Gene/Proteome Database (LMPD)
LMPD ID
LMP001120
Gene ID
Species
Homo sapiens (Human)
Gene Name
egl-9 family hypoxia-inducible factor 2
Gene Symbol
Synonyms
EIT6; HIF-PH1; HIFPH1; HPH-1; HPH-3; PHD1
Alternate Names
egl nine homolog 2; estrogen-induced tag 6; HIF-prolyl hydroxylase 1; hypoxia-inducible factor prolyl hydroxylase 1; prolyl hydroxylase domain-containing protein 1
Chromosome
19
Map Location
19q13.2
EC Number
1.14.11.29
Summary
The hypoxia inducible factor (HIF) is a transcriptional complex that is involved in oxygen homeostasis. At normal oxygen levels, the alpha subunit of HIF is targeted for degration by prolyl hydroxylation. This gene encodes an enzyme responsible for this post-translational modification. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the upstream RAB4B (RAB4B, member RAS oncogene family) gene. [provided by RefSeq, Feb 2011]
Orthologs
Proteins
| egl nine homolog 2 | |
|---|---|
| Refseq ID | NP_542770 |
| Protein GI | 145701012 |
| UniProt ID | Q96KS0 |
| mRNA ID | NM_080732 |
| Length | 407 |
| RefSeq Status | REVIEWED |
| MDSPCQPQPLSQALPQLPGSSSEPLEPEPGRARMGVESYLPCPLLPSYHCPGVPSEASAGSGTPRATATSTTASPLRDGFGGQDGGELRPLQSEGAAALVTKGCQRLAAQGARPEAPKRKWAEDGGDAPSPSKRPWARQENQEAEREGGMSCSCSSGSGEASAGLMEEALPSAPERLALDYIVPCMRYYGICVKDSFLGAALGGRVLAEVEALKRGGRLRDGQLVSQRAIPPRSIRGDQIAWVEGHEPGCRSIGALMAHVDAVIRHCAGRLGSYVINGRTKAMVACYPGNGLGYVRHVDNPHGDGRCITCIYYLNQNWDVKVHGGLLQIFPEGRPVVANIEPLFDRLLIFWSDRRNPHEVKPAYATRYAITVWYFDAKERAAAKDKYQLASGQKGVQVPVSQPPTPT | |
Gene Information
Entrez Gene ID
Gene Name
egl-9 family hypoxia-inducible factor 2
Gene Symbol
Species
Homo sapiens
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0005829 | IEA:Ensembl | C | cytosol |
| GO:0005654 | TAS:Reactome | C | nucleoplasm |
| GO:0005634 | IDA:UniProtKB | C | nucleus |
| GO:0031418 | IEA:UniProtKB-KW | F | L-ascorbic acid binding |
| GO:0008198 | NAS:UniProtKB | F | ferrous iron binding |
| GO:0016706 | IDA:UniProtKB | F | oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors |
| GO:0019826 | IDA:UniProtKB | F | oxygen sensor activity |
| GO:0031545 | IDA:FlyBase | F | peptidyl-proline 4-dioxygenase activity |
| GO:0045454 | IDA:UniProtKB | P | cell redox homeostasis |
| GO:0071456 | TAS:Reactome | P | cellular response to hypoxia |
| GO:0030520 | NAS:UniProtKB | P | intracellular estrogen receptor signaling pathway |
| GO:0018401 | IDA:FlyBase | P | peptidyl-proline hydroxylation to 4-hydroxy-L-proline |
| GO:0045732 | IDA:UniProtKB | P | positive regulation of protein catabolic process |
| GO:0001558 | NAS:UniProtKB | P | regulation of cell growth |
| GO:0043523 | IMP:UniProtKB | P | regulation of neuron apoptotic process |
| GO:0061418 | TAS:Reactome | P | regulation of transcription from RNA polymerase II promoter in response to hypoxia |
| GO:0001666 | IDA:UniProtKB | P | response to hypoxia |
KEGG Pathway Links
| KEGG Pathway ID | Description |
|---|---|
| hsa04066 | HIF-1 signaling pathway |
| hsa05200 | Pathways in cancer |
| hsa05211 | Renal cell carcinoma |
REACTOME Pathway Links
| REACTOME Pathway ID | Description |
