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Structure of the Caspase-8/cFLIP death effector domain assembly

External Resource: Annotation

Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C	PF01335	Death effector domain (DED)	Death effector domain	-	Domain
D [auth H], E [auth I], F [auth J], G [auth K]	PF01335	Death effector domain (DED)	Death effector domain	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C	Caspase-8 subunit p10	cysteine-type peptidase activity peptidase activity catalytic activity, acting on a protein hydrolase activity catalytic activity protein-containing complex binding binding protein binding signaling receptor binding cytokine receptor binding tumor necrosis factor receptor superfamily binding death receptor binding ubiquitin protein ligase binding ubiquitin-like protein ligase binding cysteine-type peptidase activity peptidase activity catalytic activity, acting on a protein hydrolase activity catalytic activity protein-containing complex binding binding protein binding signaling receptor binding cytokine receptor binding tumor necrosis factor receptor superfamily binding death receptor binding ubiquitin protein ligase binding ubiquitin-like protein ligase binding enzyme binding identical protein binding cysteine-type endopeptidase activity endopeptidase activity scaffold protein binding death effector domain binding protein domain specific binding tumor necrosis factor receptor binding	developmental process heart development multicellular organism development multicellular organismal process anatomical structure development animal organ development circulatory system development system development activation of cysteine-type endopeptidase activity regulation of cellular process regulation of catalytic activity positive regulation of protein metabolic process positive regulation of peptidase activity positive regulation of biological process developmental process heart development multicellular organism development multicellular organismal process anatomical structure development animal organ development circulatory system development system development activation of cysteine-type endopeptidase activity regulation of cellular process regulation of catalytic activity positive regulation of protein metabolic process positive regulation of peptidase activity positive regulation of biological process protein maturation regulation of primary metabolic process positive regulation of molecular function positive regulation of metabolic process regulation of proteolysis proteolysis regulation of endopeptidase activity positive regulation of macromolecule metabolic process protein metabolic process positive regulation of cellular process zymogen activation regulation of cysteine-type endopeptidase activity regulation of biological process regulation of protein metabolic process regulation of peptidase activity biological regulation positive regulation of catalytic activity primary metabolic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of molecular function positive regulation of hydrolase activity biosynthetic process positive regulation of cysteine-type endopeptidase activity regulation of hydrolase activity positive regulation of endopeptidase activity positive regulation of proteolysis protein processing metabolic process cellular process macromolecule metabolic process regulation of metabolic process cell differentiation involved in embryonic placenta development cellular developmental process placenta development reproductive process syncytiotrophoblast cell differentiation involved in labyrinthine layer development chordate embryonic development labyrinthine layer development developmental process involved in reproduction embryo development in utero embryonic development embryonic placenta development embryo development ending in birth or egg hatching cell differentiation embryonic organ development apoptotic process cell death programmed cell death positive regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death positive regulation of apoptotic process immune system process B cell activation cell activation lymphocyte activation leukocyte activation neuron apoptotic process positive regulation of neuron apoptotic process regulation of neuron apoptotic process catabolic process proteolysis involved in protein catabolic process protein catabolic process macromolecule catabolic process cellular response to stimulus response to stimulus cell surface receptor signaling pathway signaling extrinsic apoptotic signaling pathway cell communication apoptotic signaling pathway signal transduction extrinsic apoptotic signaling pathway via death domain receptors interleukin-1 production regulation of interleukin-1 beta production positive regulation of macromolecule biosynthetic 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 regulation of biosynthetic process regulation of interleukin-1 production 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 natural killer cell activation myeloid leukocyte differentiation regulation of leukocyte differentiation regulation of developmental process cell development regulation of cell differentiation mononuclear cell differentiation regulation of cell development positive regulation of developmental process positive regulation of cell differentiation positive regulation of hemopoiesis regulation of immune system process regulation of macrophage differentiation positive regulation of immune