Plasmin Information & Plasmin Links at HealthHaven.com

Plasminogen
	; PDB rendering based on 1b2i.
Available structures
	1b2i, 1bml, 1bui, 1cea, 1ceb, 1ddj, 1hpj, 1hpk, 1i5k, 1ki0, 1krn, 1l4d, 1l4z, 1pk4, 1pkr, 1pmk, 1qrz, 1rjx, 2doh, 2doi, 2pk4, 5hpg
Identifiers
Symbols	PLG; DKFZp779M0222
External IDs	OMIM: 173350 MGI: 97620 HomoloGene: 55452 GeneCards: PLG Gene
EC number	3.4.21.7
Gene ontology
Molecular function	• plasmin activity; • calcium ion binding; • protein binding; • peptidase activity;
Cellular component	• extracellular space;
Biological process	• proteolysis; • apoptosis; • induction of apoptosis; • blood coagulation; • negative regulation of cell proliferation; • negative regulation of angiogenesis; • tissue regeneration; • fibrinolysis; • negative regulation of blood vessel endothelial cell migration; • myoblast differentiation; • muscle maintenance;
RNA expression pattern
	More reference expression data
Orthologs

edit

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]

[edit] Function

Plasminogen (PLG) is a circulating zymogen that is converted to the active enzyme plasmin by cleavage of the peptide bond between Arg-560 and Val-561, which is mediated by urokinase and tissue plasminogen activator. The main function of plasmin is to dissolve fibrin blood clots. Plasmin, like trypsin, belongs to the family of serine proteases.^[1]^[2]^[3]

Plasmin is a serine protease that is released as plasminogen from the liver into the circulation and activated by tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), 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. Plasmin is inactivated by alpha 2-antiplasmin, a serine protease inhibitor (serpin).

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.

Apart from fibrinolysis, plasminogen is shown to play important role in wound healing, liver repair as well as the maintenance of liver homeostasis.

Plasmin cleavage produces angiostatin.

Fibrinolysis (simplified). Blue arrows denote stimulation, and red arrows inhibition.

[edit] Pathology

Deficiency in plasmin may lead to thrombosis, as clots are not degraded adequately. Plasminogen deficiency in mice leads to defective wound healing, defective liver repair, reproductive abnormalities.^{[citation needed]}

In human, a rare disorder called plasminogen deficiency type I (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,^[4]^[5] Alpha 2-antiplasmin^[6]^[7] and IGFBP3.^[8]

[edit] References

^ ^a ^b "Entrez Gene: plasminogen". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5340.
^ 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): 6132–6. doi:10.1073/pnas.79.20.6132. PMID 6216475. PMC 347073. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=6216475.
^ Forsgren M, Råden B, Israelsson M, Larsson K, Hedén LO (March 1987). "Molecular cloning and characterization of a full-length cDNA clone for human plasminogen". FEBS Lett. 213 (2): 254–60. doi:10.1016/0014-5793(87)81501-6. http://linkinghub.elsevier.com/retrieve/pii/0014-5793(87)81501-6.
^ 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): 1625–33. doi:10.1172/JCI111578. ISSN 0021-9738. PMID 6438154.
^ 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): 976–82. ISSN 0006-4971. PMID 2522013.
^ Wiman, B; Collen D (Sep. 1979). "On the mechanism of the reaction between human alpha 2-antiplasmin and plasmin". J. Biol. Chem. (UNITED STATES) 254 (18): 9291–7. ISSN 0021-9258. PMID 158022.
^ Shieh, B H; Travis J (May. 1987). "The reactive site of human alpha 2-antiplasmin". J. Biol. Chem. (UNITED STATES) 262 (13): 6055–9. ISSN 0021-9258. PMID 2437112.
^ 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): E321-31. ISSN 0002-9513. PMID 9688635.

[edit] Further reading

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): 10182–7. doi:10.1073/pnas.0501691102. PMID 16006527.
Anglés-Cano E, Rojas G (2003). "Apolipoprotein(a): structure-function relationship at the lysine-binding site and plasminogen activator cleavage site". Biol. Chem. 383 (1): 93–9. doi:10.1515/BC.2002.009. PMID 11928826.
Ranson M, Andronicos NM (2004). "Plasminogen binding and cancer: promises and pitfalls". Front. Biosci. 8: s294–304. doi:10.2741/1044. PMID 12700073.