Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor cell invasion and metastasis is a multifactorial process, which at each step may require the action of proteolytic enzymes such as collagenases, cathepsins, plasmin, or plasminogen activators. An enzymatically inactive proenzyme form of the urokinase-type plasminogen activator (pro-uPA) is secreted by tumor cells which may be converted to an enzymatically active two-chain uPA-molecule (HMW-uPA) by plasmin-like enzymes. Action of proteases on pro-uPA may generate the enzymatically active or inactive high-molecular-weight form of uPA (HMW-uPA). Some proteases (plasmin, cathepsin B and L, kallikrein, trypsin or thermolysin) activate pro-uPA by cleaving the peptide bond Lys158 and IIe159. Other proteases (elastase, thrombin) cleave pro-uPA at different positions to yield enzymatically inactive HMW-uPA. HMW-uPA may be split into the enzymatically active LMW-uPA and the enzymatically inactive ATF (amino terminal fragment). ATF may be cleaved between peptide sequence 20 and 40 within the receptor binding domain of uPA (GFD). Such impaired ATF does not bind to uPA-receptors. Action of the bacterial endoproteinase Asp-N from Pseudomonas fragi mutant on pro-uPA or HMW-uPA, however, generates intact ATF which efficiently competes for binding of HMW-uPA or pro-uPA to receptors on tumor cells. High uPA-antigen content (pro-uPA, HMW-uPA, or LMW-uPA) in breast cancer tissue (not in plasma) indicates an elevated risk for the patient of recurrences and shorter overall survival. Thus pro-uPA/uPA-antigen content in breast cancer tissue serves as an independent prognostic parameter for the outcome of the disease. Cathepsin D is also an independent prognostic factor for recurrences and overall survival. High content of cathepsin D in breast cancer tumors is, however, not correlated with elevated levels of pro-uPA/uPA indicating that synthesis and release of cathepsin D and pro-uPA/uPA are independent events.
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PMID:Biological and clinical relevance of the urokinase-type plasminogen activator (uPA) in breast cancer. 180 51

The amino acid sequence of a thrombin like enzyme , named elegaxobin II, isolated from the venom of Trimeresurus elegans (Sakishima-habu) was determined by Edman sequencing of the peptides which was derived from digests with cyanogen bromide, achromobacter protease I, trypsin, endoproteinase Asp-N, and chymotrypsin. Elegaxobin II consisted of 233 amino acids and showed conservation of the catalytic amino acid residues (His(57), Asp(102), and Ser(195)) of chymotrypsin family serine protease in its amino acid sequence. The carboxyterminal amino acid, Leu, was determined using carboxypeptidase Y. This enzyme contains glucosamine and an N-linked glycosylation site. Elegaxobin II was 91% homologous in sequence to elegaxobin and protease I from the same snake venom, and it was 67, 75, 31 and 26% homologous in sequences to flavoxobin, KN-BJ 2, human kallikrein and bovine thrombin, respectively. Elegaxobin II lacked thrombin's ETW (146-148) loop, as well as its functionally important YPPW (60-insertion loop).
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PMID:Amino acid sequence of a thrombin like enzyme, elegaxobin II, from the venom of Trimeresurus elegans (Sakishima-Habu). 1550 Aug 47

The amino acid sequence of a bradykinin-releasing enzyme, named KR-E-1, isolated from the venom of Agkistrodon caliginosus (Kankoku-mamushi) was determined by Edman sequencing of the peptides which was derived from digests with cyanogen bromide, hydroxylamine, achromobacter protease I, trypsin, V8 protease, arginine endopeptidase, and endoproteinase Asp-N. KR-E-1 consisted of 235 amino acids and showed conservation of the catalytic amino acid residues (His(57), Asp(102), and Ser(195)) of the chymotrypsin family of serine protease in its amino acid sequence. The carboxy-terminal amino acid, Phe, was determined using carboxypeptidase Y. This enzyme contains glucosamine and an N-linked glycosylation site. KR-E-1 showed 32, 31, 65, 65, and 67% sequence homology to human kallikrein, bovine thrombin, KN-BJ 2, elegaxobin, and elegaxobin II, respectively. The characteristic of structure of KR-E-1 was found to involve hydrophobic amino acid residues abundantly localizing in positions 1-50, with lysine residues abundantly localizing in positions 73-101.
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PMID:Amino acid sequence of a kinin-releasing enzyme, KR-E-1, from the venom of Agkistrodon caliginosus (Kankoku-mamushi). 1872 43