Kaspaza-6

Kaspaza-6
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2WDP, 3K7E, 3NKF, 3NR2, 3OD5, 3P45, 3P4U, 3QNW, 3S70, 3S8E, 3V6L, 3V6M, 4EJF, 4FXO, 4HVA, 4IYR, 4N5D, 4N6G, 4N7J, 4N7M, 4NBK, 4NBL, 4NBN
Identifikatori
Aliasi	CASP6
Vanjski ID-jevi	OMIM: 601532 MGI: 1312921 HomoloGene: 37455 GeneCards: CASP6
Lokacija gena (čovjek)
Hrom.	Hromosom 4 (čovjek)
Kraj	109,703,583 bp
Lokacija gena (miš)
Hrom.	Hromosom 3 (miš)
Kraj	129,707,752 bp
Obrazac RNK ekspresije
	; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• GO:0070122 peptidase activity; • cysteine-type endopeptidase activity; • cysteine-type peptidase activity; • endopeptidase activity; • GO:0001948, GO:0016582 vezivanje za proteine; • hydrolase activity; • vezivanje identičnih proteina; • cysteine-type endopeptidase activity involved in execution phase of apoptosis; • cysteine-type endopeptidase activity involved in apoptotic process;
Ćelijska komponenta	• citosol; • nukleoplazma; • citoplazma;
Biološki proces	• epithelial cell differentiation; • Proteoliza; • GO:0097285 apoptoza; • regulation of apoptotic process; • execution phase of apoptosis; • cellular response to staurosporine;
	Izvori:Amigo / QuickGO
Ortolozi
	839
	12368
	ENSG00000138794
	ENSMUSG00000027997
	P55212
	O08738
	NM_001226; NM_032992
	NM_009811
	NP_001217; NP_116787
	NP_033941
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Kaspaza-6 jest enzim koji je kod ljudi kodiran genom CASP6 sa hromosoma 4.^[5]^[6] Ortolozi CASP6 ^[7] identificirani su kod brojnih sisara za koje su dostupni potpuni podaci o genomu. Jedinstveni ortolozi su također prisutni kod ptica, gušterova, Lissamphibia, i teleostea. Kaspaza-6 ima poznate funkcije u apoptozi,^[8] ranom imunskom odgovoru^[9]^[10] i neurodegeneracijama u Hantingtonovoj i Alzheimerovoj bolesti.^[11]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 293 aminokiseline, a molekulska težina 33.310 Da.^[9]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MSSASGLRRG	HPAGGEENMT	ETDAFYKREM	FDPAEKYKMD	HRRRGIALIF
NHERFFWHLT	LPERRGTCAD	RDNLTRRFSD	LGFEVKCFND	LKAEELLLKI
HEVSTVSHAD	ADCFVCVFLS	HGEGNHIYAY	DAKIEIQTLT	GLFKGDKCHS
LVGKPKIFII	QACRGNQHDV	PVIPLDVVDN	QTEKLDTNIT	EVDAASVYTL
PAGADFLMCY	SVAEGYYSHR	ETVNGSWYIQ	DLCEMLGKYG	SSLEFTELLT
LVNRKVSQRR	VDFCKDPSAI	GKKQVPCFAS	MLTKKLHFFP	KSN

Funkcija

Ovaj gen kodira protein koji je član porodice cistein-aspartatnih proteaza (kaspaza). Sekvencna aktivacija kaspaza ima centralnu ulogu u fazi izvršenja ćelijskih apoptoza.^[8] Kaspaze postoje kao neaktivni proenzimi koji se podvrgavaju proteolitskoj obrada na konzerviranim asparaginskim ostacima kako bi se dobile dvije podjedinice, velika i mala, koje se dimer pretvaraju u aktivni enzim. Ovaj protein se obrađuje kaspazama 7, 8 i 10, i smatra se da funkcioniše kao nizvodni enzim u kaskadi aktivacije kaspaze. Kaspaza-6 se također može podvrgnuti samoobradi bez drugih članova porodice kaspaza.^[12] Alternativna prerada RNK ovog gena rezultira dvije varijante transkripta koje kodiraju različite izoforme.^[13]

Kaspaza-6 ima ulogu u ranom imunskom odgovoru putem derepresije. Smanjuje ekspresiju imunosupresivnog citokina interleukina-10^[9] i cijepa makrofage potiskujući IRAK-M.^[10]

Što se tiče neurodegeneracija, kaspaza-6 cijepa HTT u Huntingtonovoj i APP u Alzheimerovoj bolesti. U oba slučaja rezultira agregacijom proteinskih fragmenata.^[11]

Interakcije

Pokazalo se da kaspaza 6 reaguje sa kaspazom-8.^[14]^[15]^[16]

