Reviewed, UniProtKB/Swiss-Prot Q8IRY7 (CASP8_DROME)

Names and origin

Protein names

Recommended name:
    Caspase-8
    EC=3.4.22.61
Alternative name(s):
    Death-related Ced-3/NEDD2-like protein
Cleaved into the following 2 chains:
    1- Recommended name:
            Caspase-8 subunit p15
    2- Recommended name:
            Caspase-8 subunit p10

Gene names

Name:	Dredd
Synonyms:	DCP2
ORF Names:	CG7486

Organism

Drosophila melanogaster (Fruit fly) [Complete proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

Protein attributes

Sequence length	494 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Effector of the programmed cell death (PCD) activators rpr, grim and W. May play an apoptotic role in the germline as well as soma. Role in immune response, required to resist Gram-negative bacterial infections by regulating Dpt. BG4 interacts with Dredd, BG4 promotes cleavage of Dredd and is necessary and sufficient for enhancing Dredd-induced apoptosis. Ref.1 Ref.7 Ref.8
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 15 kDa (caspase-8 subunit p15) and a 10 kDa (caspase-8 subunit p10) subunit. Interacts with the N-terminus of Dredd. Ref.1 Ref.8
Subcellular location	Cytoplasm. Ref.1 Ref.8
Tissue specificity	Constitutively expressed in fat bodies of larvae and adults. Ref.7
Developmental stage	Expressed both maternally and zygotically. Embryos exhibit ubiquitous low level of expression until stage 11 and then expression becomes spatially and temporally restricted to areas of PCD. Ref.1
Sequence similarities	Belongs to the peptidase C14A family.

Ontologies

Keywords
Biological process	Apoptosis Immune response
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Molecular function	Hydrolase Protease Thiol protease
PTM	Zymogen
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	apoptosis Ref.1 Inferred from mutant phenotype. Source: UniProtKB defense response to Gram-negative bacterium Ref.7 Inferred from mutant phenotype. Source: UniProtKB innate immune response Traceable author statement. Source: FlyBase positive regulation of antibacterial peptide biosynthetic process Traceable author statement. Source: FlyBase protein maturation by peptide bond cleavage Inferred from direct assay. Source: FlyBase proteolysis Inferred from electronic annotation. Source: InterPro sperm individualization Inferred from mutant phenotype. Source: FlyBase
Cellular component	cytoplasm Ref.1 Inferred from direct assay. Source: UniProtKB
Molecular function	apoptotic protease activator activity Ref.1 Inferred from mutant phenotype. Source: UniProtKB cysteine-type endopeptidase activity Traceable author statement. Source: FlyBase protein binding Ref.7 Ref.8 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BG4	Q9V3B4	1	EBI-442182,EBI-104309
CG6128	Q9VTJ5	1	EBI-442182,EBI-114666
Myd88	Q9V566	1	EBI-442182,EBI-129988
Ubc84D	P52487	1	EBI-442182,EBI-122135

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform E (identifier: Q8IRY7-1)

Also known as: Caspase-8 delta;

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 D (identifier: Q8IRY7-2)

Also known as: Caspase-8 gamma;

The sequence of this isoform differs from the canonical sequence as follows:
     273-278: Missing.

Isoform F (identifier: Q8IRY7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     279-284: KFLSPD → VSSLQY
     285-494: Missing.

