Q9EST1 · GSDMA_MOUSE

  • Protein
    Gasdermin-A
  • Gene
    Gsdma
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

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).

Features

Showing features for binding site, site.

TypeIDPosition(s)Description
Binding site9-13a cardiolipin (UniProtKB | ChEBI)
Site247-248(Microbial infection) Cleavage; by bacterial effector protein SpeB

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentperinuclear region of cytoplasm
Cellular Componentplasma membrane
Molecular Functionphosphatidylinositol-4,5-bisphosphate binding
Molecular Functionphosphatidylinositol-4-phosphate binding
Molecular Functionphosphatidylserine binding
Biological Processdefense response to bacterium
Biological Processprogrammed cell death
Biological Processpyroptotic inflammatory response

Keywords

Names & Taxonomy

Protein names

Gene names

    • Name
      Gsdma
    • Synonyms
      Gsdm
      , Gsdm1, Gsdma1

Organism names

  • Taxonomic identifier
  • Strains
    • C57BL/10J
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q9EST1
  • Secondary accessions
    • A3KFN3

Proteomes

Organism-specific databases

Subcellular Location

Gasdermin-A

Cytoplasm, cytosol

Gasdermin-A, N-terminal

Cell membrane
; Multi-pass membrane protein

Features

Showing features for transmembrane.

TypeIDPosition(s)Description
Transmembrane78-95Beta stranded
Transmembrane99-120Beta stranded
Transmembrane164-180Beta stranded
Transmembrane184-198Beta stranded

Keywords

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).

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis247-248Abolished cleavage by bacterial effector protein SpeB, preventing pyroptosis.

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.

Go to variant viewer

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004516661-247Gasdermin-A, N-terminal
ChainPRO_00001481741-446Gasdermin-A
ChainPRO_0000451667248-446Gasdermin-A, C-terminal

Post-translational modification

Cleavage by bacterial SpeB relieves autoinhibition by releasing the N-terminal moiety (Gasdermin-A, N-terminal) that initiates pyroptosis.
Palmitoylated.

Keywords

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

Interaction

Subunit

Gasdermin-A, N-terminal

Homooligomer; homooligomeric ring-shaped pore complex containing 18-36 subunits when inserted in the membrane.

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for region.

TypeIDPosition(s)Description
Region1-252Triggers pyroptosis

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

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    446
  • Mass (Da)
    49,593
  • Last updated
    2001-03-01 v1
  • Checksum
    603673EC007CB305
MTMFENVTRALARQLNPRGDLTPLDSLIDFKRFHPFCLVLRKRKSTLFWGARYVHTDYTLLDVLEPGSSPSDPTDSGNFSFKNMLDARVEGDVDVPKTVKVKGTAGLSRSSTLEVQTLSVAPTALENLHKERKLSADHPFLKEMRERGENLYVVMEVVETLQEVTLERAGKAEGCFSLPFFAPLGLQGSVNHKEAVTIPKGCVLAYRVRQLMVNGKDEWGIPHICNDSMQTFPPGEKPGEGKFILIQASDVGEMHEDFKTLKEEVQRETQEVEKLSPVGRSSLLTSLSHLLGKKKELQDLEQTLEGALDKGHEVTLEALPKDVLLSKDAMDAILYFLGALTVLSEAQQKLLVKSLEKKILPVQLKLVESTMEKNFLQDKEGVFPLQPDLLSSLGEEELILTEALVGLSGLEVQRSGPQYTWDPDTLPHLCALYAGLSLLQLLSKNS

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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.

Genome annotation databases

Similar Proteins

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