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Q14790

- CASP8_HUMAN

UniProt

Q14790 - CASP8_HUMAN

Protein

Caspase-8

Gene

CASP8

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 182 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    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

    Probably negatively regulated by RFFL through proteasomal degradation. Inhibited by the effector protein NleF that is produced by pathogenic E.coli; this inhibits apoptosis.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei317 – 3171
    Active sitei360 – 3601

    GO - Molecular functioni

    1. cysteine-type endopeptidase activity Source: UniProtKB
    2. cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
    3. cysteine-type endopeptidase activity involved in apoptotic signaling pathway Source: UniProtKB
    4. cysteine-type peptidase activity Source: ProtInc
    5. death effector domain binding Source: UniProtKB
    6. peptidase activity Source: UniProtKB
    7. protein binding Source: IntAct
    8. scaffold protein binding Source: ParkinsonsUK-UCL
    9. ubiquitin protein ligase binding Source: UniProtKB

    GO - Biological processi

    1. activation of cysteine-type endopeptidase activity Source: BHF-UCL
    2. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: Reactome
    3. angiogenesis Source: Ensembl
    4. apoptotic process Source: UniProtKB
    5. apoptotic signaling pathway Source: BHF-UCL
    6. B cell activation Source: UniProtKB
    7. cellular component disassembly involved in execution phase of apoptosis Source: Reactome
    8. cellular response to mechanical stimulus Source: UniProtKB
    9. cellular response to organic cyclic compound Source: Ensembl
    10. execution phase of apoptosis Source: UniProtKB
    11. extrinsic apoptotic signaling pathway Source: UniProtKB
    12. extrinsic apoptotic signaling pathway via death domain receptors Source: RefGenome
    13. heart development Source: Ensembl
    14. hepatocyte apoptotic process Source: Ensembl
    15. innate immune response Source: Reactome
    16. intrinsic apoptotic signaling pathway Source: Reactome
    17. macrophage differentiation Source: UniProtKB
    18. MyD88-independent toll-like receptor signaling pathway Source: Reactome
    19. natural killer cell activation Source: UniProtKB
    20. negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
    21. neural tube formation Source: Ensembl
    22. nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway Source: Reactome
    23. nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
    24. positive regulation of extrinsic apoptotic signaling pathway Source: Ensembl
    25. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
    26. positive regulation of macrophage differentiation Source: UniProtKB
    27. positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway Source: Reactome
    28. positive regulation of proteolysis Source: BHF-UCL
    29. protein heterooligomerization Source: Ensembl
    30. proteolysis Source: UniProtKB
    31. proteolysis involved in cellular protein catabolic process Source: BHF-UCL
    32. regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: Reactome
    33. regulation of thymocyte apoptotic process Source: Ensembl
    34. response to antibiotic Source: Ensembl
    35. response to cobalt ion Source: Ensembl
    36. response to cold Source: Ensembl
    37. response to estradiol Source: Ensembl
    38. response to ethanol Source: Ensembl
    39. response to lipopolysaccharide Source: Ensembl
    40. response to tumor necrosis factor Source: BHF-UCL
    41. syncytiotrophoblast cell differentiation involved in labyrinthine layer development Source: UniProtKB
    42. T cell activation Source: UniProtKB
    43. toll-like receptor 3 signaling pathway Source: Reactome
    44. toll-like receptor 4 signaling pathway Source: Reactome
    45. toll-like receptor signaling pathway Source: Reactome
    46. TRAIL-activated apoptotic signaling pathway Source: ParkinsonsUK-UCL
    47. TRIF-dependent toll-like receptor signaling pathway Source: Reactome
    48. viral process Source: UniProtKB-KW

