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Plasminogen
Available structures PDB Ortholog search: PDBe, RCSB [show]List of PDB id codes
Identifiers
External OMIM: 173350 MGI: 97620 IDs HomoloGene: 55452 GeneCards: PLG Gene
EC number
3.4.21.7
[show]Gene Ontology
Orthologs
Species
Human
Mouse
Entrez
5340
18815
UniProt P00747
P20918
RefSeq (mRNA)
NM_000301.3
NM_008877.3
RefSeq (protein)
NP_000292.1
NP_032903.3
[2]
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Plasmin is an important enzyme (EC 3.4.21.7) present in blood that degrades many blood plasma proteins, most notably, fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein is encoded by the PLG gene.[1]
Contents
[hide]
1 Function 2 Structure and mechanism of plasminogen activation to plasmin 3 Pathology 4 Interactions 5 References 6 Further reading
7 External links
[edit] Function
Fibrinolysis (simplified). Blue arrows denote stimulation, and red arrows inhibition. Plasmin is a serine protease that acts to dissolve fibrin blood clots. Apart from fibrinolysis, plasmin proteolyses proteins in various other systems: It activates collagenases, some mediators of the complement system and weakens the wall of the Graafian follicle (leading to ovulation). It cleaves fibrin, fibronectin, thrombospondin, laminin, and von Willebrand factor. Plasmin, like trypsin, belongs to the family of serine proteases. 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 plasmingen 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. In 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.[1][2][3][4] Plasmin cleavage produces angiostatin.
[edit] Pathology
Deficiency in plasmin may lead to thrombosis, as clots are not degraded adequately. Plasminogen deficiency in mice leads to defective liver repair,[5] defective wound healing, reproductive abnormalities.[citation needed] In human, a rare disorder called plasminogen deficiency type I (Online 'Mendelian Inheritance in Man' (OMIM) 217090) is caused by mutations of the PLG gene and is often manifested by ligneous conjunctivitis.
[edit] Interactions
Plasmin has been shown to interact with Thrombospondin 1,[6][7] Alpha 2-antiplasmin[8][9] and IGFBP3.[10]
[edit] References
1. ^ a b "Entrez Gene: plasminogen". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=53 40. 2. ^ Miyata T, Iwanaga S, Sakata Y, Aoki N (October 1982). "Plasminogen Tochigi: inactive plasmin resulting from replacement of alanine-600 by threonine in the active site". Proc. Natl. Acad. Sci. U.S.A. 79 (20): 61326. doi:10.1073/pnas.79.20.6132. PMC 347073. PMID 6216475. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=6216475. 3. ^ Forsgren M, Rden B, Israelsson M, Larsson K, Hedn LO (March 1987). "Molecular cloning and characterization of a full-length cDNA clone for human plasminogen". FEBS Lett. 213 (2): 25460. doi:10.1016/0014-5793(87)81501-6. PMID 3030813. http://linkinghub.elsevier.com/retrieve/pii/0014-5793(87)81501-6. 4. ^ a b c Law RHP, Caradoc-Davies T, Cowieson N, Horvath AJ, Quek AJ, Encarnacao JA, Steer D, Cowan A, Zhang Q, Lu BGC, Pike RN, Smith AI, Coughlin PB, Whisstock JC (2012). "The Xray Crystal Structure of Full-Length Human Plasminogen". Cell Reports 1 (3). doi:10.1016/j.celrep.2012.02.012. 5. ^ Jorge A. Bezerra, Thomas H. Bugge, Hector Melin-Aldana, Gregg Sabla, Keith W. Kombrinck, David P. Witte, and Jay L. Degen (December 21, 1999). Plasminogen deficiency leads to impaired remodeling after a toxic injury to the liver. Proceedings of the National Academy of Sciences of the United States of America. PMID 10611352. http://www.pnas.org/content/96/26/15143.short. Retrieved June 3, 2011. 6. ^ Silverstein, R L; Leung L L, Harpel P C, Nachman R L (Nov. 1984). "Complex formation of platelet thrombospondin with plasminogen. Modulation of activation by tissue activator". J. Clin. Invest. (UNITED STATES) 74 (5): 162533. doi:10.1172/JCI111578. ISSN 0021-9738. PMC 425339. PMID 6438154. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=425339. 7. ^ DePoli, P; Bacon-Baguley T, Kendra-Franczak S, Cederholm M T, Walz D A (Mar. 1989). "Thrombospondin interaction with plasminogen. Evidence for binding to a specific region of the kringle structure of plasminogen". Blood (UNITED STATES) 73 (4): 97682. ISSN 0006-4971. PMID 2522013. 8. ^ Wiman, B; Collen D (Sep. 1979). "On the mechanism of the reaction between human alpha 2antiplasmin and plasmin". J. Biol. Chem. (UNITED STATES) 254 (18): 92917. ISSN 00219258. PMID 158022. 9. ^ Shieh, B H; Travis J (May. 1987). "The reactive site of human alpha 2-antiplasmin". J. Biol. Chem. (UNITED STATES) 262 (13): 60559. ISSN 0021-9258. PMID 2437112. 10. ^ Campbell, P G; Durham S K, Suwanichkul A, Hayes J D, Powell D R (Aug. 1998). "Plasminogen binds the heparin-binding domain of insulin-like growth factor-binding protein-3". Am. J. Physiol. (UNITED STATES) 275 (2 Pt 1): E32131. ISSN 0002-9513. PMID 9688635.
