{PDOC00020}
{PS00021; KRINGLE_1}
{PS50070; KRINGLE_2}
{BEGIN}
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* Kringle domain signature and profile *
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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.

-Consensus pattern: [FY]-C-[RH]-[NS]-x(7,8)-[WY]-C
                    [The 2 C's are involved in a disulfide bonds]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: 5

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Expert(s) to contact by email:
           Ikeo K.; kikeo@genes.nig.ac.jp

-Last update: May 2004 / Text revised.

[ 1] Castellino F.J., Beals J.M.
     "The genetic relationships between the kringle domains of human
     plasminogen, prothrombin, tissue plasminogen activator, urokinase, and
     coagulation factor XII."
     J. Mol. Evol. 26:358-369(1987).
     PubMed=3131537
[ 2] Patthy L.
     "Evolution of the proteases of blood coagulation and fibrinolysis by
     assembly from modules."
     Cell 41:657-663(1985).
     PubMed=3891096
[ 3] Ikeo K., Takahashi K., Gojobori T.
     "Evolutionary origin of numerous kringles in human and simian
     apolipoprotein(a)."
     FEBS Lett. 287:146-148(1991).
     PubMed=1879523
[ 4] Friezner Degen S.J., Stuart L.A., Han S., Jamison C.S.
     Biochemistry 30:9781-9791(1991).
[ 5] Miyazawa K., Shimomura T., Kitamura A., Kondo J., Morimoto Y.,
     Kitamura N.
     "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."
     J. Biol. Chem. 268:10024-10028(1993).
     PubMed=7683665
{END}