Annotations: 6VIE

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	Peptidase_C14	e6vieA1	A: a/b three-layered sandwiches	X: Caspase-like (From Topology)	H: Caspase-like (From Topology)	T: Caspase-like	F: Peptidase_C14	ECOD (1.6)
B	Peptidase_C14	e6vieB1	A: a/b three-layered sandwiches	X: Caspase-like (From Topology)	H: Caspase-like (From Topology)	T: Caspase-like	F: Peptidase_C14	ECOD (1.6)
C	Gasdermin_N	e6vieC2	A: beta complex topology	X: Membrane attack complex/perforin (MACPF) and cholesterol-dependent cytolysin (CDC) domains (From Topology)	H: Membrane attack complex/perforin (MACPF) and cholesterol-dependent cytolysin (CDC) domains (From Topology)	T: Membrane attack complex/perforin (MACPF) and cholesterol-dependent cytolysin (CDC) domains	F: Gasdermin_N	ECOD (1.6)
C	Gasdermin_C	e6vieC1	A: a+b two layers	X: R3H domain-like	H: PUB domain (From Topology)	T: PUB domain	F: Gasdermin_C	ECOD (1.6)
D	Gasdermin_N	e6vieD1	A: beta complex topology	X: Membrane attack complex/perforin (MACPF) and cholesterol-dependent cytolysin (CDC) domains (From Topology)	H: Membrane attack complex/perforin (MACPF) and cholesterol-dependent cytolysin (CDC) domains (From Topology)	T: Membrane attack complex/perforin (MACPF) and cholesterol-dependent cytolysin (CDC) domains	F: Gasdermin_N	ECOD (1.6)
D	Gasdermin_C	e6vieD2	A: a+b two layers	X: R3H domain-like	H: PUB domain (From Topology)	T: PUB domain	F: Gasdermin_C	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
B	3.30.70.1470	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits	Caspase-like	CATH (utative)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00656	Caspase domain (Peptidase_C14)	Caspase domain		Domain
B	PF00656	Caspase domain (Peptidase_C14)	Caspase domain		Domain
C, D	PF17708	Gasdermin PUB domain (Gasdermin_C)	Gasdermin PUB domain	The precise function of this protein is unknown. A deletion/insertion mutation is associated with an autosomal dominant non-syndromic hearing impairment form [1]. In addition, this protein has also been found to contribute to acquired etoposide resis ...	The precise function of this protein is unknown. A deletion/insertion mutation is associated with an autosomal dominant non-syndromic hearing impairment form [1]. In addition, this protein has also been found to contribute to acquired etoposide resistance in melanoma cells [2]. This family also includes the gasdermin protein [3]	Domain
C, D	PF04598	Gasdermin pore forming domain (Gasdermin)	Gasdermin pore forming domain	The precise function of this protein is unknown. A deletion/insertion mutation is associated with an autosomal dominant non-syndromic hearing impairment form [1]. In addition, this protein has also been found to contribute to acquired etoposide resis ...	The precise function of this protein is unknown. A deletion/insertion mutation is associated with an autosomal dominant non-syndromic hearing impairment form [1]. In addition, this protein has also been found to contribute to acquired etoposide resistance in melanoma cells [2]. This family also includes the gasdermin protein [3]	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Caspase-1 subunit p20	protein binding binding enzyme binding protease binding caspase binding peptidase activity catalytic activity, acting on a protein hydrolase activity catalytic activity endopeptidase activity enzyme regulator activity peptidase regulator activity molecular function activator activity cysteine-type endopeptidase activator activity involved in apoptotic process protein binding binding enzyme binding protease binding caspase binding peptidase activity catalytic activity, acting on a protein hydrolase activity catalytic activity endopeptidase activity enzyme regulator activity peptidase regulator activity molecular function activator activity cysteine-type endopeptidase activator activity involved in apoptotic process peptidase activator activity enzyme activator activity molecular function regulator activity cysteine-type endopeptidase regulator activity involved in apoptotic process peptidase activator activity involved in apoptotic process identical protein binding cysteine-type peptidase activity cysteine-type endopeptidase activity cytokine binding kinase binding CARD domain binding protein domain specific binding	cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction response to stimulus signaling positive regulation of biological process response to cytokine regulation of signal transduction positive regulation of response to cytokine stimulus cytokine-mediated signaling pathway cell communication positive regulation of tumor necrosis factor-mediated signaling pathway positive regulation of response to stimulus cellular response to tumor necrosis factor cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction response to stimulus signaling positive regulation of biological process response to cytokine regulation of signal transduction positive regulation of response to cytokine stimulus cytokine-mediated signaling pathway cell communication positive regulation of tumor necrosis factor-mediated signaling pathway positive regulation of response to stimulus cellular response to tumor necrosis factor tumor necrosis factor-mediated signaling pathway cellular response to cytokine stimulus signal transduction positive regulation of cellular process regulation of biological process regulation of signaling cell surface receptor signaling pathway regulation of tumor necrosis factor-mediated signaling pathway regulation of cytokine-mediated signaling pathway biological regulation response to peptide regulation of response to cytokine stimulus