CASP8_HUMAN
ID CASP8_HUMAN Reviewed; 479 AA.
AC Q14790; O14676; Q14791; Q14792; Q14793; Q14794; Q14795; Q14796; Q15780;
AC Q15806; Q53TT5; Q8TDI1; Q8TDI2; Q8TDI3; Q8TDI4; Q8TDI5; Q96T22; Q9C0K4;
AC Q9UQ81;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 249.
DE RecName: Full=Caspase-8 {ECO:0000303|PubMed:12010809};
DE Short=CASP-8 {ECO:0000303|PubMed:12010809};
DE EC=3.4.22.61 {ECO:0000269|PubMed:23516580, ECO:0000269|PubMed:8962078};
DE AltName: Full=Apoptotic cysteine protease;
DE AltName: Full=Apoptotic protease Mch-5 {ECO:0000303|PubMed:8962078};
DE AltName: Full=CAP4;
DE AltName: Full=FADD-homologous ICE/ced-3-like protease {ECO:0000303|PubMed:8681377};
DE AltName: Full=FADD-like ICE {ECO:0000303|PubMed:8681377};
DE Short=FLICE {ECO:0000303|PubMed:8681377};
DE AltName: Full=ICE-like apoptotic protease 5;
DE AltName: Full=MORT1-associated ced-3 homolog {ECO:0000303|PubMed:8681376};
DE Short=MACH {ECO:0000303|PubMed:8681376};
DE Contains:
DE RecName: Full=Caspase-8 subunit p18 {ECO:0000303|PubMed:8962078};
DE Contains:
DE RecName: Full=Caspase-8 subunit p10 {ECO:0000303|PubMed:8962078};
DE Flags: Precursor;
GN Name=CASP8 {ECO:0000303|PubMed:9931493, ECO:0000312|HGNC:HGNC:1509};
GN Synonyms=MCH5 {ECO:0000303|PubMed:8962078};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 5; 6; 7 AND 8), FUNCTION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=B-cell, and Thymus;
RX PubMed=8681376; DOI=10.1016/s0092-8674(00)81265-9;
RA Boldin M.P., Goncharov T.M., Goltsev Y.V., Wallach D.;
RT "Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-
RT 1- and TNF receptor-induced cell death.";
RL Cell 85:803-815(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, AND
RP FUNCTION.
RX PubMed=8681377; DOI=10.1016/s0092-8674(00)81266-0;
RA Muzio M., Chinnaiyan A.M., Kischkel F.C., O'Rourke K., Shevchenko A.,
RA Ni J., Scaffidi C., Bretz J.D., Zhang M., Gentz R., Mann M., Krammer P.H.,
RA Peter M.E., Dixit V.M.;
RT "FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to
RT the CD95 (Fas/APO-1) death-inducing signaling complex.";
RL Cell 85:817-827(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION, AND VARIANT HIS-285.
RC TISSUE=T-cell;
RX PubMed=8755496; DOI=10.1073/pnas.93.15.7464;
RA Fernandes-Alnemri T., Armstrong R.C., Krebs J.F., Srinivasula S.M.,
RA Wang L., Bullrich F., Fritz L.C., Trapani J.A., Tomaselli K.J., Litwack G.,
RA Alnemri E.S.;
RT "In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic
RT cysteine protease containing two FADD-like domains.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:7464-7469(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT HIS-285.
RX PubMed=9228018; DOI=10.1074/jbc.272.30.18542;
RA Srinivasula S.M., Ahmad M., Ottilie S., Bullrich F., Banks S., Wang Y.,
RA Fernandes-Alnemri T., Croce C.M., Litwack G., Tomaselli K.J.,
RA Armstrong R.C., Alnemri E.S.;
RT "FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates
RT Fas/TNFR1-induced apoptosis.";
RL J. Biol. Chem. 272:18542-18545(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9931493; DOI=10.1016/s0378-1119(98)00565-4;
RA Grenet J., Teitz T., Wei T., Valentine V., Kidd V.J.;
RT "Structure and chromosome localization of the human CASP8 gene.";
RL Gene 226:225-232(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT HIS-285.
RX PubMed=11161814; DOI=10.1006/geno.2000.6392;
RA Hadano S., Yanagisawa Y., Skaug J., Fichter K., Nasir J., Martindale D.,
RA Koop B.F., Scherer S.W., Nicholson D.W., Rouleau G.A., Ikeda J.-E.,
RA Hayden M.R.;
RT "Cloning and characterization of three novel genes, ALS2CR1, ALS2CR2, and
RT ALS2CR3, in the juvenile amyotrophic lateral sclerosis (ALS2) critical
RT region at chromosome 2q33-q34: candidate genes for ALS2.";
RL Genomics 71:200-213(2001).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7), AND FUNCTION (ISOFORM 7).
RC TISSUE=Leukocyte;
RX PubMed=12010809; DOI=10.1182/blood.v99.11.4070;
RA Himeji D., Horiuchi T., Tsukamoto H., Hayashi K., Watanabe T., Harada M.;
RT "Characterization of caspase-8L: a novel isoform of caspase-8 that behaves
RT as an inhibitor of the caspase cascade.";
RL Blood 99:4070-4078(2002).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 9), AND INTERACTION OF
RP ISOFORM 9 WITH BCAP31 AT THE ENDOPLASMIC RETICULUM.
RX PubMed=11917123; DOI=10.1073/pnas.072088099;
RA Breckenridge D.G., Nguyen M., Kuppig S., Reth M., Shore G.C.;
RT "The procaspase-8 isoform, procaspase-8L, recruited to the BAP31 complex at
RT the endoplasmic reticulum.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:4331-4336(2002).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-219 AND HIS-285.
RG NIEHS SNPs program;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7).
RC TISSUE=Leukocyte;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [12]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, PROTEOLYTIC PROCESSING, AND SITE.
RX PubMed=8962078; DOI=10.1073/pnas.93.25.14486;
RA Srinivasula S.M., Ahmad M., Fernandes-Alnemri T., Litwack G., Alnemri E.S.;
RT "Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease
RT Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like
RT cysteine proteases.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:14486-14491(1996).
RN [13]
RP FUNCTION.
RX PubMed=9006941; DOI=10.1074/jbc.272.5.2952;
RA Muzio M., Salvesen G.S., Dixit V.M.;
RT "FLICE induced apoptosis in a cell-free system. Cleavage of caspase
RT zymogens.";
RL J. Biol. Chem. 272:2952-2956(1997).
RN [14]
RP PROTEOLYTIC PROCESSING, SITE, AND FUNCTION.
RX PubMed=9184224; DOI=10.1093/emboj/16.10.2794;
RA Medema J.P., Scaffidi C., Kischkel F.C., Shevchenko A., Mann M.,
RA Krammer P.H., Peter M.E.;
RT "FLICE is activated by association with the CD95 death-inducing signaling
RT complex (DISC).";
RL EMBO J. 16:2794-2804(1997).
RN [15]
RP CHARACTERIZATION (ISOFORM 7).
RX PubMed=10860845; DOI=10.1006/bbrc.2000.2841;
RA Horiuchi T., Himeji D., Tsukamoto H., Harashima S., Hashimura C.,
RA Hayashi K.;
RT "Dominant expression of a novel splice variant of caspase-8 in human
RT peripheral blood lymphocytes.";
RL Biochem. Biophys. Res. Commun. 272:877-881(2000).
RN [16]
RP INTERACTION WITH BCL2; BCL2L1 AND BCAP31.
RX PubMed=9334338; DOI=10.1083/jcb.139.2.327;
RA Ng F.W.H., Nguyen M., Kwan T., Branton P.E., Nicholson D.W., Cromlish J.A.,
RA Shore G.C.;
RT "p28 Bap31, a Bcl-2/Bcl-XL- and procaspase-8-associated protein in the
RT endoplasmic reticulum.";
RL J. Cell Biol. 139:327-338(1997).
RN [17]
RP INTERACTION WITH PEA15.
RX PubMed=10442631; DOI=10.1038/sj.onc.1202831;
RA Condorelli G., Vigliotta G., Cafieri A., Trencia A., Andalo P., Oriente F.,
RA Miele C., Caruso M., Formisano P., Beguinot F.;
RT "PED/PEA-15: an anti-apoptotic molecule that regulates FAS/TNFR1-induced
RT apoptosis.";
RL Oncogene 18:4409-4415(1999).
