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TAFI (Thrombin Activatable Fibrinolysis Inhibitor)

Cat no: T0600-96A

TAFI (Thrombin Activatable Fibrinolysis Inhibitor)

Thrombin Activatable Fibrinolysis Inhibitor (TAFI, Plasma pro-carboxypeptidase B, carboxypeptidase U) is a single chain glycoprotein zymogen (Mr=60,000) synthesized in the liver and circulating at a plasma concentration of 50nM (1-4). Thrombin (plasmin, trypsin) cleavage of the zymogen releases a 92 amino acid N-terminal activation peptide containing 4 N-linked glycosylation sites (N22, N51, N63, N86) and the proposed plasminogen recognition site. The rate of thrombin catalyzed activation of TAFI is increased 1250 fold by formation of a ternary complex with thrombomodulin (5). The 309 amino acid C-terminal (Mr=35,783) catalytic domain (TAFIa, pCPB) displays the properties of a basic carboxypeptidase, hydrolyzing lysine and arginine from the C-terminal position of polypeptides. This portion of the molecule is homologous to tissue carboxypeptidase B and contains 7 conserved cystine residues (64,77,136,151,160,165,291), the active site Zn2+ coordination site (H67, E69, H196) and the basic C-terminal amino acid substrate binding pocket (D257, G244, S207). TAFI is proposed to play a key role in the interaction between procoagulant, anticoagulant and fibrinolytic systems (5-9). Effective fibrinolysis results from the formation of a ternary complex between tPA, plasminogen and C-terminal lysine residues on fibrin. Plasminogen bound to fibrin is more effectively converted to plasmin, thereby localizing the lytic activity to the area of the clot. Plasmin degradation of fibrin generates additional C-terminal lysine residues thereby amplifying the system locally. The ability of TAFI to bind specifically to plasminogen and to cleave C-terminal lysines on fibrin (and cell surfaces) results in down-regulation of fibrinolysis by reducing the number of plasminogen and tPA binding sites on fibrin. The activation of TAFI by the thrombin/thrombomodulin complex couples both the phenomenon of coagulation induced inhibition of fibrinolysis and the profibrinolytic effect of activated protein C.\n\nApplication:\nSuitable for use as a source of sheep polyclonal antibodies to human TAFI. Other applications not tested.\n\nOptimal dilutions to be determined by the researcher.\n\nStorage and Stability:\nMay be stored at 4 degrees C for short-term only. For long-term storage, store at -20 degrees C. Aliquots are stable for at least 12 months at -20 degrees C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.

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SPECIFICATIONS

Catalog Number

T0600-96A

Size

1mg

Hosts

Sheep

Reactivities

Hum

Form

Supplied in 10mM HEPES, pH 7.4, 0.15M sodium chloride in 50% glycerol.

P Type

Pab

Purity

Purified by caprylic acid and ammonium sulfate precipitations, and solid -phase adsorption to remove unwanted crossreactivity.

Isotype

IgG

Additional Info

By immunodiffusion, no reactivity was seen with TAFI-deficient plasma.

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