PPIE (gene)
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| PPIE | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | PPIE, CYP-33, CYP33, peptidylprolyl isomerase E | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 602435; MGI: 1917118; HomoloGene: 38142; GeneCards: PPIE; OMA:PPIE - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Peptidylprolyl isomerase E (cyclophilin E), also known as PPIE, is an enzyme which in humans is encoded by the PPIE gene on chromosome 1. As a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family, this protein catalyzes the cis-trans isomerization of proline imidic peptide bonds, which allows it to facilitate folding or repair of proteins.[5] In addition, PPIE participates in many biological processes, including mitochondrial metabolism, apoptosis, and inflammation, as well as related diseases and conditions, such as ischemic reperfusion injury, AIDS, influenza, and cancer.[6][7][8]
Like other cyclophilins, PPIE forms a β-barrel structure with a hydrophobic core. This β-barrel is composed of eight anti-parallel β-strands and capped by two α-helices at the top and bottom. In addition, the β-turns and loops in the strands contribute to the flexibility of the barrel. In particular, PPIE contains two RNA-binding domains at the N-terminal and a 165-bases long PPIase domain at the C-terminal. The PPIase domain is homologous to PPIA and can be bound and inhibited by CsA.[8]
Function
The protein encoded by this gene is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins.[5] Generally, PPIases are found in all eubacteria and eukaryotes, as well as in a few archaebacteria, and thus are highly conserved.[6][9] The PPIase family is further divided into three structurally distinct subfamilies: cyclophilin (CyP), FK506-binding protein (FKBP), and parvulin (Pvn).[6][8] As a cyclophilin, PPI binds cyclosporin A (CsA) and can be found within the cell or secreted by the cell.[7] In eukaryotes, cyclophilins localize ubiquitously to many cell and tissue types.[7][8] In addition to PPIase and protein chaperone activities, cyclophilins function in mitochondrial metabolism, apoptosis, immunological response, inflammation, and cell growth and proliferation.[6][7][8] PPIE in particular also exhibits RNA-binding activity.[5]
Clinical significance
Due to the close homology in the PPIase domain between PPIE and PPIA, PPIE may also be involved in the replication process of HIV.[8] Moreover, PPIE helps to prevent infections by influenza A virus.[10] As a cyclophilin, PPIE also binds the immunosuppressive drug CsA to form a CsA-cyclophilin complex, which then targets calcineurin to inhibit the signaling pathway for T-cell activation.[7]
In cardiac myogenic cells, cyclophilins have been observed to be activated by heat shock and hypoxia-reoxygenation as well as complex with heat shock proteins. Thus, cyclophilins may function in cardioprotection during ischemia-reperfusion injury.
Currently, cyclophilin expression is highly correlated with cancer pathogenesis, but the specific mechanisms remain to be elucidated.[7]