|---|---|
| REACT_120916 | Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha |
Domain Information
UniProt Annotations
Entry Information
Gene Name
egl-9 family hypoxia-inducible factor 2
Protein Entry
EGLN2_HUMAN
UniProt ID
Species
Human
Comments
| Comment Type | Description |
|---|---|
| Alternative Products | Event=Alternative initiation; Named isoforms=2; Name=p43; Synonyms=PHD1p43; IsoId=Q96KS0-1; Sequence=Displayed; Name=p40; Synonyms=PHD1p40; IsoId=Q96KS0-2; Sequence=VSP_038836; |
| 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 |
| Cofactor | Name=L-ascorbate; Xref=ChEBI |
| 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. {ECO |
| Induction | By estrogen. Isoform p43 is induced by hypoxia leading to protein stability. Isoform p40 repressed by hypoxia. Both isoforms are induced by proteasomal inhibitor MG132 (at protein level). {ECO |
| Interaction | Q16665:HIF1A; NbExp=2; IntAct=EBI-726614, EBI-447269; |
| Sequence Caution | Sequence=AAH01723.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence= ; |
| Similarity | Contains 1 Fe2OG dioxygenase domain. |
| Subcellular Location | Nucleus {ECO |
| Subunit | Interacts (preferably isoform p40) with SIAH2; the interaction targets both SIAH2 isoforms for proteasomal degradation in vitro. Interacts with LIMD1, WTIP and AJUBA. |
| Tissue Specificity | Expressed in adult and fetal heart, brain, liver, lung, skeletal muscle, and kidney. Also expressed in testis and placenta. Highest levels in adult brain, placenta, lung, kidney, and testis. Expressed in hormone responsive tissues, including normal and cancerous mammary, ovarian and prostate epithelium. |
Identical and Related Proteins
Unique RefSeq proteins for LMP001120 (as displayed in Record Overview)
Identical Sequences to LMP001120 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:145701012 | GenBank | AGA49408.1 | 407 | Sequence 2 from patent US 8329167 |
| GI:145701012 | GenBank | AGV94471.1 | 407 | Sequence 13 from patent US 8512972 |
| GI:145701012 | RefSeq | XP_008963124.1 | 407 | PREDICTED: egl nine homolog 2 isoform X1 [Pan paniscus] |
| GI:145701012 | RefSeq | XP_008963125.1 | 407 | PREDICTED: egl nine homolog 2 isoform X1 [Pan paniscus] |
| GI:145701012 | RefSeq | XP_008963126.1 | 407 | PREDICTED: egl nine homolog 2 isoform X1 [Pan paniscus] |
| GI:145701012 | RefSeq | XP_008963127.1 | 407 | PREDICTED: egl nine homolog 2 isoform X1 [Pan paniscus] |
Related Sequences to LMP001120 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:145701012 | EMBL | CAH93185.1 | 407 | hypothetical protein [Pongo abelii] |
| GI:145701012 | GenBank | AAK82943.1 | 407 | estrogen-induced tag 6 [Homo sapiens] |
| GI:145701012 | GenBank | JAA12325.1 | 407 | egl nine homolog 2 [Pan troglodytes] |
| GI:145701012 | GenBank | JAA23946.1 | 407 | egl nine homolog 2 [Pan troglodytes] |
| GI:145701012 | RefSeq | XP_005589368.1 | 405 | PREDICTED: egl nine homolog 2 isoform X1 [Macaca fascicularis] |
| GI:145701012 | RefSeq | XP_010379126.1 | 405 | PREDICTED: egl nine homolog 2 isoform X1 [Rhinopithecus roxellana] |