Q9EST1 · GSDMA_MOUSE
- ProteinGasdermin-A
- GeneGsdma
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids446 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Gasdermin-A
This form constitutes the precursor of the pore-forming protein and acts as a sensor of bacterial infection: upon infection, specifically cleaved by bacterial effector protein SpeB in epithelial cells, releasing the N-terminal moiety (Gasdermin-A, N-terminal) that binds to membranes and forms pores, triggering pyroptosis.
Gasdermin-A, N-terminal
Pore-forming protein that causes membrane permeabilization and pyroptosis (PubMed:35110732).
Released upon cleavage by bacterial effector protein SpeB, and binds to membrane inner leaflet lipids (PubMed:35110732).
Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis (By similarity).
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 (By similarity).
Released upon cleavage by bacterial effector protein SpeB, and binds to membrane inner leaflet lipids (PubMed:35110732).
Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis (By similarity).
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 (By similarity).
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 bacterial effector protein SpeB (PubMed:35110732).
The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-A, N-terminal) following cleavage by bacterial effector protein SpeB (PubMed:35110732).
Features
Showing features for binding site, site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | perinuclear region of cytoplasm | |
Cellular Component | plasma membrane | |
Molecular Function | phosphatidylinositol-4,5-bisphosphate binding | |
Molecular Function | phosphatidylinositol-4-phosphate binding | |
Molecular Function | phosphatidylserine binding | |
Biological Process | defense response to bacterium | |
Biological Process | programmed cell death | |
Biological Process | pyroptotic inflammatory response |
Keywords
- Biological process
Names & Taxonomy
Protein names
- Recommended nameGasdermin-A
- Alternative names
- Cleaved into 2 chains
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9EST1
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Gasdermin-A
Gasdermin-A, N-terminal
Cell membrane ; Multi-pass membrane protein
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 78-95 | Beta stranded | ||||
Sequence: NFSFKNMLDARVEGDVDV | ||||||
Transmembrane | 99-120 | Beta stranded | ||||
Sequence: VKVKGTAGLSRSSTLEVQTLSV | ||||||
Transmembrane | 164-180 | Beta stranded | ||||
Sequence: VTLERAGKAEGCFSLPF | ||||||
Transmembrane | 184-198 | Beta stranded | ||||
Sequence: LGLQGSVNHKEAVTI |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Mice are highly susceptible to subcutaneous group A Streptococcus (GAS) infection in an animal model (PubMed:35110732).
Mice lacking Gsdma, Gsdma2 and Gsdma3 are highly susceptible to subcutaneous group A Streptococcus (GAS) infection in an animal model (PubMed:35545676).
Mice lacking Gsdma, Gsdma2 and Gsdma3 are highly susceptible to subcutaneous group A Streptococcus (GAS) infection in an animal model (PubMed:35545676).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 247-248 | Abolished cleavage by bacterial effector protein SpeB, preventing pyroptosis. | ||||
Sequence: QA → NE |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 62 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000451666 | 1-247 | Gasdermin-A, N-terminal | |||
Sequence: MTMFENVTRALARQLNPRGDLTPLDSLIDFKRFHPFCLVLRKRKSTLFWGARYVHTDYTLLDVLEPGSSPSDPTDSGNFSFKNMLDARVEGDVDVPKTVKVKGTAGLSRSSTLEVQTLSVAPTALENLHKERKLSADHPFLKEMRERGENLYVVMEVVETLQEVTLERAGKAEGCFSLPFFAPLGLQGSVNHKEAVTIPKGCVLAYRVRQLMVNGKDEWGIPHICNDSMQTFPPGEKPGEGKFILIQ | ||||||
Chain | PRO_0000148174 | 1-446 | Gasdermin-A | |||
Sequence: MTMFENVTRALARQLNPRGDLTPLDSLIDFKRFHPFCLVLRKRKSTLFWGARYVHTDYTLLDVLEPGSSPSDPTDSGNFSFKNMLDARVEGDVDVPKTVKVKGTAGLSRSSTLEVQTLSVAPTALENLHKERKLSADHPFLKEMRERGENLYVVMEVVETLQEVTLERAGKAEGCFSLPFFAPLGLQGSVNHKEAVTIPKGCVLAYRVRQLMVNGKDEWGIPHICNDSMQTFPPGEKPGEGKFILIQASDVGEMHEDFKTLKEEVQRETQEVEKLSPVGRSSLLTSLSHLLGKKKELQDLEQTLEGALDKGHEVTLEALPKDVLLSKDAMDAILYFLGALTVLSEAQQKLLVKSLEKKILPVQLKLVESTMEKNFLQDKEGVFPLQPDLLSSLGEEELILTEALVGLSGLEVQRSGPQYTWDPDTLPHLCALYAGLSLLQLLSKNS | ||||||
Chain | PRO_0000451667 | 248-446 | Gasdermin-A, C-terminal | |||
Sequence: ASDVGEMHEDFKTLKEEVQRETQEVEKLSPVGRSSLLTSLSHLLGKKKELQDLEQTLEGALDKGHEVTLEALPKDVLLSKDAMDAILYFLGALTVLSEAQQKLLVKSLEKKILPVQLKLVESTMEKNFLQDKEGVFPLQPDLLSSLGEEELILTEALVGLSGLEVQRSGPQYTWDPDTLPHLCALYAGLSLLQLLSKNS |
Post-translational modification
Cleavage by bacterial SpeB relieves autoinhibition by releasing the N-terminal moiety (Gasdermin-A, N-terminal) that initiates pyroptosis.
Palmitoylated.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed predominantly in the gastrointestinal (GI) tract and in the skin at a lower level. In the GI tract, the expression is highly restricted to the esophagus and forestomach.
Developmental stage
Expression is first detected at 12.5 dpc.
Gene expression databases
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-252 | Triggers pyroptosis | ||||
Sequence: MTMFENVTRALARQLNPRGDLTPLDSLIDFKRFHPFCLVLRKRKSTLFWGARYVHTDYTLLDVLEPGSSPSDPTDSGNFSFKNMLDARVEGDVDVPKTVKVKGTAGLSRSSTLEVQTLSVAPTALENLHKERKLSADHPFLKEMRERGENLYVVMEVVETLQEVTLERAGKAEGCFSLPFFAPLGLQGSVNHKEAVTIPKGCVLAYRVRQLMVNGKDEWGIPHICNDSMQTFPPGEKPGEGKFILIQASDVG |
Domain
Intramolecular interactions between N- and C-terminal domains are important for autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the N-terminal domain.
Sequence similarities
Belongs to the gasdermin family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length446
- Mass (Da)49,593
- Last updated2001-03-01 v1
- Checksum603673EC007CB305
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB033595 EMBL· GenBank· DDBJ | BAB13697.1 EMBL· GenBank· DDBJ | mRNA | ||
AK028645 EMBL· GenBank· DDBJ | BAC26045.1 EMBL· GenBank· DDBJ | mRNA | ||
AK028698 EMBL· GenBank· DDBJ | BAC26073.1 EMBL· GenBank· DDBJ | mRNA | ||
AK029062 EMBL· GenBank· DDBJ | BAC26272.1 EMBL· GenBank· DDBJ | mRNA | ||
AL590963 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |