2OI0 | pdb_00002oi0

Crystal structure analysis 0f the TNF-a Coverting Enzyme (TACE) in complexed with Aryl-sulfonamide

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d2oi0a2	Alpha and beta proteins (a+b)	Zincin-like	Metalloproteases ('zincins'), catalytic domain	TNF-alpha converting enzyme, TACE, catalytic domain	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d2oi0a3	Artifacts	Tags	Tags	Tags	C-terminal Tags	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	Metalloproteases (zincins), catalytic domain	8042540	3001975	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	Reprolysin	e2oi0A1	A: mixed a+b and a/b	X: Zincin-like	H: Metalloproteases (zincins) catalytic domain (From Topology)	T: Metalloproteases (zincins) catalytic domain	F: Reprolysin	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.40.390.10	Alpha Beta	3-Layer(aba) Sandwich	Collagenase (Catalytic Domain)	Collagenase (Catalytic Domain)	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF13688	Metallo-peptidase family M12 (Reprolysin_5)	Metallo-peptidase family M12	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	TNF- a Converting Enzyme (TACE)	peptidase activity catalytic activity, acting on a protein metallopeptidase activity hydrolase activity catalytic activity protein binding binding signaling receptor binding Notch binding SH3 domain binding protein domain specific binding endopeptidase activity cation binding ion binding peptidase activity catalytic activity, acting on a protein metallopeptidase activity hydrolase activity catalytic activity protein binding binding signaling receptor binding Notch binding SH3 domain binding protein domain specific binding endopeptidase activity cation binding ion binding metal ion binding small molecule binding metalloendopeptidase activity PDZ domain binding cytokine binding cell adhesion molecule binding protein-containing complex binding integrin binding interleukin-6 receptor binding cytokine receptor binding growth factor receptor binding tumor necrosis factor binding metalloendopeptidase activity involved in amyloid precursor protein catabolic process	response to stimulus response to chemical response to xenobiotic stimulus cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction 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 response to stimulus response to chemical response to xenobiotic stimulus cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction 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 regulation of cell communication cellular process response to tumor necrosis factor positive regulation of cytokine-mediated signaling pathway positive regulation of signaling cell surface receptor protein tyrosine kinase signaling pathway positive regulation of ERBB signaling pathway regulation of epidermal growth factor receptor signaling pathway epidermal growth factor receptor signaling pathway enzyme-linked receptor protein signaling pathway positive regulation of epidermal growth factor receptor signaling pathway regulation of ERBB signaling pathway ERBB signaling pathway regulation of cell cycle phase transition cell cycle phase transition regulation of cell cycle G1/S phase transition cell cycle G1/S phase transition mitotic cell cycle regulation of mitotic cell cycle positive regulation of mitotic cell cycle phase transition positive regulation of cell cycle process positive regulation of mitotic cell cycle cell cycle regulation of cell cycle cell cycle process positive regulation of G1/S transition of mitotic cell cycle regulation of cell cycle process positive regulation of cell cycle regulation of mitotic cell cycle phase transition positive regulation of cell cycle G1/S phase transition mitotic cell cycle process regulation of G1/S transition of mitotic cell cycle positive regulation of cell cycle phase transition G1/S transition of mitotic cell cycle mitotic cell cycle phase transition developmental process multicellular organismal process cellular developmental process hemopoiesis cell activation cell development mononuclear cell differentiation lymphocyte activation lymphocyte differentiation leukocyte activation T cell differentiation in thymus T cell activation immune system process cell differentiation anatomical structure development T cell differentiation leukocyte differentiation immune system development multicellular organism development spleen development animal organ development hematopoietic or lymphoid organ development system development negative regulation of transforming growth factor beta receptor signaling pathway cell surface receptor protein serine/threonine kinase signaling pathway cellular response to growth factor stimulus negative regulation of signaling cellular response to transforming growth factor beta stimulus regulation of transmembrane receptor protein serine/threonine kinase signaling pathway negative regulation of biological process negative regulation of cell communication regulation of transforming growth factor beta receptor signaling pathway cellular response to endogenous stimulus negative regulation of cellular process negative regulation of response to stimulus regulation of cellular response to transforming growth factor beta stimulus response to endogenous stimulus regulation of cellular response to growth factor stimulus negative regulation of signal transduction response to transforming growth factor beta transforming growth factor beta receptor signaling pathway response to growth factor transforming growth factor beta receptor superfamily signaling pathway negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of biosynthetic process regulation of cytokine production cytokine production regulation of multicellular organismal process positive regulation of macromolecule metabolic process regulation of biosynthetic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of chemokine production regulation of gene expression biosynthetic process positive regulation of gene expression chemokine production positive regulation of chemokine production 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 cell population proliferation positive regulation of cell population proliferation endothelial cell proliferation positive regulation of epithelial cell proliferation regulation of vascular endothelial cell proliferation regulation of endothelial cell proliferation regulation of cell population proliferation positive regulation of endothelial cell proliferation regulation of epithelial cell proliferation vascular endothelial cell proliferation epithelial cell proliferation positive regulation of vascular endothelial cell proliferation wound healing epithelium development morphogenesis of an epithelium epiboly involved in wound healing tissue development morphogenesis of an epithelial sheet wound healing, spreading of epidermal cells tissue morphogenesis anatomical structure morphogenesis response to stress epiboly cell migration wound healing, spreading of cells cell motility response to wounding amyloid precursor protein catabolic process primary metabolic process protein metabolic process amyloid precursor protein metabolic process cell adhesion response to decreased oxygen levels response to hypoxia response to oxygen levels response to abiotic stimulus Notch signaling pathway positive regulation of locomotion regulation of cell motility regulation of response to external stimulus positive regulation of chemotaxis positive regulation of cell migration positive regulation of response to external stimulus taxis positive regulation of cell motility regulation of cell migration regulation of immune system process positive regulation of immune system process locomotion cell chemotaxis chemotaxis regulation of leukocyte chemotaxis regulation of leukocyte migration response to external stimulus positive regulation of leukocyte chemotaxis positive regulation of leukocyte migration regulation of chemotaxis leukocyte migration cellular response to chemical stimulus regulation of locomotion leukocyte chemotaxis regulation of growth regulation of cellular component organization growth positive regulation of cell growth regulation of cell growth cell growth cellular component organization positive regulation of growth cellular component organization or biogenesis B cell activation B cell differentiation neutrophil mediated immunity leukocyte mediated immunity myeloid leukocyte mediated immunity immune effector process cellular response to high density lipoprotein particle stimulus cellular response to lipoprotein particle stimulus protein maturation proteolysis protein processing positive regulation of phosphorylation regulation of catalytic activity regulation of transferase activity positive regulation of phosphate metabolic process regulation of primary metabolic process positive regulation of protein serine/threonine kinase activity positive regulation of cyclin-dependent protein serine/threonine kinase activity regulation of phosphate metabolic process regulation of cyclin-dependent protein serine/threonine kinase activity phosphate-containing compound metabolic process phosphorus metabolic process protein modification process positive regulation of protein phosphorylation protein phosphorylation positive regulation of phosphorus metabolic process phosphorylation regulation of protein metabolic process regulation of molecular function positive regulation of kinase activity regulation of kinase activity macromolecule modification regulation of protein serine/threonine kinase activity regulation of phosphorus metabolic process regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process positive regulation of cyclin-dependent protein kinase activity positive regulation of molecular function positive regulation of protein modification process positive regulation of protein kinase activity positive regulation of transferase activity positive regulation of catalytic activity regulation of protein kinase activity regulation of phosphorylation cell adhesion mediated by integrin commissural neuron axon guidance axonogenesis cell projection organization plasma membrane bounded cell projection morphogenesis neuron projection development cell morphogenesis neurogenesis cell projection morphogenesis neuron differentiation neuron projection morphogenesis plasma membrane bounded cell projection organization axon guidance nervous system development axon development cell morphogenesis involved in neuron differentiation generation of neurons neuron projection guidance neuron development homeostatic process leukocyte apoptotic process regulation of programmed cell death mast cell homeostasis myeloid cell homeostasis myeloid cell apoptotic process regulation of leukocyte apoptotic process regulation of apoptotic process cell death mast cell apoptotic process multicellular organismal-level homeostasis leukocyte homeostasis regulation of mast cell apoptotic process homeostasis of number of cells apoptotic process regulation of myeloid cell apoptotic process programmed cell death regulation of blood vessel endothelial cell migration endothelial cell migration positive regulation of blood vessel endothelial cell migration positive regulation of endothelial cell migration blood vessel endothelial cell migration regulation of endothelial cell migration Notch receptor processing adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains immune response anatomical structure formation involved in morphogenesis germinal center formation adaptive immune response peptidyl-amino acid modification positive regulation of epidermal growth factor-activated receptor activity positive regulation of signaling