CASP8

Functionⁱ

Most 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.2 Publications

Catalytic activityⁱ

Strict requirement for Asp at position P1 and has a preferred cleavage sequence of (Leu/Asp/Val)-Glu-Thr-Asp-|-(Gly/Ser/Ala).
1 Publication
Manual assertion based on experiment inⁱ
- Ref.28
  "The E. coli effector protein NleF is a caspase inhibitor."
  Blasche S., Mortl M., Steuber H., Siszler G., Nisa S., Schwarz F., Lavrik I., Gronewold T.M., Maskos K., Donnenberg M.S., Ullmann D., Uetz P., Kogl M.
  PLoS ONE 8:E58937-E58937(2013) [PubMed] [Europe PMC] [Abstract]
  Cited for: INTERACTION WITH E.COLI NLEF (MICROBIAL INFECTION), CATALYTIC ACTIVITY, FUNCTION, ACTIVITY REGULATION.
EC:3.4.22.61

Activity regulationⁱ

Inhibited by the effector protein NleF that is produced by pathogenic E.coli; this inhibits apoptosis.1 Publication

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Active siteⁱ	317			1
Active siteⁱ	360			1

GO - Molecular functionⁱ

cysteine-type endopeptidase activity
Source: UniProtKB
Inferred from direct assayⁱ
- 16920334
- 19240112
cysteine-type endopeptidase activity involved in apoptotic process
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 21737330
cysteine-type endopeptidase activity involved in apoptotic signaling pathway
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 11717445
- 21980415
cysteine-type peptidase activity
Source: ProtInc
Traceable author statementⁱ
- 8681376
death effector domain binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 11717445
death receptor binding Source: Ensembl
identical protein binding
Source: IntAct
Inferred from physical interactionⁱ
- 16169070
- 17170703
peptidase activity
Source: BHF-UCL
Inferred from direct assayⁱ
- 19740745
protein-containing complex binding Source: Ensembl
scaffold protein binding
Source: ParkinsonsUK-UCL
Inferred from physical interactionⁱ
- 21785459
tumor necrosis factor receptor binding Source: Ensembl
ubiquitin protein ligase binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 15069192

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

activation of cysteine-type endopeptidase activity
Source: BHF-UCL
Inferred from direct assayⁱ
- 18387192
activation of cysteine-type endopeptidase activity involved in apoptotic process
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway Source: Reactome
apoptotic process
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 22891283
apoptotic signaling pathway
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 11101870
B cell activation
Source: UniProtKB
Traceable author statementⁱ
- 18309324
cell surface receptor signaling pathway Source: Reactome
cellular response to mechanical stimulus
Source: UniProtKB
Inferred from expression patternⁱ
- 19593445
cellular response to organic cyclic compound Source: Ensembl
death-inducing signaling complex assembly Source: Reactome
execution phase of apoptosis
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 21737330
extrinsic apoptotic signaling pathway
Source: UniProtKB
Inferred from direct assayⁱ
- 21785459
extrinsic apoptotic signaling pathway via death domain receptors
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
macrophage differentiation
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
natural killer cell activation
Source: UniProtKB
Traceable author statementⁱ
- 18309324
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: Reactome
negative regulation of I-kappaB kinase/NF-kappaB signaling
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 17047155
nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
positive regulation of I-kappaB kinase/NF-kappaB signaling
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 12884866
positive regulation of macrophage differentiation
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 17047155
positive regulation of neuron death Source: Ensembl
positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway Source: Reactome
positive regulation of proteolysis
Source: BHF-UCL
Inferred from direct assayⁱ
- 18387192
proteolysis
Source: UniProtKB
Inferred from direct assayⁱ
- 12888622
proteolysis involved in cellular protein catabolic process
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 10521396
regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: Reactome
regulation of necroptotic process Source: Reactome
regulation of tumor necrosis factor-mediated signaling pathway Source: Reactome
response to cobalt ion Source: Ensembl
response to cold Source: Ensembl
response to estradiol Source: Ensembl
response to ethanol Source: Ensembl
response to lipopolysaccharide Source: Ensembl
response to tumor necrosis factor
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 10521396
suppression by virus of host cysteine-type endopeptidase activity involved in apoptotic process Source: Reactome
syncytiotrophoblast cell differentiation involved in labyrinthine layer development
Source: UniProtKB
Traceable author statementⁱ
- 18309324
T cell activation
Source: UniProtKB
Traceable author statementⁱ
- 18309324
toll-like receptor 3 signaling pathway Source: Reactome
TRAIL-activated apoptotic signaling pathway
Source: ParkinsonsUK-UCL
Inferred from direct assayⁱ
- 21785459
TRIF-dependent toll-like receptor signaling pathway Source: Reactome

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Hydrolase, Protease, Thiol protease
Biological process	Apoptosis, Host-virus interaction

Enzyme and pathway databases

BRENDAⁱ	3.4.22.61 2681
Reactomeⁱ	R-HSA-111465 Apoptotic cleavage of cellular proteins R-HSA-140534 Caspase activation via Death Receptors in the presence of ligand R-HSA-168638 NOD1/2 Signaling Pathway R-HSA-2562578 TRIF-mediated programmed cell death R-HSA-264870 Caspase-mediated cleavage of cytoskeletal proteins R-HSA-3371378 Regulation by c-FLIP R-HSA-5213460 RIPK1-mediated regulated necrosis R-HSA-5218900 CASP8 activity is inhibited R-HSA-5357786 TNFR1-induced proapoptotic signaling R-HSA-5357905 Regulation of TNFR1 signaling R-HSA-5660668 CLEC7A/inflammasome pathway R-HSA-5675482 Regulation of necroptotic cell death R-HSA-69416 Dimerization of procaspase-8 R-HSA-75108 Activation, myristolyation of BID and translocation to mitochondria R-HSA-75153 Apoptotic execution phase R-HSA-75157 FasL/ CD95L signaling R-HSA-75158 TRAIL signaling R-HSA-9013957 TLR3-mediated TICAM1-dependent programmed cell death R-HSA-933543 NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10
SignaLinkⁱ	Q14790
SIGNORⁱ	Q14790

Protein family/group databases

MEROPS protease database More...MEROPSⁱ	C14.009

MEROPSⁱ

C14.009

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Caspase-8 (EC:3.4.22.61) Short name: CASP-8 Alternative name(s): Apoptotic cysteine protease Apoptotic protease Mch-5 CAP4 FADD-homologous ICE/ced-3-like protease FADD-like ICE Short name: FLICE ICE-like apoptotic protease 5 MORT1-associated ced-3 homolog Short name: MACH Cleaved into the following 2 chains: Caspase-8 subunit p18 Caspase-8 subunit p10
Gene namesⁱ	Name:CASP8 Synonyms:MCH5
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 2

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000064012.21
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:1509 CASP8
MIMⁱ	601763 gene
neXtProtⁱ	NX_Q14790

Keywords - Cellular componentⁱ

Cytoplasm

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Caspase-8 deficiency (CASP8D)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionDisorder resembling autoimmune lymphoproliferative syndrome (ALPS). It is characterized by lymphadenopathy, splenomegaly, and defective CD95-induced apoptosis of peripheral blood lymphocytes (PBLs). It leads to defects in activation of T-lymphocytes, B-lymphocytes, and natural killer cells leading to immunodeficiency characterized by recurrent sinopulmonary and herpes simplex virus infections and poor responses to immunization.