regulation of response to stimulus response to chemical regulation of cell communication cellular process response to tumor necrosis factor positive regulation of cytokine-mediated signaling pathway positive regulation of signaling primary metabolic process gene expression macromolecule biosynthetic process protein maturation protein autoprocessing biosynthetic process proteolysis protein processing metabolic process protein metabolic process macromolecule metabolic process regulation of defense response regulation of response to external stimulus defense response response to external stimulus regulation of inflammatory response positive regulation of response to external stimulus positive regulation of inflammatory response regulation of response to stress response to stress positive regulation of defense response inflammatory response cellular component organization cellular component biogenesis cellular component assembly protein-containing complex organization protein-containing complex assembly AIM2 inflammasome complex assembly cellular component organization or biogenesis apoptotic process cell death programmed cell death regulation of apoptotic process regulation of programmed cell death multicellular organismal process cytokine precursor processing signaling receptor ligand precursor processing cytokine production biological process involved in interspecies interaction between organisms response to other organism response to biotic stimulus defense response to bacterium defense response to other organism response to bacterium response to external biotic stimulus interleukin-1 production regulation of interleukin-1 beta production positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of interleukin-1 beta production positive regulation of biosynthetic process regulation of cytokine production regulation of multicellular organismal process positive regulation of interleukin-1 production positive regulation of macromolecule metabolic process regulation of biosynthetic process regulation of interleukin-1 production regulation of macromolecule metabolic process regulation of gene expression interleukin-1 beta production positive regulation of gene expression positive regulation of multicellular organismal process regulation of macromolecule biosynthetic process positive regulation of cytokine production regulation of metabolic process response to osmotic stress cellular response to chemical stress cellular response to osmotic stress intracellular signal transduction cellular response to environmental stimulus cellular response to chemical stimulus osmosensory signaling pathway cellular response to stress response to abiotic stimulus cellular response to abiotic stimulus defense response to virus response to virus positive regulation of canonical NF-kappaB signal transduction regulation of intracellular signal transduction intracellular signaling cassette positive regulation of intracellular signal transduction canonical NF-kappaB signal transduction regulation of canonical NF-kappaB signal transduction response to lipid cellular response to lipopolysaccharide response to oxygen-containing compound cellular response to molecule of bacterial origin response to lipopolysaccharide cellular response to oxygen-containing compound cellular response to biotic stimulus cellular response to lipid response to molecule of bacterial origin icosanoid metabolic process small molecule biosynthetic process oxoacid metabolic process carboxylic acid metabolic process organic acid biosynthetic process organic acid metabolic process carboxylic acid biosynthetic process icosanoid biosynthetic process small molecule metabolic process immune response response to type II interferon defense response to symbiont cellular response to type II interferon immune system process innate immune response positive regulation of response to biotic stimulus regulation of response to biotic stimulus pattern recognition receptor signaling pathway immune response-activating signaling pathway immune response-regulating signaling pathway positive regulation of immune response regulation of immune system process positive regulation of immune system process innate immune response-activating signaling pathway positive regulation of innate immune response regulation of innate immune response activation of innate immune response regulation of immune response activation of immune response response to mechanical stimulus cellular response to mechanical stimulus cellular response to external stimulus positive regulation of interleukin-18 production regulation of interleukin-18 production interleukin-18 production pyroptotic inflammatory response	cellular anatomical structure intracellular anatomical structure cytoplasm cytosol canonical inflammasome complex protein-containing complex AIM2 inflammasome complex polymeric cytoskeletal fiber intracellular membraneless organelle intracellular organelle cytoskeleton organelle membraneless organelle supramolecular fiber cellular anatomical structure intracellular anatomical structure cytoplasm cytosol canonical inflammasome complex protein-containing complex AIM2 inflammasome complex polymeric cytoskeletal fiber intracellular membraneless organelle intracellular organelle cytoskeleton organelle membraneless organelle supramolecular fiber microtubule supramolecular polymer supramolecular complex microtubule cytoskeleton membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle nucleolus intracellular organelle lumen organelle lumen nuclear lumen protease inhibitor complex peptidase inhibitor complex IPAF inflammasome complex cell periphery plasma membrane membrane NLRP3 inflammasome complex NLRP1 inflammasome complex