    Keywords - Molecular functioni

    Hydrolase, Protease, Thiol protease

    Keywords - Biological processi

    Apoptosis, Host-virus interaction

    Enzyme and pathway databases

    BRENDAi3.4.22.61. 2681.
    ReactomeiREACT_107. Apoptotic cleavage of cellular proteins.
    REACT_13541. Caspase-mediated cleavage of cytoskeletal proteins.
    REACT_1432. TNF signaling.
    REACT_1503. Caspase-8 activation.
    REACT_150361. TRIF-mediated programmed cell death.
    REACT_164011. Regulation by c-FLIP.
    REACT_25039. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
    REACT_402. TRAIL signaling.
    REACT_701. Activation, myristolyation of BID and translocation to mitochondria.
    REACT_75776. NOD1/2 Signaling Pathway.
    REACT_832. Dimerization of procaspase-8.
    REACT_900. FasL/ CD95L signaling.
    REACT_995. Apoptotic execution phase.
    SignaLinkiQ14790.

    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
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:1509. CASP8.

    Subcellular locationi

    GO - Cellular componenti

    1. CD95 death-inducing signaling complex Source: UniProtKB
    2. cell body Source: Ensembl
    3. cytoplasm Source: HPA
    4. cytoskeleton Source: ProtInc
    5. cytosol Source: UniProtKB
    6. death-inducing signaling complex Source: UniProtKB
    7. membrane raft Source: Ensembl
    8. microtubule organizing center Source: HPA
    9. mitochondrial outer membrane Source: Reactome
    10. mitochondrion Source: HPA
    11. neuron projection Source: Ensembl
    12. Noc1p-Noc2p complex Source: Ensembl
    13. nucleus Source: HPA
    14. ripoptosome Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Involvement in diseasei

    Caspase-8 deficiency (CASP8D) [MIM:607271]: Disorder 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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti248 – 2481R → W in CASP8D. 1 Publication
    Corresponds to variant rs17860424 [ dbSNP | Ensembl ].
    VAR_014204

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi73 – 731D → A: Abolishes binding to FLASH. Induces NF-kappa-B activation. 1 Publication
    Mutagenesisi387 – 3871S → A: Impaired CDK1-mediated phosphorylation and enhanced apoptosis.

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi211980. phenotype.
    607271. phenotype.
    Orphaneti275517. Autoimmune lymphoproliferative syndrome with recurrent infections.
    PharmGKBiPA26092.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Propeptidei1 – 216216PRO_0000004628Add
    BLAST
    Chaini217 – 374158Caspase-8 subunit p18PRO_0000004629Add
    BLAST
    Propeptidei375 – 38410PRO_0000004630
    Chaini385 – 47995Caspase-8 subunit p10PRO_0000004631Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei188 – 1881PhosphoserineBy similarity
    Modified residuei211 – 2111PhosphoserineBy similarity
    Modified residuei224 – 2241N6-acetyllysineBy similarity
    Modified residuei334 – 3341Phosphotyrosine1 Publication
    Modified residuei387 – 3871Phosphoserine; by CDK11 Publication

    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.2 Publications

    Keywords - PTMi

    Acetylation, Phosphoprotein, Zymogen

    Proteomic databases

    MaxQBiQ14790.
    PaxDbiQ14790.
    PRIDEiQ14790.

    PTM databases

    PhosphoSiteiQ14790.

    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

    ArrayExpressiQ14790.
    BgeeiQ14790.
    GenevestigatoriQ14790.

    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. Interacts with human cytomegalovirus/HHV-5 protein vICA/UL36; this interaction inhibits CASP8 activation. Interacts with NleF from pathogenic E.coli.By similarity8 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    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
    FADDQ1315832EBI-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
    RIPK1Q1354623EBI-78060,EBI-358507
    RNF34Q969K33EBI-78060,EBI-2340642
    TNFRSF10AO002209EBI-78060,EBI-518861

    Protein-protein interaction databases

    BioGridi107291. 91 interactions.
    DIPiDIP-30915N.
    IntActiQ14790. 67 interactions.
    MINTiMINT-91645.

