Skip Header

Contribute Send feedback
Read comments (0) or add your own

Reviewed, UniProtKB/Swiss-Prot Q14790 (CASP8_HUMAN)

Last modified January 19, 2010. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Caspase-8
      Short name=CASP-8
    EC=3.4.22.61
Alternative name(s):
    ICE-like apoptotic protease 5
    MORT1-associated CED-3 homolog
      Short name=MACH
    FADD-homologous ICE/CED-3-like protease
    FADD-like ICE
      Short name=FLICE
    Apoptotic cysteine protease
    Apoptotic protease Mch-5
    CAP4
Cleaved into the following 2 chains:
    1- Recommended name:
            Caspase-8 subunit p18
    2- Recommended name:
            Caspase-8 subunit p10
Gene names
Name: CASP8
Synonyms: MCH5
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length479 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (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. Isoform 5, isoform 6, isoform 7 and isoform 8 lack the catalytic site and may interfere with the pro-apoptotic activity of the complex. Ref.7 Ref.13

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 structure

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. Ref.8 Ref.16 Ref.17 Ref.23

Subcellular location

Cytoplasm.

Tissue specificity

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.

Domain

Isoform 9 contains a N-terminal extension that is required for interaction with the BCAP31 complex.

Post-translational modification

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.

Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.19 Ref.21

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.

Involvement in 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. Ref.24

Sequence similarities

Belongs to the peptidase C14A family.

Contains 2 DED (death effector) domains.

Sequence caution

The sequence CAA66858.1 differs from that shown. Reason: Miscellaneous discrepancy.

The sequence CAA66859.1 differs from that shown. Reason: Miscellaneous discrepancy.

Alternative products

This entry describes 9 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q14790-1)

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.
Isoform 2 (identifier: Q14790-2)

Also known as: Alpha-2; MCH5-beta;

The sequence of this isoform differs from the canonical sequence as follows:
     184-198: Missing.
Isoform 3 (identifier: Q14790-3)

Also known as: Alpha-3;

The sequence of this isoform differs from the canonical sequence as follows:
     184-267: Missing.
Isoform 4 (identifier: Q14790-4)

Also known as: Alpha-4;

The sequence of this isoform differs from the canonical sequence as follows:
     102-102: R → RFHFCRMSWAEANSQCQTQSVPFWRRVDHLLIR
     184-198: Missing.
Isoform 5 (identifier: Q14790-5)

Also known as: Beta-1;

The sequence of this isoform differs from the canonical sequence as follows:
     199-235: GEELCGVMTISDSPREQDSESQTLDKVYQMKSKPRGY → DFGQSLPNEKQTSGILSDHQQSQFCKSTGESAQTSQH
     236-479: Missing.
Isoform 6 (identifier: Q14790-6)

Also known as: Beta-2;

The sequence of this isoform differs from the canonical sequence as follows:
     184-220: ERSSSLEGSPDEFSNGEELCGVMTISDSPREQDSESQ → DFGQSLPNEKQTSGILSDHQQSQFCKSTGESAQTSQH
     221-479: Missing.
Isoform 7 (identifier: Q14790-7)

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.
Isoform 8 (identifier: Q14790-8)

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.
Isoform 9 (identifier: Q14790-9)

Also known as: 8L;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Propeptide1 – 216216
PRO_0000004628
Chain217 – 374158Caspase-8 subunit p18
PRO_0000004629
Propeptide375 – 38410
PRO_0000004630
Chain385 – 47995Caspase-8 subunit p10
PRO_0000004631

Regions

Domain2 – 8079DED 1
Domain100 – 17778DED 2

Sites

Active site3171
Active site3601

Amino acid modifications

Modified residue1881Phosphoserine By similarity
Modified residue2191Phosphoserine Ref.21
Modified residue3341Phosphotyrosine Ref.19

Natural variations

Alternative sequence11M → MEGGRRARVVIESRRNFFLG AFPTPFPAEHVELGRLGDSE TAMVPGKGGADYILLPFKKM in isoform 9.
VSP_000808
Alternative sequence1021R → RFHFCRMSWAEANSQCQTQS VPFWRRVDHLLIR in isoform 4.
VSP_000809
Alternative sequence184 – 26784Missing in isoform 3.
VSP_000813
Alternative sequence184 – 22037ERSSS…DSESQ → DFGQSLPNEKQTSGILSDHQ QSQFCKSTGESAQTSQH in isoform 6.
VSP_000811
Alternative sequence184 – 19815Missing in isoform 2, isoform 4 and isoform 8.
VSP_000810
Alternative sequence199 – 23537GEELC…KPRGY → DFGQSLPNEKQTSGILSDHQ QSQFCKSTGESAQTSQH in isoform 5.
VSP_000814
Alternative sequence221 – 479259Missing in isoform 6.
VSP_000812
Alternative sequence236 – 479244Missing in isoform 5.
VSP_000815
Alternative sequence269 – 2768ALTTTFEE → TVEPKREK in isoform 7 and isoform 8.
VSP_000816
Alternative sequence277 – 479203Missing in isoform 7 and isoform 8.
VSP_000817
Natural variant2191S → T: dbSNP rs35976359. Ref.9
VAR_025816
Natural variant2481R → W in CASP8D. dbSNP rs17860424. Ref.24
VAR_014204
Natural variant2851D → H Associated with protection against breast cancer; also associated with a lower risk of cutaneous melanoma. dbSNP rs1045485. Ref.9 Ref.3 Ref.4 Ref.6 Ref.25 Ref.26 Ref.29
VAR_020127

