Alternative titles; symbols
HGNC Approved Gene Symbol: PNLIPRP2
Cytogenetic location: 10q25.3 Genomic coordinates (GRCh38) : 10:116,620,953-116,645,143 (from NCBI)
Pancreatic lipase (PNLIP; 246600) fulfills a key function in dietary fat absorption by hydrolyzing triglycerides into diglycerides and subsequently into monoglycerides and free fatty acids. By screening a human pancreas cDNA library with degenerate oligonucleotides designed from the amino acid sequences of human, canine, and porcine PNLIP, Giller et al. (1992) isolated cDNAs encoding 2 novel PNLIP-related proteins, PNLIPRP1 (604422) and PNLIPRP2, which they called PLRP1 and PLRP2, respectively. The predicted 469-amino acid PNLIPRP2 protein contains a 17-amino acid signal peptide and the conserved residues of the lipase catalytic triad and oxy-anion hole. Among known lipases, PNLIPRP2 was most related to a mouse T-cell lipase (Grusby et al., 1990), with 74% amino acid identity. PNLIPRP2 has 65% amino acid sequence identity with PNLIP, 63% identity with PNLIPRP1, and 20 to 30% identity with human gastric lipase (601980), lipoprotein lipase (238600), and hepatic lipase (151670). Western blot analysis of recombinant PNLIPRP2 expressed in mammalian cells detected a secreted, approximately 50-kD protein; the authors concluded that PNLIPRP2 was glycosylated. In a standard pancreatic lipase assay, recombinant PNLIPRP2 showed lipolytic activity that was marginally increased by the addition of colipase and was inhibited by the lipase inhibitor orlistat. Northern blot analysis of pancreas RNA detected major 2.3- and 1.8-kb PNLIPRP2 transcripts. The expression level of PNLIPRP2 in pancreas was approximately 24-fold lower and 6-fold lower than the expression levels of PNLIP and PNLIPRP1, respectively.
Zhang et al. (2006) reported a mechanism by which constant darkness regulates the gene expression of fat catabolic enzymes in mice. Genes for murine procolipase (Clps; 120105) and pancreatic lipase-related protein-2 (Plrp2) are activated in a circadian manner in peripheral organs during 12-hour dark:12-hour dark (DD) but not light-dark (LD) cycles. This mechanism is deregulated in circadian-deficient Per1/Per2 double mutant mice. Zhang et al. (2006) identified circadian-regulated 5-prime-AMP, which is elevated in the blood of DD mice, as a key mediator of this response. Synthetic 5-prime-AMP induced torpor (a hibernation-like state) and murine Clps expression in LD mice. Torpor induced by metabolic stress was associated with elevated 5-prime-AMP levels in DD mice. Levels of glucose and nonesterified fatty acid in the blood were reversed in DD and LD mice. Induction of murine Clps expression by 5-prime-AMP in LD mice was reciprocally linked to blood glucose levels. Zhang et al. (2006) concluded that their findings uncovered a circadian metabolic rhythm in mammals.
Giller, T., Buchwald, P., Blum-Kaelin, D., Hunziker, W. Two novel human pancreatic lipase related proteins, hPLRP1 and hPLRP2: differences in colipase dependence and in lipase activity. J. Biol. Chem. 267: 16509-16516, 1992. [PubMed: 1379598]
Grusby, M. J., Nabavi, N., Wong, H., Dick, R. F., Bluestone, J. A., Schotz, M. C., Glimcher, L. H. Cloning of an interleukin-4 inducible gene from cytotoxic T lymphocytes and its identification as a lipase. Cell 60: 451-459, 1990. [PubMed: 2302735] [Full Text: https://doi.org/10.1016/0092-8674(90)90596-7]
Zhang, J., Kaasik, K., Blackburn, M. R., Lee, C. C. Constant darkness is a circadian metabolic signal in mammals. Nature 439: 340-343, 2006. [PubMed: 16421573] [Full Text: https://doi.org/10.1038/nature04368]