[Gasdermin-B]: Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death (PubMed:32299851). This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-B, N-terminal) binds to membranes and forms pores, triggering pyroptosis (PubMed:32299851). Also acts as a regulator of epithelial cell repair independently of programmed cell death: translocates to the plasma membrane and promotes epithelial maintenance and repair by regulating PTK2/FAK-mediated phosphorylation of PDGFA (PubMed:35021065). ; [Gasdermin-B, N-terminal]: Pore-forming protein produced by cleavage by granzyme A (GZMA), which causes membrane permeabilization and pyroptosis in target cells of cytotoxic T and natural killer (NK) cells (PubMed:27281216, PubMed:32299851). Key downstream mediator of granzyme-mediated cell death: (1) granzyme A (GZMA), delivered to target cells from cytotoxic T- and NK-cells, (2) specifically cleaves Gasdermin-B to generate this form (PubMed:32299851). After cleavage, moves to the plasma membrane, homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis (PubMed:32299851, PubMed:36599845, PubMed:36991122, PubMed:36991125). The different isoforms recognize and bind different phospholipids on membranes, promoting cell death of different target cells (PubMed:34022140, PubMed:36157507, PubMed:36991122, PubMed:36991125). ; [Isoform 4]: Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death and mediates pyroptosis (PubMed:28154144, PubMed:36157507, PubMed:36899106, PubMed:36991122, PubMed:36991125). Following cleavage and activation by granzyme A (GZMA), the N-terminal part binds to membrane inner leaflet lipids, homooligomerizes within the human plasma membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis (PubMed:28154144, PubMed:36157507, PubMed:36899106, PubMed:36991122, PubMed:36991125). Recognizes and binds membrane inner leaflet lipids of human cells, such as phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate, and more weakly to phosphatidic acid (PubMed:28154144, PubMed:36157507). Also binds sufatide, a component of the apical membrane of epithelial cells (PubMed:28154144). ; [Isoform 6]: Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death and mediates pyroptosis of human cells (PubMed:36899106, PubMed:36991122, PubMed:36991125). Following cleavage and activation by granzyme A (GZMA), the N-terminal part binds to membrane inner leaflet lipids, homooligomerizes within the human plasma membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis (PubMed:36899106, PubMed:36991122, PubMed:36991125). ; [Isoform 1]: Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death and specifically mediates cell death of Gram-negative bacteria in response to infection (PubMed:34022140). Following cleavage and activation by granzyme A (GZMA), the N-terminal part recognizes and binds phospholipids found on Gram-negative bacterial membranes, such as lipid A and cariolipin, homooligomerizes within the bacterial membranes and forms pores, triggering pyroptosis followed by cell death (PubMed:34022140). In contrast to isoform 4, does not bind to membrane inner leaflet lipids of host human cell, such as phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate (PubMed:34022140). ; [Isoform 2]: Not able to trigger pyroptosis. ; [Isoform 3]: Not able to trigger pyroptosis.