system process regulation of multicellular organismal development hemopoiesis regulation of myeloid cell differentiation positive regulation of cell development macrophage differentiation regulation of myeloid leukocyte differentiation positive regulation of myeloid leukocyte differentiation positive regulation of macrophage differentiation myeloid cell differentiation positive regulation of myeloid cell differentiation regulation of hemopoiesis positive regulation of leukocyte differentiation leukocyte differentiation response to cytokine regulation of signal transduction cytokine-mediated signaling pathway cellular response to tumor necrosis factor tumor necrosis factor-mediated signaling pathway cellular response to cytokine stimulus regulation of signaling regulation of tumor necrosis factor-mediated signaling pathway regulation of cytokine-mediated signaling pathway response to peptide regulation of response to cytokine stimulus regulation of response to stimulus response to chemical regulation of cell communication response to tumor necrosis factor cellular response to chemical stimulus cellular response to organic cyclic compound response to organic cyclic compound self proteolysis positive regulation of cell communication positive regulation of signal transduction positive regulation of canonical NF-kappaB signal transduction intracellular signal transduction positive regulation of response to stimulus 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 positive regulation of signaling blood vessel morphogenesis tube development angiogenesis vasculature development anatomical structure morphogenesis tube morphogenesis anatomical structure formation involved in morphogenesis blood vessel development negative regulation of signaling negative regulation of intracellular signal transduction negative regulation of biological process negative regulation of canonical NF-kappaB signal transduction negative regulation of cell communication negative regulation of cellular process negative regulation of response to stimulus negative regulation of signal transduction execution phase of apoptosis response to alcohol response to oxygen-containing compound response to ethanol necroptotic process negative regulation of programmed cell death negative regulation of necroptotic process programmed necrotic cell death regulation of necroptotic process negative regulation of programmed necrotic cell death regulation of programmed necrotic cell death T cell activation regulation of defense response regulation of response to biotic stimulus biological process involved in interspecies interaction between organisms regulation of response to external stimulus response to biotic stimulus response to stress regulation of response to stress innate immune response response to external biotic stimulus immune response response to other organism defense response regulation of innate immune response defense response to symbiont response to external stimulus defense response to other organism regulation of immune response response to mechanical stimulus response to abiotic stimulus cellular response to mechanical stimulus cellular response to abiotic stimulus cellular response to external stimulus cellular response to environmental stimulus positive regulation of locomotion regulation of cell motility positive regulation of cell migration regulation of locomotion positive regulation of cell motility regulation of cell migration cell migration cell motility locomotion TRAIL-activated apoptotic signaling pathway pyroptotic inflammatory response inflammatory response response to cobalt ion response to metal ion response to lipid response to lipopolysaccharide response to bacterium response to molecule of bacterial origin response to estradiol	cell projection cellular anatomical structure cell leading edge plasma membrane bounded cell projection lamellipodium intracellular anatomical structure cytoplasm cytosol intracellular organelle cytoskeleton organelle membraneless organelle intracellular membraneless organelle membrane-bounded organelle cell projection cellular anatomical structure cell leading edge plasma membrane bounded cell projection lamellipodium intracellular anatomical structure cytoplasm cytosol intracellular organelle cytoskeleton organelle membraneless organelle intracellular membraneless organelle membrane-bounded organelle mitochondrial membrane mitochondrion membrane organelle outer membrane intracellular membrane-bounded organelle organelle envelope bounding membrane of organelle mitochondrial envelope mitochondrial outer membrane outer membrane organelle membrane cell body cell periphery protein-containing complex plasma membrane protein complex plasma membrane death-inducing signaling complex membrane protein complex nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen CD95 death-inducing signaling complex ripoptosome catalytic complex
