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Pathway Description
Plasminogen
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Physiological
Created: 2023-09-20
Last Updated: 2023-11-27
Plasminogen is a plasma glycoprotein. Plasminogen (PLG) is the zymogen of plasmin, the major enzyme that degrades fibrin clots. In addition to its binding and activation on fibrin clots, PLG also specifically interacts with cell surfaces where it is more efficiently activated by PLG activators, compared with the reaction in solution. This results in association of the broad-spectrum proteolytic activity of plasmin with cell surfaces that functions to promote cell migration. Plasmin is an important enzyme (EC 3.4.21.7) present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein (in the zymogen form of plasminogen) is encoded by the PLG gene. Plasmin is released as a zymogen called plasminogen (PLG) from the liver into the systemic circulation. Two major glycoforms of plasminogen are present in humans - type I plasminogen contains two glycosylation moieties (N-linked to N289 and O-linked to T346), whereas type II plasminogen contains only a single O-linked sugar (O-linked to T346). Type II plasminogen is preferentially recruited to the cell surface over the type I glycoform. Conversely, type I plasminogen appears more readily recruited to blood clots. n circulation, plasminogen adopts a closed, activation-resistant conformation. Upon binding to clots, or to the cell surface, plasminogen adopts an open form that can be converted into active plasmin by a variety of enzymes, including tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), kallikrein, and factor XII (Hageman factor). Fibrin is a cofactor for plasminogen activation by tissue plasminogen activator. Urokinase plasminogen activator receptor (uPAR) is a cofactor for plasminogen activation by urokinase plasminogen activator. The conversion of plasminogen to plasmin involves the cleavage of the peptide bond between Arg-561 and Val-562.
References
Plasminogen References
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Pubmed: 6216475
Forsgren M, Raden B, Israelsson M, Larsson K, Heden LO: Molecular cloning and characterization of a full-length cDNA clone for human plasminogen. FEBS Lett. 1987 Mar 23;213(2):254-60. doi: 10.1016/0014-5793(87)81501-6.
Pubmed: 3030813
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Pubmed: 22832192
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Pubmed: 17900274
Chung DW, Chan WY, Davie EW: Characterization of a complementary deoxyribonucleic acid coding for the gamma chain of human fibrinogen. Biochemistry. 1983 Jun 21;22(13):3250-6. doi: 10.1021/bi00282a033.
Pubmed: 6688357
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Pubmed: 2990550
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Pubmed: 14702039
Petersen TE, Martzen MR, Ichinose A, Davie EW: Characterization of the gene for human plasminogen, a key proenzyme in the fibrinolytic system. J Biol Chem. 1990 Apr 15;265(11):6104-11.
Pubmed: 2318848
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Pubmed: 14574404
Kurachi K, Davie EW: Isolation and characterization of a cDNA coding for human factor IX. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6461-4. doi: 10.1073/pnas.79.21.6461.
Pubmed: 6959130
Jaye M, de la Salle H, Schamber F, Balland A, Kohli V, Findeli A, Tolstoshev P, Lecocq JP: Isolation of a human anti-haemophilic factor IX cDNA clone using a unique 52-base synthetic oligonucleotide probe deduced from the amino acid sequence of bovine factor IX. Nucleic Acids Res. 1983 Apr 25;11(8):2325-35. doi: 10.1093/nar/11.8.2325.
Pubmed: 6687940
Anson DS, Choo KH, Rees DJ, Giannelli F, Gould K, Huddleston JA, Brownlee GG: The gene structure of human anti-haemophilic factor IX. EMBO J. 1984 May;3(5):1053-60.
Pubmed: 6329734
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Pubmed: 3935400
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Pubmed: 6438526
Levinson B, Kenwrick S, Gamel P, Fisher K, Gitschier J: Evidence for a third transcript from the human factor VIII gene. Genomics. 1992 Nov;14(3):585-9.
Pubmed: 1427887
Jenny RJ, Pittman DD, Toole JJ, Kriz RW, Aldape RA, Hewick RM, Kaufman RJ, Mann KG: Complete cDNA and derived amino acid sequence of human factor V. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4846-50. doi: 10.1073/pnas.84.14.4846.
Pubmed: 3110773
Cripe LD, Moore KD, Kane WH: Structure of the gene for human coagulation factor V. Biochemistry. 1992 Apr 21;31(15):3777-85. doi: 10.1021/bi00130a007.
Pubmed: 1567832
Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. doi: 10.1038/nature04727.
Pubmed: 16710414
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