    Structurei

    Secondary structure

    1
    479
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi230 – 2323
    Beta strandi235 – 2406
    Helixi245 – 2506
    Helixi252 – 2543
    Beta strandi255 – 2573
    Helixi263 – 27614
    Beta strandi280 – 2867
    Helixi289 – 30113
    Helixi304 – 3063
    Beta strandi310 – 3167
    Beta strandi322 – 3243
    Beta strandi326 – 3283
    Beta strandi330 – 3323
    Helixi333 – 3375
    Helixi338 – 3403
    Turni342 – 3443
    Helixi346 – 3483
    Beta strandi353 – 3597
    Beta strandi361 – 3644
    Beta strandi369 – 3713
    Beta strandi377 – 3793
    Beta strandi392 – 3943
    Turni395 – 3984
    Beta strandi399 – 4057
    Beta strandi412 – 4143
    Turni415 – 4173
    Helixi420 – 43213
    Helixi433 – 4353
    Helixi439 – 45012
    Turni456 – 4594
    Beta strandi465 – 4684
    Beta strandi471 – 4733

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    ProteinModelPortaliQ14790.
    SMRiQ14790. Positions 223-479.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ14790.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini2 – 8079DED 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini100 – 17778DED 2PROSITE-ProRule annotationAdd
    BLAST

    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

    eggNOGiNOG303276.
    HOVERGENiHBG050803.
    InParanoidiQ14790.
    KOiK04398.
    OMAiIFIEMEK.
    OrthoDBiEOG7CRTQM.
    PhylomeDBiQ14790.
    TreeFamiTF102023.

    Family and domain databases

    Gene3Di1.10.533.10. 2 hits.
    3.40.50.1460. 1 hit.
    InterProiIPR029030. Caspase-like_dom.
    IPR011029. DEATH-like_dom.
    IPR001875. DED.
    IPR011600. Pept_C14_caspase.
    IPR001309. Pept_C14_ICE_p20.
    IPR016129. Pept_C14_ICE_p20_AS.
    IPR002138. Pept_C14_p10.
    IPR015917. Pept_C14A_p45_core.
    [Graphical view]
    PfamiPF01335. DED. 2 hits.
    PF00656. Peptidase_C14. 1 hit.
    [Graphical view]
    PRINTSiPR00376. IL1BCENZYME.
    SMARTiSM00115. CASc. 1 hit.
    SM00031. DED. 2 hits.
    [Graphical view]
    SUPFAMiSSF47986. SSF47986. 2 hits.
    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. Align

    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

    MDFSRNLYDI GEQLDSEDLA SLKFLSLDYI PQRKQEPIKD ALMLFQRLQE    50
    KRMLEESNLS FLKELLFRIN RLDLLITYLN TRKEEMEREL QTPGRAQISA 100
    YRVMLYQISE EVSRSELRSF KFLLQEEISK CKLDDDMNLL DIFIEMEKRV 150
    ILGEGKLDIL KRVCAQINKS LLKIINDYEE FSKERSSSLE GSPDEFSNGE 200
    ELCGVMTISD SPREQDSESQ TLDKVYQMKS KPRGYCLIIN NHNFAKAREK 250
    VPKLHSIRDR NGTHLDAGAL TTTFEELHFE IKPHDDCTVE QIYEILKIYQ 300
    LMDHSNMDCF ICCILSHGDK GIIYGTDGQE APIYELTSQF TGLKCPSLAG 350
    KPKVFFIQAC QGDNYQKGIP VETDSEEQPY LEMDLSSPQT RYIPDEADFL 400
    LGMATVNNCV SYRNPAEGTW YIQSLCQSLR ERCPRGDDIL TILTEVNYEV 450
    SNKDDKKNMG KQMPQPTFTL RKKLVFPSD 479
    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 CAA66858.1 differs from that shown. Reason:
    The sequence CAA66859.1 differs from that shown. Reason:

