Alpha 2-antiplasmin

Serpin family F member 2
Identifiers
Symbols	SERPINF2 ; A2AP; AAP; ALPHA-2-PI; API; PLI
External IDs	OMIM: 613168 MGI: 107173 HomoloGene: 719 GeneCards: SERPINF2 Gene
Gene ontology Molecular function • protease binding • endopeptidase inhibitor activity • serine-type endopeptidase inhibitor activity • protein binding • protein homodimerization activity Cellular component • extracellular region • fibrinogen complex • extracellular space • cell surface • platelet alpha granule lumen • extracellular exosome • blood microparticle Biological process • regulation of blood vessel size by renin-angiotensin • platelet degranulation • acute-phase response • response to organic substance • negative regulation of plasminogen activation • negative regulation of endopeptidase activity • collagen fibril organization • positive regulation of collagen biosynthetic process • fibrinolysis • positive regulation of cell differentiation • positive regulation of transcription from RNA polymerase II promoter • positive regulation of JNK cascade • blood vessel morphogenesis • positive regulation of smooth muscle cell proliferation • positive regulation of stress fiber assembly • negative regulation of fibrinolysis • positive regulation of ERK1 and ERK2 cascade • positive regulation of transforming growth factor beta production • positive regulation of cell-cell adhesion mediated by cadherin Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5345	18816
Ensembl	ENSG00000167711	ENSMUSG00000038224
UniProt	P08697	Q61247
RefSeq (mRNA)	NM_000934	NM_008878
RefSeq (protein)	NP_000925	NP_032904
Location (UCSC)	Chr 17: 1.74 – 1.76 Mb	Chr 11: 75.43 – 75.44 Mb
PubMed search

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

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

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.^[2]

Interactions

Alpha 2-antiplasmin has been shown to interact with:

• Neutrophil elastase^[3][4] and
• Plasmin.^[3][5]

See also

• Serpin

References

1. "Entrez Gene: SERPINF2 serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 2".
2. Sattar, Husain. Fundamentals of Pathology. Pathoma LLC, 2011, p. 36.
3. Shieh BH, Travis J (May 1987). "The reactive site of human alpha 2-antiplasmin". The Journal of Biological Chemistry 262 (13): 6055–9. PMID 2437112.
4. Brower MS, Harpel PC (Aug 1982). "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. PMID 6980881.
5. Wiman B, Collen D (Sep 1979). "On the mechanism of the reaction between human alpha 2-antiplasmin and plasmin". The Journal of Biological Chemistry 254 (18): 9291–7. PMID 158022.

