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Protein

Egl nine homolog 2

Gene

Egln2

Organism
Rattus norvegicus (Rat)
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.1 Publication

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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi305 – 3051IronPROSITE-ProRule annotation
Metal bindingi307 – 3071IronPROSITE-ProRule annotation
Metal bindingi366 – 3661IronPROSITE-ProRule annotation
Binding sitei375 – 37512-oxoglutaratePROSITE-ProRule annotation

GO - Molecular functioni

  • iron ion binding Source: InterPro
  • L-ascorbic acid binding Source: UniProtKB-KW
  • oxidoreductase activity Source: RGD
  • peptidyl-proline dioxygenase activity Source: RGD

GO - Biological processi

  • regulation of neuron apoptotic process Source: UniProtKB
  • response to hypoxia Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Oxidoreductase

Keywords - Ligandi

Iron, Metal-binding, Vitamin C

Enzyme and pathway databases

ReactomeiR-RNO-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):
HPH-3
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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi631376. Egln2.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: RGD
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 415415Egl nine homolog 2PRO_0000415323Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei130 – 1301PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ6AYU4.
PRIDEiQ6AYU4.

PTM databases

iPTMnetiQ6AYU4.
PhosphoSiteiQ6AYU4.

Expressioni

Tissue specificityi

Expressed in heart, kidney, brain, liver, skeletal muscle, lung and spleen. Highest level in testis.2 Publications

Gene expression databases

BgeeiENSRNOG00000020947.
GenevisibleiQ6AYU4. RN.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000028434.

Structurei

3D structure databases

ProteinModelPortaliQ6AYU4.
SMRiQ6AYU4. Positions 184-406.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini286 – 38499Fe2OG dioxygenasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni233 – 24311Beta(2)beta(3) 'finger-like' loopBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi89 – 13446Bipartite nuclear localization signalBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi64 – 729Poly-Thr

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.
InParanoidiQ6AYU4.
KOiK09592.
OMAiEGGMSCG.
OrthoDBiEOG091G03SP.
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.

Q6AYU4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDSPCQPQAL NQALPQLPGS VSESLEPSRA RMGVESYLPC PLLPSYHRSG
60 70 80 90 100
ASGEASAGNG TPRTTATATT TTASPLREGF GGQDGGELWP LQSEGAAALV
110 120 130 140 150
TKECQRLAAQ GARPEAPKRK WAKDGGDAPS PSKRPWARQE NQEAKGESGV
160 170 180 190 200
GCDSGGGSSN STTHSSGEAS SRLREEAQPS APERLALDYI VPCMRYYGIC
210 220 230 240 250
VKDNFLGAVL GGRVLAEVEA LKWGGRLRDG QLVSQRAIPP RSIRGDQIAW
260 270 280 290 300
VEGHEPGCRS IGALMAHVDA VIRHCAGRLG NYVINGRTKA MVACYPGNGL
310 320 330 340 350
GYVRHVDNPH GDGRCITCIY YLNQNWDVKV HGGLLQIFPE GRPVVANIEP
360 370 380 390 400
LFDRLLIFWS DRRNPHEVKP AYATRYAITV WYFDAKERAA ARDKYQLASG
410
QKGVQVPVSQ PATPT
Length:415
Mass (Da):44,681
Last modified:September 13, 2004 - v1
Checksum:i2A6FE8E43254C28A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY952204 mRNA. Translation: AAX51892.1.
CH473979 Genomic DNA. Translation: EDM07971.1.
BC078907 mRNA. Translation: AAH78907.1.
BC081858 mRNA. Translation: AAH81858.1.
RefSeqiNP_001004083.1. NM_001004083.1.
XP_006228637.1. XM_006228575.2.
UniGeneiRn.43384.

Genome annotation databases

EnsembliENSRNOT00000028434; ENSRNOP00000028434; ENSRNOG00000020947.
GeneIDi308457.
KEGGirno:308457.
UCSCiRGD:631376. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY952204 mRNA. Translation: AAX51892.1.
CH473979 Genomic DNA. Translation: EDM07971.1.
BC078907 mRNA. Translation: AAH78907.1.
BC081858 mRNA. Translation: AAH81858.1.
RefSeqiNP_001004083.1. NM_001004083.1.
XP_006228637.1. XM_006228575.2.
UniGeneiRn.43384.

3D structure databases

ProteinModelPortaliQ6AYU4.
SMRiQ6AYU4. Positions 184-406.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000028434.

PTM databases

iPTMnetiQ6AYU4.
PhosphoSiteiQ6AYU4.

Proteomic databases

PaxDbiQ6AYU4.
PRIDEiQ6AYU4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000028434; ENSRNOP00000028434; ENSRNOG00000020947.
GeneIDi308457.
KEGGirno:308457.
UCSCiRGD:631376. rat.

Organism-specific databases

CTDi112398.
RGDi631376. Egln2.

Phylogenomic databases

eggNOGiKOG3710. Eukaryota.
ENOG410ZHZN. LUCA.
GeneTreeiENSGT00390000001936.
HOGENOMiHOG000013099.
HOVERGENiHBG051456.
InParanoidiQ6AYU4.
KOiK09592.
OMAiEGGMSCG.
OrthoDBiEOG091G03SP.
TreeFamiTF314595.

Enzyme and pathway databases

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

Miscellaneous databases

PROiQ6AYU4.

Gene expression databases

BgeeiENSRNOG00000020947.
GenevisibleiQ6AYU4. RN.

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_RAT
AccessioniPrimary (citable) accession number: Q6AYU4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 25, 2012
Last sequence update: September 13, 2004
Last modified: September 7, 2016
This is version 96 of the entry and version 1 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. 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.