The Annexin A2/S100A10 Complex: The Mutualistic Symbiosis of Two Distinct Proteins

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2021-12, Vol.11 (12), p.1849
• Main Authors: Bharadwaj, Alamelu, Kempster, Emma, Waisman, David Morton
• Format: Article
• Language: English
• Subjects: Actin; annexin A2; Annexin A2 - metabolism; Binding sites; Biological activity; Calcium-binding protein; Dipeptides - metabolism; Feedback, Physiological; Fibrinolysin - metabolism; Hands; Heparin; Humans; Ion channels; Kinases; Ligands; Neurotransmitter receptors; Phospholipids; Phosphorylation; Plasmin; plasminogen; Polysaccharides; Proteasomes; Proteins; Proteolysis; Review; S100 protein; S100 Proteins - metabolism; S100A10; Symbiosis; t-Plasminogen activator; Ubiquitin; Ubiquitination
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom11121849

Mutualistic symbiosis refers to the symbiotic relationship between individuals of different species in which both individuals benefit from the association. S100A10, a member of the S100 family of Ca -binding proteins, exists as a tight dimer and binds two annexin A2 molecules. This association forms the annexin A2/S100A10 complex known as AIIt, and modifies the distinct functions of both proteins. Annexin A2 is a Ca -binding protein that binds F-actin, phospholipid, RNA, and specific polysaccharides such as heparin. S100A10 does not bind Ca , but binds tPA, plasminogen, certain plasma membrane ion channels, neurotransmitter receptors, and the structural scaffold protein, AHNAK. S100A10 relies on annexin A2 for its intracellular survival: in the absence of annexin A2, it is rapidly destroyed by ubiquitin-dependent and independent proteasomal degradation. Annexin A2 requires S100A10 to increase its affinity for Ca , facilitating its participation in Ca -dependent processes such as membrane binding. S100A10 binds tissue plasminogen activator and plasminogen, and promotes plasminogen activation to plasmin, which is a process stimulated by annexin A2. In contrast, annexin A2 acts as a plasmin reductase and facilitates the autoproteolytic destruction of plasmin. This review examines the relationship between annexin A2 and S100A10, and how their mutualistic symbiosis affects the function of both proteins.