Antithrombin III (SERPINC1) (ATIII)

Antithrombin III (ATIII) is a crucial plasma glycoprotein and a member of the serpin family that functions as a primary natural anticoagulant by inhibiting serine proteases in the coagulation cascade [1][2]. Its main targets are thrombin (Factor IIa) and Factor Xa, though it also inactivates Factors IXa, XIa, and XIIa to a lesser extent [1][2]. The inhibitory mechanism involves the formation of a stable 1:1 stoichiometric complex between the inhibitor and the enzyme, effectively neutralizing the protease's activity [3]. This process is relatively slow on its own but is accelerated approximately 1,000 to 10,000-fold by the presence of heparin or endogenous heparan sulfate proteoglycans [3][4]. Clinically, ATIII is the target for indirect anticoagulants like unfractionated heparin and low-molecular-weight heparins, which catalyze its activity to prevent and treat venous thromboembolism and pulmonary embolism [5]. Deficiencies in ATIII, whether congenital or acquired (e.g., due to liver disease, nephrotic syndrome, or sepsis), lead to a significant hypercoagulable state and increased risk of life-threatening thrombosis [1][6]. Sources: [1] StatPearls: Antithrombin III Deficiency (https://www.ncbi.nlm.nih.gov/books/NBK459255/); [2] UniProt: P01008 (ANT3_HUMAN) (https://www.uniprot.org/uniprotkb/P01008/entry); [3] PubMed: Mechanism of action of heparin (https://pubmed.ncbi.nlm.nih.gov/11051241/); [4] NIH/NCBI: Antithrombin III (https://www.ncbi.nlm.nih.gov/mesh/68000925); [5] DrugBank: Heparin (https://go.drugbank.com/drugs/DB01109); [6] Wikipedia: Antithrombin III (https://en.wikipedia.org/wiki/Antithrombin_III).

Other names

AntithrombinAT3Serpin C1Heparin cofactor IThrombophobia 1

Drugs bind to a specific pentasaccharide sequence on antithrombin III, inducing a conformational change that increases its affinity for and rate of inhibition of thrombin (Factor IIa), Factor Xa, and other serine proteases by several thousand-fold.