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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/05/10 11:40:53」(JST)

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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 [edit]

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 [edit]

Alpha 2-antiplasmin has been shown to interact with Plasmin^[3]^[4] and Neutrophil elastase.^[4]^[5]

References [edit]

^ "Entrez Gene: SERPINF2 serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 2".
^ Sattar, Husain. Fundamentals of Pathology. Pathoma LLC, 2011, p. 36.
^ Wiman, B; Collen D (September 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.
^ ^a ^b 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.
^ Brower, M S; Harpel P C (August 1982). "Proteolytic cleavage and inactivation of alpha 2-plasmin inhibitor and C1 inactivator by human polymorphonuclear leukocyte elastase". J. Biol. Chem. (UNITED STATES) 257 (16): 9849–54. ISSN 0021-9258. PMID 6980881.

External links [edit]

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)

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UpToDate Contents

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1. 血栓溶解異常による血栓性および出血性疾患 thrombotic and hemorrhagic disorders due to abnormal fibrinolysis
2. 血液製剤の病原体不活化 pathogen inactivation of blood products
3. ST上昇型心筋梗塞における血栓溶解療法の特性および臨床試験 characteristics of fibrinolytic thrombolytic agents and clinical trials in acute st elevation myocardial infarction
4. 幼児および小児における播種性血管内凝固 disseminated intravascular coagulation in infants and children
5. 血管内皮機能および血栓溶解療法の基本的メカニズム vascular endothelial function and fundamental mechanisms of fibrinolysis thrombolysis

English Journal

Fibrin targeted plasminogen activation by plasminogen activator, PadA, from Streptococcus dysgalactiae.

Singh S1, Bhando T, Dikshit KL.Author information 1CSIR-Institute of Microbial Technology, Sector 39A, Chandigarh, 160036, INDIA.AbstractBacterial plasminogen activators differ from each other in their mechanism of plasminogen activation besides their host specificity. Three-domain, streptokinase and two-domain PauAgenerate non-proteolytic active site center in their cognate partner plasminogen but their binary activator complexes are resistant to α2-antiplasmin inhibition causing non-specific plasminogen activation in plasma. In contrast, single domain plasminogen activator, staphylokinase, requires proteolytic cleavage of human plasminogen into plasmin for the active site generation and this activator complex is inhibited by α2-antiplasmin. The single domain plasminogen activator, PadA, from Streptococcus dysgalatiae, having close sequence and possible structure homology with staphylokinase, was recently reported to activate bovine Pg in a non-proteolytic manner similar to streptokinase. We report hereby that the binary activator complex of PadA with bovine plasminogen is inhibited by α2-antiplasmin and PadA is recycled from this complex to catalyze the activation of plasminogen in the clot environment where it is completely protected from α2-antiplasmin inhibition. Catalytic efficiency of the activator complex formed by PadA and bovine plasminogen is amplified several folds in the presence of cyanogen bromide digested fibrinogen but not by intact fibrinogen indicating that PadA may be highly efficient at the fibrin surface. The present study, thus, demonstrates that PadA is a unique single domain plasminogen activator that activates bovine plasminogen in a fibrin-targeted manner like staphylokinase. The sequence optimization by PadA for acquiring the characteristics of both streptokinase and staphylokinase may be exploited for the development of efficient and fibrin specific plasminogen activators for thrombolytic therapy.
Protein science : a publication of the Protein Society.Protein Sci.2014 Mar 18. doi: 10.1002/pro.2455. [Epub ahead of print]
Bacterial plasminogen activators differ from each other in their mechanism of plasminogen activation besides their host specificity. Three-domain, streptokinase and two-domain PauAgenerate non-proteolytic active site center in their cognate partner plasminogen but their binary activator complexes ar
PMID 24639287

Assessment of biomarkers and predictive model for short-term prospective abdominal aortic aneurysm growth - a pilot study.

Vega de Ceniga M1, Esteban M2, Barba A3, Estallo L3, Blanco-Colio LM4, Martin-Ventura JL4.Author information 1Department of Angiology and Vascular Surgery, Hospital de Galdakao-Usansolo, Bizkaia. Electronic address: melina.vegadeceniga@osakidetza.net.2Biochemistry Laboratory, Hospital de Cruces, Bizkaia.3Department of Angiology and Vascular Surgery, Hospital de Galdakao-Usansolo, Bizkaia.4Vascular Research Laboratory, Fundación Jiménez Díaz, Autonoma University, Madrid.AbstractOBJECTIVE: Abdominal aortic aneurysms (AAA) are currently followed with serial ultrasound or CT scanning diameter measurements, but evidence shows that AAA expansion is mostly discontinuous and quite unpredictable in any given patient. A reliable predictive model of AAA growth and/or rupture risk could help individualize treatment, follow-up protocols and cost-effectiveness. Our objective is to set a predictive model of short-term prospective AAA growth, after clinical, serological and anatomical data.
Annals of vascular surgery.Ann Vasc Surg.2014 Mar 10. pii: S0890-5096(14)00145-9. doi: 10.1016/j.avsg.2014.02.025. [Epub ahead of print]
OBJECTIVE: Abdominal aortic aneurysms (AAA) are currently followed with serial ultrasound or CT scanning diameter measurements, but evidence shows that AAA expansion is mostly discontinuous and quite unpredictable in any given patient. A reliable predictive model of AAA growth and/or rupture risk co
PMID 24632318

