GSDMA
entrez
284110
canonical
uniprot
Q96QA5
canonical
ensembl
ENSG00000167914
resolver
ensp
ENSP00000301659
resolver
ensp
ENSP00000490739
resolver
enst
ENST00000301659
resolver
enst
ENST00000635792
resolver
genesymbol
GSDMA
resolver
genesymbol_syn
GSDM
resolver
genesymbol_syn
GSDM1
resolver
hgnc
HGNC:13311
resolver
uniprot
Q32MC5
resolver
uniprot
Q86VE7
resolver
uniprot
Q8N1M6
resolver
uniprot_entry
GSDMA_HUMAN
resolver
uniprot_sec
Q32MC5
resolver
uniprot_sec
Q86VE7
resolver
uniprot_sec
Q8N1M6
resolver
activity_regulation
ACTIVITY REGULATION: [Gasdermin-A]: The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal (By similarity). The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-A, N-terminal) following cleavage by S.pyogenes effector protein SpeB (PubMed:35110732, PubMed:35545676). {ECO:0000250|UniProtKB:Q5Y4Y6, ECO:0000269|PubMed:35110732, ECO:0000269|PubMed:35545676}.
uniprot
proteins
amino_acid_sequence
MTMFENVTRALARQLNPRGDLTPLDSLIDFKRFHPFCLVLRKRKSTLFWGARYVRTDYTLLDVLEPGSSPSDPTDTGNFGFKNMLDTRVEGDVDVPKTVKVKGTAGLSQNSTLEVQTLSVAPKALETVQERKLAADHPFLKEMQDQGENLYVVMEVVETVQEVTLERAGKAEACFSLPFFAPLGLQGSINHKEAVTIPKGCVLAFRVRQLMVKGKDEWDIPHICNDNMQTFPPGEKSGEEKVILIQASDVGDVHEGFRTLKEEVQRETQQVEKLSRVGQSSLLSSLSKLLGKKKELQDLELALEGALDKGHEVTLEALPKDVLLSKEAVGAILYFVGALTELSEAQQKLLVKSMEKKILPVQLKLVESTMEQNFLLDKEGVFPLQPELLSSLGDEELTLTEALVGLSGLEVQRSGPQYMWDPDTLPRLCALYAGLSLLQQLTKAS
uniprot
proteins
function
FUNCTION: [Gasdermin-A]: This form constitutes the precursor of the pore-forming protein and acts as a sensor of infection: upon infection by S.pyogenes, specifically cleaved by S.pyogenes effector protein SpeB in epithelial cells, releasing the N-terminal moiety (Gasdermin-A, N-terminal) that binds to membranes and forms pores, triggering pyroptosis. {ECO:0000269|PubMed:27281216, ECO:0000269|PubMed:35110732, ECO:0000269|PubMed:35545676}.; FUNCTION: [Gasdermin-A, N-terminal]: Pore-forming protein that causes membrane permeabilization and pyroptosis (PubMed:17471240, PubMed:27281216, PubMed:35110732, PubMed:35545676). Released upon cleavage by S.pyogenes effector protein SpeB, and binds to membrane inner leaflet lipids (PubMed:27281216, PubMed:35110732, PubMed:35545676). Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis (PubMed:27281216, PubMed:35110732, PubMed:35545676). Pyroptosis triggers the elimination of the infected skin cell, depriving the pathogen of its protective niche, while inducing an inflammatory response (PubMed:35110732, PubMed:35545676). This ultimately prevents bacterial penetration of the epithelial barrier and a subsequent systemic dissemination of the pathogen (PubMed:35110732, PubMed:35545676). Binds to cardiolipin and other acidic phospholipids, such as phosphatidylserine, which mediate its targeting to the inner leaflet membrane (PubMed:27281216, PubMed:35110732). {ECO:0000269|PubMed:17471240, ECO:0000269|PubMed:27281216, ECO:0000269|PubMed:35110732, ECO:0000269|PubMed:35545676}.
uniprot
proteins
mass_dalton
49365
uniprot
proteins
mutagenesis
MUTAGEN 245; /note="I->N: Abolished cleavage by S.pyogenes effector protein SpeB, preventing pyroptosis."; /evidence="ECO:0000269|PubMed:35110732"; MUTAGEN 246; /note="Q->E: Abolished cleavage by S.pyogenes effector protein SpeB, preventing pyroptosis."; /evidence="ECO:0000269|PubMed:35110732"; MUTAGEN 260; /note="L->D: Spontaneous pyroptosis-inducing activity."; /evidence="ECO:0000269|PubMed:27281216"; MUTAGEN 334; /note="Y->D: Spontaneous pyroptosis-inducing activity."; /evidence="ECO:0000269|PubMed:27281216"; MUTAGEN 338; /note="A->D: Spontaneous pyroptosis-inducing activity."; /evidence="ECO:0000269|PubMed:27281216
uniprot
proteins
post_translational_modification
PTM: Cleavage by S.pyogenes SpeB relieves autoinhibition by releasing the N-terminal moiety (Gasdermin-A, N-terminal) that initiates pyroptosis. {ECO:0000269|PubMed:35110732, ECO:0000269|PubMed:35545676}.; PTM: Palmitoylated. {ECO:0000269|PubMed:38599239}.
uniprot
proteins
protein_family
Gasdermin family
uniprot
proteins
pubmed
10967128
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
17471240
uniprot
proteins
pubmed
19051310
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
27281216
uniprot
proteins
pubmed
35110732
uniprot
proteins
pubmed
35545676
uniprot
proteins
pubmed
38599239
uniprot
proteins
sequence_length
445
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Gasdermin-A]: Cytoplasm, perinuclear region {ECO:0000269|PubMed:17471240}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q5Y4Y6}.; SUBCELLULAR LOCATION: [Gasdermin-A, N-terminal]: Cell membrane {ECO:0000269|PubMed:35110732, ECO:0000269|PubMed:35545676}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q5Y4Y6}.
uniprot
proteins
transmembrane_region
TRANSMEM 78..95; /note="Beta stranded"; /evidence="ECO:0000250|UniProtKB:Q5Y4Y6"; TRANSMEM 99..120; /note="Beta stranded"; /evidence="ECO:0000250|UniProtKB:Q5Y4Y6"; TRANSMEM 163..179; /note="Beta stranded"; /evidence="ECO:0000250|UniProtKB:Q5Y4Y6"; TRANSMEM 183..197; /note="Beta stranded"; /evidence="ECO:0000250|UniProtKB:Q5Y4Y6
uniprot
proteins