RN [18]
RP INTERACTION WITH HUMAN CYTOMEGALOVIRUS/HHV-5 PROTEIN UL36 (MICROBIAL
RP INFECTION).
RX PubMed=11427719; DOI=10.1073/pnas.141108798;
RA Skaletskaya A., Bartle L.M., Chittenden T., McCormick A.L., Mocarski E.S.,
RA Goldmacher V.S.;
RT "A cytomegalovirus-encoded inhibitor of apoptosis that suppresses caspase-8
RT activation.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:7829-7834(2001).
RN [19]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [20]
RP INTERACTION WITH NOL3.
RX PubMed=15509781; DOI=10.1128/mcb.24.22.9763-9770.2004;
RA Jo D.G., Jun J.I., Chang J.W., Hong Y.M., Song S., Cho D.H., Shim S.M.,
RA Lee H.J., Cho C., Kim D.H., Jung Y.K.;
RT "Calcium binding of ARC mediates regulation of caspase 8 and cell death.";
RL Mol. Cell. Biol. 24:9763-9770(2004).
RN [21]
RP INTERACTION WITH RFFL AND RNF34.
RX PubMed=15069192; DOI=10.1073/pnas.0307459101;
RA McDonald E.R. III, El-Deiry W.S.;
RT "Suppression of caspase-8- and -10-associated RING proteins results in
RT sensitization to death ligands and inhibition of tumor cell growth.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:6170-6175(2004).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-334, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [23]
RP MUTAGENESIS OF ASP-73.
RX PubMed=15592525; DOI=10.1038/sj.onc.1208186;
RA Jun J.-I., Chung C.-W., Lee H.-J., Pyo J.-O., Lee K.N., Kim N.-S.,
RA Kim Y.S., Yoo H.-S., Lee T.-H., Kim E., Jung Y.-K.;
RT "Role of FLASH in caspase-8-mediated activation of NF-kappaB: dominant-
RT negative function of FLASH mutant in NF-kappaB signaling pathway.";
RL Oncogene 24:688-696(2005).
RN [24]
RP INTERACTION WITH MOLLUSCUM CONTAGIOSUM VIRUS PROTEIN MC160 (MICROBIAL
RP INFECTION).
RX PubMed=16378960; DOI=10.1128/jvi.80.2.578-586.2006;
RA Nichols D.B., Shisler J.L.;
RT "The MC160 protein expressed by the dermatotropic poxvirus molluscum
RT contagiosum virus prevents tumor necrosis factor alpha-induced NF-kappaB
RT activation via inhibition of I kappa kinase complex formation.";
RL J. Virol. 80:578-586(2006).
RN [25]
RP INTERACTION WITH CASP8P2.
RX PubMed=17245429; DOI=10.1038/sj.emboj.7601504;
RA Milovic-Holm K., Krieghoff E., Jensen K., Will H., Hofmann T.G.;
RT "FLASH links the CD95 signaling pathway to the cell nucleus and nuclear
RT bodies.";
RL EMBO J. 26:391-401(2007).
RN [26]
RP INTERACTION WITH TNFRSF10B.
RX PubMed=18846110; DOI=10.1038/cdd.2008.124;
RA Sun M., Song L., Li Y., Zhou T., Jope R.S.;
RT "Identification of an antiapoptotic protein complex at death receptors.";
RL Cell Death Differ. 15:1887-1900(2008).
RN [27]
RP PHOSPHORYLATION AT SER-387 BY CDK1.
RX PubMed=20937773; DOI=10.1128/mcb.00731-10;
RA Matthess Y., Raab M., Sanhaji M., Lavrik I.N., Strebhardt K.;
RT "Cdk1/cyclin B1 controls Fas-mediated apoptosis by regulating caspase-8
RT activity.";
RL Mol. Cell. Biol. 30:5726-5740(2010).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [29]
RP PROTEOLYTIC CLEAVAGE.
RX PubMed=22858542; DOI=10.1038/cdd.2012.98;
RA van Raam B.J., Ehrnhoefer D.E., Hayden M.R., Salvesen G.S.;
RT "Intrinsic cleavage of receptor-interacting protein kinase-1 by caspase-
RT 6.";
RL Cell Death Differ. 20:86-96(2013).
RN [30]
RP INTERACTION WITH E.COLI NLEF (MICROBIAL INFECTION), CATALYTIC ACTIVITY,
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=23516580; DOI=10.1371/journal.pone.0058937;
RA Blasche S., Mortl M., Steuber H., Siszler G., Nisa S., Schwarz F.,
RA Lavrik I., Gronewold T.M., Maskos K., Donnenberg M.S., Ullmann D., Uetz P.,
RA Kogl M.;
RT "The E. coli effector protein NleF is a caspase inhibitor.";
RL PLoS ONE 8:E58937-E58937(2013).
RN [31]
RP INTERACTION WITH HERPES SIMPLEX VIRUS 1 AND 2 PROTEIN RIR1 (MICROBIAL
RP INFECTION).
RX PubMed=25674983; DOI=10.1016/j.chom.2015.01.003;
RA Guo H., Omoto S., Harris P.A., Finger J.N., Bertin J., Gough P.J.,
RA Kaiser W.J., Mocarski E.S.;
RT "Herpes simplex virus suppresses necroptosis in human cells.";
RL Cell Host Microbe 17:243-251(2015).
RN [32]
RP INTERACTION WITH UBR2, AND MUTAGENESIS OF CYS-360.
RX PubMed=28602583; DOI=10.1016/j.devcel.2017.05.013;
RA Weaver B.P., Weaver Y.M., Mitani S., Han M.;
RT "Coupled Caspase and N-End Rule Ligase Activities Allow Recognition and
RT Degradation of Pluripotency Factor LIN-28 during Non-Apoptotic
RT Development.";
RL Dev. Cell 41:665-673(2017).
RN [33]
RP FUNCTION.
RX PubMed=31827281; DOI=10.1038/s41586-019-1828-5;
RA Lalaoui N., Boyden S.E., Oda H., Wood G.M., Stone D.L., Chau D., Liu L.,
RA Stoffels M., Kratina T., Lawlor K.E., Zaal K.J.M., Hoffmann P.M.,
RA Etemadi N., Shield-Artin K., Biben C., Tsai W.L., Blake M.D., Kuehn H.S.,
RA Yang D., Anderton H., Silke N., Wachsmuth L., Zheng L., Moura N.S.,
RA Beck D.B., Gutierrez-Cruz G., Ombrello A.K., Pinto-Patarroyo G.P.,
RA Kueh A.J., Herold M.J., Hall C., Wang H., Chae J.J., Dmitrieva N.I.,
RA McKenzie M., Light A., Barham B.K., Jones A., Romeo T.M., Zhou Q.,
RA Aksentijevich I., Mullikin J.C., Gross A.J., Shum A.K., Hawkins E.D.,
RA Masters S.L., Lenardo M.J., Boehm M., Rosenzweig S.D., Pasparakis M.,
RA Voss A.K., Gadina M., Kastner D.L., Silke J.;
RT "Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory
RT disease.";
RL Nature 577:103-108(2020).
RN [34]
RP FUNCTION.
RX PubMed=31827280; DOI=10.1038/s41586-019-1830-y;
RA Tao P., Sun J., Wu Z., Wang S., Wang J., Li W., Pan H., Bai R., Zhang J.,
RA Wang Y., Lee P.Y., Ying W., Zhou Q., Hou J., Wang W., Sun B., Yang M.,
RA Liu D., Fang R., Han H., Yang Z., Huang X., Li H., Deuitch N., Zhang Y.,
RA Dissanayake D., Haude K., McWalter K., Roadhouse C., MacKenzie J.J.,
RA Laxer R.M., Aksentijevich I., Yu X., Wang X., Yuan J., Zhou Q.;
RT "A dominant autoinflammatory disease caused by non-cleavable variants of
RT RIPK1.";
RL Nature 577:109-114(2020).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX PubMed=10508784; DOI=10.1016/s0969-2126(99)80179-8;
RA Blanchard H., Kodandapani L., Mittl P.R.E., Di Marco S., Krebs J.F.,
RA Wu J.C., Tomaselli K.J., Gruetter M.G.;
RT "The three-dimensional structure of caspase-8: an initiator enzyme in
RT apoptosis.";
RL Structure 7:1125-1133(1999).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 211-479, SUBUNIT, AND ACTIVE SITE.
