The presence of the cyclic cystine knot (CCK) motif was discovered when cyclotides were isolated from various plant families. The CCK motif has a cyclic backbone, triple stranded beta sheet, and cystine knot conformation.[1]

The GFCK is comprised of four superfamilies. These include nerve growth factor, transforming growth factor beta, platelet-derived growth factor, and glycoprotein hormones, including human chorionic gonadotropin. These are structurally related due to the presence of the cystine knot motif but differ in sequence.[2]

The vascular endothelial growth factor subfamily, categorized as part of the platelet-derived growth factor superfamily, includes proteins that are angiogenic factors.[3]

There are currently novel proteins being added to the cystine knot motif family, which are called the C-terminal cystine knot (CTCK) proteins. They share approximately 90 amino acid residues in their cysteine-rich C terminal regions.[3]


  1. ^ "ScienceDirect". www.sciencedirect.com. Retrieved 2019-04-24.
  2. ^ Sun, P D; Davies, D R (1995). "The Cystine-Knot Growth-Factor Superfamily". Annual Review of Biophysics and Biomolecular Structure. 24 (1): 269–292. doi:10.1146/annurev.bb.24.060195.001413. PMID 7663117.
  3. ^ a b Iyer, Shalini; Acharya, K Ravi (2011-11). "Tying the knot: The cystine signature and molecular-recognition processes of the vascular endothelial growth factor family of angiogenic cytokines". The Febs Journal. 278 (22): 4304–4322. doi:10.1111/j.1742-4658.2011.08350.x. ISSN 1742-464X. PMC PMCPMC3328748. PMID 21917115. {{cite journal}}: Check |pmc= value (help); Check date values in: |date= (help)