The structures of transforming growth factor-β (TGF-β), nerve growth
factor (NGF), platelet-derived growth factor (PDGF) and gonadotropin have been
shown to be similar [1,2 and references therein]: these proteins are folded
into two highly twisted antiparallel pairs of β-strands and contain three
disulfide bonds, of which two form a cystine ring through which the third bond
passes (see the schematic representation below). This structure is called
cystine knot .
'=>': indicates the direction of the beta-strands 'b1' to 'b4'.
'C' : conserved cysteine in cystine knot.
'c' : additional conserved cysteine in C-terminal cystine knot.
':' : disulfide bridge.
Functional diverse modular proteins share a conserved domain of about 90 amino
acids in their C-terminal cysteine-rich region, that has been proposed [4,5]
to be structurally related to the cystine-knot family  and which is
therefore called C-terminal cystine-knot (CTCK). Members of the C-terminal
cystine knot family are listed below:
von Willebrand factor (vWF), a multifunctional protein which is involved in
maintaining homeostasis. It consists of 4 vWF type D domains, 3 vWF type A
domains, 3 vWF type B domains, 2 vWF type C domains (see <PDOC00928>, a
X domain and the C-terminal cystine knot.
Mucins. Human mucin 2, a highly polymorphic multidomain molecule with a
modular architecture similar to vWF. Xenopus mucin B.1 which contains a
CCP domain, a vWF type C domain, a X domain and a CTCK. Other mucins that
contain a CTCK are the human tracheobronchial mucin (gene MUC5), bovine
submaxillary mucin-like protein, pig apomucin and rat intestinal mucin-like
CCN family (cef-10/cyr61/CTFG/fisp-12/nov protein family). These growth-
factor inducible proteins are structurally related to the insulin-like
growth factor binding proteins (see <PDOC00194>) and could also function as
growth-factor binding proteins.
Drosophila slit protein which is essential for development of midline glia
and commissural axon pathways. It is composed of four leucine-rich repeats,
seven EGF-like domains, a laminin G-like repeat and the CTCK.
Norrie disease protein (NDP) which may be involved in neuroectodermal cell-
cell interaction and in a pathway that regulates neural cell
differentiation and proliferation.
Silk moth hemocytin, an humoral lectin which is involved in a self-defence
mechanism. It is composed of 2 FA58C domains (see <PDOC00988>), a C-type
lectin domain (see <PDOC00537>), 2 VWFC domains (see <PDOC00928), and a
The pattern we developed for CTCK correspond to the C-terminal half of the
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