CFC domain explained

Symbol:	CFC
CFC
Pfam:	PF09443
Interpro:	IPR019011

In molecular biology, the CFC domain (Cripto_Frl-1_Cryptic domain) is a protein domain found at the C-terminus of a number of proteins including Cripto (or teratocarcinoma-derived growth factor).^{[1] [2]} It is structurally similar to the C-terminal extracellular portions of Jagged 1 and Jagged 2.^[1] CFC is approx 40-residues long, compacted by three internal disulphide bridges, and binds Alk4 via a hydrophobic patch. CFC is structurally homologous to the VWFC-like domain.^[1]

The CFC domain appears to play a crucial role in the tumourigenic activity of Cripto proteins, as it is through the CFC domain that Cripto interferes with the onco-suppressive activity of Activins, either by blocking the Activin receptor ALK4 or by antagonising proteins of the TGF-beta family.^[3]

Notes and References

1. Foley SF, van Vlijmen HW, Boynton RE, Adkins HB, Cheung AE, Singh J, Sanicola M, Young CN, Wen D . The CRIPTO/FRL-1/CRYPTIC (CFC) domain of human Cripto. Functional and structural insights through disulfide structure analysis . Eur. J. Biochem. . 270 . 17 . 3610–8 . September 2003 . 12919325 . 10.1046/j.1432-1033.2003.03749.x. free .
2. Calvanese L, Saporito A, Marasco D, D'Auria G, Minchiotti G, Pedone C, Paolillo L, Falcigno L, Ruvo M . Solution structure of mouse Cripto CFC domain and its inactive variant Trp107Ala . J. Med. Chem. . 49 . 24 . 7054–62 . November 2006 . 17125258 . 10.1021/jm060772r .
3. Calvanese L, Saporito A, Oliva R, D' Auria G, Pedone C, Paolillo L, Ruvo M, Marasco D, Falcigno L . Structural insights into the interaction between the Cripto CFC domain and the ALK4 receptor . J. Pept. Sci. . 15 . 3 . 175–83 . March 2009 . 19035567 . 10.1002/psc.1091 .