UniProtKB - Q96QA5 (GSDMA_HUMAN)
Protein
Gasdermin-A
Gene
GSDMA
Organism
Homo sapiens (Human)
Status
Functioni
This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-A, N-terminal) binds to membranes and forms pores, triggering cell death.1 Publication
Pore-forming protein that causes membrane permeabilization and pyroptosis (PubMed:17471240, PubMed:27281216). Released upon cleavage in vitro of genetically engineered GSDMA, and binds to membrane inner leaflet lipids (PubMed:27281216). Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis (PubMed:27281216). Binds to membrane inner leaflet lipids, such as phosphatidylinositol (4,5)-bisphosphate (PubMed:27281216). The functional mechanisms and physiological proteases that cleave and activate this pore-forming protein are unknown (PubMed:27281216).2 Publications
Activity regulationi
The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-A, N-terminal).By similarity
GO - Molecular functioni
- phosphatidylinositol-4,5-bisphosphate binding Source: GO_Central
- phosphatidylinositol-4-phosphate binding Source: GO_Central
- phosphatidylserine binding Source: GO_Central
GO - Biological processi
- apoptotic process Source: UniProtKB
- defense response to bacterium Source: GO_Central
- pyroptosis Source: GO_Central
Keywordsi
Biological process | Necrosis |
Enzyme and pathway databases
PathwayCommonsi | Q96QA5 |
Protein family/group databases
TCDBi | 1.C.123.1.2, the pore-forming gasdermin (gasdermin) family |
Names & Taxonomyi
Protein namesi | Recommended name: Gasdermin-ACuratedAlternative name(s): Gasdermin-1 Cleaved into the following 2 chains: |
Gene namesi | ORF Names:FKSG91 Publication |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:13311, GSDMA |
MIMi | 611218, gene |
neXtProti | NX_Q96QA5 |
VEuPathDBi | HostDB:ENSG00000167914.10 |
Subcellular locationi
Cytosol
- cytosol By similarity
Other locations
- perinuclear region 1 Publication
Plasma membrane
- Cell membrane By similarity; Multi-pass membrane protein By similarity
Cytosol
- cytosol Source: UniProtKB-SubCell
Plasma Membrane
- plasma membrane Source: UniProtKB-SubCell
Other locations
- integral component of membrane Source: UniProtKB-KW
- perinuclear region of cytoplasm Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 78 – 95 | Beta strandedBy similarityAdd BLAST | 18 | |
Transmembranei | 99 – 120 | Beta strandedBy similarityAdd BLAST | 22 | |
Transmembranei | 163 – 179 | Beta strandedBy similarityAdd BLAST | 17 | |
Transmembranei | 183 – 197 | Beta strandedBy similarityAdd BLAST | 15 |
Keywords - Cellular componenti
Cell membrane, Cytoplasm, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 260 | L → D: Spontaneous pyroptosis-inducing activity. 1 Publication | 1 | |
Mutagenesisi | 334 | Y → D: Spontaneous pyroptosis-inducing activity. 1 Publication | 1 | |
Mutagenesisi | 338 | A → D: Spontaneous pyroptosis-inducing activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 284110 |
OpenTargetsi | ENSG00000167914 |
PharmGKBi | PA162390274 |
Miscellaneous databases
Pharosi | Q96QA5, Tbio |
Genetic variation databases
BioMutai | GSDMA |
DMDMi | 296439478 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000148173 | 1 – 445 | Gasdermin-AAdd BLAST | 445 | |
ChainiPRO_0000451664 | 1 – ? | Gasdermin-A, N-terminalCurated | ||
ChainiPRO_0000451665 | ? – 445 | Gasdermin-A, C-terminalCurated |
Post-translational modificationi
Cleavage relieves autoinhibition by releasing the N-terminal moiety (Gasdermin-A, N-terminal) that initiates pyroptosis.By similarity
Proteomic databases
EPDi | Q96QA5 |
MassIVEi | Q96QA5 |
PaxDbi | Q96QA5 |
PeptideAtlasi | Q96QA5 |
PRIDEi | Q96QA5 |
ProteomicsDBi | 77846 |
PTM databases
iPTMneti | Q96QA5 |
PhosphoSitePlusi | Q96QA5 |
Expressioni
Tissue specificityi
Expressed predominantly in the gastrointestinal tract and, at a lower level, in the skin. Also detected in mammary gland. In the gastrointestinal tract, mainly expressed in differentiated cells, including the differentiated cell layer of esophagus and mucus-secreting pit cells of the gastric epithelium. Down-regulateded in gastric cancer cells.3 Publications
Gene expression databases
Bgeei | ENSG00000167914, Expressed in skin of leg and 88 other tissues |
ExpressionAtlasi | Q96QA5, baseline and differential |
Organism-specific databases
HPAi | ENSG00000167914, Tissue enhanced (skin, tongue) |
Interactioni
Subunit structurei
Homooligomer; homooligomeric ring-shaped pore complex containing 27-28 subunits when inserted in the membrane.