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti294 – 2941E → D in AAD24962. (PubMed:9931493)Curated
    Sequence conflicti331 – 3311A → P in AAC50602. (PubMed:8681377)Curated
    Sequence conflicti331 – 3311A → P in AAD24962. (PubMed:9931493)Curated
    Sequence conflicti343 – 3442LK → FG in AAL87631. (PubMed:11917123)Curated
    Isoform 9 (identifier: Q14790-9)
    Sequence conflicti14 – 141K → R in AAL87628. (PubMed:11917123)Curated

    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.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti219 – 2191S → T.1 Publication
    Corresponds to variant rs35976359 [ dbSNP | Ensembl ].
    VAR_025816
    Natural varianti248 – 2481R → W in CASP8D. 1 Publication
    Corresponds to variant rs17860424 [ dbSNP | Ensembl ].
    VAR_014204
    Natural varianti285 – 2851D → H Associated with protection against breast cancer; also associated with a lower risk of cutaneous melanoma. 7 Publications
    Corresponds to variant rs1045485 [ dbSNP | Ensembl ].
    VAR_020127

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 11M → MEGGRRARVVIESKRNFFLG AFPTPFPAEHVELGRLGDSE TAMVPGKGGADYILLPFKKM in isoform 9. 1 PublicationVSP_000808
    Alternative sequencei102 – 1021R → RFHFCRMSWAEANSQCQTQS VPFWRRVDHLLIR in isoform 4. 1 PublicationVSP_000809
    Alternative sequencei184 – 26784Missing in isoform 3. 1 PublicationVSP_000813Add
    BLAST
    Alternative sequencei184 – 22037ERSSS…DSESQ → DFGQSLPNEKQTSGILSDHQ QSQFCKSTGESAQTSQH in isoform 6. 1 PublicationVSP_000811Add
    BLAST
    Alternative sequencei184 – 19815Missing in isoform 2, isoform 4 and isoform 8. 4 PublicationsVSP_000810Add
    BLAST
    Alternative sequencei199 – 23537GEELC…KPRGY → DFGQSLPNEKQTSGILSDHQ QSQFCKSTGESAQTSQH in isoform 5. 1 PublicationVSP_000814Add
    BLAST
    Alternative sequencei221 – 479259Missing in isoform 6. 1 PublicationVSP_000812Add
    BLAST
    Alternative sequencei236 – 479244Missing in isoform 5. 1 PublicationVSP_000815Add
    BLAST
    Alternative sequencei269 – 2768ALTTTFEE → TVEPKREK in isoform 7 and isoform 8. 3 PublicationsVSP_000816
    Alternative sequencei277 – 479203Missing in isoform 7 and isoform 8. 3 PublicationsVSP_000817Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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_005246890.1. [Q14790-1]
    XP_005246948.1. XM_005246891.2. [Q14790-1]
    XP_005246949.1. XM_005246892.1. [Q14790-2]
    XP_006712852.1. XM_006712789.1. [Q14790-1]
    XP_006712853.1. XM_006712790.1. [Q14790-1]
    XP_006712856.1. XM_006712793.1. [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]
    ENST00000392266; ENSP00000376094; ENSG00000064012. [Q14790-6]
    ENST00000432109; ENSP00000412523; ENSG00000064012. [Q14790-1]
    GeneIDi841.
    KEGGihsa:841.
    UCSCiuc002uxo.1. human. [Q14790-5]
    uc002uxp.1. human. [Q14790-4]
    uc002uxq.1. human. [Q14790-2]
    uc002uxr.1. human. [Q14790-1]
    uc002uxt.1. human. [Q14790-9]
    uc002uxv.1. human. [Q14790-8]
    uc010fte.1. human. [Q14790-6]
    uc010ftf.2. human. [Q14790-3]