B	Caspase-1 subunit p10	protein binding binding enzyme binding protease binding caspase binding peptidase activity catalytic activity, acting on a protein hydrolase activity catalytic activity endopeptidase activity enzyme regulator activity peptidase regulator activity molecular function activator activity cysteine-type endopeptidase activator activity involved in apoptotic process protein binding binding enzyme binding protease binding caspase binding peptidase activity catalytic activity, acting on a protein hydrolase activity catalytic activity endopeptidase activity enzyme regulator activity peptidase regulator activity molecular function activator activity cysteine-type endopeptidase activator activity involved in apoptotic process peptidase activator activity enzyme activator activity molecular function regulator activity cysteine-type endopeptidase regulator activity involved in apoptotic process peptidase activator activity involved in apoptotic process identical protein binding cysteine-type peptidase activity cysteine-type endopeptidase activity cytokine binding kinase binding CARD domain binding protein domain specific binding	cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction response to stimulus signaling positive regulation of biological process response to cytokine regulation of signal transduction positive regulation of response to cytokine stimulus cytokine-mediated signaling pathway cell communication positive regulation of tumor necrosis factor-mediated signaling pathway positive regulation of response to stimulus cellular response to tumor necrosis factor cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction response to stimulus signaling positive regulation of biological process response to cytokine regulation of signal transduction positive regulation of response to cytokine stimulus cytokine-mediated signaling pathway cell communication positive regulation of tumor necrosis factor-mediated signaling pathway positive regulation of response to stimulus cellular response to tumor necrosis factor tumor necrosis factor-mediated signaling pathway cellular response to cytokine stimulus signal transduction positive regulation of cellular process regulation of biological process regulation of signaling cell surface receptor signaling pathway regulation of tumor necrosis factor-mediated signaling pathway regulation of cytokine-mediated signaling pathway biological regulation response to peptide regulation of response to cytokine stimulus regulation of response to stimulus response to chemical regulation of cell communication cellular process response to tumor necrosis factor positive regulation of cytokine-mediated signaling pathway positive regulation of signaling primary metabolic process gene expression macromolecule biosynthetic process protein maturation protein autoprocessing biosynthetic process proteolysis protein processing metabolic process protein metabolic process macromolecule metabolic process regulation of defense response regulation of response to external stimulus defense response response to external stimulus regulation of inflammatory response positive regulation of response to external stimulus positive regulation of inflammatory response regulation of response to stress response to stress positive regulation of defense response inflammatory response cellular component organization cellular component biogenesis cellular component assembly protein-containing complex organization protein-containing complex assembly AIM2 inflammasome complex assembly cellular component organization or biogenesis apoptotic process cell death programmed cell death regulation of apoptotic process regulation of programmed cell death multicellular organismal process cytokine precursor processing signaling receptor ligand precursor processing cytokine production biological process involved in interspecies interaction between organisms response to other organism response to biotic stimulus defense response to bacterium defense response to other organism response to bacterium response to external biotic stimulus interleukin-1 production regulation of interleukin-1 beta production positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of interleukin-1 beta production positive regulation of biosynthetic process regulation of cytokine production regulation of multicellular organismal process positive regulation of interleukin-1 production positive regulation of macromolecule metabolic process regulation of biosynthetic process regulation of interleukin-1 production regulation of macromolecule metabolic process regulation of gene expression interleukin-1 beta production positive regulation of gene expression positive regulation of multicellular organismal process regulation of macromolecule biosynthetic process positive regulation of cytokine production regulation of metabolic process response to osmotic stress cellular response to chemical stress cellular response to osmotic stress intracellular signal transduction cellular response to environmental stimulus cellular response to chemical stimulus osmosensory signaling pathway cellular response to stress response to abiotic stimulus cellular response to abiotic stimulus defense response to virus response to virus positive regulation of canonical NF-kappaB signal transduction regulation of intracellular signal transduction intracellular signaling cassette positive regulation of intracellular signal transduction canonical NF-kappaB signal transduction regulation of canonical NF-kappaB signal