Q96KS0 · EGLN2_HUMAN
- ProteinProlyl hydroxylase EGLN2
- GeneEGLN2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids407 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Target proteins are preferentially recognized via a LXXLAP motif (PubMed:11595184, PubMed:12039559, PubMed:15925519).
Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins (PubMed:11595184, PubMed:12039559, PubMed:12181324, PubMed:15925519, PubMed:19339211).
Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A (PubMed:11595184, PubMed:12039559, PubMed:12181324, PubMed:15925519).
Also hydroxylates HIF2A (PubMed:11595184, PubMed:12039559, PubMed:15925519).
Has a preference for the CODD site for both HIF1A and HIF2A (PubMed:11595184, PubMed:12039559, PubMed:15925519).
Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex (PubMed:11595184, PubMed:12039559, PubMed:15925519).
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 (PubMed:11595184, PubMed:12039559, PubMed:15925519).
EGLN2 is involved in regulating hypoxia tolerance and apoptosis in cardiac and skeletal muscle (PubMed:11595184, PubMed:12039559, PubMed:15925519).
Also regulates susceptibility to normoxic oxidative neuronal death (PubMed:11595184, PubMed:12039559, PubMed:15925519).
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 (PubMed:23932902).
Hydroxylates IKBKB, mediating NF-kappa-B activation in hypoxic conditions (PubMed:17114296).
Also mediates hydroxylation of ATF4, leading to decreased protein stability of ATF4 (By similarity).
Catalytic activity
- 2-oxoglutarate + L-prolyl-[protein] + O2 = CO2 + succinate + trans-4-hydroxy-L-prolyl-[protein]This reaction proceeds in the forward direction.
Cofactor
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
20 μM | HIF1A DLDLEMLAPYIPMDDDFQL peptide | 7.5 | 37 | |||
50 μM | L-ascorbate | 7.5 | 37 | |||
1 μM | Fe2+ | 7.5 | 37 |
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Molecular Function | 2-oxoglutarate-dependent dioxygenase activity | |
Molecular Function | ferrous iron binding | |
Molecular Function | hypoxia-inducible factor-proline dioxygenase activity | |
Molecular Function | L-ascorbic acid binding | |
Molecular Function | oxygen sensor activity | |
Molecular Function | peptidyl-proline 4-dioxygenase activity | |
Biological Process | cell redox homeostasis | |
Biological Process | cellular response to hypoxia | |
Biological Process | estrogen receptor signaling pathway | |
Biological Process | peptidyl-proline hydroxylation to 4-hydroxy-L-proline | |
Biological Process | positive regulation of protein catabolic process | |
Biological Process | regulation of cell growth | |
Biological Process | regulation of neuron apoptotic process | |
Biological Process | response to hypoxia |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProlyl hydroxylase EGLN2
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ96KS0
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 1 | Leads to expression of isoform p40 only. | ||||
Sequence: M → A | ||||||
Mutagenesis | 34 | Leads to expression of isoform p43 only. | ||||
Sequence: M → A | ||||||
Mutagenesis | 102 | Retained in the nucleus. | ||||
Sequence: K → A | ||||||
Mutagenesis | 106 | Retained in the nucleus. | ||||
Sequence: R → A | ||||||
Mutagenesis | 113 | Retained in the nucleus. | ||||
Sequence: R → A | ||||||
Mutagenesis | 119 | Cytoplasmic and nuclear localization. Reduced transcriptional activity of HIF1A as for wild type. | ||||
Sequence: R → A | ||||||
Mutagenesis | 134 | Retained in the nucleus. | ||||
Sequence: R → A | ||||||
Mutagenesis | 297 | Eliminates hydroxylase activity. | ||||
Sequence: H → A | ||||||
Mutagenesis | 299 | Eliminates hydroxylase activity. | ||||
Sequence: D → A | ||||||
Mutagenesis | 358 | Eliminates hydroxylase activity. | ||||
Sequence: H → A | ||||||
Mutagenesis | 367 | Eliminates hydroxylase activity. | ||||
Sequence: R → A | ||||||
Mutagenesis | 367 | Eliminates hydroxylase activity on a HIF1A peptide. | ||||
Sequence: R → K |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 490 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000206664 | 1-407 | UniProt | Prolyl hydroxylase EGLN2 | |||
Sequence: MDSPCQPQPLSQALPQLPGSSSEPLEPEPGRARMGVESYLPCPLLPSYHCPGVPSEASAGSGTPRATATSTTASPLRDGFGGQDGGELRPLQSEGAAALVTKGCQRLAAQGARPEAPKRKWAEDGGDAPSPSKRPWARQENQEAEREGGMSCSCSSGSGEASAGLMEEALPSAPERLALDYIVPCMRYYGICVKDSFLGAALGGRVLAEVEALKRGGRLRDGQLVSQRAIPPRSIRGDQIAWVEGHEPGCRSIGALMAHVDAVIRHCAGRLGSYVINGRTKAMVACYPGNGLGYVRHVDNPHGDGRCITCIYYLNQNWDVKVHGGLLQIFPEGRPVVANIEPLFDRLLIFWSDRRNPHEVKPAYATRYAITVWYFDAKERAAAKDKYQLASGQKGVQVPVSQPPTPT | |||||||
Modified residue (large scale data) | 74 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 130 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 130 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Induction
Induced by proteasomal inhibitor MG132 (at protein level) (PubMed:16509823).