RX PubMed=10508785; DOI=10.1016/s0969-2126(99)80180-4;
RA Watt W., Koeplinger K.A., Mildner A.M., Heinrikson R.L., Tomasselli A.G.,
RA Watenpaugh K.D.;
RT "The atomic-resolution structure of human caspase-8, a key activator of
RT apoptosis.";
RL Structure 7:1135-1143(1999).
RN [37]
RP VARIANT CASP8D TRP-248.
RX PubMed=12353035; DOI=10.1038/nature01063;
RA Chun H.J., Zheng L., Ahmad M., Wang J., Speirs C.K., Siegel R.M.,
RA Dale J.K., Puck J., Davis J., Hall C.G., Skoda-Smith S., Atkinson T.P.,
RA Straus S.E., Lenardo M.J.;
RT "Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations
RT lead to human immunodeficiency.";
RL Nature 419:395-399(2002).
RN [38]
RP VARIANT HIS-285, AND PROTECTION AGAINST BREAST CANCER.
RX PubMed=15601643; DOI=10.1093/jnci/dji001;
RA MacPherson G., Healey C.S., Teare M.D., Balasubramanian S.P., Reed M.W.R.,
RA Pharoah P.D., Ponder B.A.J., Meuth M., Bhattacharyya N.P., Cox A.;
RT "Association of a common variant of the CASP8 gene with reduced risk of
RT breast cancer.";
RL J. Natl. Cancer Inst. 96:1866-1869(2004).
RN [39]
RP VARIANT HIS-285, AND PROTECTION AGAINST BREAST CANCER.
RX PubMed=17293864; DOI=10.1038/ng1981;
RG The Kathleen Cunningham foundation consortium for research into familial breast cancer;
RG Breast cancer association consortium;
RA Cox A., Dunning A.M., Garcia-Closas M., Balasubramanian S., Reed M.W.R.,
RA Pooley K.A., Scollen S., Baynes C., Ponder B.A.J., Chanock S.,
RA Lissowska J., Brinton L., Peplonska B., Southey M.C., Hopper J.L.,
RA McCredie M.R.E., Giles G.G., Fletcher O., Johnson N., dos Santos Silva I.,
RA Gibson L., Bojesen S.E., Nordestgaard B.G., Axelsson C.K., Torres D.,
RA Hamann U., Justenhoven C., Brauch H., Chang-Claude J., Kropp S., Risch A.,
RA Wang-Gohrke S., Schuermann P., Bogdanova N., Doerk T., Fagerholm R.,
RA Aaltonen K., Blomqvist C., Nevanlinna H., Seal S., Renwick A.,
RA Stratton M.R., Rahman N., Sangrajrang S., Hughes D., Odefrey F.,
RA Brennan P., Spurdle A.B., Chenevix-Trench G., Beesley J., Mannermaa A.,
RA Hartikainen J., Kataja V., Kosma V.M., Couch F.J., Olson J.E., Goode E.L.,
RA Broeks A., Schmidt M.K., Hogervorst F.B.L., Van't Veer L.J., Kang D.,
RA Yoo K.-Y., Noh D.-Y., Ahn S.-H., Wedren S., Hall P., Low Y.-L., Liu J.,
RA Milne R.L., Ribas G., Gonzalez-Neira A., Benitez J., Sigurdson A.J.,
RA Stredrick D.L., Alexander B.H., Struewing J.P., Pharoah P.D.P.,
RA Easton D.F.;
RT "A common coding variant in CASP8 is associated with breast cancer risk.";
RL Nat. Genet. 39:352-358(2007).
RN [40]
RP ERRATUM OF PUBMED:17293864.
RG The Kathleen Cunningham foundation consortium for research into familial breast cancer;
RG Breast cancer association consortium;
RA Cox A., Dunning A.M., Garcia-Closas M., Balasubramanian S., Reed M.W.R.,
RA Pooley K.A., Scollen S., Baynes C., Ponder B.A.J., Chanock S.,
RA Lissowska J., Brinton L., Peplonska B., Southey M.C., Hopper J.L.,
RA McCredie M.R.E., Giles G.G., Fletcher O., Johnson N., dos Santos Silva I.,
RA Gibson L., Bojesen S.E., Nordestgaard B.G., Axelsson C.K., Torres D.,
RA Hamann U., Justenhoven C., Brauch H., Chang-Claude J., Kropp S., Risch A.,
RA Wang-Gohrke S., Schuermann P., Bogdanova N., Doerk T., Fagerholm R.,
RA Aaltonen K., Blomqvist C., Nevanlinna H., Seal S., Renwick A.,
RA Stratton M.R., Rahman N., Sangrajrang S., Hughes D., Odefrey F.,
RA Brennan P., Spurdle A.B., Chenevix-Trench G., Beesley J., Mannermaa A.,
RA Hartikainen J., Kataja V., Kosma V.M., Couch F.J., Olson J.E., Goode E.L.,
RA Broeks A., Schmidt M.K., Hogervorst F.B.L., Van't Veer L.J., Kang D.,
RA Yoo K.-Y., Noh D.-Y., Ahn S.-H., Wedren S., Hall P., Low Y.-L., Liu J.,
RA Milne R.L., Ribas G., Gonzalez-Neira A., Benitez J., Sigurdson A.J.,
RA Stredrick D.L., Alexander B.H., Struewing J.P., Pharoah P.D.P.,
RA Easton D.F.;
RL Nat. Genet. 39:688-688(2007).
RN [41]
RP INVOLVEMENT IN PROTECTION AGAINST LUNG CANCER.
RX PubMed=17450141; DOI=10.1038/ng2030;
RA Sun T., Gao Y., Tan W., Ma S., Shi Y., Yao J., Guo Y., Yang M., Zhang X.,
RA Zhang Q., Zeng C., Lin D.;
RT "A six-nucleotide insertion-deletion polymorphism in the CASP8 promoter is
RT associated with susceptibility to multiple cancers.";
RL Nat. Genet. 39:605-613(2007).
RN [42]
RP VARIANT HIS-285, AND RISK FACTOR FOR CUTANEOUS MELANOMA.
RX PubMed=18563783; DOI=10.1002/humu.20803;
RA Li C., Zhao H., Hu Z., Liu Z., Wang L.-E., Gershenwald J.E., Prieto V.G.,
RA Lee J.E., Duvic M., Grimm E.A., Wei Q.;
RT "Genetic variants and haplotypes of the caspase-8 and caspase-10 genes
RT contribute to susceptibility to cutaneous melanoma.";
RL Hum. Mutat. 29:1443-1451(2008).
CC -!- FUNCTION: Thiol protease that plays a key role in programmed cell death
CC by acting as a molecular switch for apoptosis, necroptosis and
CC pyroptosis, and is required to prevent tissue damage during embryonic
CC development and adulthood (By similarity). Initiator protease that
CC induces extrinsic apoptosis by mediating cleavage and activation of
CC effector caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A
CC induced cell death (PubMed:23516580, PubMed:8681376, PubMed:8681377,
CC PubMed:9006941, PubMed:9184224, PubMed:8962078). Cleaves and activates
CC effector caspases CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10
CC (PubMed:8962078, PubMed:9006941). Binding to the adapter molecule FADD
CC recruits it to either receptor TNFRSF6/FAS mediated or TNFRSF1A
CC (PubMed:8681376, PubMed:8681377). The resulting aggregate called death-
CC inducing signaling complex (DISC) performs CASP8 proteolytic activation
CC (PubMed:9184224). The active dimeric enzyme is then liberated from the
CC DISC and free to activate downstream apoptotic proteases
CC (PubMed:9184224). Proteolytic fragments of the N-terminal propeptide
CC (termed CAP3, CAP5 and CAP6) are likely retained in the DISC
CC (PubMed:9184224). In addition to extrinsic apoptosis, also acts as a
CC negative regulator of necroptosis: acts by cleaving RIPK1 at 'Asp-324',
CC which is crucial to inhibit RIPK1 kinase activity, limiting TNF-induced
CC apoptosis, necroptosis and inflammatory response (PubMed:31827280,
CC PubMed:31827281). Also able to initiate pyroptosis by mediating
CC cleavage and activation of gasdermin-D (GSDMD): GSDMD cleavage
CC promoting release of the N-terminal moiety (Gasdermin-D, N-terminal)
CC that binds to membranes and forms pores, triggering pyroptosis (By
CC similarity). Initiates pyroptosis following inactivation of MAP3K7/TAK1
CC (By similarity). Also acts as a regulator of innate immunity by
CC mediating cleavage and inactivation of N4BP1 downstream of TLR3 or
CC TLR4, thereby promoting cytokine production (By similarity). May
CC participate in the Granzyme B (GZMB) cell death pathways
CC (PubMed:8755496). Cleaves PARP1 (PubMed:8681376).
