Recombinant Human DFNA5/GSDME protein

Specifications

Form

Liquid

General info

Function

Gasdermin-E. Precursor of a pore-forming protein that converts non-inflammatory apoptosis to pyroptosis (PubMed : 27281216, PubMed : 28459430, PubMed : 33852854, PubMed : 35594856, PubMed : 36607699). This form constitutes the precursor of the pore-forming protein : upon cleavage, the released N-terminal moiety (Gasdermin-E, N-terminal) binds to membranes and forms pores, triggering pyroptosis (PubMed : 28459430).. Gasdermin-E, N-terminal. Pore-forming protein produced by cleavage by CASP3 or granzyme B (GZMB), which converts non-inflammatory apoptosis to pyroptosis or promotes granzyme-mediated pyroptosis, respectively (PubMed : 27281216, PubMed : 28459430, PubMed : 32188940, PubMed : 33852854, PubMed : 35594856). After cleavage, moves to the plasma membrane, homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, allowing the release of mature interleukins (IL1B and IL16) and triggering pyroptosis (PubMed : 28459430, PubMed : 32188940, PubMed : 33852854, PubMed : 35594856). Binds to inner leaflet lipids, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate (PubMed : 28459430). Cleavage by CASP3 switches CASP3-mediated apoptosis induced by TNF or danger signals, such as chemotherapy drugs, to pyroptosis (PubMed : 27281216, PubMed : 28459430, PubMed : 32188940). Mediates secondary necrosis downstream of the mitochondrial apoptotic pathway and CASP3 activation as well as in response to viral agents (PubMed : 28045099). Exhibits bactericidal activity (PubMed : 27281216). Cleavage by GZMB promotes tumor suppressor activity by triggering robust anti-tumor immunity (PubMed : 21522185, PubMed : 32188940). Suppresses tumors by mediating granzyme-mediated pyroptosis in target cells of natural killer (NK) cells : cleavage by granzyme B (GZMB), delivered to target cells from NK-cells, triggers pyroptosis of tumor cells and tumor suppression (PubMed : 31953257, PubMed : 32188940). May play a role in the p53/TP53-regulated cellular response to DNA damage (PubMed : 16897187).. Gasdermin-E, N-terminal. (Microbial infection) Pore-forming protein, which promotes maternal placental pyroptosis in response to Zika virus infection, contributing to adverse fetal outcomes.

Sequence similarities

Belongs to the gasdermin family.

Post-translational modifications

Cleavage at Asp-270 by CASP3 (mature and uncleaved precursor forms) or granzyme B (GZMB) relieves autoinhibition and is sufficient to initiate pyroptosis.. Gasdermin-E. Succination by the Krebs cycle intermediate fumarate, which leads to S-(2-succinyl)cysteine residues, inhibits processing by caspases, and ability to initiate pyroptosis (PubMed:32820063). Succination modification is catalyzed by a non-enzymatic reaction caused by an accumulation of fumarate (PubMed:32820063).. Gasdermin-E. Ubiquitinated at Lys-120 and Lys-189 via 'Lys-48'-linked polyubiquitin chains, leading to proteasomal degradation. Deubiquitinated by USP48, leading to increased stability.. Palmitoylated.