Alpha 2-antiplasmin explained

Alpha 2-antiplasmin (or α₂-antiplasmin or plasmin inhibitor) is a serine protease inhibitor (serpin) responsible for inactivating plasmin.^[1] Plasmin is an important enzyme that participates in fibrinolysis and degradation of various other proteins. This protein is encoded by the SERPINF2 gene.^[2]

Role in disease

Very few cases (<20) of A2AP deficiency have been described. As plasmin degrades blood clots, impaired inhibition of plasmin leads to a bleeding tendency, which was severe in the cases reported.

In liver cirrhosis, there is decreased production of alpha 2-antiplasmin, leading to decreased inactivation of plasmin and an increase in fibrinolysis. This is associated with an increase risk of bleeding in liver disease.^[3]

Interactions

Alpha 2-antiplasmin has been shown to interact with:

• Neutrophil elastase^[4] and
• Plasmin.^{[5] [6]}

See also

• Serpin

Further reading

• Martí-Fàbregas J, Borrell M, Cocho D, Martínez-Ramírez S, Martínez-Corral M, Fontcuberta J, Martí-Vilalta JL . Change in hemostatic markers after recombinant tissue-type plasminogen activator is not associated with the chance of recanalization . Stroke: A Journal of Cerebral Circulation . 39 . 1 . 234–6 . Jan 2008 . 18048863 . 10.1161/STROKEAHA.107.493767. 10052168 .
• Nielsen VG . Hydroxyethyl starch enhances fibrinolysis in human plasma by diminishing alpha2-antiplasmin-plasmin interactions . Blood Coagulation & Fibrinolysis . 18 . 7 . 647–56 . Oct 2007 . 17890952 . 10.1097/MBC.0b013e3282a167dc . 45608070 .
• Sazonova IY, Thomas BM, Gladysheva IP, Houng AK, Reed GL . Fibrinolysis is amplified by converting alpha-antiplasmin from a plasmin inhibitor to a substrate . Journal of Thrombosis and Haemostasis . 5 . 10 . 2087–94 . Oct 2007 . 17883703 . 10.1111/j.1538-7836.2007.02652.x. 2907615 . free .
• Mutch NJ, Thomas L, Moore NR, Lisiak KM, Booth NA . TAFIa, PAI-1 and alpha-antiplasmin: complementary roles in regulating lysis of thrombi and plasma clots . Journal of Thrombosis and Haemostasis . 5 . 4 . 812–7 . Apr 2007 . 17388801 . 10.1111/j.1538-7836.2007.02430.x. 40278627 . free .
• Christiansen VJ, Jackson KW, Lee KN, McKee PA . The effect of a single nucleotide polymorphism on human alpha 2-antiplasmin activity . Blood . 109 . 12 . 5286–92 . Jun 2007 . 17317851 . 1890835 . 10.1182/blood-2007-01-065185 .
• Hayashido Y, Hamana T, Ishida Y, Shintani T, Koizumi K, Okamoto T . Induction of alpha2-antiplasmin inhibits E-cadherin processing mediated by the plasminogen activator/plasmin system, leading to suppression of progression of oral squamous cell carcinoma via upregulation of cell-cell adhesion . Oncology Reports . 17 . 2 . 417–23 . Feb 2007 . 17203182 . 10.3892/or.17.2.417. free .
• Shibata N, Kawarai T, Meng Y, Lee JH, Lee HS, Wakutani Y, Shibata E, Pathan N, Bi A, Sato C, Sorbi S, Bruni AC, Duara R, Mayeux R, Farrer LA, George-Hyslop PS, Rogaeva E . Association studies between the plasmin genes and late-onset Alzheimer's disease . Neurobiology of Aging . 28 . 7 . 1041–3 . Jul 2007 . 16828203 . 2647723 . 10.1016/j.neurobiolaging.2006.05.028.
• Liu T, Qian WJ, Gritsenko MA, Camp DG, Monroe ME, Moore RJ, Smith RD . Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry . Journal of Proteome Research . 4 . 6 . 2070–80 . December 2005 . 16335952 . 1850943 . 10.1021/pr0502065.
• Lee KN, Jackson KW, Christiansen VJ, Chung KH, McKee PA . A novel plasma proteinase potentiates alpha2-antiplasmin inhibition of fibrin digestion . Blood . 103 . 10 . 3783–8 . May 2004 . 14751930 . 10.1182/blood-2003-12-4240. free .
• Anderson NL, Polanski M, Pieper R, Gatlin T, Tirumalai RS, Conrads TP, Veenstra TD, Adkins JN, Pounds JG, Fagan R, Lobley A . The human plasma proteome: a nonredundant list developed by combination of four separate sources . Molecular & Cellular Proteomics . 3 . 4 . 311–26 . Apr 2004 . 14718574 . 10.1074/mcp.M300127-MCP200. free .
• Kapadia C, Yousef GM, Mellati AA, Magklara A, Wasney GA, Diamandis EP . Complex formation between human kallikrein 13 and serum protease inhibitors . Clinica Chimica Acta; International Journal of Clinical Chemistry . 339 . 1–2 . 157–67 . Jan 2004 . 14687906 . 10.1016/j.cccn.2003.10.009.
• Matsuno H, Okada K, Ueshima S, Matsuo O, Kozawa O . Alpha2-antiplasmin plays a significant role in acute pulmonary embolism . Journal of Thrombosis and Haemostasis . 1 . 8 . 1734–9 . Aug 2003 . 12911586 . 10.1046/j.1538-7836.2003.00252.x. 72056689 . free .
• Magklara A, Mellati AA, Wasney GA, Little SP, Sotiropoulou G, Becker GW, Diamandis EP . Characterization of the enzymatic activity of human kallikrein 6: Autoactivation, substrate specificity, and regulation by inhibitors . Biochemical and Biophysical Research Communications . 307 . 4 . 948–55 . Aug 2003 . 12878203 . 10.1016/S0006-291X(03)01271-3.
• Cardoso C, Leventer RJ, Ward HL, Toyo-Oka K, Chung J, Gross A, Martin CL, Allanson J, Pilz DT, Olney AH, Mutchinick OM, Hirotsune S, Wynshaw-Boris A, Dobyns WB, Ledbetter DH . Refinement of a 400-kb critical region allows genotypic differentiation between isolated lissencephaly, Miller-Dieker syndrome, and other phenotypes secondary to deletions of 17p13.3 . American Journal of Human Genetics . 72 . 4 . 918–30 . Apr 2003 . 12621583 . 1180354 . 10.1086/374320.
• Frank PS, Douglas JT, Locher M, Llinás M, Schaller J . Structural/functional characterization of the alpha 2-plasmin inhibitor C-terminal peptide . Biochemistry . 42 . 4 . 1078–85 . Feb 2003 . 12549929 . 10.1021/bi026917n.
• Turner RB, Liu L, Sazonova IY, Reed GL . Structural elements that govern the substrate specificity of the clot-dissolving enzyme plasmin . The Journal of Biological Chemistry . 277 . 36 . 33068–74 . Sep 2002 . 12080056 . 10.1074/jbc.M203782200 . free .
• Askew YS, Pak SC, Luke CJ, Askew DJ, Cataltepe S, Mills DR, Kato H, Lehoczky J, Dewar K, Birren B, Silverman GA . SERPINB12 is a novel member of the human ov-serpin family that is widely expressed and inhibits trypsin-like serine proteinases . The Journal of Biological Chemistry . 276 . 52 . 49320–30 . Dec 2001 . 11604408 . 10.1074/jbc.M108879200. free .
• Uszynski M, Klyszejko A, Zekanowska E . Plasminogen, alpha(2)-antiplasmin and complexes of plasmin-alpha(2)-antiplasmin (PAP) in amniotic fluid and blood plasma of parturient women . European Journal of Obstetrics, Gynecology, and Reproductive Biology . 93 . 2 . 167–71 . Dec 2000 . 11074138 . 10.1016/S0301-2115(00)00283-9 .
• Hevessy Z, Patthy A, Kárpáti L, Muszbek L . alpha(2)-plasmin inhibitor is a substrate for tissue transglutaminase: an in vitro study . . 99 . 4 . 399–406 . Aug 2000 . 10963790 . 10.1016/S0049-3848(00)00261-9 .