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_014204	248	R → W in CASP8D. 1 PublicationCorresponds to variant dbSNP:rs17860424Ensembl.		1

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	73	D → A: Abolishes binding to FLASH. Induces NF-kappa-B activation. 1 Publication	1
Mutagenesisⁱ	360	C → S: Abolishes interaction with UBR2. 1 Publication	1
Mutagenesisⁱ	387	S → A: Impaired CDK1-mediated phosphorylation and enhanced apoptosis.	1

Keywords - Diseaseⁱ

Disease mutation

Organism-specific databases

DisGeNET More...DisGeNETⁱ	841
MalaCards human disease database More...MalaCardsⁱ	CASP8
MIMⁱ	211980 phenotype 607271 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000064012
Orphanetⁱ	210159 Adult hepatocellular carcinoma 275517 Autoimmune lymphoproliferative syndrome with recurrent viral infections
PharmGKBⁱ	PA26092

Chemistry databases

ChEMBLⁱ	CHEMBL3776
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	1624

Polymorphism and mutation databases

BioMutaⁱ	CASP8
DMDMⁱ	2493531

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Length
PropeptideⁱPRO_0000004628	1 – 216	Add BLAST	216
ChainⁱPRO_0000004629	217 – 374	Caspase-8 subunit p18Add BLAST	158
PropeptideⁱPRO_0000004630	375 – 384		10
ChainⁱPRO_0000004631	385 – 479	Caspase-8 subunit p10Add BLAST	95

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	188	PhosphoserineBy similarity	1
Modified residueⁱ	211	PhosphoserineBy similarity	1
Modified residueⁱ	224	N6-acetyllysineBy similarity	1
Modified residueⁱ	334	PhosphotyrosineCombined sources	1
Modified residueⁱ	387	Phosphoserine; by CDK11 Publication	1

Post-translational modificationⁱ

Generation of the subunits requires association with the death-inducing signaling complex (DISC), whereas additional processing is likely due to the autocatalytic activity of the activated protease. GZMB and CASP10 can be involved in these processing events.2 Publications

Phosphorylation on Ser-387 during mitosis by CDK1 inhibits activation by proteolysis and prevents apoptosis. This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes.1 Publication

Keywords - PTMⁱ

Acetylation, Phosphoprotein, Zymogen

Proteomic databases

EPDⁱ	Q14790
jPOSTⁱ	Q14790
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q14790
PaxDbⁱ	Q14790
PeptideAtlas More...PeptideAtlasⁱ	Q14790
PRIDEⁱ	Q14790
ProteomicsDBⁱ	60172 60173 [Q14790-2] 60174 [Q14790-3] 60175 [Q14790-4] 60176 [Q14790-5] 60177 [Q14790-6] 60178 [Q14790-7] 60179 [Q14790-8] 60180 [Q14790-9]

PTM databases

iPTMnetⁱ	Q14790
PhosphoSitePlusⁱ	Q14790
SwissPalmⁱ	Q14790

Miscellaneous databases

PMAP-CutDBⁱ	Q14790

PMAP-CutDBⁱ

Q14790

Expressionⁱ

Tissue specificityⁱ

Isoform 1, isoform 5 and isoform 7 are expressed in a wide variety of tissues. Highest expression in peripheral blood leukocytes, spleen, thymus and liver. Barely detectable in brain, testis and skeletal muscle.

Gene expression databases

Bgeeⁱ	ENSG00000064012 Expressed in 196 organ(s), highest expression level in small intestine Peyer's patch
ExpressionAtlasⁱ	Q14790 baseline and differential
Genevisibleⁱ	Q14790 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	CAB002047 HPA001302 HPA005688 HPA006191

HPAⁱ

CAB002047
HPA001302
HPA005688
HPA006191

Interactionⁱ

Subunit structureⁱ

Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (p18) and a 10 kDa (p10) subunit (PubMed:10508784). Interacts with FADD, CFLAR and PEA15 (PubMed:10442631). Isoform 9 interacts at the endoplasmic reticulum with a complex containing BCAP31, BAP29, BCL2 and/or BCL2L1 (PubMed:11917123, PubMed:9334338). Interacts with TNFAIP8L2 (By similarity). Interacts with CASP8AP2 (PubMed:16378960). Interacts with RFFL and RNF34; negatively regulate CASP8 through proteasomal degradation (PubMed:15069192). Interacts with NOL3; decreases CASP8 activity in a mitochondria localization- and phosphorylation-dependent manner and this interaction is dissociated by calcium (PubMed:15509781). Interacts with UBR2 (PubMed:28602583).By similarity8 Publications

(Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein vICA/UL36; this interaction inhibits CASP8 activation.1 Publication

(Microbial infection) Interacts with NleF from pathogenic E.coli.1 Publication

(Microbial infection) Interacts with molluscum contagiosum virus protein MC160.1 Publication

Binary interactionsⁱ

With	Entry	#Exp.	IntAct
itself		2	EBI-78060,EBI-78060
AR	P10275	3	EBI-78060,EBI-608057
BCAP31	P51572	3	EBI-78060,EBI-77683
CASP10	Q92851	3	EBI-78060,EBI-495095
CASP8AP2	Q9UKL3	3	EBI-78060,EBI-2339650
CFLAR	O15519	9	EBI-78060,EBI-514941
CFLAR	O15519-1	3	EBI-15777741,EBI-4567563
CUL3	Q13618	6	EBI-78060,EBI-456129
FADD	Q13158	44	EBI-78060,EBI-494804
FAS	P25445	14	EBI-78060,EBI-494743
FAS	P25445-1	3	EBI-78060,EBI-15749113
FASLG	P48023	5	EBI-78060,EBI-495538
ILK	Q13418	2	EBI-78060,EBI-747644
MALT1	Q9UDY8	10	EBI-78060,EBI-1047372
NOL3	O60936	3	EBI-78060,EBI-740992
PTPN6	P29350	3	EBI-78060,EBI-78260
RIPK1	Q13546	27	EBI-78060,EBI-358507
RNF34	Q969K3	3	EBI-78060,EBI-2340642
TNFAIP3	P21580	3	EBI-78060,EBI-527670
TNFRSF10A	O00220	9	EBI-78060,EBI-518861

GO - Molecular functionⁱ

death effector domain binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 11717445
death receptor binding Source: Ensembl
identical protein binding
Source: IntAct
Inferred from physical interactionⁱ
- 16169070
- 17170703
scaffold protein binding
Source: ParkinsonsUK-UCL
Inferred from physical interactionⁱ
- 21785459
tumor necrosis factor receptor binding Source: Ensembl
ubiquitin protein ligase binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 15069192

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	107291, 151 interactors
ComplexPortalⁱ	CPX-1907 Ripoptosome CPX-975 Caspase-8 complex
CORUMⁱ	Q14790
Database of interacting proteins More...DIPⁱ	DIP-30915N
ELMⁱ	Q14790
IntActⁱ	Q14790, 122 interactors
Molecular INTeraction database More...MINTⁱ	Q14790
STRINGⁱ	9606.ENSP00000351273

