Gsdma3
entrez
450219
canonical
uniprot
Q5Y4Y6
canonical
ensembl
ENSMUSG00000064224
resolver
ensp
ENSMUSP00000073022
resolver
enst
ENSMUST00000073295
resolver
genesymbol
Gsdma3
resolver
genesymbol_syn
Gsdm3
resolver
genesymbol_syn
GsdmA-3
resolver
uniprot
A0A679AUV5
resolver
uniprot
A2A4X5
resolver
uniprot_entry
A0A679AUV5_MOUSE
resolver
uniprot_entry
GSDA3_MOUSE
resolver
uniprot_sec
A2A4X5
resolver
activity_regulation
ACTIVITY REGULATION: [Gasdermin-A3]: 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:25825937, PubMed:26100518, PubMed:26375003). The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-A3, N-terminal) (PubMed:26100518, PubMed:26375003). {ECO:0000269|PubMed:25825937, ECO:0000269|PubMed:26100518, ECO:0000269|PubMed:26375003}.
uniprot
proteins
amino_acid_sequence
MPVFEDVTRALVRELNPRGDLTPLDSLIDFKHFRPFCLVLRKRKSTLFWGARYVRTDYTLLDLLEPGSSPSDLTDSGNFSFKNMLDVQVQGLVEVPKTVKVKGTAGLSQSSTLEVQTLSVAPSALENLKKERKLSADHSFLNEMRYHEKNLYVVMEAVEAKQEVTVEQTGNANAIFSLPSLALLGLQGSLNNNKAVTIPKGCVLAYRVRLLRVFLFNLWDIPYICNDSMQTFPKIRRVPCSAFISPTQMISEEPEEEKLIGEMHEDFKTLKEEVQRETQEVEKLSPVGRSSLLTSLSHLLGKKKELQDLEQKLEGALDKGQKVTLEALPKDVLLSKDAMDAILYFLGALTELTEEQLKILVKSLEKKILPVQLKLVESTLEQNFLQDKEGVFPLQPDLLSSLGEEELTLTEALVGLSGLEVQRSGPQYAWDPDTRHNLCALYAGLSLLHLLSRKSNALTYCALS
uniprot
proteins
function
FUNCTION: [Gasdermin-A3]: Precursor of a pore-forming protein involved in the transition from catagen to telogen at the end of hair follicle morphogenesis (PubMed:15475261, PubMed:26375003, PubMed:27281216). This form constitutes the precursor of the pore: upon cleavage, the released N-terminal moiety (Gasdermin-A3, N-terminal) binds to membranes and forms pores, triggering pyroptosis (PubMed:26375003, PubMed:27281216, PubMed:35545613). This form acts as a sensor of infection: activation is triggered by cleavage by some bacterial effector protein, which releases the N-terminal moiety (Gasdermin-A3, N-terminal) (By similarity). {ECO:0000250|UniProtKB:Q9EST1, ECO:0000269|PubMed:15475261, ECO:0000269|PubMed:26375003, ECO:0000269|PubMed:27281216, ECO:0000269|PubMed:35545613}.; FUNCTION: [Gasdermin-A3, N-terminal]: Pore-forming protein that causes membrane permeabilization and pyroptosis (PubMed:26375003, PubMed:27281216, PubMed:35545613). Released upon cleavage by some bacterial effector protein, and binds to membrane inner leaflet lipids (By similarity). Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, allowing the release of mature interleukin-1 (IL1B and IL18) and triggering pyroptosis (PubMed:27281216, PubMed:33883744, PubMed:35545613). Binds to membrane inner leaflet lipids, including bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate, as well as phosphatidylinositol (3,4,5)-bisphosphate, and more weakly to monophosphorylated phosphatidylinositols (PubMed:27281216). Also binds to bacterial and mitochondrial lipids, including cardiolipin, and exhibits bactericidal activity (PubMed:27281216, PubMed:29695864). Plays a role in the transition from catagen to telogen at the end of hair follicle morphogenesis, possibly by regulating hair follicle stem cell niche maintenance (PubMed:15475261, PubMed:15737203, PubMed:17572385, PubMed:22155111, PubMed:32302611). Also required for mammary gland development (PubMed:28168650). {ECO:0000250|UniProtKB:Q9EST1, ECO:0000269|PubMed:15475261, ECO:0000269|PubMed:15737203, ECO:0000269|PubMed:17572385, ECO:0000269|PubMed:22155111, ECO:0000269|PubMed:26375003, ECO:0000269|PubMed:27281216, ECO:0000269|PubMed:28168650, ECO:0000269|PubMed:29695864, ECO:0000269|PubMed:32302611, ECO:0000269|PubMed:33883744, ECO:0000269|PubMed:35545613}.
