GSDMB
entrez
55876
canonical
uniprot
Q8TAX9
canonical
ensembl
ENSG00000073605
resolver
ensp
ENSP00000312584
resolver
ensp
ENSP00000353465
resolver
ensp
ENSP00000377729
resolver
ensp
ENSP00000377733
resolver
ensp
ENSP00000415049
resolver
ensp
ENSP00000430157
resolver
ensp
ENSP00000571493
resolver
ensp
ENSP00000571496
resolver
ensp
ENSP00000629689
resolver
genesymbol
GSDMB
resolver
genesymbol_syn
GSDML
resolver
hgnc
HGNC:23690
resolver
uniprot
B4DKK7
resolver
uniprot
Q7Z377
resolver
uniprot
Q8WY76
resolver
uniprot
Q9NX71
resolver
uniprot
Q9P163
resolver
uniprot_entry
GSDMB_HUMAN
resolver
uniprot_sec
B4DKK7
resolver
uniprot_sec
Q7Z377
resolver
uniprot_sec
Q8WY76
resolver
uniprot_sec
Q9NX71
resolver
uniprot_sec
Q9P163
resolver
activity_regulation
ACTIVITY REGULATION: [Gasdermin-B]: The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal (PubMed:36991122, PubMed:36991125). The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-B, N-terminal) following cleavage by granzyme A (GZMA) (PubMed:32299851). {ECO:0000269|PubMed:32299851, ECO:0000269|PubMed:36991122, ECO:0000269|PubMed:36991125}.
uniprot
proteins
amino_acid_sequence
MFSVFEEITRIVVKEMDAGGDMIAVRSLVDADRFRCFHLVGEKRTFFGCRHYTTGLTLMDILDTDGDKWLDELDSGLQGQKAEFQILDNVDSTGELIVRLPKEITISGSFQGFHHQKIKISENRISQQYLATLENRKLKRELPFSFRSINTRENLYLVTETLETVKEETLKSDRQYKFWSQISQGHLSYKHKGQREVTIPPNRVLSYRVKQLVFPNKETMNIHFRGKTKSFPEEKDGASSCLGKSLGSEDSRNMKEKLEDMESVLKDLTEEKRKDVLNSLAKCLGKEDIRQDLEQRVSEVLISGELHMEDPDKPLLSSLFNAAGVLVEARAKAILDFLDALLELSEEQQFVAEALEKGTLPLLKDQVKSVMEQNWDELASSPPDMDYDPEARILCALYVVVSILLELAEGPTSVSS
uniprot
proteins
function
FUNCTION: [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). {ECO:0000269|PubMed:32299851, ECO:0000269|PubMed:35021065}.; FUNCTION: [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). {ECO:0000269|PubMed:27281216, ECO:0000269|PubMed:32299851, ECO:0000269|PubMed:34022140, ECO:0000269|PubMed:36157507, ECO:0000269|PubMed:36599845, ECO:0000269|PubMed:36991122, ECO:0000269|PubMed:36991125}.; FUNCTION: [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). {ECO:0000269|PubMed:28154144, ECO:0000269|PubMed:36157507, ECO:0000269|PubMed:36899106, ECO:0000269|PubMed:36991122, ECO:0000269|PubMed:36991125}.; FUNCTION: [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). {ECO:0000269|PubMed:36899106, ECO:0000269|PubMed:36991122, ECO:0000269|PubMed:36991125}.; FUNCTION: [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). {ECO:0000269|PubMed:34022140}.; FUNCTION: [Isoform 2]: Not able to trigger pyroptosis. {ECO:0000269|PubMed:36899106, ECO:0000269|PubMed:36991122, ECO:0000269|PubMed:36991125}.; FUNCTION: [Isoform 3]: Not able to trigger pyroptosis. {ECO:0000269|PubMed:36899106, ECO:0000269|PubMed:36991122, ECO:0000269|PubMed:36991125}.
