Catalytic activity:1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H(2)O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol.,cofactor:Calcium.,Disease:Defects in PLCE1 are the cause of nephrotic syndrome type 3 (NPHS3) [MIM:610725]; also called early-onset nephrotic syndrome type 3. Nephrotic syndrome, a malfunction of the kidney glomerular filter, leads to proteinuria, hypoalbuminemia, edema. End-stage kidney disease is observed in steroid-resistant nephrotic syndrome.,Domain:The Ras-associating domain 1 is degenerated and may not bind HRAS. The Ras-associating domain 2 mediates interaction with GTP-bound HRAS, RAP1A, RAP2A and RAP2B and recruitment of HRAS to the cell membrane.,Domain:The Ras-GEF domain has a GEF activity towards HRAS and RAP1A. Mediates activation of the mitogen-activated protein kinase pathway.,enzyme regulation:Activated by the heterotrimeric G-protein subunits GNA12, GNA13 and GNB1-GNG2. Activated by HRAS, RAP1A, RHOA, RHOB, RHOC, RRAS and RRAS2. Activated by the G(s)-coupled GPCRs ADRB2, PTGER1 and CHRM3 through cyclic-AMP formation and RAP2B activation. Inhibited by G(i)-coupled GPCRs.,Function:The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. PLCE1 is a bifunctional enzyme which also regulates small GTPases of the Ras superfamily through its Ras guanine-exchange factor (RasGEF) activity. As an effector of heterotrimeric and small G-protein, it may play a role in cell survival, cell growth, actin organization and T-cell activation.,induction:Overexpressed during heart failure.,similarity:Contains 1 C2 domain.,similarity:Contains 1 PI-PLC X-box domain.,similarity:Contains 1 PI-PLC Y-box domain.,similarity:Contains 1 Ras-GEF domain.,similarity:Contains 2 Ras-associating domains.,subcellular location:Recruited to plasma membrane by activated HRAS and RAP2. Recruited to perinuclear membrane by activated RAP1A. Isoform 1 and isoform 2 associates with Golgi membranes.,subunit:Interacts with RHOA (By similarity). Interacts with IQGAP1, HRAS, RAP1A, RAP2A, RAP2B and RRAS.,tissue specificity:Widely expressed. Isoform 1 is broadly expressed and only absent in peripheral blood leukocytes. Isoform 2 is specifically expressed in placenta, lung and spleen.,
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