CC {ECO:0000250|UniProtKB:O89110, ECO:0000269|PubMed:23516580,
CC ECO:0000269|PubMed:31827280, ECO:0000269|PubMed:31827281,
CC ECO:0000269|PubMed:8681376, ECO:0000269|PubMed:8681377,
CC ECO:0000269|PubMed:8755496, ECO:0000269|PubMed:8962078,
CC ECO:0000269|PubMed:9006941, ECO:0000269|PubMed:9184224}.
CC -!- FUNCTION: [Isoform 5]: Lacks the catalytic site and may interfere with
CC the pro-apoptotic activity of the complex.
CC {ECO:0000305|PubMed:8681376}.
CC -!- FUNCTION: [Isoform 6]: Lacks the catalytic site and may interfere with
CC the pro-apoptotic activity of the complex.
CC {ECO:0000305|PubMed:8681376}.
CC -!- FUNCTION: [Isoform 7]: Lacks the catalytic site and may interfere with
CC the pro-apoptotic activity of the complex (Probable). Acts as an
CC inhibitor of the caspase cascade (PubMed:12010809).
CC {ECO:0000269|PubMed:12010809, ECO:0000305|PubMed:8681376}.
CC -!- FUNCTION: [Isoform 8]: Lacks the catalytic site and may interfere with
CC the pro-apoptotic activity of the complex.
CC {ECO:0000305|PubMed:8681376}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Strict requirement for Asp at position P1 and has a preferred
CC cleavage sequence of (Leu/Asp/Val)-Glu-Thr-Asp-|-(Gly/Ser/Ala).;
CC EC=3.4.22.61; Evidence={ECO:0000269|PubMed:23516580,
CC ECO:0000269|PubMed:8962078};
CC -!- ACTIVITY REGULATION: CASP8 activity is restricted by RIPK1 (By
CC similarity). Inhibited by the effector protein NleF that is produced by
CC pathogenic E.coli; this inhibits apoptosis (PubMed:23516580).
CC {ECO:0000250|UniProtKB:O89110, ECO:0000269|PubMed:23516580}.
CC -!- SUBUNIT: Heterotetramer that consists of two anti-parallel arranged
CC heterodimers, each one formed by a 18 kDa (p18) and a 10 kDa (p10)
CC subunit (PubMed:10508784). Interacts with FADD, CFLAR and PEA15
CC (PubMed:10442631). Interacts with TNFAIP8L2 (By similarity). Interacts
CC with CASP8AP2 (PubMed:16378960). Interacts with RFFL and RNF34;
CC negatively regulate CASP8 through proteasomal degradation
CC (PubMed:15069192). Interacts with NOL3; decreases CASP8 activity in a
CC mitochondria localization- and phosphorylation-dependent manner and
CC this interaction is dissociated by calcium (PubMed:15509781). Interacts
CC with UBR2ca (PubMed:28602583). Interacts with RIPK1 (By similarity).
CC Interacts with stimulated TNFRSF10B; this interaction is followed by
CC CASP8 proteolytic cleavage and activation (PubMed:18846110). Component
CC of the AIM2 PANoptosome complex, a multiprotein complex that drives
CC inflammatory cell death (PANoptosis) (By similarity).
CC {ECO:0000250|UniProtKB:O89110, ECO:0000250|UniProtKB:Q9JHX4,
CC ECO:0000269|PubMed:10442631, ECO:0000269|PubMed:10508784,
CC ECO:0000269|PubMed:15069192, ECO:0000269|PubMed:15509781,
CC ECO:0000269|PubMed:16378960, ECO:0000269|PubMed:18846110,
CC ECO:0000269|PubMed:28602583}.
CC -!- SUBUNIT: [Isoform 9]: Interacts at the endoplasmic reticulum with a
CC complex containing BCAP31, BAP29, BCL2 and/or BCL2L1.
CC {ECO:0000269|PubMed:11917123, ECO:0000269|PubMed:9334338}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human
CC cytomegalovirus/HHV-5 protein vICA/UL36; this interaction inhibits
CC CASP8 activation. {ECO:0000269|PubMed:11427719}.
CC -!- SUBUNIT: (Microbial infection) Interacts with NleF from pathogenic
CC E.coli. {ECO:0000269|PubMed:23516580}.
CC -!- SUBUNIT: (Microbial infection) Interacts with molluscum contagiosum
CC virus protein MC160. {ECO:0000269|PubMed:16378960}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via RIP homotypic interaction
CC motif) with herpes simplex virus 1/HHV-1 protein RIR1/ICP6 (via RIP
CC homotypic interaction motif); this interaction prevents necroptosis
CC activation. {ECO:0000269|PubMed:25674983}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via RIP homotypic interaction
CC motif) with herpes simplex virus 2/HHV-2 protein RIR1/ICP10 (via RIP
CC homotypic interaction motif); this interaction prevents necroptosis
CC activation. {ECO:0000269|PubMed:25674983}.
CC -!- INTERACTION:
CC Q14790; P05067: APP; NbExp=3; IntAct=EBI-78060, EBI-77613;
CC Q14790; P10275: AR; NbExp=3; IntAct=EBI-78060, EBI-608057;
CC Q14790; P51572: BCAP31; NbExp=3; IntAct=EBI-78060, EBI-77683;
CC Q14790; Q92851: CASP10; NbExp=3; IntAct=EBI-78060, EBI-495095;
CC Q14790; Q14790: CASP8; NbExp=2; IntAct=EBI-78060, EBI-78060;
CC Q14790; Q9UKL3: CASP8AP2; NbExp=3; IntAct=EBI-78060, EBI-2339650;
CC Q14790; O15519: CFLAR; NbExp=9; IntAct=EBI-78060, EBI-514941;
CC Q14790; O15519-1: CFLAR; NbExp=2; IntAct=EBI-78060, EBI-4567563;
CC Q14790; Q13618: CUL3; NbExp=6; IntAct=EBI-78060, EBI-456129;
CC Q14790; Q13158: FADD; NbExp=44; IntAct=EBI-78060, EBI-494804;
CC Q14790; P25445: FAS; NbExp=14; IntAct=EBI-78060, EBI-494743;
CC Q14790; P25445-1: FAS; NbExp=3; IntAct=EBI-78060, EBI-15749113;
CC Q14790; P48023: FASLG; NbExp=5; IntAct=EBI-78060, EBI-495538;
CC Q14790; Q06787-7: FMR1; NbExp=3; IntAct=EBI-78060, EBI-25856644;
CC Q14790; Q13418: ILK; NbExp=2; IntAct=EBI-78060, EBI-747644;
CC Q14790; Q9UDY8: MALT1; NbExp=10; IntAct=EBI-78060, EBI-1047372;
CC Q14790; O60936: NOL3; NbExp=3; IntAct=EBI-78060, EBI-740992;
CC Q14790; P53350: PLK1; NbExp=3; IntAct=EBI-78060, EBI-476768;
CC Q14790; P29350: PTPN6; NbExp=3; IntAct=EBI-78060, EBI-78260;
CC Q14790; P04049: RAF1; NbExp=3; IntAct=EBI-78060, EBI-365996;
CC Q14790; Q13546: RIPK1; NbExp=28; IntAct=EBI-78060, EBI-358507;
CC Q14790; Q969K3: RNF34; NbExp=3; IntAct=EBI-78060, EBI-2340642;
CC Q14790; P21580: TNFAIP3; NbExp=3; IntAct=EBI-78060, EBI-527670;
CC Q14790; O00220: TNFRSF10A; NbExp=9; IntAct=EBI-78060, EBI-518861;
CC Q14790; P13051-2: UNG; NbExp=3; IntAct=EBI-78060, EBI-25834258;
CC Q14790; Q96AX1: VPS33A; NbExp=3; IntAct=EBI-78060, EBI-2527283;
CC Q14790-1; Q13158: FADD; NbExp=5; IntAct=EBI-288309, EBI-494804;
CC Q14790-2; O15519-1: CFLAR; NbExp=3; IntAct=EBI-15777741, EBI-4567563;
CC Q14790-5; Q13158: FADD; NbExp=4; IntAct=EBI-288326, EBI-494804;
CC PRO_0000004631; PRO_0000004629 [Q14790]: CASP8; NbExp=2; IntAct=EBI-12736099, EBI-4478080;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9JHX4}. Nucleus
CC {ECO:0000250|UniProtKB:Q9JHX4}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=9;
CC Name=1; Synonyms=Alpha-1;
CC IsoId=Q14790-1; Sequence=Displayed;
CC Name=2; Synonyms=Alpha-2, MCH5-beta;
CC IsoId=Q14790-2; Sequence=VSP_000810;
CC Name=3; Synonyms=Alpha-3;
CC IsoId=Q14790-3; Sequence=VSP_000813;
CC Name=4; Synonyms=Alpha-4;
CC IsoId=Q14790-4; Sequence=VSP_000809, VSP_000810;
CC Name=5; Synonyms=Beta-1;
CC IsoId=Q14790-5; Sequence=VSP_000814, VSP_000815;
CC Name=6; Synonyms=Beta-2;
CC IsoId=Q14790-6; Sequence=VSP_000811, VSP_000812;
CC Name=7; Synonyms=Beta-3, 8L {ECO:0000303|PubMed:12010809};
CC IsoId=Q14790-7; Sequence=VSP_000816, VSP_000817;
CC Name=8; Synonyms=Beta-4;
CC IsoId=Q14790-8; Sequence=VSP_000810, VSP_000816, VSP_000817;
CC Name=9; Synonyms=8L;
CC IsoId=Q14790-9; Sequence=VSP_000808;
CC -!- TISSUE SPECIFICITY: Isoform 1, isoform 5 and isoform 7 are expressed in
CC a wide variety of tissues. Highest expression in peripheral blood
CC leukocytes, spleen, thymus and liver. Barely detectable in brain,
CC testis and skeletal muscle.