Experimental info

Mutagenesis731D → A: Abolishes binding to FLASH. Induces NF-kappa-B activation. Ref.20
Sequence conflict2941E → D in AAD24962. Ref.5
Sequence conflict3311A → P Ref.2
Sequence conflict3311A → P Ref.5
Sequence conflict343 – 3442LK → FG in AAL87631. Ref.8

Secondary structure

............................................... 479
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha-1) [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 7A5FEAA6B39B582F

FASTA47955,391
        10         20         30         40         50         60 
MDFSRNLYDI GEQLDSEDLA SLKFLSLDYI PQRKQEPIKD ALMLFQRLQE KRMLEESNLS 

        70         80         90        100        110        120 
FLKELLFRIN RLDLLITYLN TRKEEMEREL QTPGRAQISA YRVMLYQISE EVSRSELRSF 

       130        140        150        160        170        180 
KFLLQEEISK CKLDDDMNLL DIFIEMEKRV ILGEGKLDIL KRVCAQINKS LLKIINDYEE 

       190        200        210        220        230        240 
FSKERSSSLE GSPDEFSNGE ELCGVMTISD SPREQDSESQ TLDKVYQMKS KPRGYCLIIN 

       250        260        270        280        290        300 
NHNFAKAREK VPKLHSIRDR NGTHLDAGAL TTTFEELHFE IKPHDDCTVE QIYEILKIYQ 

       310        320        330        340        350        360 
LMDHSNMDCF ICCILSHGDK GIIYGTDGQE APIYELTSQF TGLKCPSLAG KPKVFFIQAC 

       370        380        390        400        410        420 
QGDNYQKGIP VETDSEEQPY LEMDLSSPQT RYIPDEADFL LGMATVNNCV SYRNPAEGTW 

       430        440        450        460        470 
YIQSLCQSLR ERCPRGDDIL TILTEVNYEV SNKDDKKNMG KQMPQPTFTL RKKLVFPSD 

« Hide

Isoform 2 (Alpha-2) (MCH5-beta).

Checksum: 7F52F14ADE6A02B6
Show »

FASTA46453,768
Isoform 3 (Alpha-3).

Checksum: 2787AE831A2B36EF
Show »

FASTA39545,929
Isoform 4 (Alpha-4).

Checksum: 68136650A49159D9
Show »

FASTA49657,701
Isoform 5 (Beta-1).

Checksum: 7C9013CEA85A77DE
Show »

FASTA23527,484
Isoform 6 (Beta-2).

Checksum: F3DA0380D12006C7
Show »

FASTA22025,862
Isoform 7 (Beta-3) (8L).

Checksum: 227ED77718788F92
Show »

FASTA27632,330
Isoform 8 (Beta-4).

Checksum: 19ACAE80171E0572
Show »

FASTA26130,707
Isoform 9 (8L).

Checksum: 54402ECFACF9F6C9
Show »