Chemistry databases

BindingDBⁱ

Q14790

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Helixⁱ	3 – 13	Combined sources	11
Helixⁱ	16 – 25	Combined sources	10
Turnⁱ	26 – 29	Combined sources	4
Helixⁱ	32 – 34	Combined sources	3
Turnⁱ	35 – 37	Combined sources	3
Helixⁱ	41 – 50	Combined sources	10
Beta strandⁱ	53 – 55	Combined sources	3
Helixⁱ	60 – 68	Combined sources	9
Helixⁱ	72 – 79	Combined sources	8
Helixⁱ	83 – 91	Combined sources	9
Turnⁱ	93 – 95	Combined sources	3
Helixⁱ	100 – 111	Combined sources	12
Helixⁱ	114 – 127	Combined sources	14
Helixⁱ	139 – 148	Combined sources	10
Beta strandⁱ	151 – 153	Combined sources	3
Helixⁱ	158 – 165	Combined sources	8
Helixⁱ	169 – 180	Combined sources	12
Beta strandⁱ	230 – 232	Combined sources	3
Beta strandⁱ	235 – 240	Combined sources	6
Helixⁱ	245 – 250	Combined sources	6
Helixⁱ	252 – 254	Combined sources	3
Beta strandⁱ	255 – 257	Combined sources	3
Helixⁱ	263 – 276	Combined sources	14
Beta strandⁱ	280 – 286	Combined sources	7
Helixⁱ	289 – 301	Combined sources	13
Helixⁱ	304 – 306	Combined sources	3
Beta strandⁱ	310 – 316	Combined sources	7
Beta strandⁱ	322 – 324	Combined sources	3
Beta strandⁱ	326 – 328	Combined sources	3
Beta strandⁱ	330 – 332	Combined sources	3
Helixⁱ	333 – 337	Combined sources	5
Helixⁱ	338 – 340	Combined sources	3
Turnⁱ	342 – 344	Combined sources	3
Helixⁱ	346 – 348	Combined sources	3
Beta strandⁱ	353 – 359	Combined sources	7
Beta strandⁱ	361 – 364	Combined sources	4
Beta strandⁱ	369 – 371	Combined sources	3
Beta strandⁱ	377 – 379	Combined sources	3
Beta strandⁱ	392 – 394	Combined sources	3
Turnⁱ	395 – 398	Combined sources	4
Beta strandⁱ	399 – 405	Combined sources	7
Beta strandⁱ	412 – 414	Combined sources	3
Turnⁱ	415 – 417	Combined sources	3
Helixⁱ	420 – 432	Combined sources	13
Helixⁱ	433 – 435	Combined sources	3
Helixⁱ	439 – 450	Combined sources	12
Turnⁱ	456 – 459	Combined sources	4
Beta strandⁱ	465 – 468	Combined sources	4
Beta strandⁱ	471 – 473	Combined sources	3

Show more details

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	1F9E	X-ray	2.90	A/C/E/G/I/K	222-374	[»]
				B/D/F/H/J/L	390-478	[»]
	1I4E	X-ray	3.00	B	222-479	[»]
	1QDU	X-ray	2.80	A/C/E/G/I/K	222-374	[»]
				B/D/F/H/J/L	390-477	[»]
	1QTN	X-ray	1.20	A	211-374	[»]
				B	385-479	[»]
	2C2Z	X-ray	1.95	A	218-374	[»]
				B	376-479	[»]
	2FUN	X-ray	3.00	B/D	222-479	[»]
	2K7Z	NMR	-	A	217-479	[»]
	2Y1L	X-ray	1.80	A/C	218-374	[»]
				B/D	376-479	[»]
	3H11	X-ray	1.90	B	217-479	[»]
	3KJN	X-ray	1.80	A	211-374	[»]
				B	385-479	[»]
	3KJQ	X-ray	1.80	A	211-374	[»]
				B	385-479	[»]
	4JJ7	X-ray	1.18	A	217-479	[»]
	4PRZ	X-ray	2.12	A	217-479	[»]
	4PS1	X-ray	1.73	A/B/C/D	217-479	[»]
	4ZBW	X-ray	2.20	A/B	2-188	[»]
	5H31	X-ray	3.17	A/B/C/D	1-188	[»]
	5H33	X-ray	3.60	A/B	1-188	[»]
	5JQE	X-ray	3.16	A	1-186	[»]
	5L08	electron microscopy	4.60	A/B/C/D/E/F/G/H/I	1-184	[»]
ProteinModelPortalⁱ	Q14790
SMRⁱ	Q14790
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	Q14790

EvolutionaryTraceⁱ

Q14790

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	2 – 80	DED 1PROSITE-ProRule annotationAdd BLAST		79
Domainⁱ	100 – 177	DED 2PROSITE-ProRule annotationAdd BLAST		78

Domainⁱ

Isoform 9 contains a N-terminal extension that is required for interaction with the BCAP31 complex.

Sequence similaritiesⁱ

Belongs to the peptidase C14A family.Curated

Keywords - Domainⁱ

Repeat

Phylogenomic databases

eggNOGⁱ	KOG3573 Eukaryota ENOG410ZQIE LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00940000160319
HOVERGENⁱ	HBG050803
InParanoidⁱ	Q14790
KEGG Orthology (KO) More...KOⁱ	K04398
OMAⁱ	RVMLFQI
Database of Orthologous Groups More...OrthoDBⁱ	939331at2759
PhylomeDBⁱ	Q14790
TreeFamⁱ	TF102023

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00032 CASc, 1 hit
InterProⁱ	View protein in InterPro IPR033170 Caspase-8 IPR029030 Caspase-like_dom_sf IPR033139 Caspase_cys_AS IPR016129 Caspase_his_AS IPR011029 DEATH-like_dom_sf IPR001875 DED_dom IPR002398 Pept_C14 IPR002138 Pept_C14_p10 IPR001309 Pept_C14_p20 IPR015917 Pept_C14A
PANTHERⁱ	PTHR10454 PTHR10454, 1 hit PTHR10454:SF162 PTHR10454:SF162, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF01335 DED, 2 hits
PRINTSⁱ	PR00376 IL1BCENZYME
SMARTⁱ	View protein in SMART SM00115 CASc, 1 hit SM00031 DED, 2 hits
SUPFAMⁱ	SSF47986 SSF47986, 2 hits SSF52129 SSF52129, 1 hit
PROSITEⁱ	View protein in PROSITE PS01122 CASPASE_CYS, 1 hit PS01121 CASPASE_HIS, 1 hit PS50207 CASPASE_P10, 1 hit PS50208 CASPASE_P20, 1 hit PS50168 DED, 2 hits

Sequences (9+)ⁱ

Sequence statusⁱ: Complete.

Sequence processingⁱ: The displayed sequence is further processed into a mature form.