uniprot
proteins
mass_dalton
47348
uniprot
proteins
mutagenesis
MUTAGEN 10..14; /note="RIVVK->AIVVA: Slightly decreased formation of pore."; /evidence="ECO:0000269|PubMed:36599845"; MUTAGEN 15; /note="E->K: Decreased ability to trigger pyroptosis. Abolished ubiquitination by S.flexneri IpaH7.8."; /evidence="ECO:0000269|PubMed:36599845, ECO:0000269|PubMed:36991125"; MUTAGEN 17..21; /note="DAGGD->AAGGA: Abolished ubiquitination by S.flexneri IpaH7.8."; /evidence="ECO:0000269|PubMed:36991125"; MUTAGEN 17; /note="D->A: Decreased interaction with S.flexneri IpaH7.8. Does not affect ability to trigger pyroptosis."; /evidence="ECO:0000269|PubMed:36599845"; MUTAGEN 21; /note="D->A: Decreased interaction with S.flexneri IpaH7.8."; /evidence="ECO:0000269|PubMed:36599845"; MUTAGEN 26; /note="R->A: Reduced ability to trigger pyroptosis; when associated with A-51."; /evidence="ECO:0000269|PubMed:36599845"; MUTAGEN 43; /note="K->A,E: Decreased ability to trigger pyroptosis."; /evidence="ECO:0000269|PubMed:36599845"; MUTAGEN 44; /note="R->A,E: Decreased ability to trigger pyroptosis."; /evidence="ECO:0000269|PubMed:36599845"; MUTAGEN 50; /note="R->A,E: Decreased ability to trigger pyroptosis."; /evidence="ECO:0000269|PubMed:36599845"; MUTAGEN 51; /note="H->A: Reduced ability to trigger pyroptosis; when associated with A-26."; /evidence="ECO:0000269|PubMed:36599845"; MUTAGEN 51; /note="H->N: Abolished ability to mediate pyroptosis."; /evidence="ECO:0000269|PubMed:36899106"; MUTAGEN 96; /note="L->D: Decreased interaction with S.flexneri IpaH7.8."; /evidence="ECO:0000269|PubMed:36599845"; MUTAGEN 97; /note="I->D: Decreased interaction with S.flexneri IpaH7.8. Does not affect ability to trigger pyroptosis."; /evidence="ECO:0000269|PubMed:36599845"; MUTAGEN 124; /note="R->A: Decreased interaction with S.flexneri IpaH7.8. Abolished ubiquitination by S.flexneri IpaH7.8; when associated with A-208."; /evidence="ECO:0000269|PubMed:36599845, ECO:0000269|PubMed:36991125"; MUTAGEN 171; /note="K->A,E: Decreased ability to trigger pyroptosis."; /evidence="ECO:0000269|PubMed:36599845"; MUTAGEN 174; /note="R->A,E: Decreased ability to trigger pyroptosis."; /evidence="ECO:0000269|PubMed:36599845"; MUTAGEN 208; /note="R->A: Decreased interaction with S.flexneri IpaH7.8. Abolished ubiquitination by S.flexneri IpaH7.8; when associated with A-124."; /evidence="ECO:0000269|PubMed:36599845, ECO:0000269|PubMed:36991125"; MUTAGEN 212; /note="L->P: Abolished ability to mediate pyroptosis."; /evidence="ECO:0000269|PubMed:36899106"; MUTAGEN 225; /note="R->A: Reduced ability to trigger pyroptosis."; /evidence="ECO:0000269|PubMed:36899106"; MUTAGEN 227; /note="K->A: Reduced ability to trigger pyroptosis."; /evidence="ECO:0000269|PubMed:36899106"; MUTAGEN 229; /note="K->A: Does not prevent cleavage by granzyme A (GZMA). Reduced ability to trigger pyroptosis."; /evidence="ECO:0000269|PubMed:32299851, ECO:0000269|PubMed:36899106"; MUTAGEN 233; /note="E->A: Reduced ability to trigger pyroptosis."; /evidence="ECO:0000269|PubMed:36899106"; MUTAGEN 244; /note="K->A: Abolished cleavage by granzyme A (GZMA), preventing release of the N-terminal moiety (Gasdermin-B, N-terminal) and ability to induce pyroptosis in target cells of cytotoxic T-cells and natural killer (NK) cells."; /evidence="ECO:0000269|PubMed:32299851"; MUTAGEN 254; /note="M->D: Does not relieve autoinhibition. Relieves autoinhibition; when associated with D-399."; /evidence="ECO:0000269|PubMed:36991125"; MUTAGEN 339..343; /note="DALLE->AALLA: Does not relieve autoinhibition."; /evidence="ECO:0000269|PubMed:36991125"; MUTAGEN 339..343; /note="DALLE->ADLLA: Relieves autoinhibition."; /evidence="ECO:0000269|PubMed:36991125"; MUTAGEN 339; /note="D->A: Does not relieve autoinhibition."; /evidence="ECO:0000269|PubMed:36991125"; MUTAGEN 340; /note="A->D: Does not relieve autoinhibition."; /evidence="ECO:0000269|PubMed:36991125"; MUTAGEN 370; /note="V->D: Does not relieve