PLCE1
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.
The Ras-GEF domain has a GEF activity towards HRAS and RAP1A. Mediates activation of the mitogen-activated protein kinase pathway.
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. In podocytes, is involved in the regulation of lamellipodia formation. Acts downstream of AVIL to allow ARP2/3 complex assembly (PubMed:29058690).
Involvement in disease
Nephrotic syndrome 3
NPHS3
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure. Most patients with NPHS3 show diffuse mesangial sclerosis on renal biopsy, which is a pathologic entity 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.
None
The disease is caused by variants affecting the gene represented in this entry.
Tissue Specificity
Widely expressed. Expressed in podocytes (PubMed:29058690).
Isoform 1
Broadly expressed and only absent in peripheral blood leukocytes.
Isoform 2
Specifically expressed in placenta, lung and spleen.
Cellular localization
- Cytoplasm
- Cytosol
- Cell membrane
- Golgi apparatus membrane
- Cell projection
- Lamellipodium
- 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 names
KIAA1516, PLCE, PPLC, PLCE1, Pancreas-enriched phospholipase C, Phosphoinositide phospholipase C-epsilon-1, Phospholipase C-epsilon-1, PLC-epsilon-1