CC -!- DOMAIN: [Isoform 9]: Contains a N-terminal extension that is required
CC for interaction with the BCAP31 complex. {ECO:0000269|PubMed:11917123}.
CC -!- PTM: (Microbial infection) Proteolytically cleaved by the cowpox virus
CC CRMA death inhibitory protein. {ECO:0000269|PubMed:8962078}.
CC -!- PTM: Generation of the subunits requires association with the death-
CC inducing signaling complex (DISC), whereas additional processing is
CC likely due to the autocatalytic activity of the activated protease.
CC GZMB and CASP10 can be involved in these processing events.
CC {ECO:0000269|PubMed:8962078, ECO:0000269|PubMed:9184224}.
CC -!- PTM: Phosphorylation on Ser-387 during mitosis by CDK1 inhibits
CC activation by proteolysis and prevents apoptosis. This phosphorylation
CC occurs in cancer cell lines, as well as in primary breast tissues and
CC lymphocytes. {ECO:0000269|PubMed:20937773}.
CC -!- POLYMORPHISM: Genetic variations in CASP8 are associated with reduced
CC risk of lung cancer [MIM:211980] in a population of Han Chinese
CC subjects. Genetic variations are also associated with decreased risk of
CC cancer of various other forms including esophageal, gastric,
CC colorectal, cervical, and breast, acting in an allele dose-dependent
CC manner. {ECO:0000269|PubMed:17450141}.
CC -!- DISEASE: Caspase-8 deficiency (CASP8D) [MIM:607271]: Disorder
CC resembling autoimmune lymphoproliferative syndrome (ALPS). It is
CC characterized by lymphadenopathy, splenomegaly, and defective CD95-
CC induced apoptosis of peripheral blood lymphocytes (PBLs). It leads to
CC defects in activation of T-lymphocytes, B-lymphocytes, and natural
CC killer cells leading to immunodeficiency characterized by recurrent
CC sinopulmonary and herpes simplex virus infections and poor responses to
CC immunization. {ECO:0000269|PubMed:12353035}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 7]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA66858.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305};
CC Sequence=CAA66859.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=CASP8base; Note=CASP8 mutation db;
CC URL="http://structure.bmc.lu.se/idbase/CASP8base/";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/casp8/";
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DR EMBL; X98172; CAA66853.1; -; mRNA.
DR EMBL; X98173; CAA66854.1; -; mRNA.
DR EMBL; X98174; CAA66855.1; -; mRNA.
DR EMBL; X98175; CAA66856.1; -; mRNA.
DR EMBL; X98176; CAA66857.1; -; mRNA.
DR EMBL; X98177; CAA66858.1; ALT_SEQ; mRNA.
DR EMBL; X98178; CAA66859.1; ALT_SEQ; mRNA.
DR EMBL; U58143; AAC50602.1; -; mRNA.
DR EMBL; U60520; AAC50645.1; -; mRNA.
DR EMBL; AF009620; AAB70913.1; -; mRNA.
DR EMBL; AF102146; AAD24962.1; -; Genomic_DNA.
DR EMBL; AF102139; AAD24962.1; JOINED; Genomic_DNA.
DR EMBL; AF102140; AAD24962.1; JOINED; Genomic_DNA.
DR EMBL; AF102141; AAD24962.1; JOINED; Genomic_DNA.
DR EMBL; AF102142; AAD24962.1; JOINED; Genomic_DNA.
DR EMBL; AF102143; AAD24962.1; JOINED; Genomic_DNA.
DR EMBL; AF102144; AAD24962.1; JOINED; Genomic_DNA.
DR EMBL; AF102145; AAD24962.1; JOINED; Genomic_DNA.
DR EMBL; AB038985; BAB32555.1; -; Genomic_DNA.
DR EMBL; AF380342; AAK57437.1; -; mRNA.
DR EMBL; AF422925; AAL87628.1; -; mRNA.
DR EMBL; AF422926; AAL87629.1; -; mRNA.
DR EMBL; AF422927; AAL87630.1; -; mRNA.
DR EMBL; AF422928; AAL87631.1; -; mRNA.
DR EMBL; AF422929; AAL87632.1; -; mRNA.
DR EMBL; DQ355026; ABC67468.1; -; Genomic_DNA.
DR EMBL; AC007256; AAY24225.1; -; Genomic_DNA.
DR EMBL; BC028223; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS2342.1; -. [Q14790-1]
DR CCDS; CCDS2343.1; -. [Q14790-2]
DR CCDS; CCDS2345.1; -. [Q14790-5]
DR CCDS; CCDS42798.1; -. [Q14790-9]
DR CCDS; CCDS42799.1; -. [Q14790-4]
DR RefSeq; NP_001073593.1; NM_001080124.1. [Q14790-2]
DR RefSeq; NP_001073594.1; NM_001080125.1. [Q14790-9]
DR RefSeq; NP_001219.2; NM_001228.4. [Q14790-4]
DR RefSeq; NP_203519.1; NM_033355.3. [Q14790-1]
DR RefSeq; NP_203520.1; NM_033356.3. [Q14790-2]
DR RefSeq; NP_203522.1; NM_033358.3. [Q14790-5]
DR RefSeq; XP_005246943.1; XM_005246886.1.
DR RefSeq; XP_005246944.1; XM_005246887.1. [Q14790-1]
DR RefSeq; XP_005246945.1; XM_005246888.1. [Q14790-1]
DR RefSeq; XP_005246946.1; XM_005246889.1. [Q14790-1]
DR RefSeq; XP_005246947.1; XM_005246890.3. [Q14790-1]
DR RefSeq; XP_005246948.1; XM_005246891.4. [Q14790-1]
DR RefSeq; XP_005246949.1; XM_005246892.1. [Q14790-2]
DR RefSeq; XP_006712852.1; XM_006712789.1. [Q14790-1]
DR RefSeq; XP_006712853.1; XM_006712790.3. [Q14790-1]
DR RefSeq; XP_006712856.1; XM_006712793.2. [Q14790-5]
DR PDB; 1F9E; X-ray; 2.90 A; A/C/E/G/I/K=222-374, B/D/F/H/J/L=390-478.
DR PDB; 1I4E; X-ray; 3.00 A; B=222-479.
DR PDB; 1QDU; X-ray; 2.80 A; A/C/E/G/I/K=222-374, B/D/F/H/J/L=390-477.
DR PDB; 1QTN; X-ray; 1.20 A; A=211-374, B=385-479.
