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Protein

Caspase-8

Gene

CASP8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

Enzyme regulationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei3171
Active sitei3601

GO - Molecular functioni

  • cysteine-type endopeptidase activity Source: UniProtKB
  • cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • cysteine-type endopeptidase activity involved in apoptotic signaling pathway Source: UniProtKB
  • cysteine-type peptidase activity Source: ProtInc
  • death effector domain binding Source: UniProtKB
  • peptidase activity Source: UniProtKB
  • scaffold protein binding Source: ParkinsonsUK-UCL
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  • activation of cysteine-type endopeptidase activity Source: BHF-UCL
  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: Reactome
  • activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway Source: Reactome
  • apoptotic process Source: UniProtKB
  • apoptotic signaling pathway Source: BHF-UCL
  • B cell activation Source: UniProtKB
  • cell surface receptor signaling pathway Source: Reactome
  • cellular component disassembly involved in execution phase of apoptosis Source: Reactome
  • cellular response to mechanical stimulus Source: UniProtKB
  • cellular response to organic cyclic compound Source: Ensembl
  • death-inducing signaling complex assembly Source: Reactome
  • execution phase of apoptosis Source: UniProtKB
  • extrinsic apoptotic signaling pathway Source: UniProtKB
  • macrophage differentiation Source: UniProtKB
  • natural killer cell activation Source: UniProtKB
  • negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: Reactome
  • negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of macrophage differentiation Source: UniProtKB
  • positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway Source: Reactome
  • positive regulation of proteolysis Source: BHF-UCL
  • protein heterooligomerization Source: Ensembl
  • proteolysis Source: UniProtKB
  • proteolysis involved in cellular protein catabolic process Source: BHF-UCL
  • regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: Reactome
  • regulation of necrotic cell death Source: Reactome
  • regulation of tumor necrosis factor-mediated signaling pathway Source: Reactome
  • response to antibiotic Source: Ensembl
  • 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
  • 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
  • T cell activation Source: UniProtKB
  • TRAIL-activated apoptotic signaling pathway Source: ParkinsonsUK-UCL
  • TRIF-dependent toll-like receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Apoptosis, Host-virus interaction

Enzyme and pathway databases

BioCyciZFISH:HS00790-MONOMER.
BRENDAi3.4.22.61. 2681.
ReactomeiR-HSA-111465. Apoptotic cleavage of cellular proteins.
R-HSA-140534. Ligand-dependent caspase activation.
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-933543. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
SignaLinkiQ14790.
SIGNORiQ14790.

Protein family/group databases

MEROPSiC14.009.

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:
Gene namesi
Name:CASP8
Synonyms:MCH5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:1509. CASP8.

Subcellular locationi

GO - Cellular componenti

  • CD95 death-inducing signaling complex Source: UniProtKB
  • cell body Source: Ensembl
  • cytoplasm Source: HPA
  • cytoskeleton Source: ProtInc
  • cytosol Source: UniProtKB
  • death-inducing signaling complex Source: UniProtKB
  • membrane raft Source: Ensembl
  • microtubule organizing center Source: HPA
  • mitochondrial outer membrane Source: Reactome
  • mitochondrion Source: HPA
  • neuron projection Source: Ensembl
  • nucleoplasm Source: HPA
  • ripoptosome Source: UniProtKB
Complete GO annotation...

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.
See also OMIM:607271
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_014204248R → W in CASP8D. 1 PublicationCorresponds to variant rs17860424dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi73D → A: Abolishes binding to FLASH. Induces NF-kappa-B activation. 1 Publication1
Mutagenesisi387S → A: Impaired CDK1-mediated phosphorylation and enhanced apoptosis. 1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi841.
MalaCardsiCASP8.
MIMi211980. phenotype.
607271. phenotype.
OpenTargetsiENSG00000064012.
Orphaneti275517. Autoimmune lymphoproliferative syndrome with recurrent viral infections.
PharmGKBiPA26092.

Chemistry databases

ChEMBLiCHEMBL3776.
GuidetoPHARMACOLOGYi1624.

Polymorphism and mutation databases

BioMutaiCASP8.
DMDMi2493531.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_00000046281 – 216Add BLAST216
ChainiPRO_0000004629217 – 374Caspase-8 subunit p18Add BLAST158
PropeptideiPRO_0000004630375 – 38410
ChainiPRO_0000004631385 – 479Caspase-8 subunit p10Add BLAST95

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei188PhosphoserineBy similarity1
Modified residuei211PhosphoserineBy similarity1
Modified residuei224N6-acetyllysineBy similarity1
Modified residuei334PhosphotyrosineCombined sources1
Modified residuei387Phosphoserine; by CDK11 Publication1

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

EPDiQ14790.
MaxQBiQ14790.
PaxDbiQ14790.
PeptideAtlasiQ14790.
PRIDEiQ14790.

