Von Willebrand factor A domain family

The above discussion makes a simplistic distincdon between extracellular and intracellular domains. Although many domain families such as kringle (KR), epidermal growth factorlike (EGF), and fibronectin type I and II (FNl, FN2) domains appear to occur only in extracellular proteins, for other domains this is not always the case. Indeed, fibronectin type III (FN3), von Willebrand factor A (VWA), and immunoglobulin domains (IG), often described as extracellular domains, are known in intracellular proteins. A more extreme example is that of PDZ domains, most frequently seen in intracellular proteins, but which have also been identified in nuclear and in extracellular proteins (SIP-1 and interleukin-16, respectively). 

Several vital processes rely on clan PA peptidases. Chief among them are blood coagulation and the immune response, which involve cascades of sequential zymogen activation. In both systems, the chymotrypsin-fold peptidase domain is combined with one more associated protein domains, including apple, CUB, EGF, fibronectin, kringle, sushi, and von Willebrand factor domains. These protein domains are on the N-terminus as an extension of the propeptide segment of the peptidase. Such a trend of N-terminal-associated domains in the SIA peptidase family is common across all forms of life. The domain architecture pairs well with the zymogen activation mechanism, which liberates the proper N-terminus to enable catalytic activity. Often, the associated protein domains remain attached to... 

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