Alternative titles; symbols
HGNC Approved Gene Symbol: PLCL1
Cytogenetic location: 2q33.1 Genomic coordinates (GRCh38): 2:197,804,593-198,149,863 (from NCBI)
Kohno et al. (1995) noted that the presence of a tumor suppressor gene in the 2q33 region had been suggested by a high incidence of allelic loss on 2q in lung carcinoma and the finding of a homozygous deletion at 2q33 in a small cell lung carcinoma cell line. They constructed a cosmid contig covering the homozygous deleted region, estimated at 220 kb, and identified a novel gene within this region. Since the gene encodes a protein with similarity to several members of a family of phospholipase C, they designated the gene PLCL for 'phospholipase C deleted in lung carcinoma.' The PLCL gene was expressed in a variety of fetal and adult organs, including the lung.
By 5-prime RACE and nested PCR of human brain total RNA, Murakami et al. (2006) identified 3 splice variants of PRIP1. The variant lacking exons 2 and 3 encodes the longest deduced protein with 1,097 amino acids. This isoform contains an N-terminal PH domain, followed by an EF hand motif, putative catalytic X and Y domains, a C2 domain, and a C-terminal D domain. Isoforms encoded by other splice variants contain 1,016 and 997 amino acids and differ from each other and the longest PRIP1 isoform predominantly at their N-terminal ends. RT-PCR detected abundant PRIP1 expression in brain, with weaker expression in kidney. Little to no expression was present in heart, skeletal muscle, liver, spleen, and lung. Western blot analysis detected PRIP1 protein in whole brain and in frontal lobe, hippocampus, thalamus, and cerebral cortex.
Murakami et al. (2006) determined that the PLCL1 gene contains 8 exons. The promoter region is GC rich and lacks a TATA box. Gel shift and reporter gene assays identified 2 functional MAZ (600999)-binding sites in the PLCL1 promoter.
By sequence analysis, Kohno et al. (1995) mapped the PLCL1 gene to chromosome 2q33.
Kohno et al. (1995) found that all of the coding exons of the PLCL gene were homozygously deleted in a small cell lung carcinoma cell line with a homozygous deletion at 2q33, while a 5-prime noncoding exon was retained. Expression of PLCL was greatly reduced in 7 of 13 (53.8%) small cell lung carcinoma and 13 of 15 (86.7%) nonsmall cell lung carcinoma cell lines. Since its homology to phospholipase C genes suggested the involvement of the PLCL gene in an inositol phospholipid-based intracellular signaling cascade, Kohno et al. (1995) considered it possible that aberrant expression of the PLCL gene contributes to the genesis and progression of human lung carcinoma.
Tsutsumi et al. (2011) stated that they had previously found that female mice lacking both Prip1 and Prip2 (PLCL2; 614276) (Prip -/- mice) were subfertile, with high plasma gonadotropin and low gonadal steroid levels. Tsutsumi et al. (2011) found that bone mineral density and trabecular bone volume were higher in female Prip -/- mice, but much less so in male Prip -/- mice. The difference in bone density between Prip -/- and wildtype females became negligible by 12 months of age. Ovariectomy resulted in no change in bone measures in Prip -/- mice, suggesting that the effect of Prip deletion was independent of hormonal imbalance. Histologic analysis revealed abnormal bone formation in Prip -/- mice, with enlarged osteoclasts containing more than 15 nuclei and loose, weakened absorbing surfaces between osteoclasts and bone. Prip -/- bone marrow cells cultured to differentiate into osteoclasts were less active and showed elevated Bmp (see 112262)-dependent Smad (see 601595) phosphorylation compared with wildtype cells. Tsutsumi et al. (2011) concluded that PRIP1 and PRIP2 are involved in negative regulation of bone formation.
Kohno, T., Otsuka, T., Takano, H., Yamamoto, T., Hamaguchi, M., Terada, M., Yokota, J. Identification of a novel phospholipase C family gene at chromosome 2q33 that is homozygously deleted in human small cell lung carcinoma. Hum. Molec. Genet. 4: 667-674, 1995. [PubMed: 7633416] [Full Text: https://doi.org/10.1093/hmg/4.4.667]
Murakami, A., Matsuda, M., Nakasima, A., Hirata, M. Characterization of the human PRIP-1 gene structure and transcriptional regulation. Gene 382: 129-139, 2006. [PubMed: 16952428] [Full Text: https://doi.org/10.1016/j.gene.2006.07.005]
Tsutsumi, K., Matsuda, M., Kotani, M., Mizokami, A., Murakami, A., Takahashi, I., Terada, Y., Kanematsu, T., Fukami, K., Takenawa, T., Jimi, E., Hirata, M. Involvement of PRIP, phospholipase C-related, but catalytically inactive protein, in bone formation. J. Biol. Chem. 286: 31032-31042, 2011. [PubMed: 21757756] [Full Text: https://doi.org/10.1074/jbc.M111.235903]