UniProtKB - Q5Y4Y6 (GSDA3_MOUSE)
Gasdermin-A3
Gsdma3
Functioni
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 cell death (PubMed:26375003, PubMed:27281216).
3 PublicationsPore-forming protein that causes membrane permeabilization and pyroptosis (PubMed:26375003, PubMed:27281216).
Released upon cleavage in vitro of genetically engineered Gsdma3, and binds to membrane inner leaflet lipids (PubMed:27281216).
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).
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).
The functional mechanisms and physiological proteases that cleave and activate this pore-forming protein are unknown (Probable). 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).
Curated10 PublicationsActivity regulationi
GO - Molecular functioni
- cardiolipin binding Source: UniProtKB
- phosphatidylinositol-4,5-bisphosphate binding Source: GO_Central
- phosphatidylinositol-4-phosphate binding Source: GO_Central
- phosphatidylserine binding Source: GO_Central
- phospholipid binding Source: UniProtKB
- wide pore channel activity Source: UniProtKB
GO - Biological processi
- apoptotic process Source: MGI
- avascular cornea development in camera-type eye Source: MGI
- defense response to bacterium Source: GO_Central
- hair cycle Source: MGI
- hair follicle development Source: UniProtKB
- hair follicle morphogenesis Source: MGI
- mammary gland development Source: UniProtKB
- negative regulation of canonical Wnt signaling pathway Source: MGI
- negative regulation of timing of anagen Source: MGI
- positive regulation of apoptotic process Source: MGI
- positive regulation of extrinsic apoptotic signaling pathway Source: MGI
- programmed cell death Source: UniProtKB
- protein complex oligomerization Source: UniProtKB
- pyroptosis Source: UniProtKB
- sebaceous gland cell differentiation Source: MGI
- skin development Source: MGI
- somatic stem cell population maintenance Source: MGI
Keywordsi
Molecular function | Developmental protein |
Biological process | Necrosis |
Names & Taxonomyi
Protein namesi | Recommended name: Gasdermin-A3CuratedAlternative name(s): Gasdermin-31 Publication Cleaved into the following 2 chains: |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:3044668, Gsdma3 |
VEuPathDBi | HostDB:ENSMUSG00000064224 |
Subcellular locationi
Cytoplasm and Cytosol
- cytosol 1 Publication
Mitochondrion
- Mitochondrion membrane 1 Publication; Multi-pass membrane protein 1 Publication
Plasma membrane
- Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication
Cytosol
- cytosol Source: UniProtKB
Mitochondrion
- mitochondrial membrane Source: UniProtKB-SubCell
- mitochondrion Source: UniProtKB
Nucleus
- nucleus Source: MGI
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- integral component of membrane Source: UniProtKB
- perinuclear region of cytoplasm Source: MGI
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 78 – 95 | Beta strandedCombined sources1 PublicationAdd BLAST | 18 | |
Transmembranei | 99 – 120 | Beta strandedCombined sources1 PublicationAdd BLAST | 22 | |
Transmembranei | 164 – 180 | Beta strandedCombined sources1 PublicationAdd BLAST | 17 | |
Transmembranei | 184 – 198 | Beta strandedCombined sources1 PublicationAdd BLAST | 15 |
Keywords - Cellular componenti
Cell membrane, Cytoplasm, Membrane, MitochondrionPathology & Biotechi
Biotechnological usei
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 9 – 18 | RALVRELNPR → AALVAELNPAA: Impaired pore-formation. 1 Publication | 10 | |
Mutagenesisi | 14 | E → K: No spontaneous pyroptosis-inducing activity; when associated with D-184. 1 Publication | 1 | |
Mutagenesisi | 41 – 44 | RKRK → EEEE: Abolished ability to form a pore. 1 Publication | 4 | |