uniprot
proteins
mass_dalton
52020
uniprot
proteins
mutagenesis
MUTAGEN 9..18; /note="RALVRELNPR->AALVAELNPAA: Impaired pore-formation."; /evidence="ECO:0000269|PubMed:29695864"; MUTAGEN 14; /note="E->K: No spontaneous pyroptosis-inducing activity; when associated with D-184."; /evidence="ECO:0000269|PubMed:27281216"; MUTAGEN 41..44; /note="RKRK->EEEE: Abolished ability to form a pore."; /evidence="ECO:0000269|PubMed:33883744"; MUTAGEN 47..49; /note="LFW->EEE: Abolished ability to form a pore."; /evidence="ECO:0000269|PubMed:33883744"; MUTAGEN 62..75; /note="DLLEPGSSPSDLTD->ALLAPGSSPSALTA: In AP1; promotes ability to release of interleukin-1 (IL1B and IL18) precursors."; /evidence="ECO:0000269|PubMed:33883744"; MUTAGEN 86..94; /note="DVQVQGLVE->AVQVQGLVA: In AP2; promotes ability to release of interleukin-1 (IL1B and IL18) precursors."; /evidence="ECO:0000269|PubMed:33883744"; MUTAGEN 132; /note="R->A: Weak or no effect on ability to induce pyroptosis. Impaired ability to induce pyroptosis; when associated with A-145."; /evidence="ECO:0000269|PubMed:29695864"; MUTAGEN 145; /note="R->A: Impaired ability to induce pyroptosis; when associated with A-132."; /evidence="ECO:0000269|PubMed:29695864"; MUTAGEN 184; /note="L->D: Markedly decreased induction of pyroptosis and defects in liposome-binding. No spontaneous pyroptosis-inducing activity; when associated with K-14."; /evidence="ECO:0000269|PubMed:27281216"; MUTAGEN 186; /note="L->E: Impaired pore-formation."; /evidence="ECO:0000269|PubMed:29695864"; MUTAGEN 262..464; /note="Missing: In Dfl mutant; gain-of-function mutation; causes an alopecia phenotype."; /evidence="ECO:0000269|PubMed:15737203"; MUTAGEN 270; /note="L->D: Spontaneous pyroptosis-inducing activity."; /evidence="ECO:0000269|PubMed:27281216"; MUTAGEN 278; /note="T->P: In Fgn mutant; gain-of-function mutation; causes an alopecia phenotype. Attenuates intramolecular interaction between the N- and C-terminal domains, hence may relieve autoinhibition; constitutively active in triggering pyroptosis."; /evidence="ECO:0000269|PubMed:15737203, ECO:0000269|PubMed:26375003"; MUTAGEN 343; /note="L->P: In Rco2 mutant; gain-of-function mutation; causes an alopecia phenotype. Attenuates intramolecular interaction between the N- and C-terminal domains, hence may relieve autoinhibition; constitutively active in triggering pyroptosis."; /evidence="ECO:0000269|PubMed:15475261, ECO:0000269|PubMed:26375003"; MUTAGEN 344; /note="Y->C: In Bsk mutant; gain-of-function mutation; causes an alopecia phenotype. Attenuates intramolecular interaction between the N- and C-terminal domains, hence may relieve autoinhibition; constitutively active in triggering pyroptosis."; /evidence="ECO:0000269|PubMed:15475261, ECO:0000269|PubMed:26375003"; MUTAGEN 344; /note="Y->D: Spontaneous pyroptosis-inducing activity."; /evidence="ECO:0000269|PubMed:27281216"; MUTAGEN 344; /note="Y->H: In AE mutant; gain-of-function mutation; causes an alopecia phenotype; constitutively active in triggering cell death. Mice