Kringles [1,2,3] are triple-looped, disulfide cross-linked domains found in a varying number of copies, in some serine proteases and plasma proteins. The kringle domain has been found in the following proteins:

• Apolipoprotein A (38 copies).
• Blood coagulation factor XII (Hageman factor) (1 copy).
• Hepatocyte growth factor (HGF) (4 copies).
• Hepatocyte growth factor like protein (4 copies) [4].
• Hepatocyte growth factor activator [1] (once) [5].
• Plasminogen (5 copies).
• Thrombin (2 copies).
• Tissue plasminogen activator (TPA) (2 copies).
• Urokinase-type plasminogen activator (1 copy).

The schematic representation of the structure of a typical kringle domain is shown below:

          +---------------------------------------+
          |                                       |
         xCxxxxxxxxxxxCxxxxxxxxxxCxxxxxCxxxxxxCxxxCx
                      |          |     |      |
                      +----------|-----+      |
                                 +------------+

'C': conserved cysteine involved in a disulfide bond.

Kringle domains are thought to play a role in binding mediators, such as membranes, other proteins or phospholipids, and in the regulation of proteolytic activity. As a signature pattern for this type of domain, we selected a conserved sequence that contains two of the cysteines invovled in disulfide bonds.