Isoform alpha Ref.1 (identifier: Q8IRY7-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-128: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Propeptide	1 – 242	242	By similarity		PRO_0000004636
	Chain	243 – 400	158	Caspase-8 subunit p15		PRO_0000004637
	Propeptide	401 – 410	10	By similarity		PRO_0000004638
	Chain	411 – 494	84	Caspase-8 subunit p10		PRO_0000004639
Sites
	Active site	345	1	By similarity
	Active site	386	1	By similarity
Natural variations
	Alternative sequence	1 – 128	128	Missing in isoform alpha.		VSP_050748
	Alternative sequence	273 – 278	6	Missing in isoform D.		VSP_050749
	Alternative sequence	279 – 284	6	KFLSPD → VSSLQY in isoform F.		VSP_050750
	Alternative sequence	285 – 494	210	Missing in isoform F.		VSP_050751
Experimental info
	Sequence conflict	481	1	K → N in AAC33117. Ref.1
	Sequence conflict	481	1	K → N in AAC33118. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform E (Caspase-8 delta) [UniParc]. Last modified June 16, 2009. Version 3. Checksum: B9730DB3FDC58D4C	FASTA	494	56,153
	10 20 30 40 50 60 MAGSNLLIHL DTIDQNDLIY VERDMNFAQK VGLCFLLYGD DHSDATYILQ KLLAMTRSDF 70 80 90 100 110 120 PQSDLLIKFA KSRPETWRRH LVEALCIIGA RKVLRRLGFC WQELRMHYLP HIAGITLHVH 130 140 150 160 170 180 PLLKSLYRMC EELSLVQSGR LLLDVREKVE SQQAGDPLRF YDPAYLEIFL LDWLTRRSIK 190 200 210 220 230 240 LGDINAAGSD VQLLVGHLKS NGLQAQANLL KDTIISNAPE PDAAGTAAMA VKQEIESDNQ 250 260 270 280 290 300 QSYCSTQIDA LKLTRENAGI ALIINQQKFH RNVSRDNMKF LSPDPLRRRD GTDVDKERLI 310 320 330 340 350 360 EVFSSMGYNV EAYDNVDHMG IIERIRSACD RSLVRDSLVV FILSHGFEEA VYASNSIAMK 370 380 390 400 410 420 ITDIEDLLCS YDTLYYKPKL LIIQACQEKL VHKKKPNELF RIDVTTVSPD QHIDMLRAMS 430 440 450 460 470 480 TVNGYAALRH TQTGSWFIGS LCDAIDRRSA SEHIADILTI VTNEVSKKRG SNDESMVPNV 490 KSTFRQHVYF PPRL
	Isoform D (Caspase-8 gamma). Checksum: 5D444CBDD2DFAC06	FASTA	488	55,451
	10 20 30 40 50 60 MAGSNLLIHL DTIDQNDLIY VERDMNFAQK VGLCFLLYGD DHSDATYILQ KLLAMTRSDF 70 80 90 100 110 120 PQSDLLIKFA KSRPETWRRH LVEALCIIGA RKVLRRLGFC WQELRMHYLP HIAGITLHVH 130 140 150 160 170 180 PLLKSLYRMC EELSLVQSGR LLLDVREKVE SQQAGDPLRF YDPAYLEIFL LDWLTRRSIK 190 200 210 220 230 240 LGDINAAGSD VQLLVGHLKS NGLQAQANLL KDTIISNAPE PDAAGTAAMA VKQEIESDNQ 250 260 270 280 290 300 QSYCSTQIDA LKLTRENAGI ALIINQQKFH RNKFLSPDPL RRRDGTDVDK ERLIEVFSSM 310 320 330 340 350 360 GYNVEAYDNV DHMGIIERIR SACDRSLVRD SLVVFILSHG FEEAVYASNS IAMKITDIED 370 380 390 400 410 420 LLCSYDTLYY KPKLLIIQAC QEKLVHKKKP NELFRIDVTT VSPDQHIDML RAMSTVNGYA 430 440 450 460 470 480 ALRHTQTGSW FIGSLCDAID RRSASEHIAD ILTIVTNEVS KKRGSNDESM VPNVKSTFRQ HVYFPPRL
	Isoform F. Checksum: CB586089EF3A87C6	FASTA	284	32,205
	10 20 30 40 50 60 MAGSNLLIHL DTIDQNDLIY VERDMNFAQK VGLCFLLYGD DHSDATYILQ KLLAMTRSDF 70 80 90 100 110 120 PQSDLLIKFA KSRPETWRRH LVEALCIIGA RKVLRRLGFC WQELRMHYLP HIAGITLHVH 130 140 150 160 170 180 PLLKSLYRMC EELSLVQSGR LLLDVREKVE SQQAGDPLRF YDPAYLEIFL LDWLTRRSIK 190 200 210 220 230 240 LGDINAAGSD VQLLVGHLKS NGLQAQANLL KDTIISNAPE PDAAGTAAMA VKQEIESDNQ 250 260 270 280 QSYCSTQIDA LKLTRENAGI ALIINQQKFH RNVSRDNMVS SLQY
	Isoform alpha. Checksum: C2BD5D03992107F9	FASTA	366	41,238
	10 20 30 40 50 60 MCEELSLVQS GRLLLDVREK VESQQAGDPL RFYDPAYLEI FLLDWLTRRS IKLGDINAAG 70 80 90 100 110 120 SDVQLLVGHL KSNGLQAQAN LLKDTIISNA PEPDAAGTAA MAVKQEIESD NQQSYCSTQI 130 140 150 160 170 180 DALKLTRENA GIALIINQQK FHRNVSRDNM KFLSPDPLRR RDGTDVDKER LIEVFSSMGY 190 200 210 220 230 240 NVEAYDNVDH MGIIERIRSA CDRSLVRDSL VVFILSHGFE EAVYASNSIA MKITDIEDLL 250 260 270 280 290 300 CSYDTLYYKP KLLIIQACQE KLVHKKKPNE LFRIDVTTVS PDQHIDMLRA MSTVNGYAAL 310 320 330 340 350 360 RHTQTGSWFI GSLCDAIDRR SASEHIADIL TIVTNEVSKK RGSNDESMVP NVKSTFRQHV YFPPRL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Dredd, a novel effector of the apoptosis activators reaper, grim, and hid in Drosophila." Chen P., Rodriguez A., Erskine R., Thach T., Abrams J.M. Dev. Biol. 201:202-216(1998) [PubMed: 9740659] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS D; E AND ALPHA), FUNCTION, SUBUNIT, PROTEOLYTIC CLEAVAGE, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE. Tissue: Embryo.
[2]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed: 10731132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[3]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION, ALTERNATIVE SPLICING.
[4]	"From sequence to chromosome: the tip of the X chromosome of D. melanogaster." Benos P.V., Gatt M.K., Ashburner M., Murphy L., Harris D., Barrell B.G., Ferraz C., Vidal S., Brun C., Demailles J., Cadieu E., Dreano S., Gloux S., Lelaure V., Mottier S., Galibert F., Borkova D., Minana B. , Kafatos F.C., Louis C., Siden-Kiamos I., Bolshakov S., Papagiannakis G., Spanos L., Cox S., Madueno E., de Pablos B., Modolell J., Peter A., Schoettler P., Werner M., Mourkioti F., Beinert N., Dowe G., Schaefer U., Jaeckle H., Bucheton A., Callister D.M., Campbell L.A., Darlamitsou A., Henderson N.S., McMillan P.J., Salles C., Tait E.A., Valenti P., Saunders R.D.C., Glover D.M. Science 287:2220-2222(2000) [PubMed: 10731137] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Oregon-R.
[5]	"A Drosophila full-length cDNA resource." Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E. Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed: 12537569] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM F). Strain: Berkeley. Tissue: Head.
[6]	"CLARP, a death effector domain-containing protein interacts with caspase-8 and regulates apoptosis." Inohara N., Koseki T., Hu Y., Chen S., Nunez G. Proc. Natl. Acad. Sci. U.S.A. 94:10717-10722(1997) [PubMed: 9380701] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 25-494 (ISOFORM E).
[7]	"The Drosophila caspase Dredd is required to resist Gram-negative bacterial infection." Leulier F., Rodriguez A., Khush R.S., Abrams J.M., Lemaitre B. EMBO Rep. 1:353-358(2000) [PubMed: 11269502] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[8]	"dFADD, a novel death domain-containing adapter protein for the Drosophila caspase DREDD." Hu S., Yang X. J. Biol. Chem. 275:30761-30764(2000) [PubMed: 10934188] [Abstract] Cited for: FUNCTION, INTERACTION WITH BG4, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF007016 mRNA. Translation: AAC31214.1. AF083894 mRNA. Translation: AAC33117.1. AF083895 mRNA. Translation: AAC33118.1. AE014298 Genomic DNA. Translation: AAF45533.3. AE014298 Genomic DNA. Translation: AAN09022.2. AE014298 Genomic DNA. Translation: AAN09023.2. AL031581 Genomic DNA. Translation: CAA20893.1. AY060275 mRNA. Translation: AAL25314.1. Different initiation. AF031652 mRNA. Translation: AAC15843.1.
PIR	T13385.
RefSeq	NP_477249.3. NP_477250.3. NP_477251.3.
UniGene	Dm.3088
3D structure databases
HSSP	HSSP built from PDB template 1NW9 based on UniProtKB P55211.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8IRY7. 11 interactions.
STRING	Q8IRY7.
Protein family/group databases
MEROPS	C14.040.
Genome annotation databases
Ensembl	FBtr0114560; FBpp0113052; FBgn0020381; Drosophila melanogaster. [Genome view]
GeneID	31011.
KEGG	dme:Dmel_CG7486.
Organism-specific databases
CTD	31011.
FlyBase	FBgn0020381. Dredd.
Phylogenomic databases
OMA	HIADILT.
Enzyme and pathway databases
BioCyc	DMEL-XXX-02:DMEL-XXX-02-000062-MON.
BRENDA	3.4.22.61. 48.
Gene expression databases
GermOnline	CG7486. Drosophila melanogaster.
Family and domain databases
InterPro	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]
PANTHER	PTHR10454. Pept_C14_p45. 1 hit.
Pfam	PF00656. Peptidase_C14. 1 hit. [Graphical view]
PRINTS	PR00376. IL1BCENZYME.
SMART	SM00115. CASc. 1 hit. [Graphical view]
PROSITE	PS01122. CASPASE_CYS. 1 hit. PS01121. CASPASE_HIS. False negative. PS50207. CASPASE_P10. 1 hit. PS50208. CASPASE_P20. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	771471.

Entry information

Entry name

CASP8_DROME

Accession

Primary (citable) accession number: Q8IRY7
Secondary accession number(s): O02433 , O76797, O76798, Q95T94, Q9UB42, Q9W5E3

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2004
Last sequence update:	June 16, 2009
Last modified:	November 3, 2009
This is version 62 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project