Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000464
UniProt IDQ14790
Primary gene name(s)CASP8
Synonym gene name(s)MCH5
Protein nameCaspase-8
Protein functionMost upstream protease of the activation cascade of caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death. Binding to the adapter molecule FADD recruits it to either receptor. The resulting aggregate called death-inducing signaling complex, DISC performs CASP8 proteolytic activation. The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases. Proteolytic fragments of the N-terminal propeptide, termed CAP3, CAP5 and CAP6 are likely retained in the DISC. Cleaves and activates CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10. May participate in the GZMB apoptotic pathways. Cleaves ADPRT. Hydrolyzes the small-molecule substrate, Ac-Asp-Glu-Val-Asp-|-AMC. Likely target for the cowpox virus CRMA death inhibitory protein. Isoform 5, isoform 6, isoform 7 and isoform 8 lack the catalytic site and may interfere with the pro-apoptotic activity of the complex. {ECO:0000269|PubMed:23516580, ECO:0000269|PubMed:9006941}.
Subcellular locationCytoplasm.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q14790
Gene Ontology
(Biological Process)
Complete annatation
activation of cysteine-type endopeptidase activity [GO:0097202];
activation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0006919];
activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway [GO:0097296];
apoptotic process [GO:0006915];
apoptotic signaling pathway [GO:0097190];
B cell activation [GO:0042113];
cell surface receptor signaling pathway [GO:0007166];
cellular component disassembly involved in execution phase of apoptosis [GO:0006921];
cellular response to mechanical stimulus [GO:0071260];
cellular response to organic cyclic compound [GO:0071407];
death-inducing signaling complex assembly [GO:0071550];
execution phase of apoptosis [GO:0097194];
extrinsic apoptotic signaling pathway [GO:0097191];
macrophage differentiation [GO:0030225];
natural killer cell activation [GO:0030101];
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors [GO:1902042];
negative regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043124];
nucleotide-binding oligomerization domain containing signaling pathway [GO:0070423];
positive regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043123];
positive regulation of macrophage differentiation [GO:0045651];
positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway [GO:1900740];
positive regulation of proteolysis [GO:0045862];
protein heterooligomerization [GO:0051291];
proteolysis [GO:0006508];
proteolysis involved in cellular protein catabolic process [GO:0051603];
regulation of extrinsic apoptotic signaling pathway via death domain receptors [GO:1902041];
regulation of necrotic cell death [GO:0010939];
regulation of tumor necrosis factor-mediated signaling pathway [GO:0010803];
response to antibiotic [GO:0046677];
response to cobalt ion [GO:0032025];
response to cold [GO:0009409];
response to estradiol [GO:0032355];
response to ethanol [GO:0045471];
response to lipopolysaccharide [GO:0032496];
response to tumor necrosis factor [GO:0034612];
suppression by virus of host cysteine-type endopeptidase activity involved in apoptotic process [GO:0039650];
syncytiotrophoblast cell differentiation involved in labyrinthine layer development [GO:0060715];
T cell activation [GO:0042110];
TRAIL-activated apoptotic signaling pathway [GO:0036462];
TRIF-dependent toll-like receptor signaling pathway [GO:0035666]
Gene Ontology
(Molecular Function)
Complete annatation
cysteine-type endopeptidase activity [GO:0004197];
cysteine-type endopeptidase activity involved in apoptotic process [GO:0097153];
cysteine-type endopeptidase activity involved in apoptotic signaling pathway [GO:0097199];
cysteine-type peptidase activity [GO:0008234];
death effector domain binding [GO:0035877];
identical protein binding [GO:0042802];
peptidase activity [GO:0008233];
scaffold protein binding [GO:0097110];
ubiquitin protein ligase binding [GO:0031625]
Gene Ontology