Further reading

• Martí-Fàbregas J, Borrell M, Cocho D, Martínez-Ramírez S, Martínez-Corral M, Fontcuberta J, Martí-Vilalta JL (Jan 2008). "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. doi:10.1161/STROKEAHA.107.493767. PMID 18048863.
• Nielsen VG (Oct 2007). "Hydroxyethyl starch enhances fibrinolysis in human plasma by diminishing alpha2-antiplasmin-plasmin interactions". Blood Coagulation & Fibrinolysis : An International Journal in Haemostasis and Thrombosis 18 (7): 647–56. doi:10.1097/MBC.0b013e3282a167dc. PMID 17890952.
• Sazonova IY, Thomas BM, Gladysheva IP, Houng AK, Reed GL (Oct 2007). "Fibrinolysis is amplified by converting alpha-antiplasmin from a plasmin inhibitor to a substrate". Journal of Thrombosis and Haemostasis : JTH 5 (10): 2087–94. doi:10.1111/j.1538-7836.2007.02652.x. PMID 17883703.
• Mutch NJ, Thomas L, Moore NR, Lisiak KM, Booth NA (Apr 2007). "TAFIa, PAI-1 and alpha-antiplasmin: complementary roles in regulating lysis of thrombi and plasma clots". Journal of Thrombosis and Haemostasis : JTH 5 (4): 812–7. doi:10.1111/j.1538-7836.2007.02430.x. PMID 17388801.
• Christiansen VJ, Jackson KW, Lee KN, McKee PA (Jun 2007). "The effect of a single nucleotide polymorphism on human alpha 2-antiplasmin activity". Blood 109 (12): 5286–92. doi:10.1182/blood-2007-01-065185. PMC: 1890835. PMID 17317851.
• Hayashido Y, Hamana T, Ishida Y, Shintani T, Koizumi K, Okamoto T (Feb 2007). "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. doi:10.3892/or.17.2.417. PMID 17203182.
• 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 (Jul 2007). "Association studies between the plasmin genes and late-onset Alzheimer's disease". Neurobiology of Aging 28 (7): 1041–3. doi:10.1016/j.neurobiolaging.2006.05.028. PMC: 2647723. PMID 16828203.
• Liu T, Qian WJ, Gritsenko MA, Camp DG, Monroe ME, Moore RJ, Smith RD (2006). "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry". Journal of Proteome Research 4 (6): 2070–80. doi:10.1021/pr0502065. PMC: 1850943. PMID 16335952.
• Lee KN, Jackson KW, Christiansen VJ, Chung KH, McKee PA (May 2004). "A novel plasma proteinase potentiates alpha2-antiplasmin inhibition of fibrin digestion". Blood 103 (10): 3783–8. doi:10.1182/blood-2003-12-4240. PMID 14751930.
• Anderson NL, Polanski M, Pieper R, Gatlin T, Tirumalai RS, Conrads TP, Veenstra TD, Adkins JN, Pounds JG, Fagan R, Lobley A (Apr 2004). "The human plasma proteome: a nonredundant list developed by combination of four separate sources". Molecular & Cellular Proteomics 3 (4): 311–26. doi:10.1074/mcp.M300127-MCP200. PMID 14718574.
• Kapadia C, Yousef GM, Mellati AA, Magklara A, Wasney GA, Diamandis EP (Jan 2004). "Complex formation between human kallikrein 13 and serum protease inhibitors". Clinica Chimica Acta; International Journal of Clinical Chemistry 339 (1-2): 157–67. doi:10.1016/j.cccn.2003.10.009. PMID 14687906.
• Matsuno H, Okada K, Ueshima S, Matsuo O, Kozawa O (Aug 2003). "Alpha2-antiplasmin plays a significant role in acute pulmonary embolism". Journal of Thrombosis and Haemostasis : JTH 1 (8): 1734–9. doi:10.1046/j.1538-7836.2003.00252.x. PMID 12911586. Check date values in: |year= / |date= mismatch (help)
• Magklara A, Mellati AA, Wasney GA, Little SP, Sotiropoulou G, Becker GW, Diamandis EP (Aug 2003). "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. doi:10.1016/S0006-291X(03)01271-3. PMID 12878203.
• 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 (Apr 2003). "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. doi:10.1086/374320. PMC: 1180354. PMID 12621583.
• Frank PS, Douglas JT, Locher M, Llinás M, Schaller J (Feb 2003). "Structural/functional characterization of the alpha 2-plasmin inhibitor C-terminal peptide". Biochemistry 42 (4): 1078–85. doi:10.1021/bi026917n. PMID 12549929.
• Turner RB, Liu L, Sazonova IY, Reed GL (Sep 2002). "Structural elements that govern the substrate specificity of the clot-dissolving enzyme plasmin". The Journal of Biological Chemistry 277 (36): 33068–74. doi:10.1074/jbc.M203782200. PMID 12080056.
• Askew YS, Pak SC, Luke CJ, Askew DJ, Cataltepe S, Mills DR, Kato H, Lehoczky J, Dewar K, Birren B, Silverman GA (Dec 2001). "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. doi:10.1074/jbc.M108879200. PMID 11604408. Check date values in: |year= / |date= mismatch (help)
• Uszynski M, Klyszejko A, Zekanowska E (Dec 2000). "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. doi:10.1016/S0301-2115(00)00283-9. PMID 11074138. Check date values in: |year= / |date= mismatch (help)
• Hevessy Z, Patthy A, Kárpáti L, Muszbek L (Aug 2000). "alpha(2)-plasmin inhibitor is a substrate for tissue transglutaminase: an in vitro study". Thrombosis Research 99 (4): 399–406. doi:10.1016/S0049-3848(00)00261-9. PMID 10963790.

External links

• The MEROPS online database for peptidases and their inhibitors: I04.023
• alpha-2 Antiplasmin at the US National Library of Medicine Medical Subject Headings (MeSH)
• SERPINF2 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)