DR PDB; 2C2Z; X-ray; 1.95 A; A=218-374, B=376-479.
DR PDB; 2FUN; X-ray; 3.00 A; B/D=222-479.
DR PDB; 2K7Z; NMR; -; A=217-479.
DR PDB; 2Y1L; X-ray; 1.80 A; A/C=218-374, B/D=376-479.
DR PDB; 3H11; X-ray; 1.90 A; B=217-479.
DR PDB; 3KJN; X-ray; 1.80 A; A=211-374, B=385-479.
DR PDB; 3KJQ; X-ray; 1.80 A; A=211-374, B=385-479.
DR PDB; 4JJ7; X-ray; 1.18 A; A=217-479.
DR PDB; 4PRZ; X-ray; 2.12 A; A=217-479.
DR PDB; 4PS1; X-ray; 1.73 A; A/B/C/D=217-479.
DR PDB; 4ZBW; X-ray; 2.20 A; A/B=2-188.
DR PDB; 5H31; X-ray; 3.17 A; A/B/C/D=1-188.
DR PDB; 5H33; X-ray; 3.60 A; A/B=1-188.
DR PDB; 5JQE; X-ray; 3.16 A; A=1-186.
DR PDB; 5L08; EM; 4.60 A; A/B/C/D/E/F/G/H/I=1-184.
DR PDB; 6AGW; X-ray; 2.09 A; A=1-180.
DR PDB; 6PX9; X-ray; 2.88 A; A/B/C/D/E/F=217-479.
DR PDB; 7LVJ; X-ray; 1.50 A; A=1-188.
DR PDB; 7LVM; X-ray; 1.47 A; A=2-188.
DR PDBsum; 1F9E; -.
DR PDBsum; 1I4E; -.
DR PDBsum; 1QDU; -.
DR PDBsum; 1QTN; -.
DR PDBsum; 2C2Z; -.
DR PDBsum; 2FUN; -.
DR PDBsum; 2K7Z; -.
DR PDBsum; 2Y1L; -.
DR PDBsum; 3H11; -.
DR PDBsum; 3KJN; -.
DR PDBsum; 3KJQ; -.
DR PDBsum; 4JJ7; -.
DR PDBsum; 4PRZ; -.
DR PDBsum; 4PS1; -.
DR PDBsum; 4ZBW; -.
DR PDBsum; 5H31; -.
DR PDBsum; 5H33; -.
DR PDBsum; 5JQE; -.
DR PDBsum; 5L08; -.
DR PDBsum; 6AGW; -.
DR PDBsum; 6PX9; -.
DR PDBsum; 7LVJ; -.
DR PDBsum; 7LVM; -.
DR AlphaFoldDB; Q14790; -.
DR BMRB; Q14790; -.
DR SMR; Q14790; -.
DR BioGRID; 107291; 174.
DR ComplexPortal; CPX-1907; Ripoptosome.
DR ComplexPortal; CPX-975; Caspase-8 complex.
DR CORUM; Q14790; -.
DR DIP; DIP-30915N; -.
DR ELM; Q14790; -.
DR IntAct; Q14790; 130.
DR MINT; Q14790; -.
DR STRING; 9606.ENSP00000351273; -.
DR BindingDB; Q14790; -.
DR ChEMBL; CHEMBL3776; -.
DR DrugBank; DB12651; Bardoxolone.
DR DrugBank; DB11752; Bryostatin 1.
DR GuidetoPHARMACOLOGY; 1624; -.
DR MEROPS; C14.009; -.
DR iPTMnet; Q14790; -.
DR PhosphoSitePlus; Q14790; -.
DR SwissPalm; Q14790; -.
DR BioMuta; CASP8; -.
DR DMDM; 2493531; -.
DR CPTAC; CPTAC-794; -.
DR CPTAC; CPTAC-795; -.
DR EPD; Q14790; -.
DR jPOST; Q14790; -.
DR MassIVE; Q14790; -.
DR MaxQB; Q14790; -.
DR PaxDb; Q14790; -.
DR PeptideAtlas; Q14790; -.
DR PRIDE; Q14790; -.
DR ProteomicsDB; 60172; -. [Q14790-1]
DR ProteomicsDB; 60173; -. [Q14790-2]
DR ProteomicsDB; 60174; -. [Q14790-3]
DR ProteomicsDB; 60175; -. [Q14790-4]
DR ProteomicsDB; 60176; -. [Q14790-5]
DR ProteomicsDB; 60177; -. [Q14790-6]
DR ProteomicsDB; 60178; -. [Q14790-7]
DR ProteomicsDB; 60179; -. [Q14790-8]
DR ProteomicsDB; 60180; -. [Q14790-9]
DR Antibodypedia; 697; 1521 antibodies from 51 providers.
DR DNASU; 841; -.
DR Ensembl; ENST00000264274.13; ENSP00000264274.9; ENSG00000064012.23. [Q14790-3]
DR Ensembl; ENST00000264275.9; ENSP00000264275.5; ENSG00000064012.23. [Q14790-4]
DR Ensembl; ENST00000323492.11; ENSP00000325722.7; ENSG00000064012.23. [Q14790-2]
DR Ensembl; ENST00000358485.8; ENSP00000351273.4; ENSG00000064012.23. [Q14790-9]
DR Ensembl; ENST00000392258.7; ENSP00000376087.3; ENSG00000064012.23. [Q14790-5]
DR Ensembl; ENST00000392263.6; ENSP00000376091.2; ENSG00000064012.23. [Q14790-2]
DR Ensembl; ENST00000432109.6; ENSP00000412523.2; ENSG00000064012.23. [Q14790-1]
DR Ensembl; ENST00000673742.1; ENSP00000501268.1; ENSG00000064012.23. [Q14790-1]
DR GeneID; 841; -.
DR KEGG; hsa:841; -.
DR MANE-Select; ENST00000673742.1; ENSP00000501268.1; NM_001372051.1; NP_001358980.1.
DR UCSC; uc002uxo.2; human. [Q14790-1]
DR CTD; 841; -.
DR DisGeNET; 841; -.
DR GeneCards; CASP8; -.
DR HGNC; HGNC:1509; CASP8.
DR HPA; ENSG00000064012; Tissue enhanced (bone).
DR MalaCards; CASP8; -.
DR MIM; 211980; phenotype.
DR MIM; 601763; gene.
DR MIM; 607271; phenotype.
DR neXtProt; NX_Q14790; -.
DR OpenTargets; ENSG00000064012; -.
DR Orphanet; 210159; Adult hepatocellular carcinoma.
DR Orphanet; 275517; Autoimmune lymphoproliferative syndrome with recurrent viral infections.
DR PharmGKB; PA26092; -.
DR VEuPathDB; HostDB:ENSG00000064012; -.
DR eggNOG; KOG3573; Eukaryota.
DR GeneTree; ENSGT00940000160319; -.
DR HOGENOM; CLU_036904_4_2_1; -.
DR InParanoid; Q14790; -.
DR OMA; VYRMESK; -.
DR OrthoDB; 939331at2759; -.
DR PhylomeDB; Q14790; -.
DR TreeFam; TF102023; -.
DR BRENDA; 3.4.22.61; 2681.
DR PathwayCommons; Q14790; -.
DR Reactome; R-HSA-111465; Apoptotic cleavage of cellular proteins.
DR Reactome; R-HSA-140534; Caspase activation via Death Receptors in the presence of ligand.
DR Reactome; R-HSA-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-HSA-2562578; TRIF-mediated programmed cell death.
DR Reactome; R-HSA-264870; Caspase-mediated cleavage of cytoskeletal proteins.
DR Reactome; R-HSA-3371378; Regulation by c-FLIP.
DR Reactome; R-HSA-5213460; RIPK1-mediated regulated necrosis.
DR Reactome; R-HSA-5218900; CASP8 activity is inhibited.
DR Reactome; R-HSA-5357786; TNFR1-induced proapoptotic signaling.
DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-HSA-5660668; CLEC7A/inflammasome pathway.
DR Reactome; R-HSA-5675482; Regulation of necroptotic cell death.
DR Reactome; R-HSA-69416; Dimerization of procaspase-8.
DR Reactome; R-HSA-75108; Activation, myristolyation of BID and translocation to mitochondria.
DR Reactome; R-HSA-75153; Apoptotic execution phase.
DR Reactome; R-HSA-75157; FasL/ CD95L signaling.
