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Protein

Caspase-8

Gene

CASP8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Activity 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

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processApoptosis, Host-virus interaction

Enzyme and pathway databases

BRENDAi3.4.22.61 2681
ReactomeiR-HSA-111465 Apoptotic cleavage of cellular proteins
R-HSA-140534 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
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

EuPathDBiHostDB:ENSG00000064012.21
HGNCiHGNC:1509 CASP8
MIMi601763 gene
neXtProtiNX_Q14790

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 dbSNP:rs17860424Ensembl.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
ProteomicsDBi60172
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

iPTMnetiQ14790
PhosphoSitePlusiQ14790
SwissPalmiQ14790

Miscellaneous databases

PMAP-CutDBiQ14790

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 Expressed in 196 organ(s), highest expression level in small intestine Peyer's patch
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 NOL3; decreases CASP8 activity in a mitochondria localization- and phosphorylation-dependent manner and this interaction is dissociated by calcium.By similarity7 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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107291, 150 interactors
ComplexPortaliCPX-1907 Ripoptosome
CORUMiQ14790
DIPiDIP-30915N
ELMiQ14790
IntActiQ14790, 122 interactors
MINTiQ14790
STRINGi9606.ENSP00000351273

Chemistry databases

BindingDBiQ14790

Structurei

Secondary structure

1479
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3573 Eukaryota
ENOG410ZQIE LUCA
GeneTreeiENSGT00760000118912
HOVERGENiHBG050803
InParanoidiQ14790
KOiK04398
OMAiIFIEMEK
OrthoDBiEOG091G05YD
PhylomeDBiQ14790
TreeFamiTF102023

Family and domain databases

CDDicd00032 CASc, 1 hit
InterProiView 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
IPR002138 Pept_C14_p10
IPR001309 Pept_C14_p20
IPR015917 Pept_C14A
PANTHERiPTHR10454:SF162 PTHR10454:SF162, 1 hit
PfamiView protein in Pfam
PF01335 DED, 2 hits
PRINTSiPR00376 IL1BCENZYME
SMARTiView protein in SMART
SM00115 CASc, 1 hit
SM00031 DED, 2 hits
SUPFAMiSSF47986 SSF47986, 2 hits
SSF52129 SSF52129, 1 hit
PROSITEiView 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. AlignAdd to basket

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

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

Computationally mapped potential isoform sequencesi

There are 9 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7C0E2H7C0E2_HUMAN
Caspase-8
CASP8
258Annotation score:
E7EQ06E7EQ06_HUMAN
Caspase-8
CASP8
209Annotation score:
E7ETB7E7ETB7_HUMAN
Caspase-8
CASP8
198Annotation score:
E7EVN1E7EVN1_HUMAN
Caspase-8
CASP8
124Annotation score:
E7EQ01E7EQ01_HUMAN
Caspase-8
CASP8
116Annotation score:
A0A0A0MS31A0A0A0MS31_HUMAN
Caspase-8
CASP8
278Annotation score:
C9JB29C9JB29_HUMAN
Caspase-8
CASP8
149Annotation score:
F8WF39F8WF39_HUMAN
Caspase-8
CASP8
58Annotation score:
H7BZM4H7BZM4_HUMAN
Caspase-8
CASP8
83Annotation score:

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 → T1 PublicationCorresponds to variant dbSNP:rs35976359Ensembl.1
Natural variantiVAR_014204248R → W in CASP8D. 1 PublicationCorresponds to variant dbSNP:rs17860424Ensembl.1
Natural variantiVAR_020127285D → 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 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

Similar proteinsi

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[»]
5H31X-ray3.17A/B/C/D1-188[»]
5H33X-ray3.60A/B1-188[»]
5JQEX-ray3.16A1-186[»]
5L08electron microscopy4.60A/B/C/D/E/F/G/H/I1-184[»]
ProteinModelPortaliQ14790
SMRiQ14790
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107291, 150 interactors
ComplexPortaliCPX-1907 Ripoptosome
CORUMiQ14790
DIPiDIP-30915N
ELMiQ14790
IntActiQ14790, 122 interactors
MINTiQ14790
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
ProteomicsDBi60172
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

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
EuPathDBiHostDB:ENSG00000064012.21
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
OMAiIFIEMEK
OrthoDBiEOG091G05YD
PhylomeDBiQ14790
TreeFamiTF102023

Enzyme and pathway databases

BRENDAi3.4.22.61 2681
ReactomeiR-HSA-111465 Apoptotic cleavage of cellular proteins
R-HSA-140534 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
SignaLinkiQ14790
SIGNORiQ14790

Miscellaneous databases

ChiTaRSiCASP8 human
EvolutionaryTraceiQ14790
GeneWikiiCaspase_8
GenomeRNAii841
PMAP-CutDBiQ14790
PROiPR:Q14790
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000064012 Expressed in 196 organ(s), highest expression level in small intestine Peyer's patch
ExpressionAtlasiQ14790 baseline and differential
GenevisibleiQ14790 HS

Family and domain databases

CDDicd00032 CASc, 1 hit
InterProiView 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
IPR002138 Pept_C14_p10
IPR001309 Pept_C14_p20
IPR015917 Pept_C14A
PANTHERiPTHR10454:SF162 PTHR10454:SF162, 1 hit
PfamiView protein in Pfam
PF01335 DED, 2 hits
PRINTSiPR00376 IL1BCENZYME
SMARTiView protein in SMART
SM00115 CASc, 1 hit
SM00031 DED, 2 hits
SUPFAMiSSF47986 SSF47986, 2 hits
SSF52129 SSF52129, 1 hit
PROSITEiView 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
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 historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: October 10, 2018
This is version 225 of the entry and version 1 of the sequence. See 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. Peptidase families
    Classification of peptidase families and list of entries
  4. SIMILARITY comments
    Index of protein domains and families
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
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