Gasdermin-B (Gasdermin-like protein) [Cleaved into: Gasdermin-B, N-terminal (GSDMB-NT) (p30); Gasdermin-B, C-terminal (GSDMB-CT) (p16)]
1_MFSVF 6_ EEITR 11_ IVVKE 16_ MDAGG 21_ DMIAV 26_ RSLVD 31_ ADRFR 36_ CFHLV 41_ GEKRT 46_ FFGCR 51_ HYTTG 56_ LTLMD 61_ ILDTD 66_ GDKWL 71_ DELDS 76_ GLQGQ 81_ KAEFQ 86_ ILDNV 91_ DSTGE 96_ LIVRL 101_ PKEIT 106_ ISGSF 111_ QGFHH 116_ QKIKI 121_ SENRI 126_ SQQYL 131_ ATLEN 136_ RKLKR 141_ ELPFS 146_ FRSIN 151_ TRENL 156_ YLVTE 161_ TLETV 166_ KEETL 171_ KSDRQ 176_ YKFWS 181_ QISQG 186_ HLSYK 191_ HKGQR 196_ EVTIP 201_ PNRVL 206_ SYRVK 211_ QLVFP 216_ NKETM 221_ NIHFR 226_ GKTKS 231_ FPEEK 236_ DGASS 241_ CLGKS 246_ LGSED 251_ SRNMK 256_ EKLED 261_ MESVL 266_ KDLTE 271_ EKRKD 276_ VLNSL 281_ AKCLG 286_ KEDIR 291_ QDLEQ 296_ RVSEV 301_ LISGE 306_ LHMED 311_ PDKPL 316_ LSSLF 321_ NAAGV 326_ LVEAR 331_ AKAIL 336_ DFLDA 341_ LLELS 346_ EEQQF 351_ VAEAL 356_ EKGTL 361_ PLLKD 366_ QVKSV 371_ MEQNW 376_ DELAS 381_ SPPDM 386_ DYDPE 391_ ARILC 396_ ALYVV 401_ VSILL 406_ ELAEG 411_PTSVS
1: 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)
2: 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)
3: 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)
4: 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)
5: 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)
6: Not able to trigger pyroptosis
7: Not able to trigger pyroptosis