ID:PLCE1_MOUSE DESCRIPTION: RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1; EC=3.1.4.11; 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 (By similarity). 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 (By similarity). SUBUNIT: Interacts with GTP-bound HRAS, RAP1A, RAP2A, RAP2B and RHOA (By similarity). Interacts with IQGAP1. SUBCELLULAR LOCATION: Cytoplasm, cytosol (By similarity). Cell membrane (By similarity). Golgi apparatus membrane (By similarity). Note=Recruited to plasma membrane by activated HRAS and RAP2. Recruited to perinuclear membrane by activated RAP1A. Associates with Golgi membranes (By similarity). TISSUE SPECIFICITY: Highly expressed in neurons and to a lower extent in skin, skeletal muscle and heart (at protein level). Expressed in the epidermis. DEVELOPMENTAL STAGE: Specifically expressed in cells committed to the neuronal lineage (at protein level). Weakly expressed at E7, expression strongly increases at later embryonic stages. Expressed abundantly in almost all neural tissues at E12.5 and also detected in tongue muscles, genital tubercle and hand plate. At E15.5 a strong expression in skeletal muscles is detected together with the strong expression in neural tissues. INDUCTION: Up-regulated during the differentiation of neural precursor cells into neurons and not glial cells. Up-regulated in heart upon induced hypertrophy. 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 (By similarity). DOMAIN: The Ras-GEF domain has a GEF activity towards HRAS and RAP1A. Mediates activation of the mitogen-activated protein kinase pathway (By similarity). DISRUPTION PHENOTYPE: Mice exhibit delayed onset and markedly reduced incidence of chemically induced skin squamous tumors. They also display cardiac malformations which mainly affects aortic and pulmonary valves and enhanced susceptibility to cardiac hypertrophy and fibrosis in response to chronic stress. 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=AAF40208.1; Type=Erroneous initiation;
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 Q8K4S1
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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:0006629 lipid metabolic process GO:0007165 signal transduction GO:0007186 G-protein coupled receptor signaling pathway GO:0007200 phospholipase C-activating G-protein coupled receptor signaling pathway GO:0007264 small GTPase mediated signal transduction GO:0007265 Ras protein signal transduction GO:0008277 regulation of G-protein coupled receptor protein signaling pathway GO:0016042 lipid catabolic process GO:0032835 glomerulus development GO:0035556 intracellular signal transduction GO:0045859 regulation of protein kinase activity GO:0046578 regulation of Ras protein signal transduction
KEGG - Kyoto Encyclopedia of Genes and Genomes mmu00562 - Inositol phosphate metabolism mmu01100 - Metabolic pathways mmu04020 - Calcium signaling pathway mmu04070 - Phosphatidylinositol signaling system
BioCarta from NCI Cancer Genome Anatomy Project m_plcePathway - Phospholipase C-epsilon pathway
Reactome (by CSHL, EBI, and GO)
Protein Q8K4S1 (Reactome details) participates in the following event(s):
R-MMU-1855221 PI(4,5)P2 is hydrolysed to I(1,4,5)P3 and DAG by tethered PLC[1] at the plasma membrane R-MMU-1855204 Synthesis of IP3 and IP4 in the cytosol R-MMU-1483249 Inositol phosphate metabolism R-MMU-1430728 Metabolism