ID:PLCE1_HUMAN DESCRIPTION: RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1; EC=3.1.4.11; AltName: Full=Pancreas-enriched phospholipase C; AltName: Full=Phosphoinositide phospholipase C-epsilon-1; AltName: Full=Phospholipase C-epsilon-1; Short=PLC-epsilon-1; 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. CATALYTIC ACTIVITY: 1-phosphatidyl-1D-myo-inositol 4,5- bisphosphate + H(2)O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol. COFACTOR: Calcium. 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. SUBUNIT: Interacts with RHOA (By similarity). Interacts with IQGAP1, HRAS, RAP1A, RAP2A, RAP2B and RRAS. SUBCELLULAR LOCATION: Cytoplasm, cytosol. Cell membrane. Golgi apparatus membrane. Note=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. 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. INDUCTION: Overexpressed during heart failure. 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. DISEASE: Defects in PLCE1 are the cause of nephrotic syndrome type 3 (NPHS3) [MIM:610725]; also known as 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. SIMILARITY: Contains 1 C2 domain. SIMILARITY: Contains 1 PI-PLC X-box domain. SIMILARITY: Contains 1 PI-PLC Y-box domain. SIMILARITY: Contains 2 Ras-associating domains. SIMILARITY: Contains 1 Ras-GEF domain. SEQUENCE CAUTION: Sequence=AAF22005.1; Type=Frameshift; Positions=1131; Sequence=AAG17145.2; Type=Frameshift; Positions=2296; Sequence=BAA96040.2; Type=Erroneous initiation; Sequence=BAB14090.1; Type=Erroneous initiation; Sequence=CAH70739.1; Type=Erroneous gene model prediction; Sequence=CAH73288.1; Type=Erroneous gene model prediction; Sequence=CAH73757.1; Type=Erroneous gene model prediction; Sequence=CAI16674.1; Type=Erroneous gene model prediction;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9P212
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000187 activation of MAPK activity GO:0001558 regulation of cell growth GO:0006629 lipid metabolic process GO:0006651 diacylglycerol biosynthetic process GO:0006940 regulation of smooth muscle contraction GO:0007010 cytoskeleton organization GO:0007165 signal transduction GO:0007173 epidermal growth factor receptor signaling pathway GO:0007200 phospholipase C-activating G-protein coupled receptor signaling pathway GO:0007204 positive regulation of cytosolic calcium ion concentration GO:0007264 small GTPase mediated signal transduction GO:0007265 Ras protein signal transduction GO:0007507 heart development GO:0008277 regulation of G-protein coupled receptor protein signaling pathway GO:0008283 cell proliferation GO:0016042 lipid catabolic process GO:0019722 calcium-mediated signaling GO:0032835 glomerulus development GO:0035556 intracellular signal transduction GO:0043647 inositol phosphate metabolic process GO:0045859 regulation of protein kinase activity GO:0046578 regulation of Ras protein signal transduction GO:0048016 inositol phosphate-mediated signaling
BioCarta from NCI Cancer Genome Anatomy Project h_plcePathway - Phospholipase C-epsilon pathway
Reactome (by CSHL, EBI, and GO)
Protein Q9P212 (Reactome details) participates in the following event(s):
R-HSA-1855221 PI(4,5)P2 is hydrolysed to I(1,4,5)P3 and DAG by tethered PLC[1] at the plasma membrane R-HSA-1855204 Synthesis of IP3 and IP4 in the cytosol R-HSA-1483249 Inositol phosphate metabolism R-HSA-1430728 Metabolism
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
