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UniProtKB/Swiss-Prot entry Q14790

[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name CASP8_HUMAN
Primary accession number Q14790
Secondary accession numbers O14676 Q14791 Q14792 Q14793 Q14794 Q14795 Q14796 Q15780 Q15806 Q53TT5 Q8TDI1 Q8TDI2 Q8TDI3 Q8TDI4 Q8TDI5 Q96T22 Q9C0K4 Q9UQ81
Integrated into Swiss-Prot on November 1, 1997
Sequence was last modified on November 1, 1996 (Sequence version 1)
Annotations were last modified on    September 2, 2008 (Entry version 111)
Name and origin of the protein
Protein name Caspase-8 [Precursor]
Synonyms CASP-8
EC 3.4.22.61
ICE-like apoptotic protease 5
MORT1-associated CED-3 homolog
MACH
FADD-homologous ICE/CED-3-like protease
FADD-like ICE
FLICE
Apoptotic cysteine protease
Apoptotic protease Mch-5
CAP4
Contains Caspase-8 subunit p18
Caspase-8 subunit p10
Gene name
Name: CASP8
Synonyms: MCH5
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
 NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 5; 6; 7 AND 8).
TISSUE=B-cell, and Thymus;
DOI=10.1016/S0092-8674(00)81265-9; PubMed=8681376 [NCBI, ExPASy, EBI, Israel, Japan]
Boldin M.P., Goncharov T.M., Goltsev Y.V., Wallach D.;
"Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death.";
Cell 85:803-815(1996).
[2]
 NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE.
DOI=10.1016/S0092-8674(00)81266-0; PubMed=8681377 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex.";
Cell 85:817-827(1996).
[3]
 NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), AND VARIANT HIS-285.
TISSUE=T-cell;
DOI=10.1073/pnas.93.15.7464; PubMed=8755496 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains.";
Proc. Natl. Acad. Sci. U.S.A. 93:7464-7469(1996).
[4]
 NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT HIS-285.
DOI=10.1074/jbc.272.30.18542; PubMed=9228018 [NCBI, ExPASy, EBI, Israel, Japan]
Srinivasula S.M., Ahmad M., Ottilie S., Bullrich F., Banks S., Wang Y., Fernandes-Alnemri T., Croce C.M., Litwack G., Tomaselli K.J., Armstrong R.C., Alnemri E.S.;
"FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis.";
J. Biol. Chem. 272:18542-18545(1997).
[5]
 NUCLEOTIDE SEQUENCE [GENOMIC DNA].
DOI=10.1016/S0378-1119(98)00565-4; PubMed=9931493 [NCBI, ExPASy, EBI, Israel, Japan]
Grenet J., Teitz T., Wei T., Valentine V., Kidd V.J.;
"Structure and chromosome localization of the human CASP8 gene.";
Gene 226:225-232(1999).
[6]
 NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT HIS-285.
DOI=10.1006/geno.2000.6392; PubMed=11161814 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"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.";
Genomics 71:200-213(2001).
[7]
 NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7), AND FUNCTION OF ISOFORM 7.
TISSUE=Leukocyte;
DOI=10.1182/blood.V99.11.4070; PubMed=12010809 [NCBI, ExPASy, EBI, Israel, Japan]
Himeji D., Horiuchi T., Tsukamoto H., Hayashi K., Watanabe T., Harada M.;
"Characterization of caspase-8L: a novel isoform of caspase-8 that behaves as an inhibitor of the caspase cascade.";
Blood 99:4070-4078(2002).
[8]
 NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 9), AND INTERACTION OF ISOFORM 9 WITH BCAP31 AT THE ENDOPLASMIC RETICULUM.
DOI=10.1073/pnas.072088099; PubMed=11917123 [NCBI, ExPASy, EBI, Israel, Japan]
Breckenridge D.G., Nguyen M., Kuppig S., Reth M., Shore G.C.;
"The procaspase-8 isoform, procaspase-8L, recruited to the BAP31 complex at the endoplasmic reticulum.";
Proc. Natl. Acad. Sci. U.S.A. 99:4331-4336(2002).
[9]
 NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-219 AND HIS-285.
Livingston R.J., Rieder M.J., Shaffer T., Bertucci C., Baier C.N., Rajkumar N., Willa H.T., Daniels M., Downing T.K., Stanaway I.B., Nguyen C.P., Gildersleeve H., Cassidy C.M., Johnson E.J., Swanson J.E., McFarland I., Yool B., Park C., Nickerson D.A.;
"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
[10]
 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature03466; PubMed=15815621 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"Generation and annotation of the DNA sequences of human chromosomes 2 and 4.";
Nature 434:724-731(2005).
