PROSITE documentation PDOC00020Kringle domain signature and profile
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.
Expert(s) to contact by email: Last update:May 2004 / Text revised.
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PROSITE methods (with tools and information) covered by this documentation:
1 | Authors | Castellino F.J. Beals J.M. |
Title | The genetic relationships between the kringle domains of human plasminogen, prothrombin, tissue plasminogen activator, urokinase, and coagulation factor XII. | |
Source | J. Mol. Evol. 26:358-369(1987). | |
PubMed ID | 3131537 |
2 | Authors | Patthy L. |
Title | Evolution of the proteases of blood coagulation and fibrinolysis by assembly from modules. | |
Source | Cell 41:657-663(1985). | |
PubMed ID | 3891096 |
3 | Authors | Ikeo K. Takahashi K. Gojobori T. |
Title | Evolutionary origin of numerous kringles in human and simian apolipoprotein(a). | |
Source | FEBS Lett. 287:146-148(1991). | |
PubMed ID | 1879523 |
4 | Authors | Friezner Degen S.J. Stuart L.A. Han S. Jamison C.S. |
Source | Biochemistry 30:9781-9791(1991). |
5 | Authors | Miyazawa K. Shimomura T. Kitamura A. Kondo J. Morimoto Y. Kitamura N. |
Title | Molecular cloning and sequence analysis of the cDNA for a human serine protease reponsible for activation of hepatocyte growth factor. Structural similarity of the protease precursor to blood coagulation factor XII. | |
Source | J. Biol. Chem. 268:10024-10028(1993). | |
PubMed ID | 7683665 |
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