View source for Caspase-8

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{{#invoke:InfoboxforTarget|run|CASP8|[https://www.uniprot.org/uniprot/Q14790 Q14790]|Homo sapiens|Cys360|[http://pfam.xfam.org/family/PF00656 Peptidase C14A family]|[[:Category:Caspase-8|Ligand list]]|Protease}}
==Summary==

===Protein Function ===
Caspases (cysteine-aspartic acid protease (caspase) family) are a family of cysteine proteases that have important intracellular roles in inflammation and apoptosis. Activation of caspases ensures that the cellular components are degraded in a controlled manner, carrying out cell death with minimal effect on surrounding tissues. Caspases exist as inactive proenzymes composed of a prodomain, a large protease subunit, and a small protease subunit. Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. <br/> 
Caspase-8 activates downstream caspases which are unable to carry out autocatalytic processing and activation. Caspase-8 is designated as an initiator caspase and is believed to sit at the apex of the Fas- or TNF-mediated apoptotic cascade. This protein is involved in the programmed cell death induced by Fas and various apoptotic stimuli. The N-terminal FADD-like death effector domain of this protein suggests that it may interact with Fas-interacting protein FADD. This protein was detected in the insoluble fraction of the affected brain region from Huntington disease patients but not in those from normal controls, which implicated the role in neurodegenerative diseases. 
<br/>

===Cys Function & Property===
The catalytic triad in caspase-8 comprises Cys360, His317 and the backbone carbonyl oxygen atom of Arg258, which points towards the Nϵ atom of His317.<br/>

* Hydrophobic property:
:[[File:592-hydro.png||600px]]
* SASA:
:Cys360: 7.975 A^2<br/>

==Protein Sequence==
<font face="Courier">
MDFSRNLYDI GEQLDSEDLA SLKFLSLDYI PQRKQEPIKD ALMLFQRLQE <br/> 
KRMLEESNLS FLKELLFRIN RLDLLITYLN TRKEEMEREL QTPGRAQISA <br/> 
YRVMLYQISE EVSRSELRSF KFLLQEEISK CKLDDDMNLL DIFIEMEKRV <br/> 
ILGEGKLDIL KRVCAQINKS LLKIINDYEE FSKERSSSLE GSPDEFSNGE <br/> 
ELCGVMTISD SPREQDSESQ TLDKVYQMKS KPRGYCLIIN NHNFAKAREK <br/> 
VPKLHSIRDR NGTHLDAGAL TTTFEELHFE IKPHDDCTVE QIYEILKIYQ <br/> 
LMDHSNMDCF ICCILSHGDK GIIYGTDGQE APIYELTSQF TGLKCPSLAG <br/> 
KPKVFFIQA<span style="background:#ffff00">'''C'''</span> QGDNYQKGIP VETDSEEQPY LEMDLSSPQT RYIPDEADFL <br/> 
LGMATVNNCV SYRNPAEGTW YIQSLCQSLR ERCPRGDDIL TILTEVNYEV <br/> 
SNKDDKKNMG KQMPQPTFTL RKKLVFPSD    <br/> 
</font>

==Structural Information==
*Known structure with covalent ligand: <br/>
:[https://www.rcsb.org/structure/1QTN 1QTN]<br/>

*Protein structure:
[[File:592.png|center|800px]]

==Related Pathway==
*[https://www.genome.jp/kegg-bin/show_pathway?ko01524 Platinum drug resistance]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko04115 p53 signaling pathway]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko04210 Apoptosis]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko04217 Necroptosis]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko04620 Toll-like receptor signaling pathway]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko04621 NOD-like receptor signaling pathway]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko04622 RIG-I-like receptor signaling pathway]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko04625 C-type lectin receptor signaling pathway]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko04657 IL-17 signaling pathway]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko04668 TNF signaling pathway]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko04932 Non-alcoholic fatty liver disease (NAFLD)]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05010 Alzheimer disease]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05016 Huntington disease]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05130 Pathogenic Escherichia coli infection]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05134 Legionellosis]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05142 Chagas disease]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05145 Toxoplasmosis]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05152 Tuberculosis]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05160 Hepatitis C]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05161 Hepatitis B]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05162 Measles]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05163 Human cytomegalovirus infection]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05164 Influenza A]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05165 Human papillomavirus infection]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05167 Kaposi sarcoma-associated herpesvirus infection]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05168 Herpes simplex virus 1 infection]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05169 Epstein-Barr virus infection]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05170 Human immunodeficiency virus 1 infection]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05200 Pathways in cancer]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05203 Viral carcinogenesis]<br/>
*[https://www.genome.jp/kegg-bin/show_pathway?ko05416 Viral myocarditis]<br/>


==Experimental Evidence==
:Crystallography   

==Reference==
# Watt W, Koeplinger K A, Mildner A M, et al. '''The atomic-resolution structure of human caspase-8, a key activator of apoptosis[J].''' Structure, 1999, 7(9): 1135-1143. [https://www.ncbi.nlm.nih.gov/pubmed/?term=10508785 10508785]<br/>

[[Category:Targets]]
[[Category:Homo sapiens]]
[[Category:Protease]]
[[Category:Peptidase C14A family]]
[[Category:Platinum drug resistance]]
[[Category:p53 signaling pathway]]
[[Category:Apoptosis]]
[[Category:Necroptosis]]
[[Category:Toll-like receptor signaling pathway]]
[[Category:NOD-like receptor signaling pathway]]
[[Category:RIG-I-like receptor signaling pathway]]
[[Category:C-type lectin receptor signaling pathway]]
[[Category:IL-17 signaling pathway]]
[[Category:TNF signaling pathway]]
[[Category:Non-alcoholic fatty liver disease (NAFLD)]]
[[Category:Alzheimer disease]]
[[Category:Huntington disease]]
[[Category:Pathogenic Escherichia coli infection]]
[[Category:Legionellosis]]
[[Category:Chagas disease]]
[[Category:Toxoplasmosis]]
[[Category:Tuberculosis]]
[[Category:Hepatitis C]]
[[Category:Hepatitis B]]
[[Category:Measles]]
[[Category:Human cytomegalovirus infection]]
[[Category:Influenza A]]
[[Category:Human papillomavirus infection]]
[[Category:Kaposi sarcoma-associated herpesvirus infection]]
[[Category:Herpes simplex virus 1 infection]]
[[Category:Epstein-Barr virus infection]]
[[Category:Human immunodeficiency virus 1 infection]]
[[Category:Pathways in cancer]]
[[Category:Viral carcinogenesis]]
[[Category:Viral myocarditis]]