Mutagenesisi | 47 – 49 | LFW → EEE: Abolished ability to form a pore. 1 Publication | 3 | |
Mutagenesisi | 62 – 75 | DLLEP…SDLTD → ALLAPGSSPSALTA in AP1; promotes ability to release of interleukin-1 (IL1B and IL18) precursors. 1 PublicationAdd BLAST | 14 | |
Mutagenesisi | 86 – 94 | DVQVQGLVE → AVQVQGLVA in AP2; promotes ability to release of interleukin-1 (IL1B and IL18) precursors. 1 Publication | 9 | |
Mutagenesisi | 132 | R → A: Weak or no effect on ability to induce pyroptosis. Impaired ability to induce pyroptosis; when associated with A-145. 1 Publication | 1 | |
Mutagenesisi | 145 | R → A: Impaired ability to induce pyroptosis; when associated with A-132. 1 Publication | 1 | |
Mutagenesisi | 184 | L → D: Markedly decreased induction of pyroptosis and defects in liposome-binding. No spontaneous pyroptosis-inducing activity; when associated with K-14. 1 Publication | 1 | |
Mutagenesisi | 186 | L → E: Impaired pore-formation. 1 Publication | 1 | |
Mutagenesisi | 262 – 464 | Missing in Dfl mutant; gain-of-function mutation; causes an alopecia phenotype. 1 PublicationAdd BLAST | 203 | |
Mutagenesisi | 270 | L → D: Spontaneous pyroptosis-inducing activity. 1 Publication | 1 | |
Mutagenesisi | 278 | 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. 2 Publications | 1 | |
Mutagenesisi | 343 | 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. 2 Publications | 1 | |
Mutagenesisi | 344 | 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. 2 Publications | 1 | |
Mutagenesisi | 344 | Y → D: Spontaneous pyroptosis-inducing activity. 1 Publication | 1 | |
Mutagenesisi | 344 | 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. 3 Publications | 1 | |
Mutagenesisi | 348 | A → D: Spontaneous pyroptosis-inducing activity. 1 Publication | 1 | |
Mutagenesisi | 348 | 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. 2 Publications | 1 | |
Mutagenesisi | 359 | I → T: Gain-of-function mutation; causes an alopecia phenotype. 1 Publication | 1 | |
Mutagenesisi | 412 | 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. 2 Publications | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000347272 | 1 – 464 | Gasdermin-A3Add BLAST | 464 | |
ChainiPRO_0000451670 | 1 – ?262 | Gasdermin-A3, N-terminal1 PublicationAdd BLAST | 262 | |
ChainiPRO_0000451671 | ?263 – 464 | Gasdermin-A3, C-terminal1 PublicationAdd BLAST | 202 |
Post-translational modificationi
Proteomic databases
PaxDbi | Q5Y4Y6 |
PeptideAtlasi | Q5Y4Y6 |
PRIDEi | Q5Y4Y6 |
ProteomicsDBi | 271445 |
PTM databases
iPTMneti | Q5Y4Y6 |
PhosphoSitePlusi | Q5Y4Y6 |
Expressioni
Tissue specificityi
Developmental stagei
Gene expression databases
Bgeei | ENSMUSG00000064224, Expressed in liver and 32 other tissues |
ExpressionAtlasi | Q5Y4Y6, baseline and differential |
Interactioni
Subunit structurei
Homooligomer; homooligomeric ring-shaped pore complex containing 27-28 subunits when inserted in the membrane.
2 PublicationsProtein-protein interaction databases
STRINGi | 10090.ENSMUSP00000073022 |
Miscellaneous databases
RNActi | Q5Y4Y6, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q5Y4Y6 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 261 | Triggers pyroptosis1 PublicationAdd BLAST | 261 | |
Regioni | 9 – 13 | Lipid-binding1 Publication | 5 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 255 – 327 | Sequence analysisAdd BLAST | 73 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Coiled coil, Transmembrane, Transmembrane beta strandPhylogenomic databases
eggNOGi | ENOG502S0IQ, Eukaryota |
GeneTreei | ENSGT00950000183140 |
InParanoidi | Q5Y4Y6 |
OrthoDBi | 747086at2759 |
PhylomeDBi | Q5Y4Y6 |
