PLCE1

Phospholipase C epsilon 1 (PLCE1) is an enzyme that in humans is encoded by the PLCE1 gene.^[5][6] This gene encodes a phospholipase enzyme (PLCE1) that catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate to generate two second messengers: inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG). Mutations in this gene cause early-onset nephrotic syndrome and have been associated with respiratory chain deficiency with diffuse mesangial sclerosis.^[7][8]

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PLCE1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2BYE, 2BYF, 2C5L
Identifiers
Aliases	PLCE1, NPHS3, PLCE, PPLC, phospholipase C epsilon 1
External IDs	OMIM: 608414; MGI: 1921305; HomoloGene: 9478; GeneCards: PLCE1; OMA:PLCE1 - orthologs
Gene location (Human) Chr. Chromosome 10 (human)[1] Band 10q23.33 Start 93,993,931 bp[1] End 94,332,823 bp[1]
Gene location (Mouse) Chr. Chromosome 19 (mouse)[2] Band 19|19 C3 Start 38,469,557 bp[2] End 38,773,474 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in glomerulus metanephric glomerulus ventricular zone retinal pigment epithelium mucosa of colon ganglionic eminence mucosa of sigmoid colon tibial arteries islet of Langerhans parotid gland Top expressed in retinal pigment epithelium vestibular membrane of cochlear duct transitional epithelium of urinary bladder primary oocyte sciatic nerve trigeminal ganglion stria vascularis Epithelium of choroid plexus vestibular sensory epithelium zygote More reference expression data BioGPS More reference expression data
Gene ontology Molecular function guanyl-nucleotide exchange factor activity signal transducer activity protein binding phosphoric diester hydrolase activity enzyme binding phospholipase C activity hydrolase activity phosphatidylinositol phospholipase C activity metal ion binding Cellular component cytosol Golgi apparatus membrane Golgi membrane plasma membrane cytoplasm Biological process intracellular signal transduction epidermal growth factor receptor signaling pathway regulation of G protein-coupled receptor signaling pathway regulation of smooth muscle contraction lipid metabolism positive regulation of cytosolic calcium ion concentration small GTPase mediated signal transduction regulation of Ras protein signal transduction glomerulus development inositol phosphate metabolic process diacylglycerol biosynthetic process lipid catabolic process phospholipase C-activating G protein-coupled receptor signaling pathway heart development cytoskeleton organization regulation of cell growth regulation of protein kinase activity cell population proliferation inositol phosphate-mediated signaling calcium-mediated signaling signal transduction Ras protein signal transduction inositol trisphosphate biosynthetic process phosphatidylinositol-mediated signaling release of sequestered calcium ion into cytosol Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 51196 74055 Ensembl ENSG00000138193 ENSMUSG00000024998 UniProt Q9P212 Q8K4S1 RefSeq (mRNA) NM_001165979 NM_001288989 NM_016341 NM_019588 RefSeq (protein) NP_001159451 NP_001275918 NP_057425 NP_062534 Location (UCSC) Chr 10: 93.99 – 94.33 Mb Chr 19: 38.47 – 38.77 Mb PubMed search [3] [4]
Wikidata
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PLCE1 is located on the q arm of chromosome 10 in position 23.33 and has 39 exons.^[7] PLCE1, the protein encoded by this gene, is located on the Golgi apparatus, the cell membrane, and in the cytosol. It contains 3 turns, 15 beta strands, and 6 alpha helixes. PLCE1 contains a 260 amino acid Ras-GEF domain at p. 531-790, a 149 amino acid PI-PLC X-box domain at p. 1392-1540, a 117 amino acid PI-PLC Y-box domain at p. 1730 – 1846, a 101 amino acid C2 domain at p. 1856 – 1956, a 103 amino acid Ras-associating 1 domain at p. 2012 – 2114, and a 104 amino acid Ras-associating 2 domain at p. 2135 – 2238. There is a region of 79 amino acids from p. 1686 – 1764 that is required for PLCE1 to be activated by RHOA, RHOB, GNA12, GNA13 and G-beta gamma. PLCE1 also has a Ca2+ cofactor.^[6][9][10] Alternative splicing results in multiple transcript variants encoding distinct isoforms.^[7]

PLCE1 belongs to the phospholipase family that catalyzes the hydrolysis of polyphosphoinositides such as phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) to generate the second messengers Ins(1,4,5)P3 and diacylglycerol. These products initiate a cascade of intracellular responses that result in cell growth and differentiation and gene expression.[supplied by OMIM]^[7]

Mutations in this gene cause early-onset nephrotic syndrome. This disease is characterized by proteinuria, edema, and diffuse mesangial sclerosis or focal and segmental glomerulosclerosis.^[7] Signs and symptoms include kidney biopsies demonstrating non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation as well as genetic tests revealing a pathogenic S1484L mutation. Diffuse mesangial proliferation is characterized by mesangial matrix expansion with no mesangial hypercellularity, hypertrophy of the podocytes, vacuolized podocytes, thickened basement membranes, and diminished patency of the capillary lumen.^[11][9][10] This disease has also been associated with mitochondrial cytopathy stemming from respiratory chain deficiency primarily affecting complex IV.^[8]

Additionally, Phospholipase C epsilon modulates beta-adrenergic receptor-dependent cardiac contraction and it has been found that this protein is over expressed during heart failure. Research has suggested that PLCE1 may thus inhibit cardiac hypertrophy.^[12][9][10]

PLCE1 gene polymorphism increases susceptibility to oesophageal, gastric, colon, and squamous cell carcinoma of the head and neck area. It is shown that PLCE1 is highly expressed in osteosarcoma and regulates its proliferation and invasion. PLCE1 also affects the survival of patients with osteosarcoma. Therefore, it is suggested as a potential diagnostic biomarker and molecular therapeutic target for osteosarcoma.^[13]

PLCE1 has been shown to have 12 binary protein-protein interactions including 8 co-complex interactions. PLCE1 appears to interact with RyR2, HRAS, NRAS, and LIMS1.^[14]