D [auth H], E [auth I], F [auth J], G [auth K]	CASP8 and FADD-like apoptosis regulator subunit p43	protein-containing complex binding binding protein binding signaling receptor binding cytokine receptor binding tumor necrosis factor receptor superfamily binding death receptor binding enzyme binding protease binding enzyme regulator activity enzyme activator activity molecular function activator activity molecular function regulator activity	regulation of biological process cellular response to growth factor stimulus response to stimulus negative regulation of response to stimulus regulation of cellular response to transforming growth factor beta stimulus cellular response to transforming growth factor beta stimulus response to endogenous stimulus regulation of cellular response to growth factor stimulus biological regulation negative regulation of biological process negative regulation of cellular response to growth factor stimulus negative regulation of cellular response to transforming growth factor beta stimulus cellular response to endogenous stimulus response to transforming growth factor beta regulation of response to stimulus regulation of biological process cellular response to growth factor stimulus response to stimulus negative regulation of response to stimulus regulation of cellular response to transforming growth factor beta stimulus cellular response to transforming growth factor beta stimulus response to endogenous stimulus regulation of cellular response to growth factor stimulus biological regulation negative regulation of biological process negative regulation of cellular response to growth factor stimulus negative regulation of cellular response to transforming growth factor beta stimulus cellular response to endogenous stimulus response to transforming growth factor beta regulation of response to stimulus response to growth factor response to ketone response to lipid response to chemical response to oxygen-containing compound response to testosterone response to organic cyclic compound response to decreased oxygen levels cellular response to stimulus cellular response to oxygen levels cellular response to hypoxia cellular response to decreased oxygen levels cellular response to chemical stimulus cellular response to stress response to hypoxia response to stress response to oxygen levels response to abiotic stimulus cellular process extrinsic apoptotic signaling pathway via death domain receptors regulation of cellular process signaling negative regulation of signaling regulation of signal transduction regulation of programmed cell death extrinsic apoptotic signaling pathway negative regulation of cell communication cell communication negative regulation of extrinsic apoptotic signaling pathway negative regulation of apoptotic signaling pathway negative regulation of cellular process signal transduction regulation of signaling cell surface receptor signaling pathway negative regulation of programmed cell death regulation of apoptotic process negative regulation of extrinsic apoptotic signaling pathway via death domain receptors cell death negative regulation of signal transduction regulation of extrinsic apoptotic signaling pathway apoptotic signaling pathway negative regulation of apoptotic process regulation of extrinsic apoptotic signaling pathway via death domain receptors regulation of cell communication apoptotic process programmed cell death regulation of apoptotic signaling pathway neuron apoptotic process positive regulation of programmed cell death positive regulation of biological process positive regulation of apoptotic process positive regulation of neuron apoptotic process positive regulation of cellular process regulation of neuron apoptotic process negative regulation of hepatocyte apoptotic process regulation of epithelial cell apoptotic process epithelial cell apoptotic process regulation of hepatocyte apoptotic process negative regulation of epithelial cell apoptotic process hepatocyte apoptotic process response to hormone response to steroid hormone cellular response to ketone cellular response to steroid hormone stimulus cellular response to hormone stimulus cellular response to dexamethasone stimulus response to glucocorticoid cellular response to organic cyclic compound cellular response to glucocorticoid stimulus cellular response to oxygen-containing compound cellular response to corticosteroid stimulus response to corticosteroid cellular response to lipid response to dexamethasone regulation of neuron projection development multicellular organismal process regulation of cellular component organization positive regulation of cellular component organization cellular developmental process cell projection organization cell development neuron projection development cellular component organization neurogenesis multicellular organism development neuron differentiation positive regulation of neuron projection development cell differentiation anatomical structure development positive regulation of cell projection organization cellular component organization or biogenesis system development developmental process plasma membrane bounded cell projection organization regulation of cell projection organization nervous system development generation of neurons neuron development regulation of plasma membrane bounded cell projection organization regulation of syncytium formation by plasma membrane fusion regulation of developmental process cell-cell fusion negative regulation of syncytium formation by plasma membrane fusion muscle cell differentiation myotube differentiation muscle structure development syncytium formation negative regulation of cellular component organization negative regulation of developmental process myoblast fusion regulation of myoblast fusion negative regulation of myoblast fusion syncytium formation by plasma membrane fusion anatomical structure morphogenesis anatomical structure formation involved in morphogenesis striated muscle cell differentiation positive