PTM databases

iPTMnetiQ14790.
PhosphoSitePlusiQ14790.
SwissPalmiQ14790.

Miscellaneous databases

PMAP-CutDBQ14790.

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

BgeeiENSG00000064012.
ExpressionAtlasiQ14790. baseline and differential.
GenevisibleiQ14790. HS.

Organism-specific databases

HPAiCAB002047.
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. Interacts with FADD, CFLAR and PEA15. Isoform 9 interacts at the endoplasmic reticulum with a complex containing BCAP31, BAP29, BCL2 and/or BCL2L1. Interacts with TNFAIP8L2 (By similarity). Interacts with CASP8AP2. Interacts with RFFL and RNF34; negatively regulate CASP8 through proteasomal degradation. Interacts with human cytomegalovirus/HHV-5 protein vICA/UL36; this interaction inhibits CASP8 activation. Interacts with NleF from pathogenic E.coli. Interacts with NOL3; decreases CASP8 activity in a mitochondria localization- and phosphorylation-dependent manner and this interaction is dissociated by calcium.By similarity9 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-78060,EBI-78060
ARP102753EBI-78060,EBI-608057
BCAP31P515723EBI-78060,EBI-77683
CASP10Q928513EBI-78060,EBI-495095
CASP8AP2Q9UKL33EBI-78060,EBI-2339650
CFLARO155199EBI-78060,EBI-514941
CFLARO15519-12EBI-78060,EBI-4567563
CUL3Q136186EBI-78060,EBI-456129
FADDQ1315839EBI-78060,EBI-494804
FASP2544514EBI-78060,EBI-494743
FASLGP480234EBI-78060,EBI-495538
ILKQ134182EBI-78060,EBI-747644
MALT1Q9UDY810EBI-78060,EBI-1047372
NOL3O609363EBI-78060,EBI-740992
PTPN6P293503EBI-78060,EBI-78260
RIPK1Q1354624EBI-78060,EBI-358507
RNF34Q969K33EBI-78060,EBI-2340642
TNFRSF10AO002209EBI-78060,EBI-518861

GO - Molecular functioni

  • death effector domain binding Source: UniProtKB
  • scaffold protein binding Source: ParkinsonsUK-UCL
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107291. 140 interactors.
DIPiDIP-30915N.
IntActiQ14790. 106 interactors.
MINTiMINT-91645.
STRINGi9606.ENSP00000351273.

Chemistry databases

BindingDBiQ14790.

Structurei

Secondary structure

1479
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 13Combined sources11
Helixi16 – 25Combined sources10
Turni26 – 29Combined sources4
Helixi32 – 34Combined sources3
Helixi41 – 50Combined sources10
Beta strandi53 – 55Combined sources3
Helixi60 – 68Combined sources9
Helixi72 – 79Combined sources8
Helixi83 – 91Combined sources9
Turni93 – 95Combined sources3
Helixi100 – 111Combined sources12
Helixi114 – 127Combined sources14
Helixi139 – 148Combined sources10
Helixi158 – 165Combined sources8
Helixi169 – 180Combined sources12
Beta strandi230 – 232Combined sources3
Beta strandi235 – 240Combined sources6
Helixi245 – 250Combined sources6
Helixi252 – 254Combined sources3
Beta strandi255 – 257Combined sources3
Helixi263 – 276Combined sources14
Beta strandi280 – 286Combined sources7
Helixi289 – 301Combined sources13
Helixi304 – 306Combined sources3
Beta strandi310 – 316Combined sources7
Beta strandi322 – 324Combined sources3
Beta strandi326 – 328Combined sources3
Beta strandi330 – 332Combined sources3
Helixi333 – 337Combined sources5
Helixi338 – 340Combined sources3
Turni342 – 344Combined sources3
Helixi346 – 348Combined sources3
Beta strandi353 – 359Combined sources7
Beta strandi361 – 364Combined sources4
Beta strandi369 – 371Combined sources3
Beta strandi377 – 379Combined sources3
Beta strandi392 – 394Combined sources3
Turni395 – 398Combined sources4
Beta strandi399 – 405Combined sources7
Beta strandi412 – 414Combined sources3
Turni415 – 417Combined sources3
Helixi420 – 432Combined sources13
Helixi433 – 435Combined sources3
Helixi439 – 450Combined sources12
Turni456 – 459Combined sources4
Beta strandi465 – 468Combined sources4
Beta strandi471 – 473Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1F9EX-ray2.90A/C/E/G/I/K222-374[»]
B/D/F/H/J/L390-478[»]
1I4EX-ray3.00B222-479[»]
1QDUX-ray2.80A/C/E/G/I/K222-374[»]
B/D/F/H/J/L390-477[»]
1QTNX-ray1.20A211-374[»]
B385-479[»]
2C2ZX-ray1.95A218-374[»]
B376-479[»]
2FUNX-ray3.00B/D222-479[»]
2K7ZNMR-A217-479[»]
2Y1LX-ray1.80A/C218-374[»]
B/D376-479[»]
3H11X-ray1.90B217-479[»]
3KJNX-ray1.80A211-374[»]
B385-479[»]
3KJQX-ray1.80A211-374[»]
B385-479[»]
4JJ7X-ray1.18A217-479[»]
4PRZX-ray2.12A217-479[»]
4PS1X-ray1.73A/B/C/D217-479[»]
4ZBWX-ray2.20A/B2-188[»]
ProteinModelPortaliQ14790.
SMRiQ14790.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ14790.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 80DED 1PROSITE-ProRule annotationAdd BLAST79
Domaini100 – 177DED 2PROSITE-ProRule annotationAdd BLAST78

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
Contains 2 DED (death effector) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3573. Eukaryota.
ENOG410ZQIE. LUCA.
GeneTreeiENSGT00760000118912.
HOVERGENiHBG050803.
InParanoidiQ14790.
KOiK04398.
OMAiQRKQEPI.
OrthoDBiEOG091G05YD.
PhylomeDBiQ14790.
TreeFamiTF102023.

Family and domain databases

CDDicd00032. CASc. 1 hit.
Gene3Di1.10.533.10. 2 hits.
3.40.50.1460. 1 hit.
InterProiIPR033170. Caspase-8.
IPR029030. Caspase-like_dom.
IPR033139. Caspase_cys_AS.
IPR016129. Caspase_his_AS.
IPR011029. DEATH-like_dom.
IPR001875. DED_dom.
IPR002138. Pept_C14_p10.
IPR001309. Pept_C14_p20.
IPR015917. Pept_C14A.
[Graphical view]
PANTHERiPTHR10454:SF162. PTHR10454:SF162. 1 hit.
PfamiPF01335. DED. 2 hits.
[Graphical view]
PRINTSiPR00376. IL1BCENZYME.
SMARTiSM00115. CASc. 1 hit.
SM00031. DED. 2 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 2 hits.
SSF52129. SSF52129. 1 hit.
PROSITEiPS01122. CASPASE_CYS. 1 hit.
PS01121. CASPASE_HIS. 1 hit.
PS50207. CASPASE_P10. 1 hit.
PS50208. CASPASE_P20. 1 hit.
PS50168. DED. 2 hits.
[Graphical view]

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. AlignAdd to basket

Isoform 1 (identifier: Q14790-1) [UniParc]FASTAAdd 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]FASTAAdd to basket
Also known as: Alpha-2, MCH5-beta

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

Show »
Length:464
Mass (Da):53,768
Checksum:i7F52F14ADE6A02B6
GO
Isoform 3 (identifier: Q14790-3) [UniParc]FASTAAdd to basket
Also known as: Alpha-3

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

Show »
Length:395
Mass (Da):45,929
Checksum:i2787AE831A2B36EF
GO
Isoform 4 (identifier: Q14790-4) [UniParc]FASTAAdd 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.

Show »
Length:496
Mass (Da):57,701
Checksum:i68136650A49159D9
GO
Isoform 5 (identifier: Q14790-5) [UniParc]FASTAAdd 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.

Show »
Length:235
Mass (Da):27,484
Checksum:i7C9013CEA85A77DE
GO
Isoform 6 (identifier: Q14790-6) [UniParc]FASTAAdd 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.

Show »
Length:220
Mass (Da):25,862
Checksum:iF3DA0380D12006C7
GO
Isoform 7 (identifier: Q14790-7) [UniParc]FASTAAdd 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.

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]FASTAAdd 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.

Show »
Length:261
Mass (Da):30,707
Checksum:i19ACAE80171E0572
GO
Isoform 9 (identifier: Q14790-9) [UniParc]FASTAAdd to basket
Also known as: 8L

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

Show »
Length:538
Mass (Da):61,836
Checksum:i54402ECFA9FE5E14
GO

Sequence cautioni

The sequence CAA66858 differs from that shown.Curated
The sequence CAA66859 differs from that shown.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti294E → D in AAD24962 (PubMed:9931493).Curated1
Sequence conflicti331A → P in AAC50602 (PubMed:8681377).Curated1
Sequence conflicti331A → P in AAD24962 (PubMed:9931493).Curated1
Sequence conflicti343 – 344LK → FG in AAL87631 (PubMed:11917123).Curated2
Isoform 9 (identifier: Q14790-9)
Sequence conflicti14K → R in AAL87628 (PubMed:11917123).Curated1

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 keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_025816219S → T.1 PublicationCorresponds to variant rs35976359dbSNPEnsembl.1
Natural variantiVAR_014204248R → W in CASP8D. 1 PublicationCorresponds to variant rs17860424dbSNPEnsembl.1
Natural variantiVAR_020127285D → H Associated with protection against breast cancer; also associated with a lower risk of cutaneous melanoma. 7 PublicationsCorresponds to variant rs1045485dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0008081M → MEGGRRARVVIESKRNFFLG AFPTPFPAEHVELGRLGDSE TAMVPGKGGADYILLPFKKM in isoform 9. 1 Publication1
Alternative sequenceiVSP_000809102R → RFHFCRMSWAEANSQCQTQS VPFWRRVDHLLIR in isoform 4. 1 Publication1
Alternative sequenceiVSP_000813184 – 267Missing in isoform 3. 1 PublicationAdd BLAST84
Alternative sequenceiVSP_000811184 – 220ERSSS…DSESQ → DFGQSLPNEKQTSGILSDHQ QSQFCKSTGESAQTSQH in isoform 6. 1 PublicationAdd BLAST37
Alternative sequenceiVSP_000810184 – 198Missing in isoform 2, isoform 4 and isoform 8. 4 PublicationsAdd BLAST15
Alternative sequenceiVSP_000814199 – 235GEELC…KPRGY → DFGQSLPNEKQTSGILSDHQ QSQFCKSTGESAQTSQH in isoform 5. 1 PublicationAdd BLAST37
Alternative sequenceiVSP_000812221 – 479Missing in isoform 6. 1 PublicationAdd BLAST259
Alternative sequenceiVSP_000815236 – 479Missing in isoform 5. 1 PublicationAdd BLAST244
Alternative sequenceiVSP_000816269 – 276ALTTTFEE → TVEPKREK in isoform 7 and isoform 8. 3 Publications8
Alternative sequenceiVSP_000817277 – 479Missing in isoform 7 and isoform 8. 3 PublicationsAdd BLAST203

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
, AF102139, AF102140, AF102141, AF102142, AF102143, AF102144, 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.
CCDSiCCDS2342.1. [Q14790-1]
CCDS2343.1. [Q14790-2]
CCDS2345.1. [Q14790-5]
CCDS42798.1. [Q14790-9]
CCDS42799.1. [Q14790-4]
RefSeqiNP_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]
UniGeneiHs.599762.

Genome annotation databases

EnsembliENST00000264274; 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]
GeneIDi841.
KEGGihsa:841.
UCSCiuc002uxo.2. human. [Q14790-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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
, AF102139, AF102140, AF102141, AF102142, AF102143, AF102144, 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.
CCDSiCCDS2342.1. [Q14790-1]
CCDS2343.1. [Q14790-2]
CCDS2345.1. [Q14790-5]
CCDS42798.1. [Q14790-9]
CCDS42799.1. [Q14790-4]
RefSeqiNP_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]
UniGeneiHs.599762.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1F9EX-ray2.90A/C/E/G/I/K222-374[»]
B/D/F/H/J/L390-478[»]
1I4EX-ray3.00B222-479[»]
1QDUX-ray2.80A/C/E/G/I/K222-374[»]
B/D/F/H/J/L390-477[»]
1QTNX-ray1.20A211-374[»]
B385-479[»]
2C2ZX-ray1.95A218-374[»]
B376-479[»]
2FUNX-ray3.00B/D222-479[»]
2K7ZNMR-A217-479[»]
2Y1LX-ray1.80A/C218-374[»]
B/D376-479[»]
3H11X-ray1.90B217-479[»]
3KJNX-ray1.80A211-374[»]
B385-479[»]
3KJQX-ray1.80A211-374[»]
B385-479[»]
4JJ7X-ray1.18A217-479[»]
4PRZX-ray2.12A217-479[»]
4PS1X-ray1.73A/B/C/D217-479[»]
4ZBWX-ray2.20A/B2-188[»]
ProteinModelPortaliQ14790.
SMRiQ14790.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107291. 140 interactors.
DIPiDIP-30915N.
IntActiQ14790. 106 interactors.
MINTiMINT-91645.
STRINGi9606.ENSP00000351273.

Chemistry databases

BindingDBiQ14790.
ChEMBLiCHEMBL3776.
GuidetoPHARMACOLOGYi1624.

Protein family/group databases

MEROPSiC14.009.

PTM databases

iPTMnetiQ14790.
PhosphoSitePlusiQ14790.
SwissPalmiQ14790.

Polymorphism and mutation databases

BioMutaiCASP8.
DMDMi2493531.

Proteomic databases

EPDiQ14790.
MaxQBiQ14790.
PaxDbiQ14790.
PeptideAtlasiQ14790.
PRIDEiQ14790.

Protocols and materials databases

DNASUi841.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264274; 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]
GeneIDi841.
KEGGihsa:841.
UCSCiuc002uxo.2. human. [Q14790-1]

Organism-specific databases

CTDi841.
DisGeNETi841.
GeneCardsiCASP8.
HGNCiHGNC:1509. CASP8.
HPAiCAB002047.
HPA001302.
HPA005688.
HPA006191.
MalaCardsiCASP8.
MIMi211980. phenotype.
601763. gene.
607271. phenotype.
neXtProtiNX_Q14790.
OpenTargetsiENSG00000064012.
Orphaneti275517. Autoimmune lymphoproliferative syndrome with recurrent viral infections.
PharmGKBiPA26092.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3573. Eukaryota.
ENOG410ZQIE. LUCA.
GeneTreeiENSGT00760000118912.
HOVERGENiHBG050803.
InParanoidiQ14790.
KOiK04398.
OMAiQRKQEPI.
OrthoDBiEOG091G05YD.
PhylomeDBiQ14790.
TreeFamiTF102023.

Enzyme and pathway databases

BioCyciZFISH:HS00790-MONOMER.
BRENDAi3.4.22.61. 2681.
ReactomeiR-HSA-111465. Apoptotic cleavage of cellular proteins.
R-HSA-140534. Ligand-dependent caspase activation.
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-933543. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
SignaLinkiQ14790.
SIGNORiQ14790.

Miscellaneous databases

ChiTaRSiCASP8. human.
EvolutionaryTraceiQ14790.
GeneWikiiCaspase_8.
GenomeRNAii841.
PMAP-CutDBQ14790.
PROiQ14790.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000064012.
ExpressionAtlasiQ14790. baseline and differential.
GenevisibleiQ14790. HS.

Family and domain databases

CDDicd00032. CASc. 1 hit.
Gene3Di1.10.533.10. 2 hits.
3.40.50.1460. 1 hit.
InterProiIPR033170. Caspase-8.
IPR029030. Caspase-like_dom.
IPR033139. Caspase_cys_AS.
IPR016129. Caspase_his_AS.
IPR011029. DEATH-like_dom.
IPR001875. DED_dom.
IPR002138. Pept_C14_p10.
IPR001309. Pept_C14_p20.
IPR015917. Pept_C14A.
[Graphical view]
PANTHERiPTHR10454:SF162. PTHR10454:SF162. 1 hit.
PfamiPF01335. DED. 2 hits.
[Graphical view]
PRINTSiPR00376. IL1BCENZYME.
SMARTiSM00115. CASc. 1 hit.
SM00031. DED. 2 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 2 hits.
SSF52129. SSF52129. 1 hit.
PROSITEiPS01122. CASPASE_CYS. 1 hit.
PS01121. CASPASE_HIS. 1 hit.
PS50207. CASPASE_P10. 1 hit.
PS50208. CASPASE_P20. 1 hit.
PS50168. DED. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCASP8_HUMAN
AccessioniPrimary (citable) accession number: Q14790
Secondary accession number(s): O14676
, Q14791, Q14792, Q14793, Q14794, Q14795, Q14796, Q15780, Q15806, Q53TT5, Q8TDI1, Q8TDI2, Q8TDI3, Q8TDI4, Q8TDI5, Q96T22, Q9C0K4, Q9UQ81
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 207 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.