transduction response to lipid cellular response to lipopolysaccharide response to oxygen-containing compound cellular response to molecule of bacterial origin response to lipopolysaccharide cellular response to oxygen-containing compound cellular response to biotic stimulus cellular response to lipid response to molecule of bacterial origin icosanoid metabolic process small molecule biosynthetic process oxoacid metabolic process carboxylic acid metabolic process organic acid biosynthetic process organic acid metabolic process carboxylic acid biosynthetic process icosanoid biosynthetic process small molecule metabolic process immune response response to type II interferon defense response to symbiont cellular response to type II interferon immune system process innate immune response positive regulation of response to biotic stimulus regulation of response to biotic stimulus pattern recognition receptor signaling pathway immune response-activating signaling pathway immune response-regulating signaling pathway positive regulation of immune response regulation of immune system process positive regulation of immune system process innate immune response-activating signaling pathway positive regulation of innate immune response regulation of innate immune response activation of innate immune response regulation of immune response activation of immune response response to mechanical stimulus cellular response to mechanical stimulus cellular response to external stimulus positive regulation of interleukin-18 production regulation of interleukin-18 production interleukin-18 production pyroptotic inflammatory response	cellular anatomical structure intracellular anatomical structure cytoplasm cytosol canonical inflammasome complex protein-containing complex AIM2 inflammasome complex polymeric cytoskeletal fiber intracellular membraneless organelle intracellular organelle cytoskeleton organelle membraneless organelle supramolecular fiber cellular anatomical structure intracellular anatomical structure cytoplasm cytosol canonical inflammasome complex protein-containing complex AIM2 inflammasome complex polymeric cytoskeletal fiber intracellular membraneless organelle intracellular organelle cytoskeleton organelle membraneless organelle supramolecular fiber microtubule supramolecular polymer supramolecular complex microtubule cytoskeleton membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle nucleolus intracellular organelle lumen organelle lumen nuclear lumen protease inhibitor complex peptidase inhibitor complex IPAF inflammasome complex cell periphery plasma membrane membrane NLRP3 inflammasome complex NLRP1 inflammasome complex
C, D	Gasdermin-D	wide pore channel activity passive transmembrane transporter activity channel activity transporter activity transmembrane transporter activity ion binding binding anion binding phosphatidic acid binding phospholipid binding lipid binding small molecule binding phosphatidylglycerol binding cardiolipin binding wide pore channel activity passive transmembrane transporter activity channel activity transporter activity transmembrane transporter activity ion binding binding anion binding phosphatidic acid binding phospholipid binding lipid binding small molecule binding phosphatidylglycerol binding cardiolipin binding phosphatidylinositol-4,5-bisphosphate binding phosphatidylinositol bisphosphate binding phosphatidylinositol phosphate binding phosphatidylinositol binding phosphatidylinositol-4-phosphate binding modified amino acid binding phosphatidylserine binding	regulation of defense response regulation of biological process response to stimulus regulation of response to external stimulus defense response biological regulation positive regulation of biological process response to external stimulus regulation of inflammatory response positive regulation of response to stimulus positive regulation of response to external stimulus positive regulation of inflammatory response regulation of response to stimulus regulation of response to stress response to stress regulation of defense response regulation of biological process response to stimulus regulation of response to external stimulus defense response biological regulation positive regulation of biological process response to external stimulus regulation of inflammatory response positive regulation of response to stimulus positive regulation of response to external stimulus positive regulation of inflammatory response regulation of response to stimulus regulation of response to stress response to stress positive regulation of defense response inflammatory response biological process involved in interspecies interaction between organisms immune response response to other organism defense response to symbiont response to biotic stimulus immune system process defense response to other organism innate immune response response to external biotic stimulus cellular component organization cellular component biogenesis cellular component assembly protein-containing complex organization protein-containing complex assembly cellular process cellular component organization or biogenesis pore complex assembly multicellular organismal process regulation of cellular process interleukin-1 production regulation of interleukin-1 beta production positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of interleukin-1 beta production positive regulation of biosynthetic process regulation of cytokine production cytokine production regulation of multicellular organismal process positive regulation of interleukin-1 production positive regulation of macromolecule metabolic process positive regulation of cellular process regulation of biosynthetic process regulation of interleukin-1 production regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of gene expression biosynthetic process interleukin-1 beta production positive regulation of gene expression positive regulation of multicellular organismal process regulation of macromolecule biosynthetic process metabolic process macromolecule metabolic process positive regulation of cytokine production regulation of metabolic process pyroptotic cell death pyroptotic inflammatory response cell death programmed cell death protein localization establishment of protein localization cellular localization nitrogen compound transport transport secretion establishment of protein localization to extracellular region export from cell protein secretion establishment of localization protein localization to extracellular region localization secretion by cell protein transport cellular macromolecule localization macromolecule localization defense response to Gram-negative bacterium defense response to bacterium response to bacterium protein complex oligomerization protein homooligomerization defense response to Gram-positive bacterium	membrane-bounded organelle mitochondrial membrane intracellular anatomical structure mitochondrion membrane intracellular membrane-bounded organelle intracellular organelle organelle envelope cellular anatomical structure organelle mitochondrial envelope cytoplasm organelle membrane cytosol membrane-bounded organelle mitochondrial membrane intracellular anatomical structure mitochondrion membrane intracellular membrane-bounded organelle intracellular organelle organelle envelope cellular anatomical structure organelle mitochondrial envelope cytoplasm organelle membrane cytosol cell periphery plasma membrane nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen canonical inflammasome complex protein-containing complex NLRP3 inflammasome complex extracellular region extracellular space

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR029030	Caspase-like domain superfamily	Homologous Superfamily
A	IPR001309	Peptidase C14, p20 domain	Domain
A	IPR011600	Peptidase C14, caspase domain	Domain
A	IPR016129	Peptidase family C14A, His active site	Active Site
A	IPR015917	Peptidase C14A, caspase catalytic domain	Domain
A	IPR011029	Death-like domain superfamily	Homologous Superfamily
A	IPR033139	Peptidase family C14A, cysteine active site	Active Site
A	IPR002138	Peptidase C14, caspase non-catalytic subunit p10	Domain
A	IPR001315	CARD domain	Domain
A	IPR002398	Peptidase C14 family	Family
B	IPR029030	Caspase-like domain superfamily	Homologous Superfamily
B	IPR001309	Peptidase C14, p20 domain	Domain
B	IPR011600	Peptidase C14, caspase domain	Domain
B	IPR016129	Peptidase family C14A, His active site	Active Site
B	IPR015917	Peptidase C14A, caspase catalytic domain	Domain
B	IPR011029	Death-like domain superfamily	Homologous Superfamily
B	IPR033139	Peptidase family C14A, cysteine active site	Active Site
B	IPR002138	Peptidase C14, caspase non-catalytic subunit p10	Domain
B	IPR001315	CARD domain	Domain
B	IPR002398	Peptidase C14 family	Family
C, D	IPR040460	Gasdermin, pore forming domain	Domain
C, D	IPR007677	Gasdermin	Family
C, D	IPR041263	Gasdermin, PUB domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P29466	status epilepticus Liver Cirrhosis, Experimental amyotrophic lateral sclerosis type 1 obesity disorder kidney disease allergic disease hyperhomocysteinemia multiple sclerosis pneumonia inflammatory bowel disease juvenile dermatomyositis lung cancer malignant glioma atherosclerosis breast cancer status epilepticus Liver Cirrhosis, Experimental amyotrophic lateral sclerosis type 1 obesity disorder kidney disease allergic disease hyperhomocysteinemia multiple sclerosis pneumonia inflammatory bowel disease juvenile dermatomyositis lung cancer malignant glioma atherosclerosis breast cancer neurodegenerative disease Crohn disease pilocytic astrocytoma pneumonitis inborn carbohydrate metabolic disorder Sjogren syndrome subependymal giant cell astrocytoma lung carcinoma malignant mesothelioma autoimmune disease chronic kidney disease cutaneous lupus erythematosus ovarian cancer plasma cell myeloma psoriasis ulcerative colitis large cell medulloblastoma lung adenocarcinoma malignant colon neoplasm arthritic joint disease B-cell chronic lymphocytic leukemia nephrosclerosis non-small cell lung carcinoma cystic fibrosis glioblastoma
B	Pharos: P29466	status epilepticus Liver Cirrhosis, Experimental amyotrophic lateral sclerosis type 1 obesity disorder kidney disease allergic disease hyperhomocysteinemia multiple sclerosis pneumonia inflammatory bowel disease juvenile dermatomyositis lung cancer malignant glioma atherosclerosis breast cancer status epilepticus Liver Cirrhosis, Experimental amyotrophic lateral sclerosis type 1 obesity disorder kidney disease allergic disease hyperhomocysteinemia multiple sclerosis pneumonia inflammatory bowel disease juvenile dermatomyositis lung cancer malignant glioma atherosclerosis breast cancer neurodegenerative disease Crohn disease pilocytic astrocytoma pneumonitis inborn carbohydrate metabolic disorder Sjogren syndrome subependymal giant cell astrocytoma lung carcinoma malignant mesothelioma autoimmune disease chronic kidney disease cutaneous lupus erythematosus ovarian cancer plasma cell myeloma psoriasis ulcerative colitis large cell medulloblastoma lung adenocarcinoma malignant colon neoplasm arthritic joint disease B-cell chronic lymphocytic leukemia nephrosclerosis non-small cell lung carcinoma cystic fibrosis glioblastoma