also display hypoplastic mammary glands, impairing lactation function."; /evidence="ECO:0000269|PubMed:22155111, ECO:0000269|PubMed:25825937, ECO:0000269|PubMed:28168650"; MUTAGEN 348; /note="A->D: Spontaneous pyroptosis-inducing activity."; /evidence="ECO:0000269|PubMed:27281216"; MUTAGEN 348; /note="A->T: In Rim3 mutant; gain-of-function mutation; causes an alopecia phenotype. Attenuates intramolecular interaction between the N- and C-terminal domains, hence may relieve autoinhibition; constitutively active in triggering pyroptosis."; /evidence="ECO:0000269|PubMed:17572385, ECO:0000269|PubMed:26375003"; MUTAGEN 359; /note="I->T: Gain-of-function mutation; causes an alopecia phenotype."; /evidence="ECO:0000269|PubMed:22682752"; MUTAGEN 412; /note="A->AEA: In Re-den mutant; gain-of-function mutation; causes an alopecia phenotype. Attenuates intramolecular interaction between the N- and C-terminal domains, hence may relieve autoinhibition; constitutively active in triggering pyroptosis."; /evidence="ECO:0000269|PubMed:15475261, ECO:0000269|PubMed:26375003
uniprot
proteins
post_translational_modification
PTM: Cleavage relieves autoinhibition by releasing the N-terminal moiety (Gasdermin-A3, N-terminal) that initiates pyroptosis (By similarity). In contrast to Gsdma, not cleaved by bacterial effector protein SpeB (PubMed:35110732). {ECO:0000250|UniProtKB:P57764, ECO:0000269|PubMed:35110732}.; PTM: Palmitoylated. {ECO:0000250|UniProtKB:Q96QA5}.
uniprot
proteins
protein_family
Gasdermin family
uniprot
proteins
pubmed
15475261
uniprot
proteins
pubmed
15737203
uniprot
proteins
pubmed
17350798
uniprot
proteins
pubmed
17572385
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
22155111
uniprot
proteins
pubmed
22682752
uniprot
proteins
pubmed
25825937
uniprot
proteins
pubmed
26100518
uniprot
proteins
pubmed
26375003
uniprot
proteins
pubmed
27281216
uniprot
proteins
pubmed
28168650
uniprot
proteins
pubmed
29695864
uniprot
proteins
pubmed
32188939
uniprot
proteins
pubmed
32302611
uniprot
proteins
pubmed
33883744
uniprot
proteins
pubmed
35110732
uniprot
proteins
pubmed
35545613
uniprot
proteins
pubmed
35545676
uniprot
proteins
sequence_length
464
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Gasdermin-A3]: Cytoplasm, cytosol {ECO:0000269|PubMed:27281216}.; SUBCELLULAR LOCATION: [Gasdermin-A3, N-terminal]: Cell membrane {ECO:0000269|PubMed:27281216}; Multi-pass membrane protein {ECO:0000269|PubMed:29695864}. Mitochondrion membrane {ECO:0000305|PubMed:26100518}; Multi-pass membrane protein {ECO:0000269|PubMed:29695864}.
uniprot
proteins
transmembrane_region
TRANSMEM 78..95; /note="Beta stranded"; /evidence="ECO:0000305|PubMed:29695864, ECO:0007744|PDB:6CB8"; TRANSMEM 99..120; /note="Beta stranded"; /evidence="ECO:0000305|PubMed:29695864, ECO:0007744|PDB:6CB8"; TRANSMEM 164..180; /note="Beta stranded"; /evidence="ECO:0000305|PubMed:29695864, ECO:0007744|PDB:6CB8"; TRANSMEM 184..198; /note="Beta stranded"; /evidence="ECO:0000305|PubMed:29695864, ECO:0007744|PDB:6CB8
uniprot
proteins