Cryptic/Cripto, CFC domain (IPR019011)

Short name: Cryptic/Cripto_CFC-dom

Overlapping homologous superfamilies


Domain relationships



This entry represents the CFC domain found in the membrane protein Cripto (or teratocarcinoma-derived growth factor), a protein over expressed in many tumours [PMID: 12919325, PMID: 17125258] and structurally similar to the C-terminal extracellular portions of Jagged 1 and Jagged 2 [PMID: 12919325]. 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 [PMID: 12919325].

The protein Cripto is the founding member of the extra-cellular EGF-CFC growth factors, which are composed of two adjacent cysteine-rich domains: the EGF-like and the CFC domains. Members of the EGF-CFC family play key roles in embryonic development and are also implicated in tumourigenesis [PMID: 19035567]. The Cripto protein could play a role in the determination of the epiblastic cells that subsequently give rise to the mesoderm. Although both the EGF and CFC domains are involved in the tumourigenic activity of Crispto proteins, the CFC domain appears to play a crucial role, as it is through the CFC domain that Crispto interferes with the onco-suppressive activity of Activins, either by blocking the Activin receptor ALK4 or by antagonising proteins of the TGF-beta family [PMID: 19035567].

The Cryptic protein is involved in the correct establishment of the left-right axis. May play a role in mesoderm and/or neural patterning during gastrulation.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.