Caspase 12

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caspase 12
Identifiers
SymbolCASP12
Alt. symbolsCASP12P1
Entrez120329
HUGO19004
OMIM608633
RefSeqNR_000035
UniProtQ6UXS9
Other data
LocusChr. 11 q22.3

Caspase 12 is a protein that belongs to a family of enzymes called caspases which cleave their substrates at C-terminal aspartic acid residues. It is closely related to caspase 1 and other members of the caspase family, known as inflammatory caspases, which process and activate inflammatory cytokines such as interleukin 1 and interleukin 18.

Gene

It is found on chromosome 11 in humans in a locus with other inflammatory caspases.[1] CASP12 orthologs[2] have been identified in numerous mammals for which complete genome data are available.

Clinical significance

The CASP12 gene is subject to polymorphism, which can generate a full length caspase protein (Csp12L) or an inactive truncated form (Csp12S). The functional form appears to be confined to people of African descent and is linked with susceptibility to sepsis; people carrying the functional gene have decreased responses to bacterial molecules such as lipopolysaccharide (LPS).[3][4]

A study in May 2009 by McGill University Health Centre has suggested that estrogen may serve to block the production of caspase-12, resulting in a stronger inflammatory reaction to bacterial pathogens. The trials were carried out on laboratory mice which had been implanted with the human caspase-12 gene.[5][6][7]

The inactive truncated form (Csp12S) of the CASP12 gene was spread and nearly fixed in non-African populations due to positive selection beginning perhaps 60–100 thousand years ago. Its selective advantage is thought to be sepsis resistance in populations that experienced more infectious diseases as population sizes and densities increased.[8][9]

References

  1. Fischer H, Koenig U, Eckhart L, Tschachler E (2002). "Human caspase 12 has acquired deleterious mutations". Biochem. Biophys. Res. Commun. 293 (2): 722–6. doi:10.1016/S0006-291X(02)00289-9. PMID 12054529.
  2. "OrthoMaM phylogenetic marker: CASP12 coding sequence".[permanent dead link]
  3. Saleh M, Vaillancourt JP, Graham RK, Huyck M, Srinivasula SM, Alnemri ES, Steinberg MH, Nolan V, Baldwin CT, Hotchkiss RS, Buchman TG, Zehnbauer BA, Hayden MR, Farrer LA, Roy S, Nicholson DW (2004). "Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms". Nature. 429 (6987): 75–9. doi:10.1038/nature02451. PMID 15129283.
  4. Saleh, Maya Mathison; John C. Wolinski; Melissa K. Bensinger; Steve J. Fitzgerald; Patrick Droin; Nathalie Ulevitch; Richard J. Green; Douglas R. Nicholson; Donald W. (2006). "Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice". Nature. 440 (7087): 1064–1068. doi:10.1038/nature04656. PMID 16625199.
  5. Yeretssian G, Doiron K, Shao W, Leavitt BR, Hayden MR, Nicholson DW, Saleh M (May 2009). "Gender differences in expression of the human caspase-12 long variant determines susceptibility to Listeria monocytogenes infection". Proc. Natl. Acad. Sci. U.S.A. 106 (22): 9016–20. doi:10.1073/pnas.0813362106. PMC 2690057. PMID 19447924.
  6. "Man flu: real or myth?". Health. NHS UK. 2009-05-18.
  7. "Women 'fight off disease better'". Health. BBC News. 2009-05-13. Retrieved 2009-05-13.
  8. "Spread of an Inactive Form of Caspase-12 in Humans Is Due to Recent Positive Selection". The American Journal of Human Genetics. 78: 659–670. doi:10.1086/503116. PMC 1424700. PMID 16532395.
  9. "Gene Losses during Human Origins". PLoS Biology. 4: e52. doi:10.1371/journal.pbio.0040052. PMC 1361800. PMID 16464126.

External links

  • The MEROPS online database for peptidases and their inhibitors: C14.013

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