic databases

eggNOGiKOG3710. Eukaryota.
ENOG410ZHZN. LUCA.
GeneTreeiENSGT00390000001936.
HOGENOMiHOG000013099.
HOVERGENiHBG051456.
InParanoidiQ91YE2.
KOiK09592.
OMAiEGGMSCG.
OrthoDBiEOG091G03SP.
PhylomeDBiQ91YE2.
TreeFamiTF314595.

Family and domain databases

InterProiIPR005123. Oxoglu/Fe-dep_dioxygenase.
IPR006620. Pro_4_hyd_alph.
[Graphical view]
PfamiPF13640. 2OG-FeII_Oxy_3. 1 hit.
[Graphical view]
SMARTiSM00702. P4Hc. 1 hit.
[Graphical view]
PROSITEiPS51471. FE2OG_OXY. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q91YE2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDSPCQPQAL NQALPQLPGS VSESLESSRA RMGVESYLPC PLLPAYHRPG
60 70 80 90 100
ASGEASAGNG TPRTTATATT TTASPLREGF GGQDGGELWP LQSEGAAALV
110 120 130 140 150
TKECQRLAAQ GARPEAPKRK WAKDGGDAPS PSKRPWARQE NQEAKGESGM
160 170 180 190 200
GCDSGASNSS SSSSNTTSSS GEASARLREE VQPSAPERLA LDYIVPCMRY
210 220 230 240 250
YGICVKDNFL GAVLGGRVLA EVEALKWGGR LRDGQLVSQR AIPPRSIRGD
260 270 280 290 300
QIAWVEGHEP GCRSIGALMA HVDAVIRHCA GRLGNYVING RTKAMVACYP
310 320 330 340 350
GNGLGYVRHV DNPHGDGRCI TCIYYLNQNW DVKVHGGLLQ IFPEGRPVVA
360 370 380 390 400
NIEPLFDRLL IFWSDRRNPH EVKPAYATRY AITVWYFDAK ERAAARDKYQ
410
LASGQKGVQV PVSQPTTPT
Length:419
Mass (Da):45,109
Last modified:June 16, 2003 - v2
Checksum:i13BAA52A0709CE98
GO

Sequence cautioni

The sequence CAC42516 differs from that shown. Reason: Frameshift at positions 118 and 125.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti8Q → H in BAC35835 (PubMed:16141072).Curated1
Sequence conflicti10L → C in BAC35835 (PubMed:16141072).Curated1
Sequence conflicti92Q → K in AAK37525 (PubMed:12360397).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ310547 mRNA. Translation: CAC42516.1. Frameshift.
AF453879 mRNA. Translation: AAL65166.1.
AF340231 mRNA. Translation: AAK37525.1.
AK075582 mRNA. Translation: BAC35835.1.
BC023299 mRNA. Translation: AAH23299.2.
CCDSiCCDS21011.1.
RefSeqiNP_444438.2. NM_053208.4.
UniGeneiMm.29978.

Genome annotation databases

EnsembliENSMUST00000080058; ENSMUSP00000078966; ENSMUSG00000058709.
ENSMUST00000108382; ENSMUSP00000104019; ENSMUSG00000058709.
GeneIDi112406.
KEGGimmu:112406.
UCSCiuc009fva.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ310547 mRNA. Translation: CAC42516.1. Frameshift.
AF453879 mRNA. Translation: AAL65166.1.
AF340231 mRNA. Translation: AAK37525.1.
AK075582 mRNA. Translation: BAC35835.1.
BC023299 mRNA. Translation: AAH23299.2.
CCDSiCCDS21011.1.
RefSeqiNP_444438.2. NM_053208.4.
UniGeneiMm.29978.

3D structure databases

ProteinModelPortaliQ91YE2.
SMRiQ91YE2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi227482. 2 interactors.
STRINGi10090.ENSMUSP00000078966.

PTM databases

iPTMnetiQ91YE2.
PhosphoSitePlusiQ91YE2.

Proteomic databases

MaxQBiQ91YE2.
PaxDbiQ91YE2.
PRIDEiQ91YE2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000080058; ENSMUSP00000078966; ENSMUSG00000058709.
ENSMUST00000108382; ENSMUSP00000104019; ENSMUSG00000058709.
GeneIDi112406.
KEGGimmu:112406.
UCSCiuc009fva.2. mouse.

Organism-specific databases

CTDi112398.
MGIiMGI:1932287. Egln2.

Phylogenomic databases

eggNOGiKOG3710. Eukaryota.
ENOG410ZHZN. LUCA.
GeneTreeiENSGT00390000001936.
HOGENOMiHOG000013099.
HOVERGENiHBG051456.
InParanoidiQ91YE2.
KOiK09592.
OMAiEGGMSCG.
OrthoDBiEOG091G03SP.
PhylomeDBiQ91YE2.
TreeFamiTF314595.

Enzyme and pathway databases

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

Miscellaneous databases

PROiQ91YE2.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000058709.
CleanExiMM_EGLN2.
ExpressionAtlasiQ91YE2. baseline and differential.
GenevisibleiQ91YE2. MM.

Family and domain databases

InterProiIPR005123. Oxoglu/Fe-dep_dioxygenase.
IPR006620. Pro_4_hyd_alph.
[Graphical view]
PfamiPF13640. 2OG-FeII_Oxy_3. 1 hit.
[Graphical view]
SMARTiSM00702. P4Hc. 1 hit.
[Graphical view]
PROSITEiPS51471. FE2OG_OXY. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiEGLN2_MOUSE
AccessioniPrimary (citable) accession number: Q91YE2
Secondary accession number(s): Q8C6I4
, Q8CIL9, Q8VHJ1, Q99MI0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 16, 2003
Last sequence update: June 16, 2003
Last modified: November 2, 2016
This is version 119 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.