Alternative titles; symbolsPHOSPHATIDIC ACID PHOSPHATASE TYPE 2C; PPAP2C; PAP2CHGNC Approved Gene Symbol: PLPP2Cytogenetic location: 19p13.3 Genomic coordina...
Alternative titles; symbols
HGNC Approved Gene Symbol: PLPP2
Cytogenetic location: 19p13.3 Genomic coordinates (GRCh38): 19:281,042-291,412 (from NCBI)
Phosphatidic acid phosphatase catalyzes the dephosphorylation of phosphatidic acid (PA) to form diacylglycerol. It has a role in metabolic pathways controlling the synthesis of glycerophospholipids and triacylglycerols, and in receptor-activated signal transduction mediated by phospholipase D (GPLD1; 602515).
▼ Cloning and Expression
Using mouse PAP as query, Roberts et al. (1998) identified PPAP2C in an EST database and obtained the full-length cDNA by PCR of HeLa cell cDNA. The deduced 288-amino acid protein has a calculated molecular mass of about 32.6 kD. PPAP2C shares approximately 54% and 43% sequence identity with PPAP2A (607124) and PPAP2B (607125), respectively. Roberts et al. (1998) noted that the C-terminal 40 amino acids of PPAP2A, PPAP2B, and PPAP2C show the highest divergence and that all 3 proteins contain 6 membrane-spanning regions of 17 to 25 amino acids and a single consensus N-glycosylation site. Western blot analysis of transfected HEK293 cells expressing PPAP2C detected bands at 33 and 34 kD.
Using PPAP2A and PPAP2B sequences as query, Hooks et al. (1998) identified, expanded, and analyzed a PPAP2C EST clone. They found that PPAP2C shares 58% and 52% sequence identity with PPAP2A and PPAP2B, respectively. Northern blot analysis detected a 1.4-kb transcript in brain and pancreas and a 1.3-kb transcript in placenta. They also noted that EST cDNAs for PPAP2C had been derived from pregnant uterus, fetal liver and spleen, infant brain, ovary tumor, placenta, and pancreas.
Gross (2017) mapped the PLPP2 gene to chromosome 19p13.3 based on an alignment of the PLPP2 sequence (GenBank AF035959) with the genomic sequence (GRCh38).
Zhang et al. (2000) mapped the mouse Plpp2 gene to chromosome 10 by interspecific backcross analysis.
▼ Gene Function
By biochemical analysis of recombinant PPAP2C expressed by sf9 insect cells, Roberts et al. (1998) found that PPAP2C activity associated with sf9 cell membranes. PPAP2C activity against phosphatidic acid was independent of Mg(2+), insensitive to N-ethylmaleimide treatment, inhibited by sphingosine and Zn(2+), and modestly inhibited by propranolol. In contrast to their findings with PPAP2A, they could not measure PPAP2C activity at the surface of intact sf9 cells. They also found significant phosphatase activity against ceramide 1-phosphate.
Using membranes harvested from transfected embryonic kidney cells, Hooks et al. (1998) compared the enzymatic activities of PPAP2A, PPAP2B, and PPAP2C. All 3 enzymes hydrolyzed PA, lyso-PA, and N-oleoyl ethanolamine phosphatidic acid (NOEPA). All showed a high affinity for NOEPA and similar affinities for PA, but differed in affinity for lyso-PA.
▼ Animal Model
Zhang et al. (2000) developed a Ppap2c-null mouse by gene targeting. Homozygous mutant mice were viable, fertile, and exhibited no obvious phenotypic defects, suggesting that Ppap2c is not essential for embryonic development or fertility in mice.