PPIE (gene)

PPIE
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1ZMF, 2CQB, 2KU7, 2KYX, 2R99, 3LPY, 3MDF, 3UCH
Identifiers
Aliases	PPIE , CYP-33, CYP33, peptidylprolyl isomerase E
External IDs	OMIM: 602435 MGI: 1917118 HomoloGene: 38142 GeneCards: PPIE
Gene location (Human)
Chr.	Chromosome 1 (human)
End	39,763,914 bp
Gene location (Mouse)
Chr.	Chromosome 4 (mouse)
End	123,033,744 bp
RNA expression pattern
	Top expressed in
	right uterine tube; ; body of pancreas; ; islet of Langerhans; ; popliteal artery; ; ascending aorta; ; tibial nerve; ; left coronary artery; ; stromal cell of endometrium; ; right coronary artery; ; left uterine tube;
	Top expressed in
	morula; ; yolk sac; ; otic placode; ; primitive streak; ; neural tube; ; spermatocyte; ; lip; ; mirror; ; thymus; ; spermatid;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	isomerase activity ; peptidyl-prolyl cis-trans isomerase activity ; protein binding ; nucleic acid binding ; cyclosporin A binding ; RNA binding ; mRNA binding ; poly(A) binding ; unfolded protein binding ;
Cellular component	catalytic step 2 spliceosome ; nucleoplasm ; spliceosomal complex ; nucleus ; extracellular region ; cytosol ; nuclear speck ; secretory granule lumen ; ficolin-1-rich granule lumen ; U2-type catalytic step 2 spliceosome ;
Biological process	regulation of transcription, DNA-templated ; mRNA processing ; protein peptidyl-prolyl isomerization ; protein folding ; RNA splicing ; positive regulation of viral genome replication ; transcription-coupled nucleotide-excision repair ; mRNA splicing, via spliceosome ; neutrophil degranulation ; protein refolding ;
	Sources:Amigo / QuickGO
Orthologs
	10450
	56031
	ENSG00000084072
	ENSMUSG00000028651
	Q9UNP9
	Q9QZH3
	NM_001195007 ; NM_006112 ; NM_203456 ; NM_203457 ; NM_001319293 Contents Structure ; Function ; Clinical significance ; Interactions ; References ; Further reading ;
	NM_019489
	NP_001181936 ; NP_001306222 ; NP_006103 ; NP_982281
	NP_062362
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated December 04, 2023

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]

Structure

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 in 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]

Interactions

PPIE (gene) has been shown to interact with CsA and MLL.^[7]^[11]

Related Research Articles

Cyclophilins (CYPs) are a family of proteins named after their ability to bind to ciclosporin, an immunosuppressant which is usually used to suppress rejection after internal organ transplants. They are found in all domains of life. These proteins have peptidyl prolyl isomerase activity, which catalyzes the isomerization of peptide bonds from trans form to cis form at proline residues and facilitates protein folding.

Prolyl isomerase is an enzyme found in both prokaryotes and eukaryotes that interconverts the cis and trans isomers of peptide bonds with the amino acid proline. Proline has an unusually conformationally restrained peptide bond due to its cyclic structure with its side chain bonded to its secondary amine nitrogen. Most amino acids have a strong energetic preference for the trans peptide bond conformation due to steric hindrance, but proline's unusual structure stabilizes the cis form so that both isomers are populated under biologically relevant conditions. Proteins with prolyl isomerase activity include cyclophilin, FKBPs, and parvulin, although larger proteins can also contain prolyl isomerase domains.

Parvulin, a 92-amino acid protein discovered in E. coli in 1994, is the smallest known protein with prolyl isomerase activity, which catalyzes the cis-trans isomerization of proline peptide bonds. Although parvulin has no homology with larger prolyl isomerases such as cyclophilin and FKBP, it does share structural features with subdomains of other proteins involved in preparing secreted proteins for export from the cell.

Peptidylprolyl isomerase A (PPIA), also known as cyclophilin A (CypA) or rotamase A is an enzyme that in humans is encoded by the PPIA gene on chromosome 7. 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 regulate many biological processes, including intracellular signaling, transcription, inflammation, and apoptosis. Due to its various functions, PPIA has been implicated in a broad range of inflammatory diseases, including atherosclerosis and arthritis, and viral infections.