regulation of DNA-binding transcription factor activity positive regulation of NF-kappaB transcription factor activity RNA metabolic process regulation of primary metabolic process nucleobase-containing compound metabolic process RNA biosynthetic process positive regulation of molecular function nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of biosynthetic process primary metabolic process regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of molecular function regulation of gene expression biosynthetic process regulation of DNA-binding transcription factor activity metabolic process regulation of macromolecule biosynthetic process regulation of DNA-templated transcription macromolecule metabolic process regulation of metabolic process necroptotic process programmed necrotic cell death regulation of necroptotic process regulation of programmed necrotic cell death homeostatic process hemopoiesis erythrocyte differentiation multicellular organismal-level homeostasis myeloid cell differentiation immune system process homeostasis of number of cells myeloid cell homeostasis erythrocyte homeostasis negative regulation of cardiac muscle cell apoptotic process muscle cell apoptotic process regulation of cardiac muscle cell apoptotic process regulation of muscle cell apoptotic process cardiac muscle cell apoptotic process regulation of striated muscle cell apoptotic process striated muscle cell apoptotic process negative regulation of muscle cell apoptotic process negative regulation of striated muscle cell apoptotic process cellular response to nitrogen compound response to nitrogen compound cellular response to nitric oxide response to nitric oxide cellular response to reactive nitrogen species epithelium development epidermal cell differentiation epidermis development animal organ development tissue development epithelial cell differentiation skin development keratinocyte differentiation positive regulation of cell communication positive regulation of signal transduction positive regulation of canonical NF-kappaB signal transduction intracellular signal transduction positive regulation of response to stimulus 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 positive regulation of signaling positive regulation of ERK1 and ERK2 cascade positive regulation of MAPK cascade regulation of MAPK cascade MAPK cascade ERK1 and ERK2 cascade regulation of ERK1 and ERK2 cascade connective tissue development positive regulation of cell population proliferation renal system development kidney vasculature development renal system vasculature development positive regulation of glomerular mesangial cell proliferation regulation of glomerular mesangial cell proliferation nephron development blood vessel development positive regulation of cell proliferation involved in kidney development cell population proliferation cell proliferation involved in kidney development glomerular mesangium development regulation of cell proliferation involved in kidney development vasculature development circulatory system development glomerulus development regulation of cell population proliferation glomerular mesangial cell proliferation glomerulus vasculature development kidney development reactive oxygen species biosynthetic process negative regulation of metabolic process reactive oxygen species metabolic process regulation of reactive oxygen species biosynthetic process negative regulation of reactive oxygen species metabolic process negative regulation of reactive oxygen species biosynthetic process negative regulation of biosynthetic process regulation of reactive oxygen species metabolic process muscle atrophy system process striated muscle adaptation skeletal muscle atrophy muscle adaptation skeletal muscle adaptation muscle system process striated muscle atrophy execution phase of apoptosis skeletal muscle organ development skeletal muscle tissue development muscle tissue development muscle organ development striated muscle tissue development regulation of hepatocyte proliferation gland development liver development gland morphogenesis animal organ morphogenesis epithelial cell proliferation liver morphogenesis positive regulation of epithelial cell proliferation epithelial cell proliferation involved in liver morphogenesis hepatocyte proliferation hepaticobiliary system development positive regulation of hepatocyte proliferation regulation of epithelial cell proliferation skeletal muscle satellite cell proliferation muscle cell proliferation regulation of skeletal muscle satellite cell proliferation skeletal muscle cell proliferation regulation of skeletal muscle cell proliferation striated muscle cell proliferation wound healing response to wounding tissue regeneration skeletal muscle tissue regeneration developmental growth growth regeneration response to estradiol cellular response to estradiol stimulus cellular component assembly involved in morphogenesis skeletal myofibril assembly membraneless organelle assembly cellular component biogenesis striated muscle cell development cellular anatomical entity morphogenesis cellular component assembly muscle cell development actin filament-based process actomyosin structure organization actin cytoskeleton organization organelle assembly myofibril assembly organelle organization supramolecular fiber organization cytoskeleton organization response to peptide hormone cellular response to peptide hormone stimulus response to insulin cellular response to insulin stimulus cellular response to epidermal growth factor stimulus response to epidermal growth factor proteolysis protein metabolic process positive regulation of extracellular matrix organization extracellular matrix organization regulation of extracellular matrix organization extracellular structure organization external encapsulating structure organization	cellular anatomical structure intracellular anatomical structure cytoplasm cytosol cell periphery protein-containing complex plasma membrane protein complex membrane plasma membrane death-inducing signaling complex membrane protein complex CD95 death-inducing signaling complex ripoptosome catalytic complex