This entry describes 9 isoformsⁱ produced by alternative splicing. Align Add to basket

This entry has 9 described isoforms and 9 potential isoforms that are computationally mapped.Show all Align All

Isoform 1 (identifier: Q14790-1) [UniParc]FASTA Add to basket

Also known as: Alpha-1

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDFSRNLYDI GEQLDSEDLA SLKFLSLDYI PQRKQEPIKD ALMLFQRLQE 
        60         70         80         90        100
KRMLEESNLS FLKELLFRIN RLDLLITYLN TRKEEMEREL QTPGRAQISA 
       110        120        130        140        150
YRVMLYQISE EVSRSELRSF KFLLQEEISK CKLDDDMNLL DIFIEMEKRV 
       160        170        180        190        200
ILGEGKLDIL KRVCAQINKS LLKIINDYEE FSKERSSSLE GSPDEFSNGE 
       210        220        230        240        250
ELCGVMTISD SPREQDSESQ TLDKVYQMKS KPRGYCLIIN NHNFAKAREK 
       260        270        280        290        300
VPKLHSIRDR NGTHLDAGAL TTTFEELHFE IKPHDDCTVE QIYEILKIYQ 
       310        320        330        340        350
LMDHSNMDCF ICCILSHGDK GIIYGTDGQE APIYELTSQF TGLKCPSLAG 
       360        370        380        390        400
KPKVFFIQAC QGDNYQKGIP VETDSEEQPY LEMDLSSPQT RYIPDEADFL 
       410        420        430        440        450
LGMATVNNCV SYRNPAEGTW YIQSLCQSLR ERCPRGDDIL TILTEVNYEV 
       460        470 
SNKDDKKNMG KQMPQPTFTL RKKLVFPSD

Length:479

Mass (Da):55,391

Last modified:November 1, 1996 - v1

Checksum:ⁱ7A5FEAA6B39B582F

GO

Isoform 2 (identifier: Q14790-2) [UniParc]FASTA Add to basket

Also known as: Alpha-2, MCH5-beta

The sequence of this isoform differs from the canonical sequence as follows:
184-198: Missing.

« Hide

        10         20         30         40         50
MDFSRNLYDI GEQLDSEDLA SLKFLSLDYI PQRKQEPIKD ALMLFQRLQE 
        60         70         80         90        100
KRMLEESNLS FLKELLFRIN RLDLLITYLN TRKEEMEREL QTPGRAQISA 
       110        120        130        140        150
YRVMLYQISE EVSRSELRSF KFLLQEEISK CKLDDDMNLL DIFIEMEKRV 
       160        170        180        190        200
ILGEGKLDIL KRVCAQINKS LLKIINDYEE FSKGEELCGV MTISDSPREQ 
       210        220        230        240        250
DSESQTLDKV YQMKSKPRGY CLIINNHNFA KAREKVPKLH SIRDRNGTHL 
       260        270        280        290        300
DAGALTTTFE ELHFEIKPHD DCTVEQIYEI LKIYQLMDHS NMDCFICCIL 
       310        320        330        340        350
SHGDKGIIYG TDGQEAPIYE LTSQFTGLKC PSLAGKPKVF FIQACQGDNY 
       360        370        380        390        400
QKGIPVETDS EEQPYLEMDL SSPQTRYIPD EADFLLGMAT VNNCVSYRNP 
       410        420        430        440        450
AEGTWYIQSL CQSLRERCPR GDDILTILTE VNYEVSNKDD KKNMGKQMPQ 
       460 
PTFTLRKKLV FPSD

Show »

Length:464

Mass (Da):53,768

Checksum:ⁱ7F52F14ADE6A02B6

GO

Isoform 3 (identifier: Q14790-3) [UniParc]FASTA Add to basket

Also known as: Alpha-3

The sequence of this isoform differs from the canonical sequence as follows:
184-267: Missing.

« Hide

        10         20         30         40         50
MDFSRNLYDI GEQLDSEDLA SLKFLSLDYI PQRKQEPIKD ALMLFQRLQE 
        60         70         80         90        100
KRMLEESNLS FLKELLFRIN RLDLLITYLN TRKEEMEREL QTPGRAQISA 
       110        120        130        140        150
YRVMLYQISE EVSRSELRSF KFLLQEEISK CKLDDDMNLL DIFIEMEKRV 
       160        170        180        190        200
ILGEGKLDIL KRVCAQINKS LLKIINDYEE FSKGALTTTF EELHFEIKPH 
       210        220        230        240        250
DDCTVEQIYE ILKIYQLMDH SNMDCFICCI LSHGDKGIIY GTDGQEAPIY 
       260        270        280        290        300
ELTSQFTGLK CPSLAGKPKV FFIQACQGDN YQKGIPVETD SEEQPYLEMD 
       310        320        330        340        350
LSSPQTRYIP DEADFLLGMA TVNNCVSYRN PAEGTWYIQS LCQSLRERCP 
       360        370        380        390 
RGDDILTILT EVNYEVSNKD DKKNMGKQMP QPTFTLRKKL VFPSD

Show »

Length:395

Mass (Da):45,929

Checksum:ⁱ2787AE831A2B36EF

GO

Isoform 4 (identifier: Q14790-4) [UniParc]FASTA Add to basket

Also known as: Alpha-4

The sequence of this isoform differs from the canonical sequence as follows:
102-102: R → RFHFCRMSWAEANSQCQTQSVPFWRRVDHLLIR
184-198: Missing.

« Hide

        10         20         30         40         50
MDFSRNLYDI GEQLDSEDLA SLKFLSLDYI PQRKQEPIKD ALMLFQRLQE 
        60         70         80         90        100
KRMLEESNLS FLKELLFRIN RLDLLITYLN TRKEEMEREL QTPGRAQISA 
       110        120        130        140        150
YRFHFCRMSW AEANSQCQTQ SVPFWRRVDH LLIRVMLYQI SEEVSRSELR 
       160        170        180        190        200
SFKFLLQEEI SKCKLDDDMN LLDIFIEMEK RVILGEGKLD ILKRVCAQIN 
       210        220        230        240        250
KSLLKIINDY EEFSKGEELC GVMTISDSPR EQDSESQTLD KVYQMKSKPR 
       260        270        280        290        300
GYCLIINNHN FAKAREKVPK LHSIRDRNGT HLDAGALTTT FEELHFEIKP 
       310        320        330        340        350
HDDCTVEQIY EILKIYQLMD HSNMDCFICC ILSHGDKGII YGTDGQEAPI 
       360        370        380        390        400
YELTSQFTGL KCPSLAGKPK VFFIQACQGD NYQKGIPVET DSEEQPYLEM 
       410        420        430        440        450
DLSSPQTRYI PDEADFLLGM ATVNNCVSYR NPAEGTWYIQ SLCQSLRERC 
       460        470        480        490 
PRGDDILTIL TEVNYEVSNK DDKKNMGKQM PQPTFTLRKK LVFPSD

Show »

Length:496

Mass (Da):57,701

Checksum:ⁱ68136650A49159D9

GO

Isoform 5 (identifier: Q14790-5) [UniParc]FASTA Add to basket

Also known as: Beta-1

The sequence of this isoform differs from the canonical sequence as follows:
199-235: GEELCGVMTISDSPREQDSESQTLDKVYQMKSKPRGY → DFGQSLPNEKQTSGILSDHQQSQFCKSTGESAQTSQH
236-479: Missing.

« Hide

        10         20         30         40         50
MDFSRNLYDI GEQLDSEDLA SLKFLSLDYI PQRKQEPIKD ALMLFQRLQE 
        60         70         80         90        100
KRMLEESNLS FLKELLFRIN RLDLLITYLN TRKEEMEREL QTPGRAQISA 
       110        120        130        140        150
YRVMLYQISE EVSRSELRSF KFLLQEEISK CKLDDDMNLL DIFIEMEKRV 
       160        170        180        190        200
ILGEGKLDIL KRVCAQINKS LLKIINDYEE FSKERSSSLE GSPDEFSNDF 
       210        220        230 
GQSLPNEKQT SGILSDHQQS QFCKSTGESA QTSQH

Show »

Length:235

Mass (Da):27,484

Checksum:ⁱ7C9013CEA85A77DE

GO

Isoform 6 (identifier: Q14790-6) [UniParc]FASTA Add to basket

Also known as: Beta-2

The sequence of this isoform differs from the canonical sequence as follows:
184-220: ERSSSLEGSPDEFSNGEELCGVMTISDSPREQDSESQ → DFGQSLPNEKQTSGILSDHQQSQFCKSTGESAQTSQH
221-479: Missing.