Shanmukhappa K, Mourya R, Sabla GE, Degen JL, Bezerra JA (July 2005). "Hepatic to pancreatic switch defines a role for hemostatic factors in cellular plasticity in mice". Proc. Natl. Acad. Sci. U.S.A. 102 (29): 101827. doi:10.1073/pnas.0501691102. PMC 1177369. PMID 16006527. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1177369. Angls-Cano E, Rojas G (2003). "Apolipoprotein(a): structure-function relationship at the lysinebinding site and plasminogen activator cleavage site". Biol. Chem. 383 (1): 939. doi:10.1515/BC.2002.009. PMID 11928826. Ranson M, Andronicos NM (2004). "Plasminogen binding and cancer: promises and pitfalls". Front. Biosci. 8: s294304. doi:10.2741/1044. PMID 12700073.
The MEROPS online database for peptidases and their inhibitors: S01.233 MeSH Plasmin
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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PDB gallery
1b2i: KRINGLE 2 DOMAIN OF HUMAN PLASMINOGEN: NMR SOLUTION STRUCTURE OF TRANS-4AMINOMETHYLCYCLOHEXANE1-CARBOXYLIC ACID (AMCHA) COMPLEX
1cea: THE STRUCTURE OF THE NON-COVALENT COMPLEX OF RECOMBINANT KRINGLE 1 DOMAIN OF HUMAN PLASMINOGEN WITH EACA (EPSILONAMINOCAPROIC ACID)
1ceb: THE STRUCTURE OF THE NON-COVALENT COMPLEX OF RECOMBINANT KRINGLE 1 DOMAIN OF HUMAN PLASMINOGEN WITH AMCHA (TRANS-4AMINOMETHYLCYCLOHEXANE1-CARBOXYLIC ACID)
1hpj: SOLUTION NMR STRUCTURE OF THE HUMAN PLASMINOGEN KRINGLE 1 DOMAIN COMPLEXED WITH 6AMINOHEXANOIC ACID AT PH 5.3, 310K, DERIVED FROM RANDOMLY GENERATED STRUCTURES USING SIMULATED ANNEALING, 12 STRUCTURES
1hpk: SOLUTION NMR STRUCTURE OF THE HUMAN PLASMINOGEN KRINGLE 1 DOMAIN COMPLEXED WITH 6AMINOHEXANOIC ACID AT PH 5.3, 310K, DERIVED FROM RANDOMLY GENERATED STRUCTURES USING SIMULATED ANNEALING, MINIMIZED AVERAGE STRUCTURE
1i5k: STRUCTURE AND BINDING DETERMINANTS OF THE RECOMBINANT KRINGLE-2 DOMAIN OF HUMAN PLASMINOGEN TO AN INTERNAL PEPTIDE FROM A GROUP
1l4z: X-RAY CRYSTAL STRUCTURE OF THE COMPLEX OF MICROPLASMINOGEN WITH ALPHA DOMAIN OF STREPTOKINASE IN THE PRESENCE CADMIUM IONS
1pk4: CRYSTAL AND MOLECULAR STRUCTURE OF HUMAN PLASMINOGEN KRINGLE 4 REFINED AT 1.9ANGSTROMS RESOLUTION
1pkr: THE STRUCTURE OF RECOMBINANT PLASMINOGEN KRINGLE 1 AND THE FIBRIN BINDING SITE
2doh: The X-ray crystallographic structure of the angiogenesis inhibitor, angiostatin, bound a to a peptide from the group A streptococcal surface protein PAM
2doi: The X-ray crystallographic structure of the angiogenesis inhibitor, angiostatin, bound to a peptide from the group A streptococcus protein PAM
2pk4: THE REFINED STRUCTURE OF THE EPSILON-AMINOCAPROIC ACID COMPLEX OF HUMAN PLASMINOGEN KRINGLE
5hpg: STRUCTURE AND LIGAND DETERMINANTS OF THE RECOMBINANT KRINGLE 5 DOMAIN OF HUMAN PLASMINOGEN [show]
v t e
alpha-2 (Alpha 2-antiplasmin) Antithrombin (Heparin cofactor II) carrier proteins: alpha-1 (Transcortin) alpha-2 (Ceruloplasmin) Retinol binding protein other: alpha-1 (Orosomucoid) alpha-2 (alpha-2-Macroglobulin, Haptoglobin) carrier proteins: Sex hormone-binding globulin Transferrin Beta globulins other: Angiostatin Hemopexin Beta-2 microglobulin Factor H Plasminogen Properdin Fibronectin (Fetal fibronectin) Macroglobulin/Microglobulin Transcobalamin
Egg white Conalbumin Ovalbumin Avidin Serum albumin Human serum albumin Bovine serum albumin Prealbumin C-reactive protein Lactalbumin (Alpha-lactalbumin) Parvalbumin Other Ricin [show]
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Proteins: coagulation
vWF Primary hemostasis platelet membrane glycoproteins: Ib (A, B, IX) IIb/IIIa (IIb, IIIa) VI HMWK/Bradykinin Prekallikrein/Kallikrein XII "Hageman" XI IX VIII
Intrinsic pathway
Extrinsic pathway III "Tissue factor" VII X V II "(Pro)thrombin" I "Fibrin" Fibrinogen (FGA, FGG) Common pathway XIII
M: MYL
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Retrieved from "http://en.wikipedia.org/w/index.php?title=Plasmin&oldid=481427466" Categories: Human proteins Acute phase proteins Fibrinolytic system EC 3.4.21 Hidden categories: All articles with unsourced statements Articles with unsourced statements from January 2009 Wikipedia articles incorporating text from the United States National Library of Medicine
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