Također pogledajte

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000138794 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000027997 - 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.
^ Tiso N, Pallavicini A, Muraro T, Zimbello R, Apolloni E, Valle G, Lanfranchi G, Danieli GA (Oct 1996). "Chromosomal localization of the human genes, CPP32, Mch2, Mch3, and Ich-1, involved in cellular apoptosis". Biochem Biophys Res Commun. 225 (3): 983–9. doi:10.1006/bbrc.1996.1282. PMID 8780721.
^ Fernandes-Alnemri T, Litwack G, Alnemri ES (Aug 1995). "Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family". Cancer Res. 55 (13): 2737–42. PMID 7796396.
^ "OrthoMaM phylogenetic marker: CASP6 coding sequence". Arhivirano s originala, 3. 3. 2016. Pristupljeno 20. 12. 2009.
^ ^a ^b Cohen, Gerald M. (15. 8. 1997). "Caspases: the executioners of apoptosis". Biochemical Journal (jezik: engleski). 326 (1): 1–16. doi:10.1042/bj3260001. ISSN 0264-6021. PMC 1218630. PMID 9337844.
^ ^a ^b ^c Bartel, Alexander; Göhler, André; Hopf, Verena; Breitbach, Katrin (7. 7. 2017). "Caspase-6 mediates resistance against Burkholderia pseudomallei infection and influences the expression of detrimental cytokines". PLOS ONE. 12 (7): e0180203. Bibcode:2017PLoSO..1280203B. doi:10.1371/journal.pone.0180203. ISSN 1932-6203. PMC 5501493. PMID 28686630.
^ ^a ^b Kobayashi, Hiroshi; Nolan, Anna; Naveed, Bushra; Hoshino, Yoshihiko; Segal, Leopoldo N.; Fujita, Yoko; Rom, William N.; Weiden, Michael D. (1. 1. 2011). "Neutrophils Activate Alveolar Macrophages by Producing Caspase-6–Mediated Cleavage of IL-1 Receptor-Associated Kinase-M". The Journal of Immunology (jezik: engleski). 186 (1): 403–410. doi:10.4049/jimmunol.1001906. ISSN 0022-1767. PMC 3151149. PMID 21098228.
^ ^a ^b Graham, Rona K.; Ehrnhoefer, Dagmar E.; Hayden, Michael R. (1. 12. 2011). "Caspase-6 and neurodegeneration". Trends in Neurosciences (jezik: engleski). 34 (12): 646–656. doi:10.1016/j.tins.2011.09.001. ISSN 0166-2236. PMID 22018804. S2CID 1603684.
^ Wang XJ, Cao Q, Liu X, Wang KT, Mi W, Zhang Y, Li LF, LeBlanc AC, Su XD (Nov 2010). "Crystal structures of human caspase 6 reveal a new mechanism for intramolecular cleavage self-activation". EMBO Rep. 11 (11): 841–7. doi:10.1038/embor.2010.141. PMC 2966951. PMID 20890311.
^ "Entrez Gene: CASP6 caspase 6, apoptosis-related cysteine peptidase".
^ Cowling V, Downward J (Oct 2002). "Caspase-6 is the direct activator of caspase-8 in the cytochrome c-induced apoptosis pathway: absolute requirement for removal of caspase-6 prodomain". Cell Death Differ. 9 (10): 1046–56. doi:10.1038/sj.cdd.4401065. PMID 12232792.
^ Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES (Apr 2002). "Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria". J. Biol. Chem. 277 (16): 13430–7. doi:10.1074/jbc.M108029200. PMID 11832478.
^ Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES (Dec 1996). "Molecular ordering of the Fas-apoptotic pathway: The Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases". Proc. Natl. Acad. Sci. U.S.A. 93 (25): 14486–91. Bibcode:1996PNAS...9314486S. doi:10.1073/pnas.93.25.14486. PMC 26159. PMID 8962078.