« Hide

        10         20         30         40         50
MDFSRNLYDI GEQLDSEDLA SLKFLSLDYI PQRKQEPIKD ALMLFQRLQE 
        60         70         80         90        100
KRMLEESNLS FLKELLFRIN RLDLLITYLN TRKEEMEREL QTPGRAQISA 
       110        120        130        140        150
YRVMLYQISE EVSRSELRSF KFLLQEEISK CKLDDDMNLL DIFIEMEKRV 
       160        170        180        190        200
ILGEGKLDIL KRVCAQINKS LLKIINDYEE FSKDFGQSLP NEKQTSGILS 
       210        220
DHQQSQFCKS TGESAQTSQH

Show »

Length:220

Mass (Da):25,862

Checksum:ⁱF3DA0380D12006C7

GO

Isoform 7 (identifier: Q14790-7) [UniParc]FASTA Add to basket

Also known as: Beta-3, 8L

The sequence of this isoform differs from the canonical sequence as follows:
269-276: ALTTTFEE → TVEPKREK
277-479: Missing.

« Hide

        10         20         30         40         50
MDFSRNLYDI GEQLDSEDLA SLKFLSLDYI PQRKQEPIKD ALMLFQRLQE 
        60         70         80         90        100
KRMLEESNLS FLKELLFRIN RLDLLITYLN TRKEEMEREL QTPGRAQISA 
       110        120        130        140        150
YRVMLYQISE EVSRSELRSF KFLLQEEISK CKLDDDMNLL DIFIEMEKRV 
       160        170        180        190        200
ILGEGKLDIL KRVCAQINKS LLKIINDYEE FSKERSSSLE GSPDEFSNGE 
       210        220        230        240        250
ELCGVMTISD SPREQDSESQ TLDKVYQMKS KPRGYCLIIN NHNFAKAREK 
       260        270 
VPKLHSIRDR NGTHLDAGTV EPKREK

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Show »

Length:276

Mass (Da):32,330

Checksum:ⁱ227ED77718788F92

GO

Isoform 8 (identifier: Q14790-8) [UniParc]FASTA Add to basket

Also known as: Beta-4

The sequence of this isoform differs from the canonical sequence as follows:
     184-198: Missing.
     269-276: ALTTTFEE → TVEPKREK
     277-479: Missing.

« Hide

        10         20         30         40         50
MDFSRNLYDI GEQLDSEDLA SLKFLSLDYI PQRKQEPIKD ALMLFQRLQE 
        60         70         80         90        100
KRMLEESNLS FLKELLFRIN RLDLLITYLN TRKEEMEREL QTPGRAQISA 
       110        120        130        140        150
YRVMLYQISE EVSRSELRSF KFLLQEEISK CKLDDDMNLL DIFIEMEKRV 
       160        170        180        190        200
ILGEGKLDIL KRVCAQINKS LLKIINDYEE FSKGEELCGV MTISDSPREQ 
       210        220        230        240        250
DSESQTLDKV YQMKSKPRGY CLIINNHNFA KAREKVPKLH SIRDRNGTHL 
       260 
DAGTVEPKRE K

Show »

Length:261

Mass (Da):30,707

Checksum:ⁱ19ACAE80171E0572

GO

Isoform 9 (identifier: Q14790-9) [UniParc]FASTA Add to basket

Also known as: 8L

The sequence of this isoform differs from the canonical sequence as follows:
1-1: M → MEGGRRARVVIESKRNFFLGAFPTPFPAEHVELGRLGDSETAMVPGKGGADYILLPFKKM

« Hide

        10         20         30         40         50
MEGGRRARVV IESKRNFFLG AFPTPFPAEH VELGRLGDSE TAMVPGKGGA 
        60         70         80         90        100
DYILLPFKKM DFSRNLYDIG EQLDSEDLAS LKFLSLDYIP QRKQEPIKDA 
       110        120        130        140        150
LMLFQRLQEK RMLEESNLSF LKELLFRINR LDLLITYLNT RKEEMERELQ 
       160        170        180        190        200
TPGRAQISAY RVMLYQISEE VSRSELRSFK FLLQEEISKC KLDDDMNLLD 
       210        220        230        240        250
IFIEMEKRVI LGEGKLDILK RVCAQINKSL LKIINDYEEF SKERSSSLEG 
       260        270        280        290        300
SPDEFSNGEE LCGVMTISDS PREQDSESQT LDKVYQMKSK PRGYCLIINN 
       310        320        330        340        350
HNFAKAREKV PKLHSIRDRN GTHLDAGALT TTFEELHFEI KPHDDCTVEQ 
       360        370        380        390        400
IYEILKIYQL MDHSNMDCFI CCILSHGDKG IIYGTDGQEA PIYELTSQFT 
       410        420        430        440        450
GLKCPSLAGK PKVFFIQACQ GDNYQKGIPV ETDSEEQPYL EMDLSSPQTR 
       460        470        480        490        500
YIPDEADFLL GMATVNNCVS YRNPAEGTWY IQSLCQSLRE RCPRGDDILT 
       510        520        530 
ILTEVNYEVS NKDDKKNMGK QMPQPTFTLR KKLVFPSD

Show »

Length:538

Mass (Da):61,836

Checksum:ⁱ54402ECFA9FE5E14

GO

Computationally mapped potential isoform sequencesⁱ

There are 9 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation

H7C0E2	H7C0E2_HUMAN	Caspase-8 Caspase-8	CASP8	258	Annotation score:
E7EQ06	E7EQ06_HUMAN	Caspase-8 Caspase-8	CASP8	209	Annotation score:
E7ETB7	E7ETB7_HUMAN	Caspase-8 Caspase-8	CASP8	198	Annotation score:
E7EVN1	E7EVN1_HUMAN	Caspase-8 Caspase-8	CASP8	124	Annotation score:
E7EQ01	E7EQ01_HUMAN	Caspase-8 Caspase-8	CASP8	116	Annotation score:
A0A0A0MS31	A0A0A0MS31_HUMAN	Caspase-8 Caspase-8	CASP8	278	Annotation score:
C9JB29	C9JB29_HUMAN	Caspase-8 Caspase-8	CASP8	149	Annotation score:
F8WF39	F8WF39_HUMAN	Caspase-8 Caspase-8	CASP8	58	Annotation score:
H7BZM4	H7BZM4_HUMAN	Caspase-8 Caspase-8	CASP8	83	Annotation score:

Sequence cautionⁱ

The sequence CAA66858 differs from that shown.Curated

The sequence CAA66859 differs from that shown.Curated

Experimental Info

Feature key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	294	E → D in AAD24962 (PubMed:9931493).Curated	1
Sequence conflictⁱ	331	A → P in AAC50602 (PubMed:8681377).Curated	1
Sequence conflictⁱ	331	A → P in AAD24962 (PubMed:9931493).Curated	1
Sequence conflictⁱ	343 – 344	LK → FG in AAL87631 (PubMed:11917123).Curated	2
Isoform 9 (identifier: Q14790-9)
Sequence conflictⁱ	14	K → R in AAL87628 (PubMed:11917123).Curated	1