DR Reactome; R-HSA-75158; TRAIL signaling.
DR Reactome; R-HSA-9013957; TLR3-mediated TICAM1-dependent programmed cell death.
DR Reactome; R-HSA-933543; NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
DR Reactome; R-HSA-9686347; Microbial modulation of RIPK1-mediated regulated necrosis.
DR Reactome; R-HSA-9693928; Defective RIPK1-mediated regulated necrosis.
DR SignaLink; Q14790; -.
DR SIGNOR; Q14790; -.
DR BioGRID-ORCS; 841; 22 hits in 1093 CRISPR screens.
DR ChiTaRS; CASP8; human.
DR EvolutionaryTrace; Q14790; -.
DR GeneWiki; Caspase_8; -.
DR GenomeRNAi; 841; -.
DR Pharos; Q14790; Tchem.
DR PRO; PR:Q14790; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q14790; protein.
DR Bgee; ENSG00000064012; Expressed in monocyte and 169 other tissues.
DR ExpressionAtlas; Q14790; baseline and differential.
DR Genevisible; Q14790; HS.
DR GO; GO:0008303; C:caspase complex; IPI:ComplexPortal.
DR GO; GO:0031265; C:CD95 death-inducing signaling complex; IDA:UniProtKB.
DR GO; GO:0044297; C:cell body; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0031264; C:death-inducing signaling complex; IDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0005741; C:mitochondrial outer membrane; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; TAS:ProtInc.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0032991; C:protein-containing complex; IDA:ARUK-UCL.
DR GO; GO:0097342; C:ripoptosome; IDA:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0097153; F:cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0097199; F:cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0097200; F:cysteine-type endopeptidase activity involved in execution phase of apoptosis; IBA:GO_Central.
DR GO; GO:0008234; F:cysteine-type peptidase activity; TAS:ProtInc.
DR GO; GO:0035877; F:death effector domain binding; IPI:UniProtKB.
DR GO; GO:0005123; F:death receptor binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008233; F:peptidase activity; IDA:BHF-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0097110; F:scaffold protein binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; IDA:BHF-UCL.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IMP:UniProtKB.
DR GO; GO:0097190; P:apoptotic signaling pathway; IMP:BHF-UCL.
DR GO; GO:0042113; P:B cell activation; TAS:UniProtKB.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0097194; P:execution phase of apoptosis; IMP:UniProtKB.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IDA:UniProtKB.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IDA:ComplexPortal.
DR GO; GO:0007507; P:heart development; ISS:UniProtKB.
DR GO; GO:0030225; P:macrophage differentiation; IBA:GO_Central.
DR GO; GO:0030101; P:natural killer cell activation; TAS:UniProtKB.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0060546; P:negative regulation of necroptotic process; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IMP:ARUK-UCL.
DR GO; GO:0045651; P:positive regulation of macrophage differentiation; IMP:UniProtKB.
DR GO; GO:1901216; P:positive regulation of neuron death; IEA:Ensembl.
DR GO; GO:0045862; P:positive regulation of proteolysis; IDA:BHF-UCL.
DR GO; GO:0006508; P:proteolysis; IDA:ComplexPortal.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IMP:BHF-UCL.
DR GO; GO:0070269; P:pyroptosis; ISS:UniProtKB.
DR GO; GO:0001817; P:regulation of cytokine production; ISS:UniProtKB.
DR GO; GO:0045088; P:regulation of innate immune response; ISS:UniProtKB.
DR GO; GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0046677; P:response to antibiotic; IEA:Ensembl.
DR GO; GO:0032025; P:response to cobalt ion; IEA:Ensembl.
DR GO; GO:0009409; P:response to cold; IEA:Ensembl.
DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0034612; P:response to tumor necrosis factor; IMP:BHF-UCL.
DR GO; GO:0097264; P:self proteolysis; ISS:UniProtKB.
DR GO; GO:0060715; P:syncytiotrophoblast cell differentiation involved in labyrinthine layer development; TAS:UniProtKB.
DR GO; GO:0042110; P:T cell activation; TAS:UniProtKB.
DR GO; GO:0036462; P:TRAIL-activated apoptotic signaling pathway; IDA:ParkinsonsUK-UCL.
DR CDD; cd00032; CASc; 1.
DR Gene3D; 1.10.533.10; -; 2.
DR InterPro; IPR033170; Caspase-8.
DR InterPro; IPR029030; Caspase-like_dom_sf.
DR InterPro; IPR033139; Caspase_cys_AS.
DR InterPro; IPR016129; Caspase_his_AS.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR001875; DED_dom.
DR InterPro; IPR002398; Pept_C14.
DR InterPro; IPR002138; Pept_C14_p10.
DR InterPro; IPR001309; Pept_C14_p20.
DR InterPro; IPR015917; Pept_C14A.
DR PANTHER; PTHR10454; PTHR10454; 1.
DR PANTHER; PTHR10454:SF162; PTHR10454:SF162; 1.
DR Pfam; PF01335; DED; 2.
DR PRINTS; PR00376; IL1BCENZYME.
DR SMART; SM00115; CASc; 1.
DR SMART; SM00031; DED; 2.
DR SUPFAM; SSF47986; SSF47986; 2.
DR SUPFAM; SSF52129; SSF52129; 1.
DR PROSITE; PS01122; CASPASE_CYS; 1.
DR PROSITE; PS01121; CASPASE_HIS; 1.
DR PROSITE; PS50207; CASPASE_P10; 1.
DR PROSITE; PS50208; CASPASE_P20; 1.
DR PROSITE; PS50168; DED; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; Cytoplasm;
KW Direct protein sequencing; Disease variant; Host-virus interaction;
KW Hydrolase; Nucleus; Phosphoprotein; Protease; Reference proteome; Repeat;
KW Thiol protease; Zymogen.
FT PROPEP 1..216
FT /evidence="ECO:0000269|PubMed:8962078,
FT ECO:0000269|PubMed:9184224"
FT /id="PRO_0000004628"
FT CHAIN 217..374
FT /note="Caspase-8 subunit p18"
FT /id="PRO_0000004629"
FT PROPEP 375..384
FT /evidence="ECO:0000269|PubMed:8962078,
FT ECO:0000269|PubMed:9184224"
FT /id="PRO_0000004630"
FT CHAIN 385..479
FT /note="Caspase-8 subunit p10"
FT /id="PRO_0000004631"
FT DOMAIN 2..80
FT /note="DED 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00065"
FT DOMAIN 100..177
FT /note="DED 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00065"
FT ACT_SITE 317
FT /evidence="ECO:0000269|PubMed:10508785"
FT ACT_SITE 360
FT /evidence="ECO:0000269|PubMed:10508785"
FT SITE 216..217
FT /note="Cleavage; by autocatalytic cleavage"
FT /evidence="ECO:0000269|PubMed:8962078,
FT ECO:0000269|PubMed:9184224"
FT SITE 374..375
FT /note="Cleavage; by CASP6"
FT /evidence="ECO:0000269|PubMed:22858542"
FT SITE 384..385
FT /note="Cleavage; by autocatalytic cleavage"
FT /evidence="ECO:0000269|PubMed:8962078,
FT ECO:0000269|PubMed:9184224"
FT MOD_RES 188
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O89110"
FT MOD_RES 211
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O89110"
FT MOD_RES 224
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O89110"
FT MOD_RES 334
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT MOD_RES 387
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000269|PubMed:20937773"
FT VAR_SEQ 1
FT /note="M -> MEGGRRARVVIESKRNFFLGAFPTPFPAEHVELGRLGDSETAMVPGK
FT GGADYILLPFKKM (in isoform 9)"
FT /evidence="ECO:0000303|PubMed:11917123"
FT /id="VSP_000808"
FT VAR_SEQ 102
FT /note="R -> RFHFCRMSWAEANSQCQTQSVPFWRRVDHLLIR (in isoform
FT 4)"
FT /evidence="ECO:0000303|PubMed:8755496"
FT /id="VSP_000809"
FT VAR_SEQ 184..267
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:8681376"
FT /id="VSP_000813"
FT VAR_SEQ 184..220
FT /note="ERSSSLEGSPDEFSNGEELCGVMTISDSPREQDSESQ -> DFGQSLPNEKQ
FT TSGILSDHQQSQFCKSTGESAQTSQH (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:8681376"
FT /id="VSP_000811"
FT VAR_SEQ 184..198
FT /note="Missing (in isoform 2, isoform 4 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:11917123,
FT ECO:0000303|PubMed:8681376, ECO:0000303|PubMed:8755496,
FT ECO:0000303|PubMed:9228018"
FT /id="VSP_000810"
FT VAR_SEQ 199..235
FT /note="GEELCGVMTISDSPREQDSESQTLDKVYQMKSKPRGY -> DFGQSLPNEKQ
FT TSGILSDHQQSQFCKSTGESAQTSQH (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:8681376"
FT /id="VSP_000814"
FT VAR_SEQ 221..479
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:8681376"
FT /id="VSP_000812"
FT VAR_SEQ 236..479
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:8681376"
FT /id="VSP_000815"
FT VAR_SEQ 269..276
FT /note="ALTTTFEE -> TVEPKREK (in isoform 7 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:12010809,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:8681376"
FT /id="VSP_000816"
FT VAR_SEQ 277..479
FT /note="Missing (in isoform 7 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:12010809,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:8681376"
FT /id="VSP_000817"
FT VARIANT 219
FT /note="S -> T (in dbSNP:rs35976359)"
FT /evidence="ECO:0000269|Ref.9"
FT /id="VAR_025816"
FT VARIANT 248
FT /note="R -> W (in CASP8D; dbSNP:rs17860424)"
FT /evidence="ECO:0000269|PubMed:12353035"
FT /id="VAR_014204"
FT VARIANT 285
FT /note="D -> H (associated with protection against breast
FT cancer; also associated with a lower risk of cutaneous
FT melanoma; dbSNP:rs1045485)"
FT /evidence="ECO:0000269|PubMed:11161814,
FT ECO:0000269|PubMed:15601643, ECO:0000269|PubMed:17293864,
FT ECO:0000269|PubMed:18563783, ECO:0000269|PubMed:8755496,
FT ECO:0000269|PubMed:9228018, ECO:0000269|Ref.9"
FT /id="VAR_020127"
FT MUTAGEN 73
FT /note="D->A: Abolishes binding to FLASH. Induces NF-kappa-B
FT activation."
