9.B.101 The Cytotoxin-associated Gene Product (CagA) Family Sequence analyses of the virulence determinant CagA revealed three main groups strikingly similar to the three groups of VacA sequences (see TC family 1.C.9). Thus, positive selection has shaped the phylogenetic structure of VacA and CagA, and each of these virulence determinants has evolved separately from the core genome. CagA may also be related to members of the Bacillus thuringiensis Vegetative Insecticidal Protein-3 (Vip3) Family (e.g., 1.C.105.2.2). Hydrogen oxidation provides an alternative high-energy substrate for some pathogens. Wang et al. 2016 demonstrated roles of H₂ oxidation in energizing transport of CagA, a carcinogenic toxin.
References:
Gangwer, K.A., C.L. Shaffer, S. Suerbaum, D.B. Lacy, T.L. Cover, and S.R. Bordenstein. (2010). Molecular evolution of the Helicobacter pylori vacuolating toxin gene vacA. J. Bacteriol. 192: 6126-6135.
Sibony, M. and N.L. Jones. (2012). Recent advances in Helicobacter pylori pathogenesis. Curr Opin Gastroenterol 28: 30-35.
Wang, G., J. Romero-Gallo, S.L. Benoit, M.B. Piazuelo, R.L. Dominguez, D.R. Morgan, R.M. Peek, Jr, and R.J. Maier. (2016). Hydrogen Metabolism in Helicobacter pylori Plays a Role in Gastric Carcinogenesis through Facilitating CagA Translocation. MBio 7:.
Examples:
TC#	Name	Organismal Type	Example
9.B.101.1.1	Cytotoxin-associated gene product, CagA. It may mediate carcinogenesis in the human stomach (Sibony and Jones, 2012). (May be related to VacA and other Cag pathogenicity island proteins (Gangwer et al., 2010)).	Bacteria	*CagA of Helicobacter pylori* (O07910)**

Examples:
TC#	Name	Organismal Type	Example
9.B.101.2.1	Uncharacterized protein of 1272 aas, sharing a C-terminal repeat sequence with CagA.		UP of Podarcis muralis

Examples:
TC#	Name	Organismal Type	Example
9.B.101.3.1	Uncharacterized protein of 376 aas		UP of Bacteroides coprocola