Peptidyl-prolyl cis-trans isomerase FKBP1A is an enzyme that in humans is encoded by the FKBP1A gene. It is also commonly referred to as FKBP-12 or FKBP12 and is a member of a family of FK506-binding proteins (FKBPs).

Peptidyl-prolyl cis-trans isomerase B is an enzyme that is encoded by the PPIB gene. 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 regulate protein folding of type I collagen. Generally, PPIases are found in all eubacteria and eukaryotes, as well as in a few archaebacteria, and thus are highly conserved.

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 is an enzyme that in humans is encoded by the PIN1 gene.

FK506-binding protein 3 also known as FKBP25 is a protein that in humans is encoded by the FKBP3 gene.

Peptidylprolyl isomerase D (cyclophilin D), also known as PPID, is an enzyme which in humans is encoded by the PPID gene on chromosome 4. 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. In addition, PPID participates in many biological processes, including mitochondrial metabolism, apoptosis, redox, and inflammation, as well as in related diseases and conditions, such as ischemic reperfusion injury, AIDS, and cancer.

Peptidyl-prolyl cis-trans isomerase, mitochondrial (PPIF) is an enzyme that in humans is encoded by the PPIF gene. It has also been referred to as, but should not be confused with, cyclophilin D (CypD), which is encoded by the PPID gene. 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. PPIF is a major component of the mitochondrial permeability transition pore (MPTP) and, thus, highly involved in mitochondrial metabolism and apoptosis, as well as in mitochondrial diseases and related conditions, including cardiac diseases, neurodegenerative diseases, and muscular dystrophy. In addition, PPIF participates in inflammation, as well as in ischemic reperfusion injury, AIDS, and cancer.

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 4 is an enzyme that in humans is encoded by the PIN4 gene.

Peptidyl-prolyl cis-trans isomerase-like 1 is an enzyme that in humans is encoded by the PPIL1 gene.

Peptidyl-prolyl cis-trans isomerase H is an enzyme that in humans is encoded by the PPIH gene.

Peptidyl-prolyl cis-trans isomerase C (PPIC) is an enzyme that in humans is encoded by the PPIC gene on chromosome 5. 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. In addition, PPIC participates in many biological processes, including mitochondrial metabolism, apoptosis, redox, and inflammation, as well as in related diseases and conditions, such as ischemic reperfusion injury, AIDS, and cancer.

Peptidyl-prolyl cis-trans isomerase-like 3 is an enzyme that in humans is encoded by the PPIL3 gene.

Peptidyl-prolyl cis-trans isomerase G is an enzyme that in humans is encoded by the PPIG gene.

Peptidyl-prolyl cis-trans isomerase-like 2 is an enzyme that in humans is encoded by the PPIL2 gene.

Peptidyl-prolyl cis-trans isomerase-like 4 is an enzyme that in humans is encoded by the PPIL4 gene.

In epigenetics, proline isomerization is the effect that cis-trans isomerization of the amino acid proline has on the regulation of gene expression. Similar to aspartic acid, the amino acid proline has the rare property of being able to occupy both cis and trans isomers of its prolyl peptide bonds with ease. Peptidyl-prolyl isomerase, or PPIase, is an enzyme very commonly associated with proline isomerization due to their ability to catalyze the isomerization of prolines. PPIases are present in three types: cyclophilins, FK507-binding proteins, and the parvulins. PPIase enzymes catalyze the transition of proline between cis and trans isomers and are essential to the numerous biological functions controlled and affected by prolyl isomerization Without PPIases, prolyl peptide bonds will slowly switch between cis and trans isomers, a process that can lock proteins in a nonnative structure that can affect render the protein temporarily ineffective. Although this switch can occur on its own, PPIases are responsible for most isomerization of prolyl peptide bonds. The specific amino acid that precedes the prolyl peptide bond also can have an effect on which conformation the bond assumes. For instance, when an aromatic amino acid is bonded to a proline the bond is more favorable to the cis conformation. Cyclophilin A uses an "electrostatic handle" to pull proline into cis and trans formations. Most of these biological functions are affected by the isomerization of proline when one isomer interacts differently than the other, commonly causing an activation/deactivation relationship. As an amino acid, proline is present in many proteins. This aids in the multitude of effects that isomerization of proline can have in different biological mechanisms and functions.