Kaspaza-12

Kaspaza-12
Identifikatori
Aliasi	CASP12
Vanjski ID-jevi	OMIM: 608633 MGI: 1312922 GeneCards: CASP12
Lokacija gena (čovjek)
Hrom.	Hromosom 11 (čovjek)
Kraj	104,898,670 bp
Lokacija gena (miš)
Hrom.	Hromosom 9 (miš)
Kraj	5,373,032 bp
Ontologija gena
Molekularna funkcija	• 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;
Ćelijska komponenta	• NLRP3 inflammasome complex; • AIM2 inflammasome complex; • IPAF inflammasome complex; • Endoplazmatski retikulum; • citoplazma;
Biološki proces	• regulation of apoptotic process; • regulation of inflammatory response; • Proteoliza; • execution phase of apoptosis; • GO:0097285 apoptoza; • activation of cysteine-type endopeptidase activity involved in apoptotic process; • apoptotic signaling pathway;
	Izvori:Amigo / QuickGO
Ortolozi
	100506742
	12364
	ENSG00000204403
	ENSMUSG00000025887
	Q6UXS9
	O08736
	NM_001191016
	NM_009808
	NP_001177945
	NP_033938
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Kaspaza 12 jest protein koji je kod ljudi kodiran genom CASP12 sa hromosoma 11. Pripada porodici enzima zvanih kaspaze koji cijepaju svoje supstrate na C-terminalnim ostacima aspartata . Usko je povezan sa kaspazom-1 i drugim članovima porodice kaspaza, poznatim kao upalne kaspaze, koje obrađuju i aktiviraju upalne citokine, kao što su interleukin-1 i interleukin-18 .

Gen

Gen CASP12 kod ljudi nalazi se na hromolsolmu 11 u lokusu sa drugim genima upalinih kaspaza.^[5] Ortolozi CASP12 ^[6] identificirani su kod brojnih sisara za koje su dostupni potpuni podaci o genomu.

Klinički značaj

CASP12 gen je podložan polimorfizmu, koji može generirati kaspazni protein pune dužine (Csp12L) ili neaktivni skraćeni oblik (Csp12S). Čini se da je funkcionalna forma ograničena na ljude afričkog porijekla i povezana je sa osjetljivošću na sepsu; ljudi koji nose funkcionalni gen imaju smanjene odgovore na bakterijske molekule kao što je lipopolisaharid (LPS).^[7]^[8]

Studija u maju 2009. koju je sproveo Zdravstveni centar Univerziteta McGill sugerira da estrogen može poslužiti za blokiranje proizvodnje kaspaze-12, što rezultira jačom upalnom reakcijom na bakterijske patogene. Ispitivanja su provedena na laboratorijskim miševima kojima je implantiran gen za ljudsku kaspazu-12.^[9]^[10]^[11]

Neaktivni skraćeni oblik (Csp12S) gena CASP12 bio je rasprostranjen i skoro fiksiran u neafričkim populacijama zbog pozitivne selekcije počevši možda prije 60-100 hiljada godina. Smatra se da je njegova selektivna prednost otpornost na sepsu u populacijama koje su imale više zaraznih bolesti kako su se povećavale veličine i gustine populacije.^[12]^[13]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000204403 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000025887 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ "OrthoMaM phylogenetic marker: CASP12 coding sequence".^{[trajno mrtav link]}
^ 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.
^ 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.
^ Yeretssian G, Doiron K, Shao W, Leavitt BR, Hayden MR, Nicholson DW, Saleh M (maj 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.
^ "Man flu: real or myth?". Health. NHS UK. 18. 5. 2009. Arhivirano s originala, 16. 2. 2010. Pristupljeno 30. 3. 2023.
^ "Women 'fight off disease better'". Health. BBC News. 13. 5. 2009. Pristupljeno 13. 5. 2009.
^ 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.
^ 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.

Vanjski linkovi

The MEROPS online database for peptidases and their inhibitors: C14.013 Arhivirano 6. 9. 2005. na Wayback Machine

Portal Biologija

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000204403 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000025887 - Ensembl, maj 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.

[OrthoMaM-6] "OrthoMaM phylogenetic marker: CASP12 coding sequence".^{[trajno mrtav link]}

[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.

[pmid19447924-9] Yeretssian G, Doiron K, Shao W, Leavitt BR, Hayden MR, Nicholson DW, Saleh M (maj 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.

[urlNHS-10] "Man flu: real or myth?". Health. NHS UK. 18. 5. 2009. Arhivirano s originala, 16. 2. 2010. Pristupljeno 30. 3. 2023.

[urlBBC-11] "Women 'fight off disease better'". Health. BBC News. 13. 5. 2009. Pristupljeno 13. 5. 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.

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