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C	IPR029030	Caspase-like domain superfamily	Homologous Superfamily
A, B, C	IPR001875	Death effector domain	Domain
A, B, C	IPR001309	Peptidase C14, p20 domain	Domain
A, B, C	IPR011600	Peptidase C14, caspase domain	Domain
A, B, C	IPR016129	Peptidase family C14A, His active site	Active Site
A, B, C	IPR033170	Caspase-8, death effector domain 1	Domain
A, B, C	IPR015917	Peptidase C14A, caspase catalytic domain	Domain
A, B, C	IPR011029	Death-like domain superfamily	Homologous Superfamily
A, B, C	IPR051290	CASP8/FADD-like_regulator	Unknown
A, B, C	IPR033139	Peptidase family C14A, cysteine active site	Active Site
A, B, C	IPR002138	Peptidase C14, caspase non-catalytic subunit p10	Domain
D [auth H], E [auth I], F [auth J], G [auth K]	IPR029030	Caspase-like domain superfamily	Homologous Superfamily
D [auth H], E [auth I], F [auth J], G [auth K]	IPR001875	Death effector domain	Domain
D [auth H], E [auth I], F [auth J], G [auth K]	IPR001309	Peptidase C14, p20 domain	Domain
D [auth H], E [auth I], F [auth J], G [auth K]	IPR011600	Peptidase C14, caspase domain	Domain
D [auth H], E [auth I], F [auth J], G [auth K]	IPR015917	Peptidase C14A, caspase catalytic domain	Domain
D [auth H], E [auth I], F [auth J], G [auth K]	IPR011029	Death-like domain superfamily	Homologous Superfamily
D [auth H], E [auth I], F [auth J], G [auth K]	IPR051290	CASP8/FADD-like_regulator	Unknown

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C	Pharos: Q14790	melanoma non-small cell lung carcinoma breast carcinoma status epilepticus autoimmune lymphoproliferative syndrome type 2B type 2 diabetes mellitus esophageal cancer autoimmune lymphoproliferative syndrome skin neoplasm tubular adenocarcinoma Myocardial Reperfusion Injury adenocarcinoma gastric cancer lung cancer colorectal cancer melanoma non-small cell lung carcinoma breast carcinoma status epilepticus autoimmune lymphoproliferative syndrome type 2B type 2 diabetes mellitus esophageal cancer autoimmune lymphoproliferative syndrome skin neoplasm tubular adenocarcinoma Myocardial Reperfusion Injury adenocarcinoma gastric cancer lung cancer colorectal cancer cutaneous melanoma allergic contact dermatitis granular cell carcinoma B-cell chronic lymphocytic leukemia hepatocellular carcinoma breast cancer cervical cancer skin cancer contact dermatitis head and neck squamous cell carcinoma ischemia reperfusion injury Sjogren syndrome childhood acute lymphoblastic leukemia lung disease malignant ependymoma cutaneous lupus erythematosus adult hepatocellular carcinoma osteosarcoma atypical teratoid rhabdoid tumor hematologic disease breast adenocarcinoma human papilloma virus infection prostate carcinoma breast disease rheumatoid arthritis skin basal cell carcinoma squamous cell carcinoma malignant glioma cribriform carcinoma maturity-onset diabetes of the young neoplasm of esophagus gastric neoplasm ovarian cancer intracerebral hemorrhage psoriasis cancer lung carcinoma colorectal carcinoma lymphatic system disease subependymal giant cell astrocytoma cribriform carcinoma of breast esophageal squamous cell carcinoma oral cavity squamous cell carcinoma glioblastoma pancreatic intraductal papillary-mucinous neoplasm pilocytic astrocytoma bipolar disorder hereditary diffuse gastric adenocarcinoma carcinoma of esophagus lung benign neoplasm
D [auth H], E [auth I], F [auth J], G [auth K]	Pharos: O15519	myelodysplastic syndrome Lymphoma, Extranodal NK-T-Cell Hodgkins lymphoma leukemia non-small cell lung carcinoma spina bifida interstitial cystitis lung cancer adenoma amyotrophic lateral sclerosis breast cancer nodular lymphocyte predominant Hodgkin lymphoma dermatomyositis ovarian cancer glioblastoma myelodysplastic syndrome Lymphoma, Extranodal NK-T-Cell Hodgkins lymphoma leukemia non-small cell lung carcinoma spina bifida interstitial cystitis lung cancer adenoma amyotrophic lateral sclerosis breast cancer nodular lymphocyte predominant Hodgkin lymphoma dermatomyositis ovarian cancer glioblastoma pancreatic neoplasm prostate carcinoma Hodgkin's lymphoma, lymphocytic-histiocytic predominance sarcoidosis ulcerative colitis lung carcinoma malignant colon neoplasm malignant pancreatic neoplasm adrenal cortex carcinoma B-cell chronic lymphocytic leukemia cancer extranodal nasal NK/T cell lymphoma pancreatic ductal adenocarcinoma Pick disease psoriasis Hodgkin's lymphoma, mixed cellularity skin basal cell carcinoma Huntington disease lung adenocarcinoma malignant mesothelioma medulloblastoma bipolar disorder myopathy cutaneous lupus erythematosus osteosarcoma Gaucher disease pancreatic intraductal papillary-mucinous neoplasm pituitary cancer Hodgkin's lymphoma, lymphocytic depletion rheumatoid arthritis

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.