1RTF

COMPLEX OF BENZAMIDINE WITH THE CATALYTIC DOMAIN OF HUMAN TWO CHAIN TISSUE PLASMINOGEN ACTIVATOR [(TC)-T-PA]

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations
Structure Motif: Primary M-CSA Annotation

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
B	d1rtf.1	All beta proteins	Trypsin-like serine proteases	Trypsin-like serine proteases	Eukaryotic proteases	Two-chain tissue plasminogen activator (TC)-T-PA	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d1rtf.1	All beta proteins	Trypsin-like serine proteases	Trypsin-like serine proteases	Eukaryotic proteases	Two-chain tissue plasminogen activator (TC)-T-PA	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)
B	SCOP2B Superfamily	Trypsin-like serine proteases	8042245	3000114	SCOP2B (2022-06-29)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
B	2.40.10.10	Mainly Beta	Beta Barrel	Thrombin, subunit H	Trypsin-like serine proteases	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
B	PF00089	Trypsin (Trypsin)	Trypsin	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
B	TWO CHAIN TISSUE PLASMINOGEN ACTIVATOR	protein binding binding signaling receptor binding phosphoprotein binding peptidase activity catalytic activity, acting on a protein serine hydrolase activity serine-type peptidase activity hydrolase activity serine-type endopeptidase activity catalytic activity endopeptidase activity	multicellular organismal process regulation of body fluid levels wound healing response to stimulus hemostasis biological regulation blood coagulation response to stress coagulation regulation of biological quality response to wounding muscle cell migration cell migration cellular process multicellular organismal process regulation of body fluid levels wound healing response to stimulus hemostasis biological regulation blood coagulation response to stress coagulation regulation of biological quality response to wounding muscle cell migration cell migration cellular process cell motility smooth muscle cell migration macromolecule modification metabolic process primary metabolic process protein metabolic process macromolecule metabolic process protein modification process regulation of response to external stimulus negative regulation of biological process regulation of response to wounding regulation of coagulation regulation of response to stress regulation of multicellular organismal process regulation of hemostasis regulation of biological process negative regulation of response to stimulus negative regulation of wound healing regulation of blood coagulation negative regulation of blood coagulation response to external stimulus negative regulation of response to wounding negative regulation of hemostasis fibrinolysis negative regulation of coagulation regulation of response to stimulus negative regulation of response to external stimulus regulation of wound healing negative regulation of multicellular organismal process zymogen activation gene expression macromolecule biosynthetic process protein maturation biosynthetic process proteolysis protein processing plasminogen activation trans-synaptic signaling regulation of signaling regulation of cellular process signaling trans-synaptic signaling, modulating synaptic transmission modulation of chemical synaptic transmission cell-cell signaling cell communication chemical synaptic transmission trans-synaptic signaling by BDNF, modulating synaptic transmission synaptic signaling regulation of trans-synaptic signaling anterograde trans-synaptic signaling regulation of cell communication trans-synaptic signaling by BDNF negative regulation of proteolysis regulation of protein metabolic process negative regulation of metabolic process regulation of macromolecule metabolic process regulation of primary metabolic process regulation of proteolysis negative regulation of cellular process regulation of metabolic process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process cellular response to stimulus cell surface receptor signaling pathway platelet-derived growth factor receptor signaling pathway cell surface receptor protein tyrosine kinase signaling pathway signal transduction enzyme-linked receptor protein signaling pathway positive regulation of coagulation positive regulation of biological process positive regulation of blood coagulation positive regulation of response to stimulus positive regulation of response to external stimulus positive regulation of hemostasis positive regulation of response to wounding positive regulation of wound healing regulation of fibrinolysis positive regulation of multicellular organismal process negative regulation of fibrinolysis regulation of protein maturation negative regulation of plasminogen activation negative regulation of protein maturation regulation of plasminogen activation regulation of biosynthetic process regulation of gene