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CASP12
Identifiers
Aliases	CASP12, CASP-12, CASP12P1, caspase 12 (gene/pseudogene), caspase 12, Caspase-12, Caspase_12, IPR035713
External IDs	OMIM: 608633; MGI: 1312922; GeneCards: CASP12; OMA:CASP12 - orthologs
Gene location (Human) Chr. Chromosome 11 (human) Band 11q22.3 Start 104,885,718 bp End 104,898,670 bp
Gene location (Mouse) Chr. Chromosome 9 (mouse) Band 9 A1|9 2.46 cM Start 5,345,430 bp End 5,373,032 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in testicle right lung left ovary gastric mucosa ascending aorta Descending thoracic aorta popliteal artery tibial arteries left coronary artery right ovary Top expressed in temporal muscle tunica media of zone of aorta sternocleidomastoid muscle lumbar spinal ganglion triceps brachii muscle intercostal muscle uterus carotid body ascending aorta semi-lunar valve More reference expression data BioGPS n/a
Gene ontology Molecular function cysteine-type endopeptidase activity involved in apoptotic process cysteine-type peptidase activity cysteine-type endopeptidase activity cysteine-type endopeptidase activity involved in apoptotic signaling pathway Cellular component NLRP3 inflammasome complex AIM2 inflammasome complex IPAF inflammasome complex endoplasmic reticulum cytoplasm Biological process regulation of apoptotic process regulation of inflammatory response proteolysis execution phase of apoptosis apoptotic process activation of cysteine-type endopeptidase activity involved in apoptotic process apoptotic signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 100506742 12364 Ensembl ENSG00000204403 ENSMUSG00000025887 UniProt Q6UXS9 O08736 RefSeq (mRNA) NM_001191016 NM_009808 RefSeq (protein) NP_001177945 NP_033938 Location (UCSC) Chr 11: 104.89 – 104.9 Mb Chr 9: 5.35 – 5.37 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Caspase 12 is a protein that in humans is encoded by the CASP12 gene. The protein 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. CASP12 orthologs 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).

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.

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.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000204403 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000025887 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. "OrthoMaM phylogenetic marker: CASP12 coding sequence".
7. 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. Bibcode:2004Natur.429...75S. doi:10.1038/nature02451. PMID 15129283.
8. 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. Bibcode:2006Natur.440.1064S. doi:10.1038/nature04656. PMID 16625199. S2CID 4321520. (Erratum: doi:10.1038/nature04656, PMID 16625199)
9. 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. Bibcode:2009PNAS..106.9016Y. doi:10.1073/pnas.0813362106. PMC 2690057. PMID 19447924.
10. "Man flu: real or myth?". Health. NHS UK. 18 May 2009. Archived from the original on 16 February 2010. Retrieved 23 May 2009.
11. "Women 'fight off disease better'". Health. BBC News. 13 May 2009. Retrieved 13 May 2009.
12. Xue, Yali; Daly, Allan; Yngvadottir, Bryndis; Liu, Mengning; Coop, Graham; Kim, Yuseob; Sabeti, Pardis; Chen, Yuan; Stalker, Jim; Huckle, Elizabeth; Burton, John; Leonard, Steven; Rogers, Jane; Tyler-Smith, Chris (2006). "Spread of an Inactive Form of Caspase-12 in Humans Is Due to Recent Positive Selection". The American Journal of Human Genetics. 78 (4): 659–670. doi:10.1086/503116. PMC 1424700. PMID 16532395.
13. Wang, Xiaoxia; Grus, Wendy E.; Zhang, Jianzhi (2006). "Gene Losses during Human Origins". PLOS Biology. 4 (3): e52. doi:10.1371/journal.pbio.0040052. PMC 1361800. PMID 16464126.

External links

• The MEROPS online database for peptidases and their inhibitors: C14.013 Archived 6 September 2005 at the Wayback Machine

• Biology

• Genes on human chromosome 11
• EC 3.4.22
• Caspases