APPLE domain
SMART accession number:SM00223
Description: Four-fold repeat in plasma kallikrein and coagulation factor XI. Factor XI apple 3 mediates binding to platelets. Factor XI apple 1 binds high-molecular-mass kininogen. Apple 4 in factor XI mediates dimer formation and binds to factor XIIa. Mutations in apple 4 cause factor XI deficiency, an inherited bleeding disorder.
Interpro abstract (IPR000177): Plasma kallikrein (EC and coagulation factor XI (EC are two related plasma serine proteases activated by factor XIIA and which share the same domain topology: an N-terminal region that contains four tandem repeats of about 90 amino acids and a C-terminal catalytic domain. The 90 amino-acid repeated domain contains 6 conserved cysteines. It has been shown [(PUBMED:1998666)] that three disulphide bonds link the first and sixth, second and fifth, and third and fourth cysteines. The domain can be drawn in the shape of an apple (see below) and has been accordingly called the 'apple domain'.

x x x x x x
x C---C x
x x x x
x Cx x x x
x | x x x Schematic representation of an
x Cx x x x apple domain.
x x x x
x x x x
x x x x x
x x
x x x x
.....x x.....
Apart from the cysteines, there are a number of other conserved positions in the apple domain. The apple domains of plasma prekallikrein are known to mediate its binding to high molecular weight kininogen [(PUBMED:8662705)], the apple domains of factor XI bind to factor XIIa, platelets, kininogen, factor IX and heparin [(PUBMED:9632702)].
GO process:blood coagulation (GO:0007596), proteolysis (GO:0006508)
GO component:extracellular region (GO:0005576)
GO function:protein binding (GO:0005515)
Family alignment:
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There are 1089 APPLE domains in 259 proteins in SMART's nrdb database.

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