TreeFami | TF331886 |
Family and domain databases
InterProi | View protein in InterPro IPR007677, Gasdermin IPR040460, Gasdermin_pore IPR041263, Gasdermin_PUB |
PANTHERi | PTHR16399, PTHR16399, 1 hit |
Pfami | View protein in Pfam PF04598, Gasdermin, 1 hit PF17708, Gasdermin_C, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
10 20 30 40 50
MPVFEDVTRA LVRELNPRGD LTPLDSLIDF KHFRPFCLVL RKRKSTLFWG
60 70 80 90 100
ARYVRTDYTL LDLLEPGSSP SDLTDSGNFS FKNMLDVQVQ GLVEVPKTVK
110 120 130 140 150
VKGTAGLSQS STLEVQTLSV APSALENLKK ERKLSADHSF LNEMRYHEKN
160 170 180 190 200
LYVVMEAVEA KQEVTVEQTG NANAIFSLPS LALLGLQGSL NNNKAVTIPK
210 220 230 240 250
GCVLAYRVRL LRVFLFNLWD IPYICNDSMQ TFPKIRRVPC SAFISPTQMI
260 270 280 290 300
SEEPEEEKLI GEMHEDFKTL KEEVQRETQE VEKLSPVGRS SLLTSLSHLL
310 320 330 340 350
GKKKELQDLE QKLEGALDKG QKVTLEALPK DVLLSKDAMD AILYFLGALT
360 370 380 390 400
ELTEEQLKIL VKSLEKKILP VQLKLVESTL EQNFLQDKEG VFPLQPDLLS
410 420 430 440 450
SLGEEELTLT EALVGLSGLE VQRSGPQYAW DPDTRHNLCA LYAGLSLLHL
460
LSRKSNALTY CALS
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketZ4YKL5 | Z4YKL5_MOUSE | Gasdermin-A3 | Gsdma3 | 455 | Annotation score: |
Sequence cautioni
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY679090 mRNA Translation: AAU95732.1 AL591125 Genomic DNA Translation: CAM24379.1 Sequence problems. |
CCDSi | CCDS25356.1 |
RefSeqi | NP_001007462.1, NM_001007461.1 XP_006533737.1, XM_006533674.2 |
Genome annotation databases
Ensembli | ENSMUST00000073295; ENSMUSP00000073022; ENSMUSG00000064224 |
GeneIDi | 450219 |
KEGGi | mmu:450219 |
UCSCi | uc007lgs.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY679090 mRNA Translation: AAU95732.1 AL591125 Genomic DNA Translation: CAM24379.1 Sequence problems. |
CCDSi | CCDS25356.1 |
RefSeqi | NP_001007462.1, NM_001007461.1 XP_006533737.1, XM_006533674.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5B5R | X-ray | 1.90 | A | 1-464 | [»] | |
6CB8 | electron microscopy | 3.80 | A | 1-262 | [»] | |
SMRi | Q5Y4Y6 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000073022 |
PTM databases
iPTMneti | Q5Y4Y6 |
PhosphoSitePlusi | Q5Y4Y6 |
Proteomic databases
PaxDbi | Q5Y4Y6 |
PeptideAtlasi | Q5Y4Y6 |
PRIDEi | Q5Y4Y6 |
ProteomicsDBi | 271445 |
Protocols and materials databases
DNASUi | 450219 |
Genome annotation databases
Ensembli | ENSMUST00000073295; ENSMUSP00000073022; ENSMUSG00000064224 |
GeneIDi | 450219 |
KEGGi | mmu:450219 |
UCSCi | uc007lgs.1, mouse |
Organism-specific databases
CTDi | 450219 |
MGIi | MGI:3044668, Gsdma3 |
VEuPathDBi | HostDB:ENSMUSG00000064224 |
Phylogenomic databases
eggNOGi | ENOG502S0IQ, Eukaryota |
GeneTreei | ENSGT00950000183140 |
InParanoidi | Q5Y4Y6 |
OrthoDBi | 747086at2759 |
PhylomeDBi | Q5Y4Y6 |
TreeFami | TF331886 |
Miscellaneous databases
BioGRID-ORCSi | 450219, 0 hits in 65 CRISPR screens |
PROi | PR:Q5Y4Y6 |
RNActi | Q5Y4Y6, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000064224, Expressed in liver and 32 other tissues |
ExpressionAtlasi | Q5Y4Y6, baseline and differential |
Family and domain databases
InterProi | View protein in InterPro IPR007677, Gasdermin IPR040460, Gasdermin_pore IPR041263, Gasdermin_PUB |
PANTHERi | PTHR16399, PTHR16399, 1 hit |
Pfami | View protein in Pfam PF04598, Gasdermin, 1 hit PF17708, Gasdermin_C, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | GSDA3_MOUSE | |
Accessioni | Q5Y4Y6Primary (citable) accession number: Q5Y4Y6 Secondary accession number(s): A2A4X5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 2, 2008 |
Last sequence update: | November 23, 2004 | |
Last modified: | February 23, 2022 | |
This is version 99 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families