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Alpha 2-antiplasmin

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SERPINF2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSERPINF2, A2AP, AAP, ALPHA-2-PI, API, PLI, serpin family F member 2, alpha2AP
External IDsOMIM: 613168; MGI: 107173; HomoloGene: 719; GeneCards: SERPINF2; OMA:SERPINF2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

5345

18816

Ensembl

ENSG00000167711
ENSG00000276838

ENSMUSG00000038224

UniProt

P08697

Q61247

RefSeq (mRNA)

NM_000934
NM_001165920
NM_001165921

NM_008878

RefSeq (protein)

NP_000925
NP_001159392
NP_001159393

NP_032904

Location (UCSC)Chr 17: 1.74 – 1.76 MbChr 11: 75.32 – 75.33 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Alpha 2-antiplasmin (or α2-antiplasmin or plasmin inhibitor) is a serine protease inhibitor (serpin) responsible for inactivating plasmin.[5] Plasmin is an important enzyme that participates in fibrinolysis and degradation of various other proteins. This protein is encoded by the SERPINF2 gene.[6]

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

Structure

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Alpha 2-antiplasmin (α2AP) is a member of the serine protease inhibitor (serpin) superfamily and is structurally characterized by a central serpin domain flanked by unique N- and C-terminal extensions.[7][8] The mature human α2AP protein consists of 452 amino acids, with a 12-residue N-terminus, a central serpin domain, and a C-terminal tail of approximately 55 residues.[7][8] The reactive center loop, which is crucial for its inhibitory function, protrudes from the central serpin domain and contains the Arg364-Met365 peptide bond that is specifically targeted and cleaved by plasmin.[8] There are two main circulating forms: Met-α2AP, which has methionine at the N-terminus, and Asn-α2AP, which is N-terminally shortened and starts with asparagine; the latter form constitutes about 70% of plasma α2AP and is more efficiently cross-linked to fibrin.[9][8] The C-terminal region, rich in lysine residues, mediates the initial non-covalent binding to plasmin, facilitating the formation of a stable 1:1 stoichiometric complex.[8] This structural arrangement allows α2AP to efficiently interact with plasmin and be incorporated into fibrin clots via cross-linking by factor XIIIa.[8][10]

Function

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Alpha 2-antiplasmin serves as the primary physiological inhibitor of plasmin, the key enzyme responsible for fibrin degradation during fibrinolysis.[9][10] By rapidly forming a covalent complex with plasmin, α2AP prevents excessive breakdown of fibrin clots, thereby maintaining hemostatic balance.[9][10][11] In addition to direct inhibition, α2AP interferes with the binding of plasminogen to fibrin, further regulating the initiation of fibrinolysis.[10][11] During clot formation, α2AP is cross-linked to fibrin by activated factor XIII, which increases the resistance of the clot to lysis and enhances clot stability.[10][11] This function is critical in preventing premature clot dissolution, but elevated levels of α2AP have been associated with increased risk of thrombotic events, such as stroke and myocardial infarction, due to impaired fibrinolysis.[12] Conversely, α2AP deficiency leads to increased susceptibility to bleeding because of uncontrolled plasmin activity and rapid clot breakdown.[11] Thus, α2AP is essential for fine-tuning the balance between clot formation and dissolution, making it a potential therapeutic target in both thrombotic and bleeding disorders.[9]

Clinical significance

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Very few cases (<20) of alpha-2-antiplasmin 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 increased risk of bleeding in liver disease.[13] It has been suggested, however, that the observed decreases in alpha 2-antiplasmin levels are due to a chronic state of disseminated intravascular coagulation in cirrhosis rather than defective protein synthesis.[14]

Interactions

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Alpha 2-antiplasmin has been shown to interact with:

See also

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References

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  1. ^ a b c ENSG00000276838 GRCh38: Ensembl release 89: ENSG00000167711, ENSG00000276838 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000038224 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Wu G, Quek AJ, Caradoc-Davies TT, Ekkel SM, Mazzitelli B, Whisstock JC, et al. (2019-03-05). "Structural studies of plasmin inhibition". Biochemical Society Transactions. 47 (2): 541–557. doi:10.1042/bst20180211. ISSN 0300-5127. PMID 30837322. S2CID 73463150.
  6. ^ "Entrez Gene: SERPINF2 serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 2".
  7. ^ a b Holmes WE, Nelles L, Lijnen HR, Collen D (February 1987). "Primary structure of human alpha 2-antiplasmin, a serine protease inhibitor (serpin)". The Journal of Biological Chemistry. 262 (4): 1659–1664. doi:10.1016/S0021-9258(19)75687-7. PMID 2433286.
  8. ^ a b c d e f Singh S, Saleem S, Reed GL (2020). "Alpha2-Antiplasmin: The Devil You Don't Know in Cerebrovascular and Cardiovascular Disease". Frontiers in Cardiovascular Medicine. 7: 608899. doi:10.3389/fcvm.2020.608899. PMC 7785519. PMID 33426005.
  9. ^ a b c d Lee KN, Jackson KW, Christiansen VJ, Chung KH, McKee PA (October 2004). "Alpha2-antiplasmin: potential therapeutic roles in fibrin survival and removal". Current Medicinal Chemistry. Cardiovascular and Hematological Agents. 2 (4): 303–310. doi:10.2174/1568016043356228. PMID 15320781.
  10. ^ a b c d e Baugh RF (September 2019). "Coagulation Theory, Principles, and Concepts". Handbook of Hematologic Pathology. pp. 493–520. ISBN 9780429115721.
  11. ^ a b c d "Alpha 2-Antiplasmin Deficiency". Rare Coagulation Disorders. Retrieved 1 June 2025.
  12. ^ Hou Y, Okada K, Okamoto C, Ueshima S, Matsuo O (July 2008). "Alpha2-antiplasmin is a critical regulator of angiotensin II-mediated vascular remodeling". Arteriosclerosis, Thrombosis, and Vascular Biology. 28 (7): 1257–1262. doi:10.1161/ATVBAHA.108.165688. PMID 18436805.
  13. ^ Sattar H (2011). Fundamentals of Pathology. Pathoma LLC. p. 36.
  14. ^ Marongiu F, Mamusa AM, Mameli G, Mulas G, Solinas A, Demelia L, et al. (Jan 1985). "α2Antiplasmin and Disseminated Intravascular Coagulation in Liver Cirrhosis". Thrombosis Research. 37 (2): 287–294. doi:10.1016/0049-3848(85)90017-9. PMID 3975873.
  15. ^ a b Shieh BH, Travis J (May 1987). "The reactive site of human alpha 2-antiplasmin". The Journal of Biological Chemistry. 262 (13): 6055–6059. doi:10.1016/S0021-9258(18)45536-6. PMID 2437112.
  16. ^ 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): 9849–9854. doi:10.1016/S0021-9258(18)34149-8. PMID 6980881.
  17. ^ 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): 9291–9297. doi:10.1016/S0021-9258(19)86843-6. PMID 158022.

Further reading

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