[11]
 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7).
TISSUE=Leukocyte;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[12]
 PARTIAL PROTEIN SEQUENCE, AND PROTEOLYTIC PROCESSING.
DOI=10.1073/pnas.93.25.14486; PubMed=8962078 [NCBI, ExPASy, EBI, Israel, Japan]
Srinivasula S.M., Ahmad M., Fernandes-Alnemri T., Litwack G., Alnemri E.S.;
"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.";
Proc. Natl. Acad. Sci. U.S.A. 93:14486-14491(1996).
[13]
 FUNCTION.
DOI=10.1074/jbc.272.5.2952; PubMed=9006941 [NCBI, ExPASy, EBI, Israel, Japan]
Muzio M., Salvesen G.S., Dixit V.M.;
"FLICE induced apoptosis in a cell-free system. Cleavage of caspase zymogens.";
J. Biol. Chem. 272:2952-2956(1997).
[14]
 PROTEOLYTIC PROCESSING.
DOI=10.1093/emboj/16.10.2794; PubMed=9184224 [NCBI, ExPASy, EBI, Israel, Japan]
Medema J.P., Scaffidi C., Kischkel F.C., Shevchenko A., Mann M., Krammer P.H., Peter M.E.;
"FLICE is activated by association with the CD95 death-inducing signaling complex (DISC).";
EMBO J. 16:2794-2804(1997).
[15]
 CHARACTERIZATION OF ISOFORM 7.
DOI=10.1006/bbrc.2000.2841; PubMed=10860845 [NCBI, ExPASy, EBI, Israel, Japan]
Horiuchi T., Himeji D., Tsukamoto H., Harashima S., Hashimura C., Hayashi K.;
"Dominant expression of a novel splice variant of caspase-8 in human peripheral blood lymphocytes.";
Biochem. Biophys. Res. Commun. 272:877-881(2000).
[16]
 INTERACTION WITH BCL2; BCL2L1 AND BCAP31.
DOI=10.1083/jcb.139.2.327; PubMed=9334338 [NCBI, ExPASy, EBI, Israel, Japan]
Ng F.W.H., Nguyen M., Kwan T., Branton P.E., Nicholson D.W., Cromlish J.A., Shore G.C.;
"p28 Bap31, a Bcl-2/Bcl-XL- and procaspase-8-associated protein in the endoplasmic reticulum.";
J. Cell Biol. 139:327-338(1997).
[17]
 INTERACTION WITH PEA15.
DOI=10.1038/sj.onc.1202831; PubMed=10442631 [NCBI, ExPASy, EBI, Israel, Japan]
Condorelli G., Vigliotta G., Cafieri A., Trencia A., Andalo P., Oriente F., Miele C., Caruso M., Formisano P., Beguinot F.;
"PED/PEA-15: an anti-apoptotic molecule that regulates FAS/TNFR1-induced apoptosis.";
Oncogene 18:4409-4415(1999).
[18]
 SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
DOI=10.1186/gb-2004-5-2-r8; PubMed=14759258 [NCBI, ExPASy, EBI, Israel, Japan]
Hillman R.T., Green R.E., Brenner S.E.;
"An unappreciated role for RNA surveillance.";
Genome Biol. 5:RESEARCH008.1-RESEARCH008.16(2004).
[19]
 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-334, AND MASS SPECTROMETRY.
DOI=10.1038/nbt1046; PubMed=15592455 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
Nat. Biotechnol. 23:94-101(2005).
[20]
 MUTAGENESIS OF ASP-73.
DOI=10.1038/sj.onc.1208186; PubMed=15592525 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"Role of FLASH in caspase-8-mediated activation of NF-kappaB: dominant-negative function of FLASH mutant in NF-kappaB signaling pathway.";
Oncogene 24:688-696(2005).
[21]
 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-219, AND MASS SPECTROMETRY.
DOI=10.1126/science.1140321; PubMed=17525332 [NCBI, ExPASy, EBI, Israel, Japan]
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.";
Science 316:1160-1166(2007).
[22]
 X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
DOI=10.1016/S0969-2126(99)80179-8; PubMed=10508784 [NCBI, ExPASy, EBI, Israel, Japan]
Blanchard H., Kodandapani L., Mittl P.R.E., Di Marco S., Krebs J.F., Wu J.C., Tomaselli K.J., Gruetter M.G.;
"The three-dimensional structure of caspase-8: an initiator enzyme in apoptosis.";
Structure 7:1125-1133(1999).