    Polymorphism databases

    DMDMi2493531.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    CASP8base

    CASP8 mutation db

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.
    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_005246890.1. [Q14790-1 ]
    XP_005246948.1. XM_005246891.2. [Q14790-1 ]
    XP_005246949.1. XM_005246892.1. [Q14790-2 ]
    XP_006712852.1. XM_006712789.1. [Q14790-1 ]
    XP_006712853.1. XM_006712790.1. [Q14790-1 ]
    XP_006712856.1. XM_006712793.1. [Q14790-5 ]
    UniGenei Hs.599762.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 [» ]
    ProteinModelPortali Q14790.
    SMRi Q14790. Positions 223-479.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107291. 91 interactions.
    DIPi DIP-30915N.
    IntActi Q14790. 67 interactions.
    MINTi MINT-91645.

    Chemistry

    BindingDBi Q14790.
    ChEMBLi CHEMBL3776.
    GuidetoPHARMACOLOGYi 1624.

    Protein family/group databases

    MEROPSi C14.009.

    PTM databases

    PhosphoSitei Q14790.

    Polymorphism databases

    DMDMi 2493531.

    Proteomic databases

    MaxQBi Q14790.
    PaxDbi Q14790.
    PRIDEi Q14790.

    Protocols and materials databases

    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 ]
    ENST00000392266 ; ENSP00000376094 ; ENSG00000064012 . [Q14790-6 ]
    ENST00000432109 ; ENSP00000412523 ; ENSG00000064012 . [Q14790-1 ]
    GeneIDi 841.
    KEGGi hsa:841.
    UCSCi uc002uxo.1. human. [Q14790-5 ]
    uc002uxp.1. human. [Q14790-4 ]
    uc002uxq.1. human. [Q14790-2 ]
    uc002uxr.1. human. [Q14790-1 ]
    uc002uxt.1. human. [Q14790-9 ]
    uc002uxv.1. human. [Q14790-8 ]
    uc010fte.1. human. [Q14790-6 ]
    uc010ftf.2. human. [Q14790-3 ]

    Organism-specific databases

    CTDi 841.
    GeneCardsi GC02P202062.
    HGNCi HGNC:1509. CASP8.
    HPAi CAB002047.
    HPA001302.
    HPA005688.
    HPA006191.
    MIMi 211980. phenotype.
    601763. gene.
    607271. phenotype.
    neXtProti NX_Q14790.
    Orphaneti 275517. Autoimmune lymphoproliferative syndrome with recurrent infections.
    PharmGKBi PA26092.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG303276.
    HOVERGENi HBG050803.
    InParanoidi Q14790.
    KOi K04398.
    OMAi IFIEMEK.
    OrthoDBi EOG7CRTQM.
    PhylomeDBi Q14790.
    TreeFami TF102023.

    Enzyme and pathway databases

    BRENDAi 3.4.22.61. 2681.
    Reactomei REACT_107. Apoptotic cleavage of cellular proteins.
    REACT_13541. Caspase-mediated cleavage of cytoskeletal proteins.
    REACT_1432. TNF signaling.
    REACT_1503. Caspase-8 activation.
    REACT_150361. TRIF-mediated programmed cell death.
    REACT_164011. Regulation by c-FLIP.
    REACT_25039. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
    REACT_402. TRAIL signaling.
    REACT_701. Activation, myristolyation of BID and translocation to mitochondria.
    REACT_75776. NOD1/2 Signaling Pathway.
    REACT_832. Dimerization of procaspase-8.
    REACT_900. FasL/ CD95L signaling.
    REACT_995. Apoptotic execution phase.
    SignaLinki Q14790.

    Miscellaneous databases

    ChiTaRSi CASP8. human.
    EvolutionaryTracei Q14790.
    GeneWikii Caspase_8.
    GenomeRNAii 841.
    NextBioi 3510.
    PMAP-CutDB Q14790.
    PROi Q14790.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q14790.
    Bgeei Q14790.
    Genevestigatori Q14790.

    Family and domain databases

    Gene3Di 1.10.533.10. 2 hits.
    3.40.50.1460. 1 hit.
    InterProi IPR029030. Caspase-like_dom.
    IPR011029. DEATH-like_dom.
    IPR001875. DED.
    IPR011600. Pept_C14_caspase.
    IPR001309. Pept_C14_ICE_p20.
    IPR016129. Pept_C14_ICE_p20_AS.
    IPR002138. Pept_C14_p10.
    IPR015917. Pept_C14A_p45_core.
    [Graphical view ]
    Pfami PF01335. DED. 2 hits.
    PF00656. Peptidase_C14. 1 hit.
    [Graphical view ]
    PRINTSi PR00376. IL1BCENZYME.
    SMARTi SM00115. CASc. 1 hit.
    SM00031. DED. 2 hits.
    [Graphical view ]
    SUPFAMi SSF47986. SSF47986. 2 hits.
    PROSITEi PS01122. 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 ]
    ProtoNeti Search...

    Publicationsi

    1. "Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death."
      Boldin M.P., Goncharov T.M., Goltsev Y.V., Wallach D.
      Cell 85:803-815(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 5; 6; 7 AND 8).
      Tissue: B-cell and Thymus.
    2. "FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex."
      Muzio M., Chinnaiyan A.M., Kischkel F.C., O'Rourke K., Shevchenko A., Ni J., Scaffidi C., Bretz J.D., Zhang M., Gentz R., Mann M., Krammer P.H., Peter M.E., Dixit V.M.
      Cell 85:817-827(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
    3. "In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains."
      Fernandes-Alnemri T., Armstrong R.C., Krebs J.F., Srinivasula S.M., Wang L., Bullrich F., Fritz L.C., Trapani J.A., Tomaselli K.J., Litwack G., Alnemri E.S.
      Proc. Natl. Acad. Sci. U.S.A. 93:7464-7469(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), VARIANT HIS-285.
      Tissue: T-cell.
    4. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT HIS-285.
    5. "Structure and chromosome localization of the human CASP8 gene."
      Grenet J., Teitz T., Wei T., Valentine V., Kidd V.J.
      Gene 226:225-232(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    6. "Cloning and characterization of three novel genes, ALS2CR1, ALS2CR2, and ALS2CR3, in the juvenile amyotrophic lateral sclerosis (ALS2) critical region at chromosome 2q33-q34: candidate genes for ALS2."
      Hadano S., Yanagisawa Y., Skaug J., Fichter K., Nasir J., Martindale D., Koop B.F., Scherer S.W., Nicholson D.W., Rouleau G.A., Ikeda J.-E., Hayden M.R.
      Genomics 71:200-213(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT HIS-285.
    7. "Characterization of caspase-8L: a novel isoform of caspase-8 that behaves as an inhibitor of the caspase cascade."
      Himeji D., Horiuchi T., Tsukamoto H., Hayashi K., Watanabe T., Harada M.
      Blood 99:4070-4078(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7), FUNCTION (ISOFORM 7).
      Tissue: Leukocyte.
    8. "The procaspase-8 isoform, procaspase-8L, recruited to the BAP31 complex at the endoplasmic reticulum."
      Breckenridge D.G., Nguyen M., Kuppig S., Reth M., Shore G.C.
      Proc. Natl. Acad. Sci. U.S.A. 99:4331-4336(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 9), INTERACTION OF ISOFORM 9 WITH BCAP31 AT THE ENDOPLASMIC RETICULUM.
    9. NIEHS SNPs program
      Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-219 AND HIS-285.
    10. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
      Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
      , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
      Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    11. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7).
      Tissue: Leukocyte.
    12. "Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases."
      Srinivasula S.M., Ahmad M., Fernandes-Alnemri T., Litwack G., Alnemri E.S.
      Proc. Natl. Acad. Sci. U.S.A. 93:14486-14491(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: PARTIAL PROTEIN SEQUENCE, PROTEOLYTIC PROCESSING.
    13. "FLICE induced apoptosis in a cell-free system. Cleavage of caspase zymogens."
      Muzio M., Salvesen G.S., Dixit V.M.
      J. Biol. Chem. 272:2952-2956(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    14. "FLICE is activated by association with the CD95 death-inducing signaling complex (DISC)."
      Medema J.P., Scaffidi C., Kischkel F.C., Shevchenko A., Mann M., Krammer P.H., Peter M.E.
      EMBO J. 16:2794-2804(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEOLYTIC PROCESSING.
    15. "Dominant expression of a novel splice variant of caspase-8 in human peripheral blood lymphocytes."
      Horiuchi T., Himeji D., Tsukamoto H., Harashima S., Hashimura C., Hayashi K.
      Biochem. Biophys. Res. Commun. 272:877-881(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION (ISOFORM 7).
    16. "p28 Bap31, a Bcl-2/Bcl-XL- and procaspase-8-associated protein in the endoplasmic reticulum."
      Ng F.W.H., Nguyen M., Kwan T., Branton P.E., Nicholson D.W., Cromlish J.A., Shore G.C.
      J. Cell Biol. 139:327-338(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH BCL2; BCL2L1 AND BCAP31.
    17. "PED/PEA-15: an anti-apoptotic molecule that regulates FAS/TNFR1-induced apoptosis."
      Condorelli G., Vigliotta G., Cafieri A., Trencia A., Andalo P., Oriente F., Miele C., Caruso M., Formisano P., Beguinot F.
      Oncogene 18:4409-4415(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PEA15.
    18. "A cytomegalovirus-encoded inhibitor of apoptosis that suppresses caspase-8 activation."
      Skaletskaya A., Bartle L.M., Chittenden T., McCormick A.L., Mocarski E.S., Goldmacher V.S.
      Proc. Natl. Acad. Sci. U.S.A. 98:7829-7834(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HHV-5 PROTEIN UL36.
    19. Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
    20. "Suppression of caspase-8- and -10-associated RING proteins results in sensitization to death ligands and inhibition of tumor cell growth."
      McDonald E.R. III, El-Deiry W.S.
      Proc. Natl. Acad. Sci. U.S.A. 101:6170-6175(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH RFFL.
    21. "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
      Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
      Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-334, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    22. "Role of FLASH in caspase-8-mediated activation of NF-kappaB: dominant-negative function of FLASH mutant in NF-kappaB signaling pathway."
      Jun J.-I., Chung C.-W., Lee H.-J., Pyo J.-O., Lee K.N., Kim N.-S., Kim Y.S., Yoo H.-S., Lee T.-H., Kim E., Jung Y.-K.
      Oncogene 24:688-696(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF ASP-73.
    23. "FLASH links the CD95 signaling pathway to the cell nucleus and nuclear bodies."
      Milovic-Holm K., Krieghoff E., Jensen K., Will H., Hofmann T.G.
      EMBO J. 26:391-401(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CASP8P2.
    24. "Cdk1/cyclin B1 controls Fas-mediated apoptosis by regulating caspase-8 activity."
      Matthess Y., Raab M., Sanhaji M., Lavrik I.N., Strebhardt K.
      Mol. Cell. Biol. 30:5726-5740(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-387 BY CDK1.
    25. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    26. "The E.coli effector protein NleF is a caspase inhibitor."
      Blasche S., Moertl M., Steuber H., Siszler G., Nisa S., Schwarz F., Lavrik I., Gronewold T.M.A., Maskos K., Donnenberg M.S., Ullmann D., Uetz P., Koegl M.
      PLoS ONE 0:0-0(2013)
      Cited for: INTERACTION WITH E.COLI NLEF, CATALYTIC ACTIVITY, FUNCTION, ENZYME REGULATION.
    27. "The three-dimensional structure of caspase-8: an initiator enzyme in apoptosis."
      Blanchard H., Kodandapani L., Mittl P.R.E., Di Marco S., Krebs J.F., Wu J.C., Tomaselli K.J., Gruetter M.G.
      Structure 7:1125-1133(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
    28. "The atomic-resolution structure of human caspase-8, a key activator of apoptosis."
      Watt W., Koeplinger K.A., Mildner A.M., Heinrikson R.L., Tomasselli A.G., Watenpaugh K.D.
      Structure 7:1135-1143(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 211-479, SUBUNIT.
    29. "Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency."
      Chun H.J., Zheng L., Ahmad M., Wang J., Speirs C.K., Siegel R.M., Dale J.K., Puck J., Davis J., Hall C.G., Skoda-Smith S., Atkinson T.P., Straus S.E., Lenardo M.J.
      Nature 419:395-399(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CASP8D TRP-248.
    30. Cited for: VARIANT HIS-285, PROTECTION AGAINST BREAST CANCER.
    31. "A common coding variant in CASP8 is associated with breast cancer risk."
      The Kathleen Cunningham foundation consortium for research into familial breast cancer, Breast cancer association consortium
      Cox A., Dunning A.M., Garcia-Closas M., Balasubramanian S., Reed M.W.R., Pooley K.A., Scollen S., Baynes C., Ponder B.A.J., Chanock S., Lissowska J., Brinton L., Peplonska B., Southey M.C., Hopper J.L., McCredie M.R.E., Giles G.G., Fletcher O.
      , Johnson N., dos Santos Silva I., Gibson L., Bojesen S.E., Nordestgaard B.G., Axelsson C.K., Torres D., Hamann U., Justenhoven C., Brauch H., Chang-Claude J., Kropp S., Risch A., Wang-Gohrke S., Schuermann P., Bogdanova N., Doerk T., Fagerholm R., Aaltonen K., Blomqvist C., Nevanlinna H., Seal S., Renwick A., Stratton M.R., Rahman N., Sangrajrang S., Hughes D., Odefrey F., Brennan P., Spurdle A.B., Chenevix-Trench G., Beesley J., Mannermaa A., Hartikainen J., Kataja V., Kosma V.M., Couch F.J., Olson J.E., Goode E.L., Broeks A., Schmidt M.K., Hogervorst F.B.L., Van't Veer L.J., Kang D., Yoo K.-Y., Noh D.-Y., Ahn S.-H., Wedren S., Hall P., Low Y.-L., Liu J., Milne R.L., Ribas G., Gonzalez-Neira A., Benitez J., Sigurdson A.J., Stredrick D.L., Alexander B.H., Struewing J.P., Pharoah P.D.P., Easton D.F.
      Nat. Genet. 39:352-358(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HIS-285, PROTECTION AGAINST BREAST CANCER.
    32. "A six-nucleotide insertion-deletion polymorphism in the CASP8 promoter is associated with susceptibility to multiple cancers."
      Sun T., Gao Y., Tan W., Ma S., Shi Y., Yao J., Guo Y., Yang M., Zhang X., Zhang Q., Zeng C., Lin D.
      Nat. Genet. 39:605-613(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN PROTECTION AGAINST LUNG CANCER.
    33. "Genetic variants and haplotypes of the caspase-8 and caspase-10 genes contribute to susceptibility to cutaneous melanoma."
      Li C., Zhao H., Hu Z., Liu Z., Wang L.-E., Gershenwald J.E., Prieto V.G., Lee J.E., Duvic M., Grimm E.A., Wei Q.
      Hum. Mutat. 29:1443-1451(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HIS-285, RISK FACTOR FOR CUTANEOUS MELANOMA.

    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: October 1, 2014
    This is version 182 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

    External Data

    Dasty 3