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1  structure 47  species 0  interactions 108  sequences 3  architectures

Family: CFC (PF09443)

Summary: Cripto_Frl-1_Cryptic (CFC)

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CFC domain Edit Wikipedia article

CFC
PDB 2j5h EBI.jpg
nmr analysis of mouse cripto cfc domain
Identifiers
Symbol 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]

References[edit]

  1. ^ a b c Foley SF, van Vlijmen HW, Boynton RE, Adkins HB, Cheung AE, Singh J, Sanicola M, Young CN, Wen D (September 2003). "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. doi:10.1046/j.1432-1033.2003.03749.x. PMID 12919325. 
  2. ^ Calvanese L, Saporito A, Marasco D, D'Auria G, Minchiotti G, Pedone C, Paolillo L, Falcigno L, Ruvo M (November 2006). "Solution structure of mouse Cripto CFC domain and its inactive variant Trp107Ala". J. Med. Chem. 49 (24): 7054–62. doi:10.1021/jm060772r. PMID 17125258. 
  3. ^ Calvanese L, Saporito A, Oliva R, D' Auria G, Pedone C, Paolillo L, Ruvo M, Marasco D, Falcigno L (March 2009). "Structural insights into the interaction between the Cripto CFC domain and the ALK4 receptor". J. Pept. Sci. 15 (3): 175–83. doi:10.1002/psc.1091. PMID 19035567. 

This article incorporates text from the public domain Pfam and InterPro IPR019011

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Cripto_Frl-1_Cryptic (CFC) Provide feedback

CFC domain is one half of the membrane protein Cripto, a protein overexpressed in many tumours [1,2] and 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].

Literature references

  1. Foley SF, van Vlijmen HW, Boynton RE, Adkins HB, Cheung AE, Singh J, Sanicola M, Young CN, Wen D; , Eur J Biochem. 2003;270:3610-3618.: The CRIPTO/FRL-1/CRYPTIC (CFC) domain of human Cripto. Functional and structural insights through disulfide structure analysis. PUBMED:12919325 EPMC:12919325

  2. Calvanese L, Saporito A, Marasco D, D'Auria G, Minchiotti G, Pedone C, Paolillo L, Falcigno L, Ruvo M; , J Med Chem. 2006;49:7054-7062.: Solution structure of mouse Cripto CFC domain and its inactive variant Trp107Ala. PUBMED:17125258 EPMC:17125258


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR019011

This entry represents the CFC domain found in the membrane protein Cripto (or teratocarcinoma-derived growth factor), a protein over expressed in many tumours [PUBMED:12919325, PUBMED:17125258] and structurally similar to the C-terminal extracellular portions of Jagged 1 and Jagged 2 [PUBMED: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 [PUBMED: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 (INTERPRO) and the CFC domains. Members of the EGF-CFC family play key roles in embryonic development and are also implicated in tumourigenesis [PUBMED: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 [PUBMED: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.

Domain organisation

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Alignments

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  Seed
(9)
Full
(108)
Representative proteomes NCBI
(92)
Meta
(0)
RP15
(6)
RP35
(8)
RP55
(16)
RP75
(44)
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  Seed
(9)
Full
(108)
Representative proteomes NCBI
(92)
Meta
(0)
RP15
(6)
RP35
(8)
RP55
(16)
RP75
(44)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

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Curation and family details

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Seed source: pdb_2j5h
Previous IDs: none
Type: Domain
Author: Coggill P
Number in seed: 9
Number in full: 108
Average length of the domain: 33.30 aa
Average identity of full alignment: 52 %
Average coverage of the sequence by the domain: 19.83 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.2 20.2
Trusted cut-off 20.5 20.5
Noise cut-off 19.6 18.7
Model length: 36
Family (HMM) version: 5
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Species distribution

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the CFC domain has been found. There are 1 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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