Isoform p43
Isoform p40
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with LIMD1, WTIP and AJUBA (PubMed:22286099).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q96KS0 | HIF1A Q16665 | 2 | EBI-726614, EBI-447269 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for compositional bias, region, motif, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-19 | Polar residues | ||||
Sequence: MDSPCQPQPLSQALPQLPG | ||||||
Region | 1-34 | Disordered | ||||
Sequence: MDSPCQPQPLSQALPQLPGSSSEPLEPEPGRARM | ||||||
Region | 50-89 | Disordered | ||||
Sequence: CPGVPSEASAGSGTPRATATSTTASPLRDGFGGQDGGELR | ||||||
Compositional bias | 60-77 | Polar residues | ||||
Sequence: GSGTPRATATSTTASPLR | ||||||
Motif | 89-134 | Bipartite nuclear localization signal | ||||
Sequence: RPLQSEGAAALVTKGCQRLAAQGARPEAPKRKWAEDGGDAPSPSKR | ||||||
Region | 108-157 | Disordered | ||||
Sequence: AAQGARPEAPKRKWAEDGGDAPSPSKRPWARQENQEAEREGGMSCSCSSG | ||||||
Region | 225-235 | Beta2beta3 'finger-like' loop | ||||
Sequence: VSQRAIPPRSI | ||||||
Domain | 278-376 | Fe2OG dioxygenase | ||||
Sequence: GRTKAMVACYPGNGLGYVRHVDNPHGDGRCITCIYYLNQNWDVKVHGGLLQIFPEGRPVVANIEPLFDRLLIFWSDRRNPHEVKPAYATRYAITVWYFD |
Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative initiation.
Q96KS0-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Namep43
- SynonymsPHD1p43
- Length407
- Mass (Da)43,650
- Last updated2001-12-01 v1
- ChecksumF172E9B0482C9CF3
Q96KS0-2
- Namep40
- SynonymsPHD1p40
- Differences from canonical
- 1-33: Missing
Computationally mapped potential isoform sequences
There are 11 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
M0R1A3 | M0R1A3_HUMAN | EGLN2 | 51 | ||
M0R1L0 | M0R1L0_HUMAN | EGLN2 | 96 | ||
M0R110 | M0R110_HUMAN | EGLN2 | 101 | ||
M0R0Z6 | M0R0Z6_HUMAN | EGLN2 | 139 | ||
M0R035 | M0R035_HUMAN | EGLN2 | 87 | ||
M0R350 | M0R350_HUMAN | EGLN2 | 128 | ||
M0R2X9 | M0R2X9_HUMAN | EGLN2 | 67 | ||
M0R1W4 | M0R1W4_HUMAN | EGLN2 | 72 | ||
M0QXR0 | M0QXR0_HUMAN | EGLN2 | 94 | ||
M0QXM8 | M0QXM8_HUMAN | EGLN2 | 77 | ||
A0A0C4DGR4 | A0A0C4DGR4_HUMAN | EGLN2 | 125 |
Sequence caution
Features
Showing features for compositional bias, alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-19 | Polar residues | ||||
Sequence: MDSPCQPQPLSQALPQLPG | ||||||
Alternative sequence | VSP_038836 | 1-33 | in isoform p40 | |||
Sequence: Missing | ||||||
Compositional bias | 60-77 | Polar residues | ||||
Sequence: GSGTPRATATSTTASPLR | ||||||
Sequence conflict | 176 | in Ref. 2; AAK82943 | ||||
Sequence: R → P |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ310544 EMBL· GenBank· DDBJ | CAC42510.1 EMBL· GenBank· DDBJ | mRNA | ||
AY040565 EMBL· GenBank· DDBJ | AAK82943.1 EMBL· GenBank· DDBJ | mRNA | ||
AK291385 EMBL· GenBank· DDBJ | BAF84074.1 EMBL· GenBank· DDBJ | mRNA | ||
AL832506 EMBL· GenBank· DDBJ | - | mRNA | No translation available. | |
AC008537 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471126 EMBL· GenBank· DDBJ | EAW57008.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC001723 EMBL· GenBank· DDBJ | AAH01723.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC036051 EMBL· GenBank· DDBJ | AAH36051.1 EMBL· GenBank· DDBJ | mRNA |