FASTA53861,864

References

« Hide 'large scale' references
[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: 8681376] [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: 8681377] [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: 8755496] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), VARIANT HIS-285.
Tissue: T-cell.
[4]"FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis."
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.
J. Biol. Chem. 272:18542-18545(1997) [PubMed: 9228018] [Abstract]
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: 9931493] [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: 11161814] [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: 12010809] [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: 11917123] [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. expand/collapse author list , 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: 15815621] [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: 15489334] [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: 8962078] [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: 9006941] [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: 9184224] [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: 10860845] [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: 9334338] [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: 10442631] [Abstract]
Cited for: INTERACTION WITH PEA15.
[18]"An unappreciated role for RNA surveillance."
Hillman R.T., Green R.E., Brenner S.E.
Genome Biol. 5:R8.1-R8.16(2004) [PubMed: 14759258] [Abstract]
Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[19]"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: 15592455] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-334, MASS SPECTROMETRY.
[20]"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: 15592525] [Abstract]
Cited for: MUTAGENESIS OF ASP-73.
[21]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
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.
Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-219, MASS SPECTROMETRY.
[22]"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: 10508784] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
[23]"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: 10508785] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 211-479, SUBUNIT.
[24]"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: 12353035] [Abstract]
Cited for: VARIANT CASP8D TRP-248.
[25]"Association of a common variant of the CASP8 gene with reduced risk of breast cancer."
MacPherson G., Healey C.S., Teare M.D., Balasubramanian S.P., Reed M.W.R., Pharoah P.D., Ponder B.A.J., Meuth M., Bhattacharyya N.P., Cox A.
J. Natl. Cancer Inst. 96:1866-1869(2004) [PubMed: 15601643] [Abstract]
Cited for: VARIANT HIS-285, PROTECTION AGAINST BREAST CANCER.
[26]"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. expand/collapse author list , 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: 17293864] [Abstract]
Cited for: VARIANT HIS-285, PROTECTION AGAINST BREAST CANCER.
[27]Erratum
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. expand/collapse author list , 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. 39:688-688(2007)
[28]"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: 17450141] [Abstract]
Cited for: INVOLVEMENT IN PROTECTION AGAINST LUNG CANCER.
[29]"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: 18563783] [Abstract]
Cited for: VARIANT HIS-285, RISK FACTOR FOR CUTANEOUS MELANOMA.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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 expand/collapse EMBL AC list , 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.
IPIIPI00000149.
IPI00073318.
IPI00220721.
IPI00220722.
IPI00220723.
IPI00220724.
IPI00220726.
IPI00305242.
IPI00793235.
RefSeqNP_001073593.1.
NP_001073594.1.
NP_001219.2.
NP_203519.1.
NP_203520.1.
NP_203522.1.
UniGeneHs.599762

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
3H11X-ray1.90B217-479[»]
ModBaseSearch...

Protein-protein interaction databases

IntActQ14790. 41 interactions.
STRINGQ14790.

Protein family/group databases

MEROPSC14.009.

PTM databases

PhosphoSiteQ14790.

Proteomic databases

PRIDEQ14790.

Genome annotation databases

EnsemblENST00000303385; ENSP00000307131; ENSG00000064012; Homo sapiens. [Genome view]
ENST00000358485; ENSP00000351273; ENSG00000064012; Homo sapiens. [Genome view]
ENST00000432109; ENSP00000412523; ENSG00000064012; Homo sapiens. [Genome view]
GeneID841.
KEGGhsa:841.
UCSCuc002uxo.1. human.
uc002uxp.1. human.
uc002uxq.1. human.
uc002uxr.1. human.
uc002uxs.1. human.
uc002uxv.1. human.
uc002uxy.1. human.

Organism-specific databases

CTD841.
GeneCardsGC02P201807.
H-InvDBHIX0002736.
HGNCHGNC:1509. CASP8.
HPACAB002047.
HPA001302.
HPA005688.
HPA008936.
MIM211980. phenotype.
601763. gene.
607271. phenotype.
Orphanet3261. Autoimmune lymphoproliferative syndrome.
PharmGKBPA26092.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG05678.
HOVERGENQ14790.
InParanoidQ14790.

Enzyme and pathway databases

BRENDA3.4.22.61. 247.
Pathway_Interaction_DBcaspase_pathway. Caspase cascade in apoptosis.
ceramidepathway. Ceramide signaling pathway.
ar_pathway. Coregulation of Androgen receptor activity.
faspathway. FAS signaling pathway (CD95).
hivnefpathway. HIV-1 Nef: Negative effector of Fas and TNF-alpha.
avb3_integrin_pathway. Integrins in angiogenesis.
tnfpathway. TNF receptor signaling pathway.
trail_pathway. TRAIL signaling pathway.
ReactomeREACT_578. Apoptosis.

Gene expression databases

ArrayExpressQ14790.
BgeeQ14790.
GenevestigatorQ14790.
GermOnlineENSG00000064012. Homo sapiens.

Family and domain databases

InterProIPR011029. 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]
Gene3DG3DSA:1.10.533.10. DEATH_like. 2 hits.
PANTHERPTHR10454. Pept_C14_p45. 1 hit.
PfamPF01335. DED. 2 hits.
PF00656. Peptidase_C14. 1 hit.
[Graphical view]
PRINTSPR00376. IL1BCENZYME.
SMARTSM00115. CASc. 1 hit.
SM00031. DED. 2 hits.
[Graphical view]
PROSITEPS01122. 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]
ProtoNetSearch...

Other Resources

BindingDBQ14790.
NextBio3510.
PMAP-CutDBQ14790.
SOURCESearch...

Entry information

Entry nameCASP8_HUMAN
AccessionPrimary (citable) accession number: Q14790
Secondary accession number(s): O14676 expand/collapse secondary AC list , Q14791, Q14792, Q14793, Q14794, Q14795, Q14796, Q15780, Q15806, Q53TT5, Q8TDI1, Q8TDI2, Q8TDI3, Q8TDI4, Q8TDI5, Q96T22, Q9C0K4, Q9UQ81
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: January 19, 2010
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

Relevant documents

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents