Gene/Proteome Database (LMPD)

LMPD ID
LMP013296
Gene ID
Species
Rattus norvegicus (Rat)
Gene Name
egl-9 family hypoxia-inducible factor 2
Gene Symbol
Synonyms
PHD1; HPH-1; HPH-3; PHD-1; HIF-PH1;
Alternate Names
egl nine homolog 2; HIF-prolyl hydroxylase 1; HIF-1alpha prolyl-4-hydroxylase-1; hypoxia-inducible factor prolyl hydroxylase 1; prolyl hydroxylase domain-containing protein 1;
Chromosome
1
Map Location
1q21
EC Number
1.14.11.29
Summary
HIF-prolyl hydroxylase 1; might be involved in might play a role in hypoxic preconditioning [RGD, Feb 2006]
Orthologs

Proteins

egl nine homolog 2
Refseq ID NP_001004083
Protein GI 51854225
UniProt ID Q6AYU4
mRNA ID NM_001004083
Length 415
MDSPCQPQALNQALPQLPGSVSESLEPSRARMGVESYLPCPLLPSYHRSGASGEASAGNGTPRTTATATTTTASPLREGFGGQDGGELWPLQSEGAAALVTKECQRLAAQGARPEAPKRKWAKDGGDAPSPSKRPWARQENQEAKGESGVGCDSGGGSSNSTTHSSGEASSRLREEAQPSAPERLALDYIVPCMRYYGICVKDNFLGAVLGGRVLAEVEALKWGGRLRDGQLVSQRAIPPRSIRGDQIAWVEGHEPGCRSIGALMAHVDAVIRHCAGRLGNYVINGRTKAMVACYPGNGLGYVRHVDNPHGDGRCITCIYYLNQNWDVKVHGGLLQIFPEGRPVVANIEPLFDRLLIFWSDRRNPHEVKPAYATRYAITVWYFDAKERAAARDKYQLASGQKGVQVPVSQPATPT

Gene Information

Entrez Gene ID
Gene Name
egl-9 family hypoxia-inducible factor 2
Gene Symbol
Species
Rattus norvegicus

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005829 IDA:RGD C cytosol
GO:0005634 ISS:UniProtKB C nucleus
GO:0031418 IEA:UniProtKB-KW F L-ascorbic acid binding
GO:0005506 IEA:InterPro F iron ion binding
GO:0016491 IDA:RGD F oxidoreductase activity
GO:0019826 IEA:Ensembl F oxygen sensor activity
GO:0031545 IEA:Ensembl F peptidyl-proline 4-dioxygenase activity
GO:0031543 IDA:RGD F peptidyl-proline dioxygenase activity
GO:0045454 IEA:Ensembl P cell redox homeostasis
GO:0018401 IEA:Ensembl P peptidyl-proline hydroxylation to 4-hydroxy-L-proline
GO:0045732 IEA:Ensembl P positive regulation of protein catabolic process
GO:0043523 ISS:UniProtKB P regulation of neuron apoptotic process
GO:0001666 IDA:RGD P response to hypoxia

KEGG Pathway Links

KEGG Pathway ID Description
rno04066 HIF-1 signaling pathway
rno05200 Pathways in cancer
ko05211 Renal cell carcinoma
rno05211 Renal cell carcinoma

REACTOME Pathway Links

REACTOME Pathway ID Description
5954417 Cellular response to hypoxia
5953238 Cellular responses to stress
5954415 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
5954416 Regulation of Hypoxia-inducible Factor (HIF) by oxygen

Domain Information

InterPro Annotations

Accession Description
IPR005123 Oxoglutarate/iron-dependent dioxygenase
IPR006620 Prolyl 4-hydroxylase, alpha subunit

UniProt Annotations

Entry Information

Gene Name
egl-9 family hypoxia-inducible factor 2
Protein Entry
EGLN2_RAT
UniProt ID
Species
Rat

Comments

Comment Type Description
Catalytic Activity Hypoxia-inducible factor-L-proline + 2- oxoglutarate + O(2) = hypoxia-inducible factor-trans-4-hydroxy-L- proline + succinate + CO(2).
Cofactor Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Note=Binds 1 Fe(2+) ion per subunit.;
Cofactor Name=L-ascorbate; Xref=ChEBI:CHEBI:38290;
Domain The beta(2)beta(3) 'finger-like' loop domain is important for substrate (HIFs' CODD/NODD) selectivity
Function 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 preferencially recognized via a LXXLAP motif
Similarity Contains 1 Fe2OG dioxygenase domain
Subcellular Location Nucleus .
Subunit Interacts with E3 ligase SIAH2. Interacts with LIMD1, WTIP and AJUBA
Tissue Specificity Expressed in heart, kidney, brain, liver, skeletal muscle, lung and spleen. Highest level in testis

Identical and Related Proteins

Unique RefSeq proteins for LMP013296 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
51854225 RefSeq NP_001004083 415 egl nine homolog 2

Identical Sequences to LMP013296 proteins

Reference Database Accession Length Protein Name
GI:51854225 GenBank AAX51892.1 415 HIF-1alpha prolyl-4-hydroxylase-1 [Rattus norvegicus]
GI:51854225 GenBank EDM07971.1 415 EGL nine homolog 2 (C. elegans), isoform CRA_a [Rattus norvegicus]
GI:51854225 RefSeq XP_006228637.1 415 PREDICTED: egl nine homolog 2 isoform X1 [Rattus norvegicus]
GI:51854225 SwissProt Q6AYU4.1 415 RecName: Full=Egl nine homolog 2; AltName: Full=HPH-3; AltName: Full=Hypoxia-inducible factor prolyl hydroxylase 1; Short=HIF-PH1; Short=HIF-prolyl hydroxylase 1; Short=HPH-1; AltName: Full=Prolyl hydroxylase domain-containing protein 1; Short=PHD1 [Rattus norvegicus]

Related Sequences to LMP013296 proteins

Reference Database Accession Length Protein Name
GI:51854225 GenBank AAH78907.1 415 EGL nine homolog 2 (C. elegans) [Rattus norvegicus]
GI:51854225 GenBank AAH81858.1 415 Egln2 protein [Rattus norvegicus]
GI:51854225 GenBank AAX51892.1 415 HIF-1alpha prolyl-4-hydroxylase-1 [Rattus norvegicus]
GI:51854225 SwissProt Q6AYU4.1 415 RecName: Full=Egl nine homolog 2; AltName: Full=HPH-3; AltName: Full=Hypoxia-inducible factor prolyl hydroxylase 1; Short=HIF-PH1; Short=HIF-prolyl hydroxylase 1; Short=HPH-1; AltName: Full=Prolyl hydroxylase domain-containing protein 1; Short=PHD1 [Rattus norvegicus]