Q9D8T2

SS
Gene name
Gsdmd
Protein name
Gasdermin-D
Names
Gasdermin domain-containing protein 1
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:69146
EC number
Protein Class

Descriptions

Gasdermin proteins are a pore-forming protein causing membrane permeabilization and pyroptosis, and functions downstream of the inflammatory caspases. In human Gasdermin-D protein (GSDMD, P57764), its C-terminal gasdermin domain adopts an intramolecular complex with the N-terminal domain, which inhibits the activation of the N-terminal gasdermin domain. The N- and C-terminal gasdermin domains of Gsdmd can interact each other, implying a similar autoinhibitory mechanism.

Autoinhibitory domains (AIDs)

280-459 (C-terminal gasdermin domain) SS

Target domain

4-243 (N-terminal gasdermin domain)

Relief mechanism

Cleavage

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

5 structures for Q9D8T2

Entry ID Method Resolution Chain Position Source
6AO3 X-ray 176 A A/B/C/D 277-487 PDB
6KMV X-ray 335 A PDB
6N9N X-ray 330 A A/B 1-487 PDB
6VIE X-ray 340 A C/D 1-487 PDB
AF-Q9D8T2-F1 Predicted AlphaFoldDB

10 variants for Q9D8T2

Variant ID(s) Position Change Description Diseaes Association Provenance
rs265945110 91 I>V No Ensembl
rs245939094 233 V>I No Ensembl
rs37791112 308 M>T No Ensembl
rs264191939 309 E>A No Ensembl
rs220408390 314 I>L No Ensembl
rs864288592 367 V>A No Ensembl
rs239891108 368 P>S No Ensembl
rs864276041 412 L>S No Ensembl
rs36886474 441 T>N No Ensembl
rs37105413 463 P>L No Ensembl

No associated diseases with Q9D8T2

2 regional properties for Q9D8T2

Type Name Position InterPro Accession
domain Gasdermin, pore forming domain 4 - 243 IPR040460
domain Gasdermin, PUB domain 287 - 459 IPR041263

Functions

Description
EC Number
Subcellular Localization
  • [Gasdermin-D]: Cytoplasm, cytosol
  • Inflammasome
  • In response to a canonical inflammasome stimulus, such as nigericin, recruited to NLRP3 inflammasone with similar kinetics to that of uncleaved CASP1 precursor
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

6 GO annotations of cellular component

Name Definition
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
extracellular space That part of a multicellular organism outside the cells proper, usually taken to be outside the plasma membranes, and occupied by fluid.
integral component of membrane The component of a membrane consisting of the gene products and protein complexes having at least some part of their peptide sequence embedded in the hydrophobic region of the membrane.
NLRP3 inflammasome complex An inflammasome complex that consists of three components, NLRP3 (NALP3), PYCARD and caspase-1. It is activated upon exposure to whole pathogens, as well as a number of structurally diverse pathogen- and danger-associated molecular patterns (PAMPs and DAMPs) and environmental irritants. Whole pathogens demonstrated to activate the NLRP3 inflammasome complex include the fungi Candida albicans and Saccharomyces cerevisiae, bacteria that produce pore-forming toxins, including Listeria monocytogenes and Staphylococcus aureus, and viruses such as Sendai virus, adenovirus, and influenza virus.
nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

6 GO annotations of molecular function

Name Definition
cardiolipin binding Binding to cardiolipin.
phosphatidic acid binding Binding to phosphatidic acid, any of a class of glycerol phosphate in which both the remaining hydroxyl groups of the glycerol moiety are esterified with fatty acids.
phosphatidylinositol-4,5-bisphosphate binding Binding to phosphatidylinositol-4,5-bisphosphate, a derivative of phosphatidylinositol in which the inositol ring is phosphorylated at the 4' and 5' positions.
phosphatidylinositol-4-phosphate binding Binding to phosphatidylinositol-4-phosphate, a derivative of phosphatidylinositol in which the inositol ring is phosphorylated at the 4' position.
phosphatidylserine binding Binding to phosphatidylserine, a class of glycophospholipids in which a phosphatidyl group is esterified to the hydroxyl group of L-serine.
wide pore channel activity Enables the transport of a solute across a membrane via a large pore, un-gated channel. Examples include gap junctions, which transport substances from one cell to another; and porins which transport substances in and out of bacteria, mitochondria and chloroplasts.