autoinhibition."; /evidence="ECO:0000269|PubMed:36991125"; MUTAGEN 394..399; /note="LCALYV->DCALYD: Relieves autoinhibition."; /evidence="ECO:0000269|PubMed:36991125"; MUTAGEN 394; /note="L->D: Does not relieve autoinhibition."; /evidence="ECO:0000269|PubMed:36991125"; MUTAGEN 399; /note="V->D: Does not relieve autoinhibition. Relieves autoinhibition; when associated with 339-A--A-343."; /evidence="ECO:0000269|PubMed:36991125"; MUTAGEN Q8TAX9-1:166; /note="K->R: Does not abolish ubiquitination by S.flexneri IpaH7.8; when associated with R-308."; /evidence="ECO:0000269|PubMed:34022140"; MUTAGEN Q8TAX9-1:308; /note="K->R: Does not abolish ubiquitination by S.flexneri IpaH7.8; when associated with R-166."; /evidence="ECO:0000269|PubMed:34022140
uniprot
proteins
post_translational_modification
PTM: Cleavage by granzyme A (GZMA) relieves autoinhibition by releasing the N-terminal moiety (Gasdermin-B, N-terminal) that initiates pyroptosis (PubMed:32299851, PubMed:34022140, PubMed:36157507, PubMed:36899106, PubMed:36991125). Not cleaved by other granzymes (PubMed:32299851). Major cleavage site takes places after Lys-244; a minor cleavage site takes place after Lys-229 (PubMed:32299851). Cleavage by neutrophil elastase ELANE, inhibits its ability to trigger pyroptosis (PubMed:36899106). {ECO:0000269|PubMed:32299851, ECO:0000269|PubMed:34022140, ECO:0000269|PubMed:36157507, ECO:0000269|PubMed:36899106, ECO:0000269|PubMed:36991125}.; PTM: Palmitoylated. {ECO:0000269|PubMed:38599239}.; PTM: (Microbial infection) Ubiquitinated by S.flexneri IpaH7.8, leading to its degradation by the proteasome, thereby preventing its ability to form pores in bacterial-derived membranes. {ECO:0000269|PubMed:34022140, ECO:0000269|PubMed:36599845, ECO:0000269|PubMed:36991122, ECO:0000269|PubMed:36991125}.
uniprot
proteins
protein_family
Gasdermin family
uniprot
proteins
pubmed
11483580
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15498874
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
16625320
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17350798
uniprot
proteins
pubmed
17391312
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18038310
uniprot
proteins
pubmed
19051310
uniprot
proteins
pubmed
27281216
uniprot
proteins
pubmed
28154144
uniprot
proteins
pubmed
32299851
uniprot
proteins
pubmed
34022140
uniprot
proteins
pubmed
35021065
uniprot
proteins
pubmed
36157507
uniprot
proteins
pubmed
36599845
uniprot
proteins
pubmed
36899106
uniprot
proteins
pubmed
36991122
uniprot
proteins
pubmed
36991125
uniprot
proteins
pubmed
38599239
uniprot
proteins
sequence_length
416
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Gasdermin-B]: Cytoplasm {ECO:0000269|PubMed:18038310}. Note=Vesicular localization in the apical region of gastric chief cells and colonic surface mucous cells, and the basal region of neuroendocrine cells. {ECO:0000269|PubMed:18038310}.; SUBCELLULAR LOCATION: [Gasdermin-B, N-terminal]: Cell membrane {ECO:0000269|PubMed:36157507, ECO:0000269|PubMed:36899106}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q5Y4Y6}.
uniprot
proteins
transmembrane_region
TRANSMEM 83..101; /note="Beta stranded"; /evidence="ECO:0000269|PubMed:36991122, ECO:0000269|PubMed:36991125, ECO:0007744|PDB:8EFP, ECO:0007744|PDB:8ET1, ECO:0007744|PDB:8ET2, ECO:0007744|PDB:8GTJ, ECO:0007744|PDB:8GTN"; TRANSMEM 102..125; /note="Beta stranded"; /evidence="ECO:0000269|PubMed:36991122, ECO:0000269|PubMed:36991125, ECO:0007744|PDB:8EFP, ECO:0007744|PDB:8ET1, ECO:0007744|PDB:8ET2, ECO:0007744|PDB:8GTJ, ECO:0007744|PDB:8GTN"; TRANSMEM 167..183; /note="Beta stranded"; /evidence="ECO:0000269|PubMed:36991122, ECO:0000269|PubMed:36991125, ECO:0007744|PDB:8EFP, ECO:0007744|PDB:8ET1, ECO:0007744|PDB:8ET2, ECO:0007744|PDB:8GTJ, ECO:0007744|PDB:8GTN"; TRANSMEM 184..198; /note="Beta stranded"; /evidence="ECO:0000269|PubMed:36991122, ECO:0000269|PubMed:36991125, ECO:0007744|PDB:8EFP, ECO:0007744|PDB:8ET1, ECO:0007744|PDB:8ET2, ECO:0007744|PDB:8GTJ, ECO:0007744|PDB:8GTN
uniprot
proteins