expression negative regulation of gene expression negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of protein processing regulation of macromolecule biosynthetic process negative regulation of protein processing response to decreased oxygen levels response to hypoxia response to oxygen levels response to abiotic stimulus sexual reproduction regulation of reproductive process reproductive process fertilization egg activation cell activation regulation of fertilization negative regulation of fertilization negative regulation of reproductive process prevention of polyspermy single fertilization	cellular anatomical structure apical part of cell extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle cell surface intracellular anatomical structure intracellular vesicle cellular anatomical structure apical part of cell extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle cell surface intracellular anatomical structure intracellular vesicle intracellular membrane-bounded organelle endomembrane system intracellular organelle cytoplasmic vesicle secretory granule secretory vesicle cytoplasm synapse cell junction glutamatergic synapse protein-containing complex serine protease inhibitor complex protease inhibitor complex peptidase inhibitor complex Schaffer collateral - CA1 synapse
A	TWO CHAIN TISSUE PLASMINOGEN ACTIVATOR	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
B	IPR026280	Tissue plasminogen activator	Family
B	IPR018056	Kringle, conserved site	Conserved Site
B	IPR000742	EGF-like domain	Domain
B	IPR018114	Serine proteases, trypsin family, histidine active site	Active Site
B	IPR013806	Kringle-like fold	Homologous Superfamily
B	IPR038178	Kringle superfamily	Homologous Superfamily
B	IPR009003	Peptidase S1, PA clan	Homologous Superfamily
B	IPR000083	Fibronectin, type I	Domain
B	IPR001314	Peptidase S1A, chymotrypsin family	Family
B	IPR033116	Serine proteases, trypsin family, serine active site	Active Site
B	IPR001254	Serine proteases, trypsin domain	Domain
B	IPR043504	Peptidase S1, PA clan, chymotrypsin-like fold	Homologous Superfamily
B	IPR050127	Serine Proteases (Peptidase S1 Family)	Family
B	IPR000001	Kringle	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
B	Pharos: P00750	pulmonary embolism hypertensive disorder thrombophilia, familial, due to decreased release of tissue plasminogen activator angioedema respiratory failure Hematoma, Subdural cerebrovascular disorder atherosclerosis middle cerebral artery infarction myocardial infarction intracranial hemorrhage brain infarction intracranial vasospasm venous thromboembolism cardiac tamponade pulmonary embolism hypertensive disorder thrombophilia, familial, due to decreased release of tissue plasminogen activator angioedema respiratory failure Hematoma, Subdural cerebrovascular disorder atherosclerosis middle cerebral artery infarction myocardial infarction intracranial hemorrhage brain infarction intracranial vasospasm venous thromboembolism cardiac tamponade cerebral infarction meningoencephalitis cholesterol embolism congestive heart failure allergic contact dermatitis coronary thrombosis thrombotic disease hemopericardium bacterial infectious disease with sepsis amphetamine abuse intracranial thrombosis brain ischemia pericardial effusion aphasia psoriasis glioblastoma lung carcinoma heart failure malignant glioma medulloblastoma schizophrenia acquired lactic acidosis systemic lupus erythematosus Barrett esophagus coronary artery disease oligodendroglioma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia ulcerative colitis breast carcinoma periodontitis malignant colon neoplasm malignant mesothelioma arteriosclerosis disorder atopic eczema hypotensive disorder intracerebral hemorrhage ovarian cancer ischemia reperfusion injury drug-induced liver injury breast fibroadenoma pilocytic astrocytoma heart disease malignant ependymoma malignant pancreatic neoplasm sinusitis adrenal cortex carcinoma cystic fibrosis pancreatic ductal adenocarcinoma toxic encephalopathy lactic acidosis breast cancer C1 inhibitor deficiency

Structure Motif Annotation: Mechanism and Catalytic Site Atlas M-CSA Database Homepage

Chains	Enzyme Name	Description	Catalytic Residues
B	t-plasminogen activator M-CSA #798	Tissue-type plasminogen activator is a serine proteinase of the trypsin-family. It catalyses the activation of the zymogen plasminogen to the fibrin-degrading proteinase plasmin in fibrinolysis. Human tissue-type plasminogen activator is being studied for therapeutic use in cases such as myocardial infarctions and other thromboembolic disorders.	Defined by 4 residues: HIS:B-47 [auth B-57]ASP:B-96 [auth B-102]GLY:B-201 [auth B-193]SER:B-203 [auth B-195] \| Explore in 3D: M-CSA Motif Definition Search M-CSA Motif EC: 3.4.21.68 (PDB Primary Data) Search M-CSA Motif + EC 3.4.21.68

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.