Polymorphismⁱ

Genetic variations in CASP8 are associated with reduced risk of lung cancer [MIMⁱ:211980] in a population of Han Chinese subjects. Genetic variations are also associated with decreased risk of cancer of various other forms including esophageal, gastric, colorectal, cervical, and breast, acting in an allele dose-dependent manner.1 Publication

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_025816	219	S → T1 PublicationCorresponds to variant dbSNP:rs35976359Ensembl.	1
Natural variantⁱVAR_014204	248	R → W in CASP8D. 1 PublicationCorresponds to variant dbSNP:rs17860424Ensembl.	1
Natural variantⁱVAR_020127	285	D → H Associated with protection against breast cancer; also associated with a lower risk of cutaneous melanoma. 7 PublicationsCorresponds to variant dbSNP:rs1045485Ensembl.	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Length
Alternative sequenceⁱVSP_000808	1	M → MEGGRRARVVIESKRNFFLG AFPTPFPAEHVELGRLGDSE TAMVPGKGGADYILLPFKKM in isoform 9. 1 Publication	1
Alternative sequenceⁱVSP_000809	102	R → RFHFCRMSWAEANSQCQTQS VPFWRRVDHLLIR in isoform 4. 1 Publication	1
Alternative sequenceⁱVSP_000813	184 – 267	Missing in isoform 3. 1 PublicationAdd BLAST	84
Alternative sequenceⁱVSP_000811	184 – 220	ERSSS…DSESQ → DFGQSLPNEKQTSGILSDHQ QSQFCKSTGESAQTSQH in isoform 6. 1 PublicationAdd BLAST	37
Alternative sequenceⁱVSP_000810	184 – 198	Missing in isoform 2, isoform 4 and isoform 8. 4 PublicationsAdd BLAST	15
Alternative sequenceⁱVSP_000814	199 – 235	GEELC…KPRGY → DFGQSLPNEKQTSGILSDHQ QSQFCKSTGESAQTSQH in isoform 5. 1 PublicationAdd BLAST	37
Alternative sequenceⁱVSP_000812	221 – 479	Missing in isoform 6. 1 PublicationAdd BLAST	259
Alternative sequenceⁱVSP_000815	236 – 479	Missing in isoform 5. 1 PublicationAdd BLAST	244
Alternative sequenceⁱVSP_000816	269 – 276	ALTTTFEE → TVEPKREK in isoform 7 and isoform 8. 3 Publications	8
Alternative sequenceⁱVSP_000817	277 – 479	Missing in isoform 7 and isoform 8. 3 PublicationsAdd BLAST	203

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	X98172 mRNA Translation: CAA66853.1 X98173 mRNA Translation: CAA66854.1 X98174 mRNA Translation: CAA66855.1 X98175 mRNA Translation: CAA66856.1 X98176 mRNA Translation: CAA66857.1 X98177 mRNA Translation: CAA66858.1 Sequence problems. X98178 mRNA Translation: CAA66859.1 Sequence problems. U58143 mRNA Translation: AAC50602.1 U60520 mRNA Translation: AAC50645.1 AF009620 mRNA Translation: AAB70913.1 AF102146 AF102145 Genomic DNA Translation: AAD24962.1 AB038985 Genomic DNA Translation: BAB32555.1 AF380342 mRNA Translation: AAK57437.1 AF422925 mRNA Translation: AAL87628.1 AF422926 mRNA Translation: AAL87629.1 AF422927 mRNA Translation: AAL87630.1 AF422928 mRNA Translation: AAL87631.1 AF422929 mRNA Translation: AAL87632.1 DQ355026 Genomic DNA Translation: ABC67468.1 AC007256 Genomic DNA Translation: AAY24225.1 BC028223 mRNA No translation available.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS2342.1 [Q14790-1] CCDS2343.1 [Q14790-2] CCDS2345.1 [Q14790-5] CCDS42798.1 [Q14790-9] CCDS42799.1 [Q14790-4]
NCBI Reference Sequences More...RefSeqⁱ	NP_001073593.1, NM_001080124.1 [Q14790-2] NP_001073594.1, NM_001080125.1 [Q14790-9] NP_001219.2, NM_001228.4 [Q14790-4] NP_203519.1, NM_033355.3 [Q14790-1] NP_203520.1, NM_033356.3 [Q14790-2] NP_203522.1, NM_033358.3 [Q14790-5] XP_005246943.1, XM_005246886.1 [Q14790-1] XP_005246944.1, XM_005246887.1 [Q14790-1] XP_005246945.1, XM_005246888.1 [Q14790-1] XP_005246946.1, XM_005246889.1 [Q14790-1] XP_005246947.1, XM_005246890.3 [Q14790-1] XP_005246948.1, XM_005246891.4 [Q14790-1] XP_005246949.1, XM_005246892.1 [Q14790-2] XP_006712852.1, XM_006712789.1 [Q14790-1] XP_006712853.1, XM_006712790.3 [Q14790-1] XP_006712856.1, XM_006712793.2 [Q14790-5]
UniGeneⁱ	Hs.599762

Genome annotation databases

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q14790	Isoform 9 of Caspase-8		HUMAN		538	UniRef100_Q14790
Caspase 8		GORGO		479
Caspase-8 (Fragment)		HUMAN		198
UPI0008DB4258		HUMAN		184
UPI0005CFF0BD		HUMAN		334
+1
Q14790-2	HCG16983, isoform CRA_b		HUMAN		464	UniRef100_A0A024R3Z8
Caspase-8 (Fragment)		HUMAN		149
UPI000387CDA2		HUMAN		523
Q14790-3	Caspase 8		GORGO		395	UniRef100_G3QD95
Caspase-8 (Fragment)		HUMAN		258
Q14790-5	Caspase 8		GORGO		235	UniRef100_A0A2I2Y3T4
UPI000387B265		HUMAN		294
Q14790-6	Caspase-8 (Fragment)		HUMAN		83	UniRef100_Q14790-6
Caspase-8 (Fragment)		HUMAN		209
UPI000387B5F8		HUMAN		279
Q14790-7	HCG16983, isoform CRA_a		HUMAN		276	UniRef100_A0A024R3Z9
Caspase 8 isoform i (Fragment)		HUMAN		12

Protein	Similar proteins		Species	Score	Length	Source
Q14790	Isoform 9 of Caspase-8		HUMAN		538	UniRef90_Q14790
Caspase 8		GORGO		479
Caspase 8		RHIRO		542
Caspase 8		RHIBE		542
CASP8 isoform 11		PANTR		538
+38
Q14790-3	Caspase 8 splice variant		HUMAN		395	UniRef90_B6CGU5
Caspase 8		RHIRO		398
Caspase 8		RHIBE		398
CASP8 isoform 1		PANTR		395
Caspase 8		PANPA		395
+15
Q14790-4	CASP8 isoform 5		PANTR		496	UniRef90_Q14790-4
Caspase 8		PANPA		496
Caspase 8		COLAP		496
CASP8 isoform 5		PONAB		496
Caspase 8		NOMLE		496
+10
Q14790-5	Isoform 6 of Caspase-8		HUMAN		220	UniRef90_Q14790-6
Caspase 8		GORGO		235
CASP8 isoform 9		PANTR		235
Caspase-8 (Fragment)		HUMAN		83
Caspase-8 (Fragment)		HUMAN		209
+3
Q14790-6	Caspase-8 (Fragment)		HUMAN		83	UniRef90_Q14790-6
Caspase 8		GORGO		235
CASP8 isoform 9		PANTR		235
Caspase-8 (Fragment)		HUMAN		209
Isoform 5 of Caspase-8		HUMAN		235
+3
Q14790-7	Isoform 8 of Caspase-8		HUMAN		261	UniRef90_Q14790-8
Caspase 8		MACMU		279
Uncharacterized protein		MACFA		278
Caspase 8		MANLE		278
Caspase 8		PAPAN		278
+8
Q14790-8	Caspase 8		MACMU		279	UniRef90_Q14790-8
Uncharacterized protein		MACFA		278
Caspase 8		MANLE		278
Caspase 8		PAPAN		278
Caspase 8		MACNE		278
+8