External links

• The MEROPS online database for peptidases and their inhibitors: I04.023

Notes and References

1. Wu. Guojie. Quek. Adam J.. Caradoc-Davies. Tom T.. Ekkel. Sue M.. Mazzitelli. Blake. Whisstock. James C.. Law. Ruby H.P.. 2019-03-05. Structural studies of plasmin inhibition. Biochemical Society Transactions. 47. 2. 541–557. 10.1042/bst20180211. 30837322. 73463150 . 0300-5127.
2. Web site: Entrez Gene: SERPINF2 serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 2.
3. Sattar, Husain. Fundamentals of Pathology. Pathoma LLC, 2011, p. 36.
4. Brower MS, Harpel PC . Proteolytic cleavage and inactivation of alpha 2-plasmin inhibitor and C1 inactivator by human polymorphonuclear leukocyte elastase . The Journal of Biological Chemistry . 257 . 16 . 9849–54 . Aug 1982 . 10.1016/S0021-9258(18)34149-8 . 6980881 . free .
5. Shieh BH, Travis J . The reactive site of human alpha 2-antiplasmin . The Journal of Biological Chemistry . 262 . 13 . 6055–9 . May 1987 . 10.1016/S0021-9258(18)45536-6 . 2437112 . free .
6. Wiman B, Collen D . On the mechanism of the reaction between human alpha 2-antiplasmin and plasmin . The Journal of Biological Chemistry . 254 . 18 . 9291–7 . Sep 1979 . 10.1016/S0021-9258(19)86843-6 . 158022 . free .