UniProtKB - Q8IRY7 (CASP8_DROME)
Caspase-8
Dredd
Functioni
Effector of the programmed cell death (PCD) activators rpr, grim and hid (PubMed:9740659).
May play an apoptotic role in the germline as well as soma. Fadd interacts with Dredd to promote cleavage of Dredd and is necessary and sufficient for enhancing Dredd-induced apoptosis (PubMed:10934188).
Plays a role in the innate immune response. Required for resistance to Gram-negative bacterial infection (PubMed:11269502).
Diap2-mediated ubiquitination of Dredd is critical for processing of imd and rel and the subsequent expression of antimicrobial genes such as DptA (PubMed:22549468).
4 PublicationsCatalytic activityi
- Strict requirement for Asp at position P1 and has a preferred cleavage sequence of (Leu/Asp/Val)-Glu-Thr-Asp-|-(Gly/Ser/Ala). EC:3.4.22.61
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 345 | By similarity | 1 | |
Active sitei | 386 | By similarity | 1 |
GO - Molecular functioni
- cysteine-type endopeptidase activator activity involved in apoptotic process Source: UniProtKB
- cysteine-type endopeptidase activity Source: FlyBase
- cysteine-type endopeptidase activity involved in apoptotic process Source: GO_Central
- endopeptidase activity Source: FlyBase
GO - Biological processi
- apoptotic process Source: UniProtKB
- defense response Source: FlyBase
- defense response to Gram-negative bacterium Source: UniProtKB
- immune response Source: FlyBase
- innate immune response Source: FlyBase
- negative regulation of programmed cell death Source: FlyBase
- peptidoglycan recognition protein signaling pathway Source: FlyBase
- peripheral nervous system neuron development Source: FlyBase
- positive regulation of antibacterial peptide biosynthetic process Source: FlyBase
- positive regulation of biosynthetic process of antibacterial peptides active against Gram-negative bacteria Source: UniProtKB
- positive regulation of defense response to virus by host Source: FlyBase
- positive regulation of innate immune response Source: FlyBase
- protein processing Source: FlyBase
- sperm individualization Source: FlyBase
Keywordsi
Molecular function | Hydrolase, Protease, Thiol protease |
Biological process | Apoptosis, Immunity, Innate immunity |
Enzyme and pathway databases
Reactomei | R-DME-198323, AKT phosphorylates targets in the cytosol R-DME-214397, Assembly of the PGN:PGRP-LC/LE receptor 'signalling complex' R-DME-214399, Activated IkappaB kinase (IKK) complex, Phospho IRD5:KEY dimer, phosphorylates REL in the PGN:PGRP-LC/LE receptor 'signalling complex' R-DME-214411, REL binds to DREDD in the PGN:PGRP-LC/LE receptor 'signalling complex' R-DME-214416, Phosphorylated REL is cleaved by and dissociates from DREDD R-DME-448706, Interleukin-1 processing |
SignaLinki | Q8IRY7 |
Protein family/group databases
MEROPSi | C14.040 |
Names & Taxonomyi
Protein namesi | 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: |
Gene namesi | Name:Dredd Synonyms:DCP2 ORF Names:CG7486 |
Organismi | Drosophila melanogaster (Fruit fly) |
Taxonomic identifieri | 7227 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Ecdysozoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora › |
Proteomesi |
|
Organism-specific databases
FlyBasei | FBgn0020381, Dredd |
VEuPathDBi | VectorBase:FBgn0020381 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 2 Publications
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 98 | G → R in D44; reduces polyubiquitination by Diap2, abolishes rel cleavage and blocks expression of DptA following bacterial infection. No effect on binding to Diap2 or Fadd, processing, dimerization, catalytic activity or stability. 2 Publications | 1 | |
Mutagenesisi | 436 | W → R in L23; blocks expression of DptA following bacterial infection. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
PropeptideiPRO_0000004636 | 1 – 242 | By similarityAdd BLAST | 242 | |
ChainiPRO_0000004637 | 243 – 400 | Caspase-8 subunit p15Add BLAST | 158 | |
PropeptideiPRO_0000004638 | 401 – 410 | By similarity | 10 | |
ChainiPRO_0000004639 | 411 – 494 | Caspase-8 subunit p10Add BLAST | 84 |
Post-translational modificationi
Keywords - PTMi
Ubl conjugation, ZymogenProteomic databases
PaxDbi | Q8IRY7 |
Expressioni
Tissue specificityi
Developmental stagei
Gene expression databases
Bgeei | FBgn0020381, Expressed in eye disc (Drosophila) and 46 other tissues |
ExpressionAtlasi | Q8IRY7, baseline and differential |
Genevisiblei | Q8IRY7, DM |
Interactioni
Subunit structurei
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 (PubMed:9740659).