[23]
 X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 211-479, AND SUBUNIT.
DOI=10.1016/S0969-2126(99)80180-4; PubMed=10508785 [NCBI, ExPASy, EBI, Israel, Japan]
Watt W., Koeplinger K.A., Mildner A.M., Heinrikson R.L., Tomasselli A.G., Watenpaugh K.D.;
"The atomic-resolution structure of human caspase-8, a key activator of apoptosis.";
Structure 7:1135-1143(1999).
[24]
 VARIANT CASP8D TRP-248.
DOI=10.1038/nature01063; PubMed=12353035 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency.";
Nature 419:395-399(2002).
[25]
 INVOLVEMENT IN PROTECTION AGAINST LUNG CANCER.
DOI=10.1038/ng2030; PubMed=17450141 [NCBI, ExPASy, EBI, Israel, Japan]
Sun T., Gao Y., Tan W., Ma S., Shi Y., Yao J., Guo Y., Yang M., Zhang X., Zhang Q., Zeng C., Lin D.;
"A six-nucleotide insertion-deletion polymorphism in the CASP8 promoter is associated with susceptibility to multiple cancers.";
Nat. Genet. 39:605-613(2007).
Comments
  • FUNCTION: 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. Isoforms 5, 6, 7 and 8 lack the catalytic site and may interfere with the pro-apoptotic activity of the complex.
  • CATALYTIC ACTIVITY: Strict requirement for Asp at position P1 and has a preferred cleavage sequence of (Leu/Asp/Val)-Glu-Thr-Asp-|-(Gly/Ser/Ala).
  • SUBUNIT: 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.
  • INTERACTION:
    Self; NbExp=2; IntAct=EBI-78060, EBI-78060;
    P51572:BCAP31; NbExp=1; IntAct=EBI-288343, EBI-77683;
    P51572:BCAP31; NbExp=1; IntAct=EBI-78060, EBI-77683;
    Q92851:CASP10; NbExp=2; IntAct=EBI-78060, EBI-495095;
    P30429:ced-4 (xeno); NbExp=1; IntAct=EBI-78060, EBI-494118;
    Q9HAV5:EDA2R; NbExp=1; IntAct=EBI-288343, EBI-526033;
    Q13158:FADD; NbExp=2; IntAct=EBI-78060, EBI-494804;
    Q13158:FADD; NbExp=1; IntAct=EBI-288326, EBI-494804;
    P25445:FAS; NbExp=3; IntAct=EBI-78060, EBI-494743;
    Q13418:ILK; NbExp=1; IntAct=EBI-78060, EBI-747644;
    O60936:NOL3; NbExp=3; IntAct=EBI-78060, EBI-740992;
    P08160:P35 (xeno); NbExp=1; IntAct=EBI-78060, EBI-1030934;
    Q13546:RIPK1; NbExp=1; IntAct=EBI-78060, EBI-358507;
    Q9D8Y7:Tnfaip8l2 (xeno); NbExp=1; IntAct=EBI-78060, EBI-1781612;
  • SUBCELLULAR LOCATION: Cytoplasm.
  • ALTERNATIVE PRODUCTS: 9 named isoforms [FASTA] produced by alternative splicing.
    Name1
    SynonymsAlpha-1
    Isoform IDQ14790-1
    This is the isoform sequence displayed in this entry.
    Name2
    SynonymsAlpha-2, MCH5-beta
    Isoform IDQ14790-2
    Features which should be applied to build the isoform sequence: VSP_000810.
    Name3
    SynonymsAlpha-3
    Isoform IDQ14790-3
    Features which should be applied to build the isoform sequence: VSP_000813.
    Name4
    SynonymsAlpha-4
    Isoform IDQ14790-4
    Features which should be applied to build the isoform sequence: VSP_000809, VSP_000810.
    Name5
    SynonymsBeta-1
    Isoform IDQ14790-5
    Features which should be applied to build the isoform sequence: VSP_000814, VSP_000815.
    Name6
    SynonymsBeta-2
    Isoform IDQ14790-6
    Features which should be applied to build the isoform sequence: VSP_000811, VSP_000812.
    Name7
    SynonymsBeta-3, 8L
    Isoform IDQ14790-7
    Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
    Features which should be applied to build the isoform sequence: VSP_000816, VSP_000817.