Dopunska literatura

Fernandes-Alnemri T, Litwack G, Alnemri ES (1995). "CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme". J. Biol. Chem. 269 (49): 30761–4. doi:10.1016/S0021-9258(18)47344-9. PMID 7983002.
Takahashi A, Alnemri ES, Lazebnik YA, Fernandes-Alnemri T, Litwack G, Moir RD, Goldman RD, Poirier GG, Kaufmann SH, Earnshaw WC (1996). "Cleavage of lamin A by Mch2 alpha but not CPP32: multiple interleukin 1 beta-converting enzyme-related proteases with distinct substrate recognition properties are active in apoptosis". Proc. Natl. Acad. Sci. U.S.A. 93 (16): 8395–400. Bibcode:1996PNAS...93.8395T. doi:10.1073/pnas.93.16.8395. PMC 38682. PMID 8710882.
Bullrich F, Fernandes-Alnemri T, Litwack G, Alnemri ES, Croce CM (1997). "Chromosomal mapping of cell death proteases CPP32, MCH2, and MCH3". Genomics. 36 (2): 362–5. doi:10.1006/geno.1996.0476. PMID 8812467.
Srinivasula SM, Fernandes-Alnemri T, Zangrilli J, Robertson N, Armstrong RC, Wang L, Trapani JA, Tomaselli KJ, Litwack G, Alnemri ES (1996). "The Ced-3/interleukin 1beta converting enzyme-like homolog Mch6 and the lamin-cleaving enzyme Mch2alpha are substrates for the apoptotic mediator CPP32". J. Biol. Chem. 271 (43): 27099–106. doi:10.1074/jbc.271.43.27099. PMID 8900201.
Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES (1997). "Molecular ordering of the Fas-apoptotic pathway: The Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases". Proc. Natl. Acad. Sci. U.S.A. 93 (25): 14486–91. Bibcode:1996PNAS...9314486S. doi:10.1073/pnas.93.25.14486. PMC 26159. PMID 8962078.
Rao L, Perez D, White E (1997). "Lamin proteolysis facilitates nuclear events during apoptosis". J. Cell Biol. 135 (6 Pt 1): 1441–55. doi:10.1083/jcb.135.6.1441. PMC 2133948. PMID 8978814.
Kim TW, Pettingell WH, Jung YK, Kovacs DM, Tanzi RE (1998). "Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease". Science. 277 (5324): 373–6. CiteSeerX 10.1.1.1025.8052. doi:10.1126/science.277.5324.373. PMID 9219695.
Srinivasula SM, Ahmad M, Ottilie S, Bullrich F, Banks S, Wang Y, Fernandes-Alnemri T, Croce CM, Litwack G, Tomaselli KJ, Armstrong RC, Alnemri ES (1997). "FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis". J. Biol. Chem. 272 (30): 18542–5. doi:10.1074/jbc.272.30.18542. PMID 9228018.
Caulín C, Salvesen GS, Oshima RG (1997). "Caspase Cleavage of Keratin 18 and Reorganization of Intermediate Filaments during Epithelial Cell Apoptosis". J. Cell Biol. 138 (6): 1379–94. doi:10.1083/jcb.138.6.1379. PMC 2132555. PMID 9298992.
Hirata H, Takahashi A, Kobayashi S, Yonehara S, Sawai H, Okazaki T, Yamamoto K, Sasada M (1998). "Caspases Are Activated in a Branched Protease Cascade and Control Distinct Downstream Processes in Fas-induced Apoptosis". J. Exp. Med. 187 (4): 587–600. doi:10.1084/jem.187.4.587. PMC 2212161. PMID 9463409.
Harvey KF, Harvey NL, Michael JM, Parasivam G, Waterhouse N, Alnemri ES, Watters D, Kumar S (1998). "Caspase-mediated cleavage of the ubiquitin-protein ligase Nedd4 during apoptosis". J. Biol. Chem. 273 (22): 13524–30. doi:10.1074/jbc.273.22.13524. PMID 9593687.
Utz PJ, Hottelet M, Le TM, Kim SJ, Geiger ME, van Venrooij WJ, Anderson P (1999). "The 72-kDa component of signal recognition particle is cleaved during apoptosis". J. Biol. Chem. 273 (52): 35362–70. doi:10.1074/jbc.273.52.35362. PMID 9857079.
Samejima K, Svingen PA, Basi GS, Kottke T, Mesner PW, Stewart L, Durrieu F, Poirier GG, Alnemri ES, Champoux JJ, Kaufmann SH, Earnshaw WC (1999). "Caspase-mediated cleavage of DNA topoisomerase I at unconventional sites during apoptosis". J. Biol. Chem. 274 (7): 4335–40. doi:10.1074/jbc.274.7.4335. PMID 9933635.
Walter J, Schindzielorz A, Grünberg J, Haass C (1999). "Phosphorylation of presenilin-2 regulates its cleavage by caspases and retards progression of apoptosis". Proc. Natl. Acad. Sci. U.S.A. 96 (4): 1391–6. Bibcode:1999PNAS...96.1391W. doi:10.1073/pnas.96.4.1391. PMC 15473. PMID 9990034.
van de Craen M, de Jonghe C, van den Brande I, Declercq W, van Gassen G, van Criekinge W, Vanderhoeven I, Fiers W, van Broeckhoven C, Hendriks L, Vandenabeele P (1999). "Identification of caspases that cleave presenilin-1 and presenilin-2. Five presenilin-1 (PS1) mutations do not alter the sensitivity of PS1 to caspases" (PDF). FEBS Lett. 445 (1): 149–54. doi:10.1016/S0014-5793(99)00108-8. hdl:10067/238040151162165141. PMID 10069390. S2CID 31218178.
Xanthoudakis S, Roy S, Rasper D, Hennessey T, Aubin Y, Cassady R, Tawa P, Ruel R, Rosen A, Nicholson DW (1999). "Hsp60 accelerates the maturation of pro-caspase-3 by upstream activator proteases during apoptosis". EMBO J. 18 (8): 2049–56. doi:10.1093/emboj/18.8.2049. PMC 1171289. PMID 10205159.