Interacts (via N-terminus) with Diap2; likely to bind Diap2 simultaneously with Fadd to form a trimeric complex (PubMed:10934188, PubMed:22549468).
3 PublicationsProtein-protein interaction databases
BioGRIDi | 57579, 74 interactors |
IntActi | Q8IRY7, 5 interactors |
MINTi | Q8IRY7 |
STRINGi | 7227.FBpp0113052 |
Family & Domainsi
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG3573, Eukaryota |
GeneTreei | ENSGT00940000160994 |
InParanoidi | Q8IRY7 |
PhylomeDBi | Q8IRY7 |
Family and domain databases
CDDi | cd00032, CASc, 1 hit |
InterProi | View protein in InterPro IPR029030, Caspase-like_dom_sf IPR002398, Pept_C14 IPR002138, Pept_C14_p10 IPR001309, Pept_C14_p20 IPR015917, Pept_C14A |
PANTHERi | PTHR10454, PTHR10454, 1 hit |
PRINTSi | PR00376, IL1BCENZYME |
SMARTi | View protein in SMART SM00115, CASc, 1 hit |
SUPFAMi | SSF52129, SSF52129, 1 hit |
PROSITEi | View protein in PROSITE PS01122, CASPASE_CYS, 1 hit PS50207, CASPASE_P10, 1 hit PS50208, CASPASE_P20, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAGSNLLIHL DTIDQNDLIY VERDMNFAQK VGLCFLLYGD DHSDATYILQ
60 70 80 90 100
KLLAMTRSDF PQSDLLIKFA KSRPETWRRH LVEALCIIGA RKVLRRLGFC
110 120 130 140 150
WQELRMHYLP HIAGITLHVH PLLKSLYRMC EELSLVQSGR LLLDVREKVE
160 170 180 190 200
SQQAGDPLRF YDPAYLEIFL LDWLTRRSIK LGDINAAGSD VQLLVGHLKS
210 220 230 240 250
NGLQAQANLL KDTIISNAPE PDAAGTAAMA VKQEIESDNQ QSYCSTQIDA
260 270 280 290 300
LKLTRENAGI ALIINQQKFH RNVSRDNMKF LSPDPLRRRD GTDVDKERLI
310 320 330 340 350
EVFSSMGYNV EAYDNVDHMG IIERIRSACD RSLVRDSLVV FILSHGFEEA
360 370 380 390 400
VYASNSIAMK ITDIEDLLCS YDTLYYKPKL LIIQACQEKL VHKKKPNELF
410 420 430 440 450
RIDVTTVSPD QHIDMLRAMS TVNGYAALRH TQTGSWFIGS LCDAIDRRSA
460 470 480 490
SEHIADILTI VTNEVSKKRG SNDESMVPNV KSTFRQHVYF PPRL
The sequence of this isoform differs from the canonical sequence as follows:
1-128: Missing.