By similarityBinary interactionsi
Hide detailsQ96QA5
With | #Exp. | IntAct |
---|---|---|
APOC1 [P02654] | 3 | EBI-11320924,EBI-1220105 |
APOC4 [P55056] | 3 | EBI-11320924,EBI-18302142 |
Protein-protein interaction databases
BioGRIDi | 129762, 33 interactors |
IntActi | Q96QA5, 9 interactors |
MINTi | Q96QA5 |
STRINGi | 9606.ENSP00000301659 |
Miscellaneous databases
RNActi | Q96QA5, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 251 | Triggers pyroptosis1 PublicationAdd BLAST | 251 | |
Regioni | 9 – 13 | Lipid-bindingBy similarity | 5 |
Domaini
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.By similarity
Sequence similaritiesi
Belongs to the gasdermin family.Curated
Keywords - Domaini
Transmembrane, Transmembrane beta strandPhylogenomic databases
eggNOGi | ENOG502S0IQ, Eukaryota |
GeneTreei | ENSGT00950000183140 |
HOGENOMi | CLU_040752_0_0_1 |
InParanoidi | Q96QA5 |
OMAi | HICNDSM |
OrthoDBi | 747086at2759 |
PhylomeDBi | Q96QA5 |
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
Q96QA5-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MTMFENVTRA LARQLNPRGD LTPLDSLIDF KRFHPFCLVL RKRKSTLFWG
60 70 80 90 100
ARYVRTDYTL LDVLEPGSSP SDPTDTGNFG FKNMLDTRVE GDVDVPKTVK
110 120 130 140 150
VKGTAGLSQN STLEVQTLSV APKALETVQE RKLAADHPFL KEMQDQGENL
160 170 180 190 200
YVVMEVVETV QEVTLERAGK AEACFSLPFF APLGLQGSIN HKEAVTIPKG
210 220 230 240 250
CVLAFRVRQL MVKGKDEWDI PHICNDNMQT FPPGEKSGEE KVILIQASDV
260 270 280 290 300
GDVHEGFRTL KEEVQRETQQ VEKLSRVGQS SLLSSLSKLL GKKKELQDLE
310 320 330 340 350
LALEGALDKG HEVTLEALPK DVLLSKEAVG AILYFVGALT ELSEAQQKLL
360 370 380 390 400
VKSMEKKILP VQLKLVESTM EQNFLLDKEG VFPLQPELLS SLGDEELTLT
410 420 430 440
EALVGLSGLE VQRSGPQYMW DPDTLPRLCA LYAGLSLLQQ LTKAS
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketJ3KRG2 | J3KRG2_HUMAN | Gasdermin-A | GSDMA | 158 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 131 | R → RR in AAL14426 (Ref. 2) Curated | 1 | |
Sequence conflicti | 181 – 186 | APLGLQ → LPIGAT in AAL14426 (Ref. 2) Curated | 6 | |
Sequence conflicti | 235 – 242 | EKSGEEKV → GKPGEGKF in AAL14426 (Ref. 2) Curated | 8 | |
Sequence conflicti | 252 – 253 | DV → EM in AAL14426 (Ref. 2) Curated | 2 | |
Sequence conflicti | 367 – 368 | ES → RG in AAL14426 (Ref. 2) Curated | 2 | |
Sequence conflicti | 437 | L → H in BAC04790 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_035010 | 18 | R → Q. Corresponds to variant dbSNP:rs3894194Ensembl. | 1 | |
Natural variantiVAR_035011 | 128 | V → L3 PublicationsCorresponds to variant dbSNP:rs7212938Ensembl. | 1 | |
Natural variantiVAR_035012 | 130 | E → K1 PublicationCorresponds to variant dbSNP:rs7212944Ensembl. | 1 | |
Natural variantiVAR_062005 | 314 | T → N1 PublicationCorresponds to variant dbSNP:rs56030650Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB093591 mRNA Translation: BAC75636.1 AF307953 mRNA Translation: AAL14426.1 AK096439 mRNA Translation: BAC04790.1 AC090844 Genomic DNA No translation available. BC109197 mRNA Translation: AAI09198.1 |
CCDSi | CCDS45669.1 |
RefSeqi | NP_835465.2, NM_178171.4 XP_006721895.1, XM_006721832.2 |
Genome annotation databases
Ensembli | ENST00000301659; ENSP00000301659; ENSG00000167914 ENST00000635792; ENSP00000490739; ENSG00000167914 |
GeneIDi | 284110 |
KEGGi | hsa:284110 |
UCSCi | uc002htl.1, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB093591 mRNA Translation: BAC75636.1 AF307953 mRNA Translation: AAL14426.1 AK096439 mRNA Translation: BAC04790.1 AC090844 Genomic DNA No translation available. BC109197 mRNA Translation: AAI09198.1 |
CCDSi | CCDS45669.1 |
RefSeqi | NP_835465.2, NM_178171.4 XP_006721895.1, XM_006721832.2 |
3D structure databases
SMRi | Q96QA5 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 129762, 33 interactors |
IntActi | Q96QA5, 9 interactors |
MINTi | Q96QA5 |
STRINGi | 9606.ENSP00000301659 |
Protein family/group databases
TCDBi | 1.C.123.1.2, the pore-forming gasdermin (gasdermin) family |
PTM databases
iPTMneti | Q96QA5 |
PhosphoSitePlusi | Q96QA5 |
Genetic variation databases
BioMutai | GSDMA |
DMDMi | 296439478 |
Proteomic databases
EPDi | Q96QA5 |
MassIVEi | Q96QA5 |
PaxDbi | Q96QA5 |
PeptideAtlasi | Q96QA5 |
PRIDEi | Q96QA5 |
ProteomicsDBi | 77846 |
Protocols and materials databases
Antibodypediai | 7880, 105 antibodies |
Genome annotation databases
Ensembli | ENST00000301659; ENSP00000301659; ENSG00000167914 ENST00000635792; ENSP00000490739; ENSG00000167914 |
GeneIDi | 284110 |
KEGGi | hsa:284110 |
UCSCi | uc002htl.1, human |
Organism-specific databases
CTDi | 284110 |
DisGeNETi | 284110 |
GeneCardsi | GSDMA |
HGNCi | HGNC:13311, GSDMA |
HPAi | ENSG00000167914, Tissue enhanced (skin, tongue) |
MIMi | 611218, gene |
neXtProti | NX_Q96QA5 |
OpenTargetsi | ENSG00000167914 |
PharmGKBi | PA162390274 |
VEuPathDBi | HostDB:ENSG00000167914.10 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502S0IQ, Eukaryota |
GeneTreei | ENSGT00950000183140 |
HOGENOMi | CLU_040752_0_0_1 |
InParanoidi | Q96QA5 |
OMAi | HICNDSM |
OrthoDBi | 747086at2759 |
PhylomeDBi | Q96QA5 |
TreeFami | TF331886 |
Enzyme and pathway databases
PathwayCommonsi | Q96QA5 |
Miscellaneous databases
BioGRID-ORCSi | 284110, 208 hits in 869 CRISPR screens |
GenomeRNAii | 284110 |
Pharosi | Q96QA5, Tbio |
PROi | PR:Q96QA5 |
RNActi | Q96QA5, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000167914, Expressed in skin of leg and 88 other tissues |
ExpressionAtlasi | Q96QA5, 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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | GSDMA_HUMAN | |
Accessioni | Q96QA5Primary (citable) accession number: Q96QA5 Secondary accession number(s): Q32MC5, Q86VE7, Q8N1M6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 19, 2005 |
Last sequence update: | May 18, 2010 | |
Last modified: | February 10, 2021 | |
This is version 123 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 17
Human chromosome 17: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families