Human Gene PLCE1 (uc001kjk.3) Description and Page Index
Description: Homo sapiens phospholipase C, epsilon 1 (PLCE1), transcript variant 1, mRNA. RefSeq Summary (NM_016341): This gene encodes a phospholipase enzyme that catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate to generate two second messengers: inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG). These second messengers subsequently regulate various processes affecting cell growth, differentiation, and gene expression. This enzyme is regulated by small monomeric GTPases of the Ras and Rho families and by heterotrimeric G proteins. In addition to its phospholipase C catalytic activity, this enzyme has an N-terminal domain with guanine nucleotide exchange (GEF) activity. Mutations in this gene cause early-onset nephrotic syndrome; characterized by proteinuria, edema, and diffuse mesangial sclerosis or focal and segmental glomerulosclerosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Sep 2009]. Transcript (Including UTRs) Position: hg19 chr10:95,753,746-96,088,148 Size: 334,403 Total Exon Count: 33 Strand: + Coding Region Position: hg19 chr10:95,790,804-96,084,837 Size: 294,034 Coding Exon Count: 31
ID:PLCE1_HUMAN DESCRIPTION: RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1; EC=126.96.36.199; 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;
Genetic Association Studies of Complex Diseases and Disorders
Blood Pressure Louise V Wain et al. Nature genetics 2011, Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure., Nature genetics.
Blood Pressure Georg B Ehret et al. Nature 2011, Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk., Nature.
Death, Sudden, Cardiac Bradley E Aouizerat et al. BMC cardiovascular disorders 2012, GWAS for discovery and replication of genetic loci associated with sudden cardiac arrest in patients with coronary artery disease., BMC cardiovascular disorders.
We demonstrate 11 gene associations for sudden cardiac arrest due to ventricular tachycardia/ventricular fibrillation in patients with coronary artery disease. Validation studies in independent cohorts and functional studies are required to confirm these associations.
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.