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketX2JHT0 | X2JHT0_DROME | Death related ced-3/Nedd2-like casp... | Dredd anon-1BCa, CASP8_DROME, DCP-2, Dcp-2, dcp-2 | 440 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 481 | K → N in AAC33117 (PubMed:9740659).Curated | 1 | |
Sequence conflicti | 481 | K → N in AAC33118 (PubMed:9740659).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_050748 | 1 – 128 | Missing in isoform alpha. 1 PublicationAdd BLAST | 128 | |
Alternative sequenceiVSP_050749 | 273 – 278 | Missing in isoform D. 1 Publication | 6 | |
Alternative sequenceiVSP_050750 | 279 – 284 | KFLSPD → VSSLQY in isoform F. 1 Publication | 6 | |
Alternative sequenceiVSP_050751 | 285 – 494 | Missing in isoform F. 1 PublicationAdd BLAST | 210 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 |
PIRi | T13385 |
RefSeqi | NP_477249.3, NM_057901.4 [Q8IRY7-1] NP_477250.3, NM_057902.4 [Q8IRY7-3] NP_477251.3, NM_057903.4 [Q8IRY7-2] |
Genome annotation databases
EnsemblMetazoai | FBtr0114559; FBpp0113051; FBgn0020381 [Q8IRY7-2] FBtr0114560; FBpp0113052; FBgn0020381 [Q8IRY7-1] FBtr0114561; FBpp0113053; FBgn0020381 [Q8IRY7-3] |
GeneIDi | 31011 |
KEGGi | dme:Dmel_CG7486 |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 |
PIRi | T13385 |
RefSeqi | NP_477249.3, NM_057901.4 [Q8IRY7-1] NP_477250.3, NM_057902.4 [Q8IRY7-3] NP_477251.3, NM_057903.4 [Q8IRY7-2] |
3D structure databases
SMRi | Q8IRY7 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 57579, 74 interactors |
IntActi | Q8IRY7, 5 interactors |
MINTi | Q8IRY7 |
STRINGi | 7227.FBpp0113052 |
Protein family/group databases
MEROPSi | C14.040 |
Proteomic databases
PaxDbi | Q8IRY7 |
Protocols and materials databases
DNASUi | 31011 |
Genome annotation databases
EnsemblMetazoai | FBtr0114559; FBpp0113051; FBgn0020381 [Q8IRY7-2] FBtr0114560; FBpp0113052; FBgn0020381 [Q8IRY7-1] FBtr0114561; FBpp0113053; FBgn0020381 [Q8IRY7-3] |
GeneIDi | 31011 |
KEGGi | dme:Dmel_CG7486 |
Organism-specific databases
CTDi | 31011 |
FlyBasei | FBgn0020381, Dredd |
VEuPathDBi | VectorBase:FBgn0020381 |
Phylogenomic databases
eggNOGi | KOG3573, Eukaryota |
GeneTreei | ENSGT00940000160994 |
InParanoidi | Q8IRY7 |
PhylomeDBi | Q8IRY7 |
Enzyme and pathway databases
Reactomei | R-DME-198323, AKT phosphorylates targets in the cytosol R-DME-214397, Assembly of the PGN:PGRP-LC/LE receptor 'signalling complex' R-DME-214399, Activated IkappaB kinase (IKK) complex, Phospho IRD5:KEY dimer, phosphorylates REL in the PGN:PGRP-LC/LE receptor 'signalling complex' R-DME-214411, REL binds to DREDD in the PGN:PGRP-LC/LE receptor 'signalling complex' R-DME-214416, Phosphorylated REL is cleaved by and dissociates from DREDD R-DME-448706, Interleukin-1 processing |
SignaLinki | Q8IRY7 |
Miscellaneous databases
BioGRID-ORCSi | 31011, 0 hits in 3 CRISPR screens |
ChiTaRSi | gem, fly |
GenomeRNAii | 31011 |
PROi | PR:Q8IRY7 |
Gene expression databases
Bgeei | FBgn0020381, Expressed in eye disc (Drosophila) and 46 other tissues |
ExpressionAtlasi | Q8IRY7, baseline and differential |
Genevisiblei | Q8IRY7, DM |
Family and domain databases
CDDi | cd00032, CASc, 1 hit |
InterProi | View protein in InterPro IPR029030, Caspase-like_dom_sf IPR002398, Pept_C14 IPR002138, Pept_C14_p10 IPR001309, Pept_C14_p20 IPR015917, Pept_C14A |
PANTHERi | PTHR10454, PTHR10454, 1 hit |
PRINTSi | PR00376, IL1BCENZYME |
SMARTi | View protein in SMART SM00115, CASc, 1 hit |
SUPFAMi | SSF52129, SSF52129, 1 hit |
PROSITEi | View protein in PROSITE PS01122, CASPASE_CYS, 1 hit PS50207, CASPASE_P10, 1 hit PS50208, CASPASE_P20, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CASP8_DROME | |
Accessioni | Q8IRY7Primary (citable) accession number: Q8IRY7 Secondary accession number(s): O02433 Q9W5E3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 7, 2004 |
Last sequence update: | June 16, 2009 | |
Last modified: | February 23, 2022 | |
This is version 161 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Drosophila annotation project |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Peptidase families
Classification of peptidase families and list of entries - Drosophila
Drosophila: entries, gene names and cross-references to FlyBase - SIMILARITY comments
Index of protein domains and families