Editing Plasmin (section)

== Function ==

[[File:Fibrinolysis.svg|thumb|left|300px|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 [[proteolysis|proteolyses]] proteins in various other systems: It activates [[collagenase]]s, some mediators of the [[complement system]], and weakens the wall of the [[Graafian follicle]], leading to [[ovulation]]. Plasmin is also integrally involved in inflammation.<ref>{{cite journal | vauthors = Atsev S, Tomov N | title = Using antifibrinolytics to tackle neuroinflammation | journal = Neural Regeneration Research | volume = 15 | issue = 12 | pages = 2203–2206 | date = December 2020 | pmid = 32594031 | pmc = 7749481 | doi = 10.4103/1673-5374.284979 | doi-access = free }}</ref>  It cleaves [[fibrin]], [[fibronectin]], [[thrombospondin]], laminin, and [[von Willebrand factor]]. Plasmin, like [[trypsin]], belongs to the family of [[serine protease]]s.

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.

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 receptor|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.<ref name="entrez"/><ref name="pmid6216475">{{cite journal | vauthors = Miyata T, Iwanaga S, Sakata Y, Aoki N | title = Plasminogen Tochigi: inactive plasmin resulting from replacement of alanine-600 by threonine in the active site | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 79 | issue = 20 | pages = 6132–6136 | date = October 1982 | pmid = 6216475 | pmc = 347073 | doi = 10.1073/pnas.79.20.6132 | doi-access = free | bibcode = 1982PNAS...79.6132M }}</ref><ref name="pmid">{{cite journal | vauthors = Forsgren M, Råden B, Israelsson M, Larsson K, Hedén LO | title = Molecular cloning and characterization of a full-length cDNA clone for human plasminogen | journal = FEBS Letters | volume = 213 | issue = 2 | pages = 254–260 | date = March 1987 | pmid = 3030813 | doi = 10.1016/0014-5793(87)81501-6 | s2cid = 9075872 | doi-access = free }}</ref><ref name=Law_2012>{{cite journal | vauthors = Law RH, Caradoc-Davies T, Cowieson N, Horvath AJ, Quek AJ, Encarnacao JA, Steer D, Cowan A, Zhang Q, Lu BG, Pike RN, Smith AI, Coughlin PB, Whisstock JC | display-authors = 6 | title = The X-ray crystal structure of full-length human plasminogen | journal = Cell Reports | volume = 1 | issue = 3 | pages = 185–190 | date = March 2012 | pmid = 22832192 | doi = 10.1016/j.celrep.2012.02.012 | doi-access = free }}</ref>

Plasmin cleavage produces [[angiostatin]].