11 GO annotations of biological process

Name Definition
cellular response to extracellular stimulus Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an extracellular stimulus.
defense response to bacterium Reactions triggered in response to the presence of a bacterium that act to protect the cell or organism.
defense response to Gram-negative bacterium Reactions triggered in response to the presence of a Gram-negative bacterium that act to protect the cell or organism.
defense response to Gram-positive bacterium Reactions triggered in response to the presence of a Gram-positive bacterium that act to protect the cell or organism.
inflammatory response The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages.
innate immune response Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens.
pore complex assembly The aggregation, arrangement and bonding together of a set of components to form a pore complex. A pore complex is a small opening in a membrane that allows the passage of liquids and/or gases.
pore formation in membrane of other organism The aggregation, arrangement and bonding together of a set of components by an organism to form a pore complex in a membrane of another organism.
positive regulation of interleukin-1 beta production Any process that activates or increases the frequency, rate, or extent of interleukin-1 beta production.
protein homooligomerization The process of creating protein oligomers, compounds composed of a small number, usually between three and ten, of identical component monomers. Oligomers may be formed by the polymerization of a number of monomers or the depolymerization of a large protein polymer.
pyroptosis A caspase-1-dependent cell death subroutine that is associated with the generation of pyrogenic mediators such as IL-1beta and IL-18.

12 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q96QA5 GSDMA Gasdermin-A Homo sapiens (Human) SS
Q9BYG8 GSDMC Gasdermin-C Homo sapiens (Human) SS
P57764 GSDMD Gasdermin-D Homo sapiens (Human) EV
Q8TAX9 GSDMB Gasdermin-B Homo sapiens (Human) EV
Q8CB12 Gsdmc3 Gasdermin-C3 Mus musculus (Mouse) SS
Q2KHK6 Gsdmc2 Gasdermin-C2 Mus musculus (Mouse) SS
Q3TR54 Gsdmc4 Gasdermin-C4 Mus musculus (Mouse) SS
Q5Y4Y6 Gsdma3 Gasdermin-A3 Mus musculus (Mouse) EV
Q99NB5 Gsdmc Gasdermin-C Mus musculus (Mouse) SS
Q9EST1 Gsdma Gasdermin-A Mus musculus (Mouse) SS
Q32M21 Gsdma2 Gasdermin-A2 Mus musculus (Mouse) SS
P85967 Gsdmc Gasdermin-C Rattus norvegicus (Rat) SS
10 20 30 40 50 60
MPSAFEKVVK NVIKEVSGSR GDLIPVDSLR NSTSFRPYCL LNRKFSSSRF WKPRYSCVNL
70 80 90 100 110 120
SIKDILEPSA PEPEPECFGS FKVSDVVDGN IQGRVMLSGM GEGKISGGAA VSDSSSASMN
130 140 150 160 170 180
VCILRVTQKT WETMQHERHL QQPENKILQQ LRSRGDDLFV VTEVLQTKEE VQITEVHSQE
190 200 210 220 230 240
GSGQFTLPGA LCLKGEGKGH QSRKKMVTIP AGSILAFRVA QLLIGSKWDI LLVSDEKQRT
250 260 270 280 290 300
FEPSSGDRKA VGQRHHGLNV LAALCSIGKQ LSLLSDGIDE EELIEAADFQ GLYAEVKACS
310 320 330 340 350 360
SELESLEMEL RQQILVNIGK ILQDQPSMEA LEASLGQGLC SGGQVEPLDG PAGCILECLV
370 380 390 400 410 420
LDSGELVPEL AAPIFYLLGA LAVLSETQQQ LLAKALETTV LSKQLELVKH VLEQSTPWQE
430 440 450 460 470 480
QSSVSLPTVL LGDCWDEKNP TWVLLEECGL RLQVESPQVH WEPTSLIPTS ALYASLFLLS
SLGQKPC