Tag Content
SG ID
SG00020995 
UniProt Accession
Theoretical PI
7.88  
Molecular Weight
17971 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
Ppia 
Gene Synonyms/Alias
 
Protein Name
Peptidyl-prolyl cis-trans isomerase A 
Protein Synonyms/Alias
PPIase AEC=5.2.1.8 Cyclophilin A; Cyclosporin A-binding protein; Rotamase A; SP18; 
Organism
Mus musculus (Mouse) 
NCBI Taxonomy ID
10090 
Chromosome Location
chr:11;6315446-6319820;1
View in Ensembl genome browser  
Function in Stage
Uncertain 
Function in Cell Type
Uncertain 
Probability (GAS) of Function in Spermatogenesis
0.006188763 
The probability was calculated by GAS algorithm, ranging from 0 to 1. The closer it is to 1, the more possibly it functions in spermatogenesis.
Description
Temporarily unavailable 
Abstract of related literatures

2. This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development. PMID: [16141072] 

3. The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline. PMID: [15489334] 

4. We have isolated an 18-kDa peptide (designated sp18, for 18-kDa secreted protein) from the conditioned medium of lipopolysaccharide-stimulated RAW 264.7 murine macrophages. Purified sp18 had in vivo inflammatory activity and in vitro chemotactic activity for human peripheral blood polymorphonuclear leukocytes and monocytes. Surprisingly, N-terminal sequencing and tryptic mapping studies revealed that sp18 and cyclophilin, an intracellular protein that binds the immunosuppressive drug cyclosporin A, are highly homologous. The in vitro chemotactic activity of sp18 on monocytes was blocked by cyclosporin A but not by cyclosporin H, a structural analog of cyclosporin A that does not bind cyclophilin. Like purified porcine cyclophilin, mouse sp18 exhibited peptidyl-prolyl cis-trans isomerase activity. Medium conditioned by lipopolysaccharide-stimulated resident peritoneal exudate macrophages isolated from C57BL/6 mice contained substantially higher levels of sp18/cyclophilin than medium conditioned by nonstimulated macrophages. The observation that sp18/cyclophilin exhibits proinflammatory activity and is secreted by macrophages in response to endotoxin suggests that this protein may function as a cytokine, and invites the hypothesis that the immunosuppressive action of cyclosporin A results in part from interaction with an extracellular form of cyclophilin released as a mediator of immune and inflammatory functions. PMID: [1565646] 

5. The association of cyclosporin A (CsA) immunosuppression with inhibition of transcription factor-dependent lymphokine gene activation formed the basis of our decision to investigate nuclear-associated Cyp isoforms. Immunofluorescence microscopy of mouse macrophages cell line with a monoclonal antibody mAb7F1 raised against CypA shows a co-localisation of CypA in the nucleus and in the cytosol. Nuclear CypA binds to DNA in a zinc ion-dependent manner, in contrast to recombinant CypB. Peptidyl-prolyl cisltrans isomerase (PPIase) activity of nuclear CypA is inhibited by zinc ions. The zinc inhibited CypA does not bind cyclosporin A (CsA). We suggest that nuclear Cyp in complex with zinc ions recognizes DNA sequences and is involved in transcription modulating processes. PMID: [7664883] 

6. Cyclophilins (CyPs) are a family of proteins found in organisms ranging from prokaryotes to humans. These molecules exhibit peptidyl-prolyl isomerase activity in vitro, suggesting that they influence the conformation of proteins in cells. CyPs also bind with varying affinities to the immunosuppressive drug cyclosporin A (CsA), a compound used clinically to prevent allograft rejection. The founding member of the family, cyclophilin A (CyPA), is an abundant, ubiquitously expressed protein of unknown function that binds with nanomolar affinity to CsA. Here, we describe the isolation and characterization of mouse Ppia (mPpia), the gene encoding CyPA. Ppia was isolated using a PCR screen that distinguishes the expressed gene from multiple pseudogenes present in the mouse genome. mPpia consists of 5 exons and 4 introns spanning roughly 4.5 kb and maps to chromosome 11 near the centromere. Sequence analysis of a 369-bp fragment from the proximal promoter region of mPpia revealed the presence of a TATA box and sites recognized by several transcriptional regulators, including Sp1, AP-2, GATA factors, c-Myb, and NF-IL-6. This region is sufficient to drive high-level reporter gene expression in transfected cells. Both copies of Ppia were disrupted in murine embryonic stem (ES) cells via gene targeting. Ppia(-/-) ES cells grow normally and differentiate into hematopoeitic precursor cells in vitro, indicating that CyPA is not essential for mammalian cell viability. PMID: [10964515] 

7. While phosphorylation and O-GlcNAc (cytoplasmic and nuclear glycosylation) are linked to normal and pathological changes in cell states, these post-translational modifications have been difficult to analyze in proteomic studies. We describe advances in beta-elimination / Michael addition-based approaches which allow for mass spectrometry-based identification and comparative quantification of O-phosphate or O-GlcNAc-modified peptides, as well as cysteine-containing peptides for expression analysis. The method (BEMAD) involves differential isotopic labeling through Michael addition with normal dithiothreitol (DTT) (d0) or deuterated DTT (d6), and enrichment of these peptides by thiol chromatography. BEMAD was comparable to isotope-coded affinity tags (ICAT; a commercially available differential isotopic quantification technique) in protein expression analysis, but also provided the identity and relative amounts of both O-phosphorylation and O-GlcNAc modification sites. Specificity of O-phosphate vs. O-GlcNAc mapping is achieved through coupling enzymatic dephosphorylation or O-GlcNAc hydrolysis with differential isotopic labeling. Blocking of cysteine labeling by prior oxidation of a cytosolic lysate from mouse brain allowed specific targeting of serine / threonine post-translational modifications as demonstrated through identification of 21 phosphorylation sites (5 previously reported) in a single mass spectrometry analysis. These results demonstate BEMAD is suitable for large-scale quantitative analysis of both protein expression and serine / threonine post-translational modifications. PMID: [15648052] 

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Function
PPIases accelerate the folding of proteins. It catalyzesthe cis-trans isomerization of proline imidic peptide bonds inoligopeptides. 
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Subcellular Location
Cytoplasm. Secreted (By similarity).Note=Secretion occurs in response to oxidative stress in vascularsmooth muscle through a vesicular secretory pathway that involvesactin remodeling and myosin II activation, and mediates ERK1/2activation (By similarity). 
Tissue Specificity
 
Gene Ontology
GO IDGO termEvidence
GO:0005829 C:cytosol ISS:UniProtKB.
GO:0005576 C:extracellular region IEA:UniProtKB-SubCell.
GO:0005634 C:nucleus ISS:UniProtKB.
GO:0042277 F:peptide binding IEA:UniProtKB-KW.
GO:0003755 F:peptidyl-prolyl cis-trans isomerase activity ISS:UniProtKB.
GO:0006457 P:protein folding IEA:UniProtKB-KW.
GO:0045069 P:regulation of viral genome replication ISS:UniProtKB.
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Interpro
IPR002130;    Cyclophilin-like_PPIase_dom.
IPR024936;    Cyclophilin-type_PPIase.
IPR020892;    Cyclophilin-type_PPIase_CS.
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Pfam
PF00160;    Pro_isomerase;    1.
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SMART
PROSITE
PS00170;    CSA_PPIASE_1;    1.
PS50072;    CSA_PPIASE_2;    1.
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PRINTS
PR00153;    CSAPPISMRASE.;   
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Created Date
18-Oct-2012 
Record Type
GAS predicted 
Sequence Annotation
INIT_MET      1      1       Removed.
CHAIN         2    164       Peptidyl-prolyl cis-trans isomerase A.
                             /FTId=PRO_0000064117.
DOMAIN        7    163       PPIase cyclophilin-type.
MOD_RES       2      2       N-acetylvaline (By similarity).
MOD_RES      21     21       Phosphoserine.
MOD_RES      28     28       N6-acetyllysine (By similarity).
MOD_RES      44     44       N6-acetyllysine (By similarity).
MOD_RES      49     49       N6-acetyllysine (By similarity).
MOD_RES      82     82       N6-acetyllysine (By similarity).
MOD_RES     125    125       N6-acetyllysine (By similarity).
MOD_RES     131    131       N6-acetyllysine (By similarity).
MOD_RES     157    157       Phosphothreonine (By similarity).
CARBOHYD    108    108       N-linked (GlcNAc...) (Potential).
CROSSLNK     28     28       Glycyl lysine isopeptide (Lys-Gly)
                             (interchain with G-Cter in ubiquitin) (By
                             similarity).
CONFLICT     13     14       DD -> NE (in Ref. 2; BAB27089).
CONFLICT     18     20       GRV -> TXP (in Ref. 4; AA sequence).
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Nucleotide Sequence
Length: 736 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 164 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
UniProt
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String database  
View Microarray data
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