FT /evidence="ECO:0000269|PubMed:15592525"
FT MUTAGEN 360
FT /note="C->S: Abolishes interaction with UBR2."
FT /evidence="ECO:0000269|PubMed:28602583"
FT MUTAGEN 387
FT /note="S->A: Impaired CDK1-mediated phosphorylation and
FT enhanced apoptosis."
FT CONFLICT 294
FT /note="E -> D (in Ref. 5; AAD24962)"
FT /evidence="ECO:0000305"
FT CONFLICT 331
FT /note="A -> P (in Ref. 2; AAC50602 and 5; AAD24962)"
FT /evidence="ECO:0000305"
FT CONFLICT 343..344
FT /note="LK -> FG (in Ref. 8; AAL87631)"
FT /evidence="ECO:0000305"
FT HELIX 3..12
FT /evidence="ECO:0007829|PDB:6AGW"
FT HELIX 16..25
FT /evidence="ECO:0007829|PDB:6AGW"
FT TURN 26..29
FT /evidence="ECO:0007829|PDB:6AGW"
FT HELIX 32..34
FT /evidence="ECO:0007829|PDB:4ZBW"
FT TURN 35..37
FT /evidence="ECO:0007829|PDB:5H31"
FT HELIX 41..50
FT /evidence="ECO:0007829|PDB:6AGW"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:4ZBW"
FT HELIX 60..68
FT /evidence="ECO:0007829|PDB:6AGW"
FT HELIX 72..79
FT /evidence="ECO:0007829|PDB:6AGW"
FT HELIX 83..91
FT /evidence="ECO:0007829|PDB:6AGW"
FT TURN 93..95
FT /evidence="ECO:0007829|PDB:4ZBW"
FT HELIX 100..111
FT /evidence="ECO:0007829|PDB:6AGW"
FT HELIX 114..129
FT /evidence="ECO:0007829|PDB:6AGW"
FT HELIX 139..148
FT /evidence="ECO:0007829|PDB:6AGW"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:6AGW"
FT HELIX 158..165
FT /evidence="ECO:0007829|PDB:6AGW"
FT HELIX 169..178
FT /evidence="ECO:0007829|PDB:6AGW"
FT STRAND 230..232
FT /evidence="ECO:0007829|PDB:3H11"
FT STRAND 235..240
FT /evidence="ECO:0007829|PDB:4JJ7"
FT HELIX 245..250
FT /evidence="ECO:0007829|PDB:4JJ7"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:4JJ7"
FT STRAND 255..257
FT /evidence="ECO:0007829|PDB:2K7Z"
FT HELIX 263..276
FT /evidence="ECO:0007829|PDB:4JJ7"
FT STRAND 280..286
FT /evidence="ECO:0007829|PDB:4JJ7"
FT HELIX 289..301
FT /evidence="ECO:0007829|PDB:4JJ7"
FT HELIX 304..306
FT /evidence="ECO:0007829|PDB:1QDU"
FT STRAND 310..316
FT /evidence="ECO:0007829|PDB:4JJ7"
FT STRAND 322..324
FT /evidence="ECO:0007829|PDB:4JJ7"
FT STRAND 326..328
FT /evidence="ECO:0007829|PDB:1I4E"
FT STRAND 330..332
FT /evidence="ECO:0007829|PDB:4JJ7"
FT HELIX 333..337
FT /evidence="ECO:0007829|PDB:4JJ7"
FT HELIX 338..340
FT /evidence="ECO:0007829|PDB:4JJ7"
FT TURN 342..344
FT /evidence="ECO:0007829|PDB:4JJ7"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:4JJ7"
FT STRAND 349..351
FT /evidence="ECO:0007829|PDB:6PX9"
FT STRAND 353..359
FT /evidence="ECO:0007829|PDB:4JJ7"
FT STRAND 361..364
FT /evidence="ECO:0007829|PDB:4JJ7"
FT STRAND 369..371
FT /evidence="ECO:0007829|PDB:1QDU"
FT STRAND 377..379
FT /evidence="ECO:0007829|PDB:2K7Z"
FT STRAND 392..394
FT /evidence="ECO:0007829|PDB:1QDU"
FT TURN 395..398
FT /evidence="ECO:0007829|PDB:4JJ7"
FT STRAND 399..405
FT /evidence="ECO:0007829|PDB:4JJ7"
FT STRAND 412..414
FT /evidence="ECO:0007829|PDB:3H11"
FT TURN 415..417
FT /evidence="ECO:0007829|PDB:4JJ7"
FT HELIX 420..432
FT /evidence="ECO:0007829|PDB:4JJ7"
FT HELIX 433..435
FT /evidence="ECO:0007829|PDB:4JJ7"
FT HELIX 439..450
FT /evidence="ECO:0007829|PDB:4JJ7"
FT TURN 456..459
FT /evidence="ECO:0007829|PDB:4JJ7"
FT STRAND 465..468
FT /evidence="ECO:0007829|PDB:4JJ7"
FT STRAND 471..473
FT /evidence="ECO:0007829|PDB:1QDU"
FT CONFLICT Q14790-9:14
FT /note="K -> R (in Ref. 8; AAL87628)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 479 AA; 55391 MW; 7A5FEAA6B39B582F CRC64;
MDFSRNLYDI GEQLDSEDLA SLKFLSLDYI PQRKQEPIKD ALMLFQRLQE KRMLEESNLS
FLKELLFRIN RLDLLITYLN TRKEEMEREL QTPGRAQISA YRVMLYQISE EVSRSELRSF
KFLLQEEISK CKLDDDMNLL DIFIEMEKRV ILGEGKLDIL KRVCAQINKS LLKIINDYEE
FSKERSSSLE GSPDEFSNGE ELCGVMTISD SPREQDSESQ TLDKVYQMKS KPRGYCLIIN
NHNFAKAREK VPKLHSIRDR NGTHLDAGAL TTTFEELHFE IKPHDDCTVE QIYEILKIYQ
LMDHSNMDCF ICCILSHGDK GIIYGTDGQE APIYELTSQF TGLKCPSLAG KPKVFFIQAC
QGDNYQKGIP VETDSEEQPY LEMDLSSPQT RYIPDEADFL LGMATVNNCV SYRNPAEGTW
YIQSLCQSLR ERCPRGDDIL TILTEVNYEV SNKDDKKNMG KQMPQPTFTL RKKLVFPSD