Age-Based Difference in Activation Markers of Coagulation and Fibrinolysis in Extracorporeal Membrane Oxygenation.

Hundalani SG1, Nguyen KT, Soundar E, Kostousov V, Bomgaars L, Moise A, Hui SK, Teruya J.Author information 11Section of Neonatology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX. 2Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX. 3Department of Pathology & Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX. 4Cancer and Hematology Centers, Baylor College of Medicine, Texas Children's Hospital, Houston, TX. 5Department of Medicine, Baylor College of Medicine, Texas Children's Hospital, Houston, TX.AbstractOBJECTIVE:: Coagulation system activation in extracorporeal membrane oxygenation results in hemostatic derangements. Thrombin generation markers like prothrombin fragment 1+2 and thrombin-antithrombin complex are sensitive markers of hypercoagulability. Plasmin-antiplasmin complex is a sensitive marker for fibrinolysis. D-dimers reflect thrombin generation and fibrinolysis. The aim was to identify the extent of hemostasis activation during extracorporeal membrane oxygenation by measuring thrombin-antithrombin complex, prothrombin fragment 1+2, plasmin-antiplasmin complex, and D-dimer.
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.Pediatr Crit Care Med.2014 Mar 7. [Epub ahead of print]
OBJECTIVE:: Coagulation system activation in extracorporeal membrane oxygenation results in hemostatic derangements. Thrombin generation markers like prothrombin fragment 1+2 and thrombin-antithrombin complex are sensitive markers of hypercoagulability. Plasmin-antiplasmin complex is a sensitive mar
PMID 24614609

Japanese Journal

Genetically Disparate Fayoumi Chicken Lines Show Different Response to Avian Necrotic Enteritis

Kim Duk K.,Lillehoj Hyun S.,Jang Seung I.,Lee Sung H.,Hong Yeong H.,Lamont Susan J.
The Journal of Poultry Science advpub(0), 2015
… lines are genetically disparate at their major histocompatibility complex (MHC) and this difference was reflected in the differential expression patterns of several inflammatory genes such as suppressor of cytokine signaling 3 (SOCS3), interleukin 8 (IL8), nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, zeta (NFKBIZ), serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1 (SERPINF1), and gap junction protein, alpha 1, 43kDa (GJA1) between NE-afflicted and uninfected …
NAID 130005073191

Short-term Venous Stasis Induces Fibrinolytic Activation but not Thrombin Formation

Rühl Heiko,Müller Jens,Wäschenbach Jana,Oldenburg Johannes,Dewald Oliver,Pötzsch Bernd
Journal of Atherosclerosis and Thrombosis 21(12), 1260-1270, 2014
… The plasma levels of activated protein C (APC) were additionally measured using an APC-OECA.Results: VO induced a significant (p＜0.05) increase in the levels of tissue-type plasminogen activator and plasmin-α2-antiplasmin-complexes. …
NAID 130004845465

Short-term Venous Stasis Induces Fibrinolytic Activation but not Thrombin Formation

Rühl Heiko,Müller Jens,Wäschenbach Jana,Oldenburg Johannes,Dewald Oliver,Pötzsch Bernd
Journal of Atherosclerosis and Thrombosis, 2014
… The plasma levels of activated protein C (APC) were additionally measured using an APC-OECA.Results: VO induced a significant (p＜0.05) increase in the levels of tissue-type plasminogen activator and plasmin-α2-antiplasmin-complexes. …
NAID 130004677964

「plasmin inhibitor」

Serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), 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; • eukaryotic cell surface binding;
Cellular component	• extracellular region; • fibrinogen complex; • extracellular space; • platelet alpha granule lumen;
Biological process	• regulation of blood vessel size by renin-angiotensin; • platelet degranulation; • acute-phase response; • blood coagulation; • response to organic substance; • negative regulation of plasminogen activation; • negative regulation of endopeptidase activity; • regulation of proteolysis; • platelet activation; • 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
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