Vanjski linkovi

The MEROPS online database for peptidases and their inhibitors: C14.005 Arhivirano 5. 2. 2008. na Wayback Machine
P55212

Portal Biologija

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000138794 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000027997 - 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.

[pmid8780721-5] Tiso N, Pallavicini A, Muraro T, Zimbello R, Apolloni E, Valle G, Lanfranchi G, Danieli GA (Oct 1996). "Chromosomal localization of the human genes, CPP32, Mch2, Mch3, and Ich-1, involved in cellular apoptosis". Biochem Biophys Res Commun. 225 (3): 983–9. doi:10.1006/bbrc.1996.1282. PMID 8780721.

[pmid7796396-6] Fernandes-Alnemri T, Litwack G, Alnemri ES (Aug 1995). "Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family". Cancer Res. 55 (13): 2737–42. PMID 7796396.

[OrthoMaM-7] "OrthoMaM phylogenetic marker: CASP6 coding sequence". Arhivirano s originala, 3. 3. 2016. Pristupljeno 20. 12. 2009.

[:0-8] Cohen, Gerald M. (15. 8. 1997). "Caspases: the executioners of apoptosis". Biochemical Journal (jezik: engleski). 326 (1): 1–16. doi:10.1042/bj3260001. ISSN 0264-6021. PMC 1218630. PMID 9337844.

[:1-9] Bartel, Alexander; Göhler, André; Hopf, Verena; Breitbach, Katrin (7. 7. 2017). "Caspase-6 mediates resistance against Burkholderia pseudomallei infection and influences the expression of detrimental cytokines". PLOS ONE. 12 (7): e0180203. Bibcode:2017PLoSO..1280203B. doi:10.1371/journal.pone.0180203. ISSN 1932-6203. PMC 5501493. PMID 28686630.

[:2-10] Kobayashi, Hiroshi; Nolan, Anna; Naveed, Bushra; Hoshino, Yoshihiko; Segal, Leopoldo N.; Fujita, Yoko; Rom, William N.; Weiden, Michael D. (1. 1. 2011). "Neutrophils Activate Alveolar Macrophages by Producing Caspase-6–Mediated Cleavage of IL-1 Receptor-Associated Kinase-M". The Journal of Immunology (jezik: engleski). 186 (1): 403–410. doi:10.4049/jimmunol.1001906. ISSN 0022-1767. PMC 3151149. PMID 21098228.

[:3-11] Graham, Rona K.; Ehrnhoefer, Dagmar E.; Hayden, Michael R. (1. 12. 2011). "Caspase-6 and neurodegeneration". Trends in Neurosciences (jezik: engleski). 34 (12): 646–656. doi:10.1016/j.tins.2011.09.001. ISSN 0166-2236. PMID 22018804. S2CID 1603684.

[pmid20890311-12] Wang XJ, Cao Q, Liu X, Wang KT, Mi W, Zhang Y, Li LF, LeBlanc AC, Su XD (Nov 2010). "Crystal structures of human caspase 6 reveal a new mechanism for intramolecular cleavage self-activation". EMBO Rep. 11 (11): 841–7. doi:10.1038/embor.2010.141. PMC 2966951. PMID 20890311.

[13] "Entrez Gene: CASP6 caspase 6, apoptosis-related cysteine peptidase".

[pmid12232792-14] Cowling V, Downward J (Oct 2002). "Caspase-6 is the direct activator of caspase-8 in the cytochrome c-induced apoptosis pathway: absolute requirement for removal of caspase-6 prodomain". Cell Death Differ. 9 (10): 1046–56. doi:10.1038/sj.cdd.4401065. PMID 12232792.

[pmid11832478-15] Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES (Apr 2002). "Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria". J. Biol. Chem. 277 (16): 13430–7. doi:10.1074/jbc.M108029200. PMID 11832478.

[pmid8962078-16] Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES (Dec 1996). "Molecular ordering of the Fas-apoptotic pathway: The Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases". Proc. Natl. Acad. Sci. U.S.A. 93 (25): 14486–91. Bibcode:1996PNAS...9314486S. doi:10.1073/pnas.93.25.14486. PMC 26159. PMID 8962078.

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