    Name8
    SynonymsBeta-4
    Isoform IDQ14790-8
    Features which should be applied to build the isoform sequence: VSP_000810, VSP_000816, VSP_000817.
    Name9
    Synonyms8L
    Isoform IDQ14790-9
    Features which should be applied to build the isoform sequence: VSP_000808.
  • TISSUE SPECIFICITY: Isoforms 1, 5 and 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.
  • DOMAIN: Isoform 9 contains a N-terminal extension that is required for interaction with the BCAP31 complex.
  • PTM: 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.
  • PTM: Phosphorylated upon DNA damage, probably by ATM or ATR.
  • POLYMORPHISM: Genetic vaiations in CASP8 are associated with reduced risk of lung cancer [MIM:211980] in a population of Han Chinese subjects. Genetic vaiations 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.
  • DISEASE: Defects in CASP8 are the cause of caspase-8 deficiency (CASP8D) [MIM:607271]. CASP8D is a 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.
  • SIMILARITY: Belongs to the peptidase C14 family [view classification].
  • SIMILARITY: Contains 2 DED (death effector) domains.
  • SEQUENCE CAUTION:
    • Sequence=CAA66858.1; Type=Miscellaneous discrepancy;
    • Sequence=CAA66859.1; Type=Miscellaneous discrepancy;
  • WEB RESOURCE: Name=CASP8base; Note=CASP8 mutation db; URL="http://bioinf.uta.fi/CASP8base/";.
  • WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=CASP8";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
X98172; CAA66853.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X98173; CAA66854.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X98174; CAA66855.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X98175; CAA66856.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X98176; CAA66857.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X98177; CAA66858.1; ALT_SEQ; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X98178; CAA66859.1; ALT_SEQ; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U58143; AAC50602.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U60520; AAC50645.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF009620; AAB70913.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF102146; AAD24962.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF102139; AAD24962.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF102140; AAD24962.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF102141; AAD24962.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF102142; AAD24962.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF102143; AAD24962.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF102144; AAD24962.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF102145; AAD24962.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB038985; BAB32555.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF380342; AAK57437.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF422925; AAL87628.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF422926; AAL87629.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF422927; AAL87630.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF422928; AAL87631.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF422929; AAL87632.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
DQ355026; ABC67468.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AC007256; AAY24225.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC028223; -; NOT_ANNOTATED_CDS; mRNA.[EMBL / GenBank / DDBJ]
RefSeq NP_001073593.1; -.
NP_001073594.1; -.
NP_001219.2; -.
NP_203519.1; -.
NP_203520.1; -.
NP_203522.1; -.
UniGene Hs.655983
3D structure databases
PDB
1F9E; X-ray; 2.90 A; A/C/E/G/I/K=222-374, B/D/F/H/J/L=390-478.[ExPASy / RCSB / EBI]
1I4E; X-ray; 3.00 A; B=222-479.[ExPASy / RCSB / EBI]
1QDU; X-ray; 2.80 A; A/C/E/G/I/K=222-374, B/D/F/H/J/L=390-477.[ExPASy / RCSB / EBI]
1QTN; X-ray; 1.20 A; A=211-374, B=385-479.[ExPASy / RCSB / EBI]
2C2Z; X-ray; 1.95 A; A=218-374, B=375-479.[ExPASy / RCSB / EBI]
2FUN; X-ray; 3.00 A; B/D=222-479.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1F9E; -.
1I4E; -.
1QDU; -.
1QTN; -.
2C2Z; -.
2FUN; -.
ModBase Q14790.
Protein-protein interaction databases
IntAct Q14790; -.
Protein family/group databases
MEROPS C14.009; -.
PTM databases
PhosphoSite Q14790; -.
Enzyme and pathway databases
Reactome REACT_578; Apoptosis.
Polymorphism databases
NIEHS-SNPs CASP8.
Organism-specific databases
H-InvDB HIX0002736; -.
HGNC HGNC:1509; CASP8.
GenAtlas CASP8.
HPA CAB002047; -.
HPA001302; -.
HPA005688; -.
HPA006191; -.
HPA008936; -.
MIM 211980; phenotype. [NCBI / EBI]
601763; gene. [NCBI / EBI]
607271; phenotype. [NCBI / EBI]
Orphanet 3261; Autoimmune lymphoproliferative syndrome.
PharmGKB PA26092; -.
GeneCards Q14790.
Gene expression databases
ArrayExpress Q14790; -.
GermOnline ENSG00000064012; Homo sapiens.