Protein	Similar proteins		Species	Score	Length	Source
Q14790	Isoform 9 of Caspase-8		HUMAN		538	UniRef50_Q14790
Caspase 8		GORGO		479
Caspase 8		RHIRO		542
Caspase 8		RHIBE		542
Caspase 8		NOMLE		538
+305
Q14790-3	Caspase 8 splice variant		HUMAN		395	UniRef50_B6CGU5
Caspase 8		RHIRO		398
Caspase 8		RHIBE		398
Uncharacterized protein		MACFA		395
CASP8 isoform 2		PONAB		395
+23
Q14790-4	CASP8 isoform 5		PANTR		496	UniRef50_Q14790-4
Caspase 8		PANPA		496
Caspase 8		COLAP		496
Caspase 8		NOMLE		496
CASP8 isoform 5		PONAB		496
+20
Q14790-5	Isoform 6 of Caspase-8		HUMAN		220	UniRef50_Q14790-6
Caspase 8		GORGO		235
CASP8 isoform 9		PANTR		235
CASP8 (Fragment)		CAPHI		341
UPI00080A4964		Cebus capucinus imitator		296
+6
Q14790-6	Caspase-8 (Fragment)		HUMAN		83	UniRef50_Q14790-6
Caspase 8		GORGO		235
CASP8 isoform 9		PANTR		235
CASP8 (Fragment)		CAPHI		341
UPI00080A4964		Cebus capucinus imitator		296
+6
Q14790-7	Isoform 8 of Caspase-8		HUMAN		261	UniRef50_Q14790-8
Caspase 8		MACMU		279
Uncharacterized protein		MACFA		278
Caspase 8		MACNE		278
Caspase 8		MANLE		278
+10
Q14790-8	Caspase 8		MACMU		279	UniRef50_Q14790-8
Uncharacterized protein		MACFA		278
Caspase 8		MACNE		278
Caspase 8		MANLE		278
Caspase 8		PAPAN		278
+10

Cross-referencesⁱ

Web resourcesⁱ

CASP8base

CASP8 mutation db

NIEHS-SNPs

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	X98172 mRNA Translation: CAA66853.1 X98173 mRNA Translation: CAA66854.1 X98174 mRNA Translation: CAA66855.1 X98175 mRNA Translation: CAA66856.1 X98176 mRNA Translation: CAA66857.1 X98177 mRNA Translation: CAA66858.1 Sequence problems. X98178 mRNA Translation: CAA66859.1 Sequence problems. U58143 mRNA Translation: AAC50602.1 U60520 mRNA Translation: AAC50645.1 AF009620 mRNA Translation: AAB70913.1 AF102146 AF102145 Genomic DNA Translation: AAD24962.1 AB038985 Genomic DNA Translation: BAB32555.1 AF380342 mRNA Translation: AAK57437.1 AF422925 mRNA Translation: AAL87628.1 AF422926 mRNA Translation: AAL87629.1 AF422927 mRNA Translation: AAL87630.1 AF422928 mRNA Translation: AAL87631.1 AF422929 mRNA Translation: AAL87632.1 DQ355026 Genomic DNA Translation: ABC67468.1 AC007256 Genomic DNA Translation: AAY24225.1 BC028223 mRNA No translation available.
CCDSⁱ	CCDS2342.1 [Q14790-1] CCDS2343.1 [Q14790-2] CCDS2345.1 [Q14790-5] CCDS42798.1 [Q14790-9] CCDS42799.1 [Q14790-4]
RefSeqⁱ	NP_001073593.1, NM_001080124.1 [Q14790-2] NP_001073594.1, NM_001080125.1 [Q14790-9] NP_001219.2, NM_001228.4 [Q14790-4] NP_203519.1, NM_033355.3 [Q14790-1] NP_203520.1, NM_033356.3 [Q14790-2] NP_203522.1, NM_033358.3 [Q14790-5] XP_005246943.1, XM_005246886.1 [Q14790-1] XP_005246944.1, XM_005246887.1 [Q14790-1] XP_005246945.1, XM_005246888.1 [Q14790-1] XP_005246946.1, XM_005246889.1 [Q14790-1] XP_005246947.1, XM_005246890.3 [Q14790-1] XP_005246948.1, XM_005246891.4 [Q14790-1] XP_005246949.1, XM_005246892.1 [Q14790-2] XP_006712852.1, XM_006712789.1 [Q14790-1] XP_006712853.1, XM_006712790.3 [Q14790-1] XP_006712856.1, XM_006712793.2 [Q14790-5]
UniGeneⁱ	Hs.599762

3D structure databases

Select the link destinations: PDBeⁱ RCSB PDBⁱ PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	1F9E	X-ray	2.90	A/C/E/G/I/K	222-374	[»]
				B/D/F/H/J/L	390-478	[»]
	1I4E	X-ray	3.00	B	222-479	[»]
	1QDU	X-ray	2.80	A/C/E/G/I/K	222-374	[»]
				B/D/F/H/J/L	390-477	[»]
	1QTN	X-ray	1.20	A	211-374	[»]
				B	385-479	[»]
	2C2Z	X-ray	1.95	A	218-374	[»]
				B	376-479	[»]
	2FUN	X-ray	3.00	B/D	222-479	[»]
	2K7Z	NMR	-	A	217-479	[»]
	2Y1L	X-ray	1.80	A/C	218-374	[»]
				B/D	376-479	[»]
	3H11	X-ray	1.90	B	217-479	[»]
	3KJN	X-ray	1.80	A	211-374	[»]
				B	385-479	[»]
	3KJQ	X-ray	1.80	A	211-374	[»]
				B	385-479	[»]
	4JJ7	X-ray	1.18	A	217-479	[»]
	4PRZ	X-ray	2.12	A	217-479	[»]
	4PS1	X-ray	1.73	A/B/C/D	217-479	[»]
	4ZBW	X-ray	2.20	A/B	2-188	[»]
	5H31	X-ray	3.17	A/B/C/D	1-188	[»]
	5H33	X-ray	3.60	A/B	1-188	[»]
	5JQE	X-ray	3.16	A	1-186	[»]
	5L08	electron microscopy	4.60	A/B/C/D/E/F/G/H/I	1-184	[»]
ProteinModelPortalⁱ	Q14790
SMRⁱ	Q14790
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	107291, 151 interactors
ComplexPortalⁱ	CPX-1907 Ripoptosome CPX-975 Caspase-8 complex
CORUMⁱ	Q14790
DIPⁱ	DIP-30915N
ELMⁱ	Q14790
IntActⁱ	Q14790, 122 interactors
MINTⁱ	Q14790
STRINGⁱ	9606.ENSP00000351273

Chemistry databases

BindingDBⁱ	Q14790
ChEMBLⁱ	CHEMBL3776
GuidetoPHARMACOLOGYⁱ	1624

Protein family/group databases

MEROPSⁱ	C14.009

MEROPSⁱ

C14.009

PTM databases

iPTMnetⁱ	Q14790
PhosphoSitePlusⁱ	Q14790
SwissPalmⁱ	Q14790

Polymorphism and mutation databases

BioMutaⁱ	CASP8
DMDMⁱ	2493531

Proteomic databases

EPDⁱ	Q14790
jPOSTⁱ	Q14790
MaxQBⁱ	Q14790
PaxDbⁱ	Q14790
PeptideAtlasⁱ	Q14790
PRIDEⁱ	Q14790
ProteomicsDBⁱ	60172 60173 [Q14790-2] 60174 [Q14790-3] 60175 [Q14790-4] 60176 [Q14790-5] 60177 [Q14790-6] 60178 [Q14790-7] 60179 [Q14790-8] 60180 [Q14790-9]

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	841
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000264274; ENSP00000264274; ENSG00000064012 [Q14790-3] ENST00000264275; ENSP00000264275; ENSG00000064012 [Q14790-4] ENST00000323492; ENSP00000325722; ENSG00000064012 [Q14790-2] ENST00000358485; ENSP00000351273; ENSG00000064012 [Q14790-9] ENST00000392258; ENSP00000376087; ENSG00000064012 [Q14790-5] ENST00000392263; ENSP00000376091; ENSG00000064012 [Q14790-2] ENST00000432109; ENSP00000412523; ENSG00000064012 [Q14790-1]
GeneIDⁱ	841
KEGGⁱ	hsa:841
UCSCⁱ	uc002uxo.2 human [Q14790-1]

Organism-specific databases

CTDⁱ	841
DisGeNETⁱ	841
EuPathDBⁱ	HostDB:ENSG00000064012.21
GeneCardsⁱ	CASP8
HGNCⁱ	HGNC:1509 CASP8
HPAⁱ	CAB002047 HPA001302 HPA005688 HPA006191
MalaCardsⁱ	CASP8
MIMⁱ	211980 phenotype 601763 gene 607271 phenotype
neXtProtⁱ	NX_Q14790
OpenTargetsⁱ	ENSG00000064012
Orphanetⁱ	210159 Adult hepatocellular carcinoma 275517 Autoimmune lymphoproliferative syndrome with recurrent viral infections
PharmGKBⁱ	PA26092
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG3573 Eukaryota ENOG410ZQIE LUCA
GeneTreeⁱ	ENSGT00940000160319
HOVERGENⁱ	HBG050803
InParanoidⁱ	Q14790
KOⁱ	K04398
OMAⁱ	RVMLFQI
OrthoDBⁱ	939331at2759
PhylomeDBⁱ	Q14790
TreeFamⁱ	TF102023

Enzyme and pathway databases

BRENDAⁱ	3.4.22.61 2681
Reactomeⁱ	R-HSA-111465 Apoptotic cleavage of cellular proteins R-HSA-140534 Caspase activation via Death Receptors in the presence of ligand R-HSA-168638 NOD1/2 Signaling Pathway R-HSA-2562578 TRIF-mediated programmed cell death R-HSA-264870 Caspase-mediated cleavage of cytoskeletal proteins R-HSA-3371378 Regulation by c-FLIP R-HSA-5213460 RIPK1-mediated regulated necrosis R-HSA-5218900 CASP8 activity is inhibited R-HSA-5357786 TNFR1-induced proapoptotic signaling R-HSA-5357905 Regulation of TNFR1 signaling R-HSA-5660668 CLEC7A/inflammasome pathway R-HSA-5675482 Regulation of necroptotic cell death R-HSA-69416 Dimerization of procaspase-8 R-HSA-75108 Activation, myristolyation of BID and translocation to mitochondria R-HSA-75153 Apoptotic execution phase R-HSA-75157 FasL/ CD95L signaling R-HSA-75158 TRAIL signaling R-HSA-9013957 TLR3-mediated TICAM1-dependent programmed cell death R-HSA-933543 NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10
SignaLinkⁱ	Q14790
SIGNORⁱ	Q14790

Miscellaneous databases

ChiTaRSⁱ	CASP8 human
EvolutionaryTraceⁱ	Q14790
GeneWikiⁱ	Caspase_8
GenomeRNAiⁱ	841
PMAP-CutDBⁱ	Q14790
Protein Ontology More...PROⁱ	PR:Q14790
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000064012 Expressed in 196 organ(s), highest expression level in small intestine Peyer's patch
ExpressionAtlasⁱ	Q14790 baseline and differential
Genevisibleⁱ	Q14790 HS

Family and domain databases

CDDⁱ	cd00032 CASc, 1 hit
InterProⁱ	View protein in InterPro IPR033170 Caspase-8 IPR029030 Caspase-like_dom_sf IPR033139 Caspase_cys_AS IPR016129 Caspase_his_AS IPR011029 DEATH-like_dom_sf IPR001875 DED_dom IPR002398 Pept_C14 IPR002138 Pept_C14_p10 IPR001309 Pept_C14_p20 IPR015917 Pept_C14A
PANTHERⁱ	PTHR10454 PTHR10454, 1 hit PTHR10454:SF162 PTHR10454:SF162, 1 hit
Pfamⁱ	View protein in Pfam PF01335 DED, 2 hits
PRINTSⁱ	PR00376 IL1BCENZYME
SMARTⁱ	View protein in SMART SM00115 CASc, 1 hit SM00031 DED, 2 hits
SUPFAMⁱ	SSF47986 SSF47986, 2 hits SSF52129 SSF52129, 1 hit
PROSITEⁱ	View protein in PROSITE PS01122 CASPASE_CYS, 1 hit PS01121 CASPASE_HIS, 1 hit PS50207 CASPASE_P10, 1 hit PS50208 CASPASE_P20, 1 hit PS50168 DED, 2 hits
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	CASP8_HUMAN
Accessionⁱ	Q14790Primary (citable) accession number: Q14790 Secondary accession number(s): O14676 Q9UQ81
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
	Last sequence update:	November 1, 1996
	Last modified:	January 16, 2019
	This is version 228 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

Peptidase families
Classification of peptidase families and list of entries
SIMILARITY comments
Index of protein domains and families
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PDB cross-references
Index of Protein Data Bank (PDB) cross-references
Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - Q14790 (CASP8_HUMAN)

Your basket is currently empty. i <p>When browsing through different UniProt proteins, you can use the ‘basket’ to save them, so that you can back to find or analyse them later.<p><a href='/help/basket' target='_top'>More...</a></p>

Caspase-8

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

Sites

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Other locations

Cytoskeleton

Cytosol

Mitochondrion

Nucleus

Plasma Membrane

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Keywords - Diseasei

Organism-specific databases

Chemistry databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

Miscellaneous databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

Chemistry databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Phylogenomic databases

Family and domain databases

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

Experimental Info

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

Protein family/group databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Your basket is currently empty. ⁱ

Functionⁱ

Catalytic activityⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Sequence cautionⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Web resourcesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