The reference OMIM entry for this protein is 600230

Phospholipase c, beta-3; plcb3

DESCRIPTION

PLCB3 plays an important role in initiating receptor-mediated signal transduction. Activation of PLC takes place in many cells as a response to stimulation by hormones, growth factors, neurotransmitters, and other ligands (Lagercrantz et al., 1995).

CLONING

Weber et al. (1994) mapped the gene for multiple endocrine neoplasia type I (MEN1; 131100) to a region of less than 900 kb by deletion mapping in 27 primary parathyroid tumors. One of the cDNA clones isolated from this region showed expression of a 4.4-kb message in multiple tissues, including those affected in MEN1, while in 5 endocrine tumors from MEN1 patients no transcript was detected. Sequence characterization showed that this gene encodes PLCB3, a key enzyme in signal transduction. Lagercrantz et al. (1995) determined that the full-length PLCB3 cDNA has an open reading frame of 1,234 amino acids. Northern blot analysis revealed a 4.4-kb transcript in all tissues tested. Mazuruk et al. (1995) cloned the PLCB3 gene. It was highly expressed in several human tissues, including retina, brain, and kidney. PLCB3 mRNA was detected at a much lower level in liver.

GENE STRUCTURE

Lagercrantz et al. (1995) estimated that the size of the complete PLCB3 transcription unit is on the order of 15 kb. The gene contains 31 exons, with all splice donor and acceptor sites conforming to the GT/AG rule. No exon exceeds 571 bp in length, and the shortest exon spans only 36 bp. More than half of the introns are shorter than 200 bp, with the shortest being only 79 bp. Mazuruk et al. (1995) determined that the PLCB3 gene spans approximately 17 kb and contains 31 exons.

BIOCHEMICAL FEATURES

- Crystal Structure Waldo et al. (2010) described how heterotrimeric guanine nucleotide-binding proteins (G proteins) activate PLC-betas and in turn are deactivated by the downstream effectors. The 2.7-angstrom structure of PLC-beta-3 bound to activated G-alpha-q (600998) revealed a conserved module found within PLC-betas and other effectors optimized for rapid engagement of activated G proteins. The active site of PLC-beta-3 in the complex is occluded by an intramolecular plug that is likely removed upon G protein-dependent anchoring and orientation of the lipase at membrane surfaces. A second domain of PLC-beta-3 subsequently accelerates guanosine triphosphate hydrolysis by G-alpha-q, causing the complex to dissociate and terminate signal propagation. Mutations within this domain dramatically delay signal termination in vitro and in vivo. Waldo et al. (2010) concluded that their work suggested a dynamic catch-and-release mechanism used to sharpen spatiotemporal signals mediated by diverse sensory inputs.

MAPPING

In the course of the molecular characterization of a human extragonadal germ cell tumor (EGCT)-associated chromosomal translocation, Sinke and Geurts van Kessel (1995) identified YACs and cosmids from the 11q13 region. The end clone of one of these YACs appeared to contain a stretch of DNA homologous to part of the PLCB3 gene. They cloned the entire cDNA and confirmed the location of the gene to 11q13. No aberrantly hybridizing fragments were observed in EGCT DNAs. This result, together with mRNA studies, excluded the PLCB3 gene as a candidate in the development of EGCTs. Courseaux et al. (1996) used a combination of methods to refine maps of the approximately 5-Mb region of 11q13 that includes MEN1. They proposed the following gene order: ce ... More on the omim web site

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Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 15, 2016: Protein entry updated
Automatic update: OMIM entry 600230 was added.