Jump to content

Alpha 2-antiplasmin

From Wikipedia, the free encyclopedia

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

[edit]

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

[edit]

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 signficance

[edit]

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

[edit]

Alpha 2-antiplasmin has been shown to interact with:

See also

[edit]

References

[edit]
  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

[edit]
[edit]
Retrieved from "https://en.wikipedia.org/w/index.php?title=Alpha_2-antiplasmin&oldid=1293424435"