Ontologies
GO
GO:0005856; Cellular component: cytoskeleton (traceable author statement from ProtInc).
GO:0005829; Cellular component: cytosol (inferred from experiment from Reactome).
GO:0005739; Cellular component: mitochondrion (traceable author statement from ProtInc).
GO:0030693; Molecular function: caspase activity (traceable author statement from ProtInc).
GO:0042802; Molecular function: identical protein binding (inferred from physical interaction from IntAct).
GO:0008633; Biological process: activation of pro-apoptotic gene products (inferred from experiment from Reactome).
GO:0008624; Biological process: induction of apoptosis by extracellular signals (inferred from experiment from Reactome).
GO:0043123; Biological process: positive regulation of I-kappaB kinase/NF-kappaB cascade (inferred from expression pattern from UniProtKB).
GO:0006508; Biological process: proteolysis (inferred from direct assay from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR011029; DEATH_like.
IPR001875; DED.
IPR011600; Pept_C14_cat.
IPR001309; Pept_C14_ICE_p20.
IPR016129; Pept_C14_ICE_p20_AS.
IPR002138; Pept_C14_p10.
IPR002398; Pept_C14_p45.
IPR015917; Pept_C14_p45_core.
Graphical view of domain structure.
Gene3D G3DSA:1.10.533.10; DEATH_like; 2.
PANTHER PTHR10454; Pept_C14_p45; 1.
Pfam PF01335; DED; 2.
PF00656; Peptidase_C14; 1.
Pfam graphical view of domain structure.
PRINTS PR00376; IL1BCENZYME.
SMART SM00115; CASc; 1.
SM00031; DED; 2.
SMART graphical view of domain structure.
PROSITE PS01122; CASPASE_CYS; 1.
PS01121; CASPASE_HIS; 1.
PS50207; CASPASE_P10; 1.
PS50208; CASPASE_P20; 1.
PS50168; DED; 2.
PROSITE graphical view of domain structure (profiles).
BLOCKS Q14790.
Genome annotation databases
Ensembl ENSG00000064012; Homo sapiens. [Contig view]
GeneID 841; -.
KEGG hsa:841; -.
Phylogenomic databases
HOVERGEN Q14790; -.
Other
SOURCE CASP8; Homo sapiens.
ProtoNet Q14790.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Alternative splicing; Apoptosis; Cytoplasm; Direct protein sequencing; Disease mutation; Hydrolase; Phosphoprotein; Polymorphism; Protease; Repeat; Thiol protease; Zymogen.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
PROPEP   1   216  216      PRO_0000004628
CHAIN   217   374  158     Caspase-8 subunit p18. PRO_0000004629
PROPEP   375   384  10      PRO_0000004630
CHAIN   385   479  95     Caspase-8 subunit p10. PRO_0000004631
DOMAIN   2    80  79     DED 1. 
DOMAIN   100   177  78     DED 2. 
ACT_SITE   317   317         
ACT_SITE   360   360         
MOD_RES   188   188        Phosphoserine (By similarity). 
MOD_RES   219   219        Phosphoserine. 
MOD_RES   334   334        Phosphotyrosine. 
VAR_SEQ   1     1        M -> MEGGRRARVVIESRRNFFLGAFPTPFPAEHVELGRLGDSE TAMVPGKGGADYILLPFKKM (in isoform 9). VSP_000808
VAR_SEQ   102   102        R -> RFHFCRMSWAEANSQCQTQSVPFWRRVDHLLIR (in isoform 4). VSP_000809
VAR_SEQ   184   267        Missing (in isoform 3). VSP_000813
VAR_SEQ   184   220        ERSSSLEGSPDEFSNGEELCGVMTISDSPREQDSESQ -> DFGQSLPNEKQTSGILSDHQQSQFCKSTGESAQTSQH (in isoform 6). VSP_000811
VAR_SEQ   184   198        Missing (in isoform 2, isoform 4 and isoform 8). VSP_000810
VAR_SEQ   199   235        GEELCGVMTISDSPREQDSESQTLDKVYQMKSKPRGY -> DFGQSLPNEKQTSGILSDHQQSQFCKSTGESAQTSQH (in isoform 5). VSP_000814
VAR_SEQ   221   479        Missing (in isoform 6). VSP_000812
VAR_SEQ   236   479        Missing (in isoform 5). VSP_000815
VAR_SEQ   269   276        ALTTTFEE -> TVEPKREK (in isoform 7 and isoform 8). VSP_000816
VAR_SEQ   277   479        Missing (in