receptor activity regulation of protein tyrosine kinase activity regulation of epidermal growth factor-activated receptor activity regulation of signaling receptor activity peptidyl-tyrosine modification positive regulation of peptidyl-tyrosine phosphorylation positive regulation of protein tyrosine kinase activity regulation of peptidyl-tyrosine phosphorylation peptidyl-tyrosine phosphorylation positive regulation of T cell chemotaxis regulation of lymphocyte chemotaxis regulation of mononuclear cell migration positive regulation of lymphocyte migration lymphocyte migration regulation of T cell migration regulation of T cell chemotaxis lymphocyte chemotaxis regulation of lymphocyte migration positive regulation of lymphocyte chemotaxis positive regulation of mononuclear cell migration T cell chemotaxis positive regulation of T cell migration mononuclear cell migration T cell migration secretion transport cell-cell signaling export from cell establishment of localization localization secretion by cell signal release regulation of tumor necrosis factor production positive regulation of tumor necrosis factor superfamily cytokine production tumor necrosis factor superfamily cytokine production positive regulation of tumor necrosis factor production tumor necrosis factor production regulation of tumor necrosis factor superfamily cytokine production negative regulation of cold-induced thermogenesis negative regulation of metabolic process adaptive thermogenesis regulation of cold-induced thermogenesis cold-induced thermogenesis temperature homeostasis negative regulation of multicellular organismal process biological process involved in interspecies interaction between organisms response to lipid response to other organism response to oxygen-containing compound response to lipopolysaccharide response to biotic stimulus response to bacterium response to external biotic stimulus response to molecule of bacterial origin membrane protein proteolysis membrane protein ectodomain proteolysis defense response defense response to Gram-positive bacterium defense response to bacterium defense response to other organism	cellular anatomical structure membrane intracellular organelle intracellular anatomical structure cytoskeleton organelle membraneless organelle intracellular membraneless organelle actin cytoskeleton cytoplasm cytosol membrane-bounded organelle membrane-enclosed lumen intracellular membrane-bounded organelle cellular anatomical structure membrane intracellular organelle intracellular anatomical structure cytoskeleton organelle membraneless organelle intracellular membraneless organelle actin cytoskeleton cytoplasm cytosol membrane-bounded organelle membrane-enclosed lumen intracellular membrane-bounded organelle endomembrane system intracellular organelle lumen endoplasmic reticulum lumen organelle lumen endoplasmic reticulum Golgi membrane Golgi apparatus bounding membrane of organelle organelle membrane cell periphery apical part of cell plasma membrane plasma membrane region apical plasma membrane cell surface membrane microdomain membrane raft

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR001590	Peptidase M12B, ADAM/reprolysin	Domain
A	IPR032029	ADAM17, membrane-proximal domain	Domain
A	IPR034025	ADAM10/ADAM17 catalytic domain	Domain
A	IPR001762	Disintegrin domain	Domain
A	IPR036436	Disintegrin domain superfamily	Homologous Superfamily
A	IPR024079	Metallopeptidase, catalytic domain superfamily	Homologous Superfamily
A	IPR051489	Disintegrin and Metalloproteinase Domain-Containing	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P78536	inflammatory skin and bowel disease, neonatal, 1 colitis Liver Cirrhosis, Experimental systemic lupus erythematosus chronic beryllium disease tenosynovitis idiopathic acute eosinophilic pneumonia primitive neuroectodermal tumor contact dermatitis iritis Crohn disease uveitis acquired thrombocytopenia pulmonary eosinophilia dermatitis herpetiformis inflammatory skin and bowel disease, neonatal, 1 colitis Liver Cirrhosis, Experimental systemic lupus erythematosus chronic beryllium disease tenosynovitis idiopathic acute eosinophilic pneumonia primitive neuroectodermal tumor contact dermatitis iritis Crohn disease uveitis acquired thrombocytopenia pulmonary eosinophilia dermatitis herpetiformis lung carcinoma adrenocortical insufficiency rheumatic heart disease Diamond-Blackfan anemia medulloblastoma angioedema sarcoidosis eosinophilic pneumonia multiple sclerosis asthma nephrotic syndrome atypical teratoid rhabdoid tumor skin disease exanthem osteosarcoma autoimmune thrombocytopenic purpura pemphigus blepharoconjunctivitis granuloma annulare pneumocystosis bursitis temporal arteritis Hodgkins lymphoma thyroiditis inherited aplastic anemia juvenile idiopathic arthritis psoriasis acute lymphoblastic leukemia pulmonary fibrosis diabetes mellitus malignant ependymoma allergic bronchopulmonary aspergillosis rheumatoid arthritis ankylosing spondylitis epicondylitis musculoskeletal system disease atopic conjunctivitis autoimmune disease Stevens-Johnson syndrome extrinsic allergic alveolitis ovarian cancer bacterial conjunctivitis sympathetic ophthalmia glioblastoma pilocytic astrocytoma polymyalgia rheumatica tendinitis primary cutaneous T-cell lymphoma congenital adrenal hyperplasia inflammatory bowel disease iridocyclitis corneal ulcer ulcerative colitis keratitis psoriatic arthritis dacryocystitis lung cancer Addison disease malignant glioma allergic rhinitis rosacea miliary tuberculosis aspiration pneumonitis seborrheic dermatitis erythema multiforme mycosis fungoides atopic eczema Sjogren syndrome autoimmune hemolytic anemia subependymal giant cell astrocytoma eye disease pancreatic intraductal papillary-mucinous neoplasm synovitis gout

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.