(Cellular Component)
Complete annatation
CD95 death-inducing signaling complex [GO:0031265];
cell body [GO:0044297];
cytoplasm [GO:0005737];
cytoskeleton [GO:0005856];
cytosol [GO:0005829];
death-inducing signaling complex [GO:0031264];
membrane raft [GO:0045121];
microtubule organizing center [GO:0005815];
mitochondrial outer membrane [GO:0005741];
mitochondrion [GO:0005739];
neuron projection [GO:0043005];
nucleoplasm [GO:0005654];
ripoptosome [GO:0097342]
Protein-protein interaction107291
Phylogenetic treeQ14790
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3-1.5403942187015.26420304847175e-063.47534245933273e-05
AZA vs. DISU0.3864608973609590.2651502059559240.843224767128808
AZA vs. IL7-0.2681548276048540.1627873345081140.930759564799561
AZA vs. SAHA0.0831563154961120.7328147573592720.925643771606674
DISU vs. CD31.911702833420817.4143045081243e-077.41135451959322e-06
DISU vs. IL7-0.6630243932021170.05533629650719910.309534200313924
DISU vs. SAHA-0.3019700663268230.3708232523632170.741456428522685
DMSO vs. AZA0.05358412668632960.7710988275908491
DMSO vs. CD31.579382142736371.90250014864279e-061.28583062984763e-05
DMSO vs. DISU-0.3354189551207260.3373523762879150.836856018215452
DMSO vs. IL7-0.3142354058230950.08597390715923180.548585498333456
DMSO vs. SAHA0.02307843730307360.9219276599520680.981876243091941
HIV vs. Mock in Activation-0.01883815774646580.9758462541005920.999983755607037
HIV vs. Mock in Latency0.07165792003021040.6646192816538320.999834320637052
IL7 vs. CD31.281008920970570.0001041645014192570.000603873665343255
SAHA vs. CD31.597813218369531.18434321366712e-057.27304491848551e-05
SAHA vs. IL70.3463010860704830.1549802994359340.373488894276142
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
0.3874 0.02865

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) TRUE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.398571 0.00342251
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
0.992 1.098 1.386 1.438 1.221
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1F9E X-ray 2.9Å A/C/E/G/I/K=222-374# B/D/F/H/J/L=390-478.
1I4E X-ray 3.0Å B=222-479.
1QDU X-ray 2.8Å A/C/E/G/I/K=222-374# B/D/F/H/J/L=390-477.
1QTN X-ray 1.2Å A=211-374# B=385-479.
2C2Z X-ray 1.9Å A=218-374# B=376-479.
2FUN X-ray 3.0Å B/D=222-479.
2K7Z NMR - A=217-479.
2Y1L X-ray 1.8Å A/C=218-374# B/D=376-479.
3H11 X-ray 1.9Å B=217-479.
3KJN X-ray 1.8Å A=211-374# B=385-479.
3KJQ X-ray 1.8Å A=211-374# B=385-479.
4JJ7 X-ray 1.1Å A=217-479.
4PRZ X-ray 2.1Å A=217-479.
4PS1 X-ray 1.7Å A/B/C/D=217-479.
4ZBW X-ray 2.2Å A/B=2-188.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 downregulates 23867815
retropepsin cleaves 17442709
Nef inactivates 11177389
Vpu cooperates with 25352594
Tat upregulates 22632162
Envelope surface glycoprotein gp120 upregulates 19125371
Envelope surface glycoprotein gp120 activates 17488272
Vpr activates 10438581
Envelope transmembrane glycoprotein gp41 activates 17653867
Tat interacts with 23364796
retropepsin activates 12404116

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa01524 Platinum drug resistance - Homo sapiens (human)
hsa04115 p53 signaling pathway - Homo sapiens (human)
hsa04210 Apoptosis - Homo sapiens (human)
hsa04215 Apoptosis - multiple species - Homo sapiens (human)
hsa04620 Toll-like receptor signaling pathway - Homo sapiens (human)
hsa04621 NOD-like receptor signaling pathway - Homo sapiens (human)
hsa04622 RIG-I-like receptor signaling pathway - Homo sapiens (human)
hsa04657 IL-17 signaling pathway - Homo sapiens (human)
hsa04668 TNF signaling pathway - Homo sapiens (human)
hsa04932 Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
hsa05010 Alzheimer's disease - Homo sapiens (human)
hsa05016 Huntington's disease - Homo sapiens (human)
hsa05134 Legionellosis - Homo sapiens (human)
hsa05142 Chagas disease (American trypanosomiasis) - Homo sapiens (human)
hsa05145 Toxoplasmosis - Homo sapiens (human)
hsa05152 Tuberculosis - Homo sapiens (human)
hsa05161 Hepatitis B - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)
hsa05416 Viral myocarditis - Homo sapiens (human)