Cripto

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Cripto, FRL-1, cryptic family 1B
2J5H.pdb.jpg
Solution structure of mouse Cripto CFC domain.[1]
Identifiers
Symbols CFC1B ; MGC133213; HTX2; CRYPTIC; FLJ77897
External IDs OMIM605194 HomoloGene50007 GeneCards: CFC1B Gene
Orthologs
Species Human Mouse
Entrez 653275 12627
Ensembl ENSG00000152093 ENSMUSG00000026124
UniProt P0CG36 P97766
RefSeq (mRNA) NM_001079530 NM_007685
RefSeq (protein) NP_001072998 NP_031711
Location (UCSC) Chr 2:
131.28 – 131.29 Mb
Chr 1:
34.54 – 34.54 Mb
PubMed search [1] [2]

Cryptic family protein 1B is a protein that in humans is encoded by the CFC1B gene.[2][3] Cryptic family protein 1B acts as a receptor for the TGF beta signaling pathway.

Cryptic is a glycosylphosphatidylinositol-anchored coreceptor that binds nodal and the activin type I (ALK)-4 receptor (ALK4).[4]

Structure[edit]

Cripto is composed of two adjacent cysteine-rich motifs, the EGF-like and the CFC, of a N-terminal signal peptide and of a C-terminal hydrophobic region attached by a GPI anchor.[1]

NMR data confirm that the CFC domain has a C1-C4, C2-C6, C3-C5 disulfide pattern and show that structures are rather flexible and globally extended, with three noncanonical antiparallel strands.[1]

Clinical significance[edit]

CFC1B has oncogene potential.[1] Furthermore the cryptic protein is highly overexpressed in many tumors.[1]

Cripto is one of the key regulators of embryonic stem cells differentiation into cardiomyocyte vs neuronal fate.[5]

Expression levels of cripto1 is associated with resistance to EGFR inhibitors.[6]

References[edit]

  1. ^ a b c d e 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. 
  2. ^ "Entrez Gene: cripto". 
  3. ^ Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548. 
  4. ^ Lonardo E, Parish CL, Ponticelli S, Marasco D, Ribeiro D, Ruvo M, De Falco S, Arenas E, Minchiotti G (August 2010). "A small synthetic cripto blocking Peptide improves neural induction, dopaminergic differentiation, and functional integration of mouse embryonic stem cells in a rat model of Parkinson's disease". Stem Cells 28 (8): 1326–37. doi:10.1002/stem.458. PMID 20641036. 
  5. ^ Chambery A, Vissers JP, Langridge JI, Lonardo E, Minchiotti G, Ruvo M, Parente A (February 2009). "Qualitative and quantitative proteomic profiling of cripto(-/-) embryonic stem cells by means of accurate mass LC-MS analysis". J. Proteome Res. 8 (2): 1047–58. doi:10.1021/pr800485c. PMID 19152270. 
  6. ^ Park KS, Raffeld M, Moon YW, Xi L, Bianco C, Pham T, Lee LC, Mitsudomi T, Yatabe Y, Okamoto I, Subramaniam D, Mok T, Rosell R, Luo J, Salomon DS, Wang Y, Giaccone G (2014). "CRIPTO1 expression in EGFR-mutant NSCLC elicits intrinsic EGFR-inhibitor resistance". J. Clin. Invest. doi:10.1172/JCI73048. PMID 24911146. 

External links[edit]