Protein: PLCE1_HUMAN
1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase epsilon-1
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.
ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; Synonyms=PLCepsilon1a; IsoId=Q9P212-1; Sequence=Displayed; Name=2; Synonyms=PLCepsilon1b; IsoId=Q9P212-2; Sequence=VSP_021335, VSP_021336; Note=Ref.2 (AAG28341) sequence is in conflict in position: 69:L->P;
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;
GENE SYNONYMS: KIAA1516 PLCE PPLC.
COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.
Organism:
- Homo sapiens
Gene Symbol:
- PLCE1
Synonyms:
- PLC-epsilon-1
- Phospholipase C-epsilon-1
- Phosphoinositide phospholipase C-epsilon-1
- Pancreas-enriched phospholipase C
- 3.1.4.11
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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. more...