Phosphoinositide phospholipase C family (IPR001192)

Short name: PI-PLC_fam

Overlapping homologous superfamilies

Family relationships


This entry represents phosphoinositol-specific phospholipase C (PLC) from eukaryotes. Proteins in this entry include PLC-beta, gamma, delta, epsilon, eta, zeta and inactive phospholipase C-like protein 2 (PLC-L2).

Phosphoinositol-specific phospholipase C (PLC; (EC: plays an important role in signal transduction processes [PMID: 9048554], mediating the cellular actions of a variety of hormones, neurotransmitters and growth factors. Upon agonist-dependent activation, PLC catalyses the hydrolysis of membrane phosphatidylinositol 4,5-bisphosphate (PIP2), generating the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 binds specific intracellular receptors to trigger Ca2+ mobilisation, while DAG mediates activation of a family of protein kinase C isozymes. This catalytic process is tightly regulated by reversible phosphorylation and binding of regulatory proteins [PMID: 9062102, PMID: 1319994, PMID: 1335185]. Based on molecular size, immunoreactivity and amino acid sequence, several subtypes have been classified. Overall, sequence identity between sub-types is low, yet all isoforms share a split TIM barrel containing two conserved domains, designated X and Y [PMID: 23140367].

The core eukaryotic PLC enzyme is composed of a pleckstrin homology (PH) domain, four tandem EF hand domains, a split TIM barrel, and a C2 domain [PMID: 23140367]. The presence of an insert in the TIM barrel led to the naming of the N- and C-terminal halves of the TIM barrel as 'X-box' and 'Y-box'. The order of these two regions is always the same (NH2-X-Y-COOH), but the spacing is variable. In most isoforms, the distance between these two regions is only 50-100 residues, for example, in PLC-beta subtypes, X and Y domains are separated by a stretch of 70-120 amino acids rich in Ser, Thr and acidic residues (their C terminus is rich in basic residues). However, in PLC-gammas, there is an insert of more than 400 residues containing a PH domain, two SH2 domains, and one SH3 domain. The two conserved X and Y domains have been shown to be important for the catalytic activity. C-terminal to the Y-box, there is a C2 domain, possibly involved in Ca-dependent membrane attachment.

GO terms

Biological Process

GO:0035556 intracellular signal transduction

Molecular Function

No terms assigned in this category.

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.