PEPTIDYL-PROLYL ISOMERASE G; PPIG

Alternative titles; symbols

• CYCLOPHILIN G

HGNC Approved Gene Symbol: PPIG

Cytogenetic location: 2q31.1 Genomic coordinates (GRCh38): 2:169,584,342-169,641,405 (from NCBI)

▼ TEXT
The peptidyl-prolyl cis/trans isomerase protein family (PPIases) includes the cyclophilin, FK506-binding protein (e.g., FKBP1A; 186945), and parvulin (e.g., PIN4, 300252) subfamilies. The cyclophilins have been implicated in the folding, transport, and assembly of proteins.

▼ Cloning and Expression
Using a yeast 2-hybrid screen to identify proteins that interact with Clk (CLK1; 601951), Nestel et al. (1996) isolated partial clones of a mouse gene, which they called CARS-Cyp. By screening a thymus cDNA library with the mouse clone, they assembled a full-length cDNA of the human homolog, PPIG. Using a yeast 2-hybrid screen to identify proteins that interact with the phosphorylated C-terminal domain (CTD) of the largest subunit of RNA polymerase II (POLR2A; 180660), Bourquin et al. (1997) independently cloned PPIG, which they called SRcyp/CASP10, from a B-lymphocyte cDNA library. PPIG is predicted to encode a 754-amino acid protein containing 2 Nopp140 (nucleolar phosphoprotein of 140 kD)-related domains and a large C-terminal serine/arginine (SR)-rich domain found predominantly in pre-mRNA splicing factors. The N-terminal region of PPIG contains a peptidyl-prolyl cis-trans isomerase domain characteristic of immunophilins/cyclophilins. PPIG shares 37.8% sequence identity with NKTR (161565), a myeloid-specific nuclear protein. By Northern blot analysis, Nestel et al. (1996) detected PPIG expression at similar levels in lung, liver, kidney, small intestine, testis, and brain. They detected major 4-kb and minor 10-kb PPIG transcripts in human B-cell RNA. Although PPIG was widely expressed, it appeared to be absent from NK cells. By Northern blot analysis, Bourquin et al. (1997) detected a broadly expressed single 3.0-kb PPIG transcript.

Using deletion mutant analysis, Bourquin et al. (1997) determined that the SR domain of PPIG is required for interaction with the CTD of POLR2A in yeast 2-hybrid assays. Using GST fusion proteins, they confirmed that PPIG directly interacts with the CTD. Using immunostaining, they demonstrated that PPIG is distributed in nuclear speckles, a nuclear compartment rich in splicing factors, and colocalizes with the splicing factor SC35 (SFRS2; 600813). They concluded that PPIG may be a component of splicing factor complexes that bind the CTD, thereby linking RNA processing to transcription.

▼ Mapping
The International Radiation Hybrid Mapping Consortium mapped the PPIG gene to chromosome 2 (SHGC-33882).