Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Caspase-8

Gene

Casp8

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.By similarity

Catalytic activityi

Strict requirement for Asp at position P1 and has a preferred cleavage sequence of (Leu/Asp/Val)-Glu-Thr-Asp-|-(Gly/Ser/Ala).By similarity

Enzyme regulationi

Inhibited by CRMA and P35.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei319By similarity1
Active sitei362By similarity1

GO - Molecular functioni

GO - Biological processi

  • activation of cysteine-type endopeptidase activity Source: Ensembl
  • apoptotic process Source: RGD
  • cellular response to mechanical stimulus Source: Ensembl
  • cellular response to organic cyclic compound Source: RGD
  • execution phase of apoptosis Source: UniProtKB
  • extrinsic apoptotic signaling pathway via death domain receptors Source: GO_Central
  • macrophage differentiation Source: GO_Central
  • negative regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  • positive regulation of macrophage differentiation Source: Ensembl
  • positive regulation of neuron death Source: RGD
  • proteolysis Source: RGD
  • proteolysis involved in cellular protein catabolic process Source: Ensembl
  • regulation of apoptotic process Source: InterPro
  • response to antibiotic Source: RGD
  • response to cobalt ion Source: RGD
  • response to cold Source: RGD
  • response to estradiol Source: RGD
  • response to ethanol Source: RGD
  • response to lipopolysaccharide Source: RGD
  • response to tumor necrosis factor Source: Ensembl
  • TRAIL-activated apoptotic signaling pathway Source: Ensembl

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processApoptosis

Enzyme and pathway databases

BRENDAi3.4.22.61 5301
ReactomeiR-RNO-111465 Apoptotic cleavage of cellular proteins
R-RNO-168638 NOD1/2 Signaling Pathway
R-RNO-264870 Caspase-mediated cleavage of cytoskeletal proteins
R-RNO-3371378 Regulation by c-FLIP
R-RNO-5213460 RIPK1-mediated regulated necrosis
R-RNO-5218900 CASP8 activity is inhibited
R-RNO-5357905 Regulation of TNFR1 signaling
R-RNO-5660668 CLEC7A/inflammasome pathway
R-RNO-69416 Dimerization of procaspase-8
R-RNO-75108 Activation, myristolyation of BID and translocation to mitochondria
R-RNO-75153 Apoptotic execution phase
R-RNO-75157 FasL/ CD95L signaling
R-RNO-75158 TRAIL signaling

Protein family/group databases

MEROPSiC14.009

Names & Taxonomyi

Protein namesi
Recommended name:
Caspase-81 PublicationCurated (EC:3.4.22.61)
Short name:
CASP-8
Cleaved into the following 2 chains:
Gene namesi
Name:Casp8Imported
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 9

Organism-specific databases

RGDi620945 Casp8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_00004324251 – 218By similarityAdd BLAST218
ChainiPRO_0000432426219 – 378Caspase-8 subunit p18Add BLAST160
PropeptideiPRO_0000432427379 – 388By similarity10
ChainiPRO_0000432428389 – 482Caspase-8 subunit p10Add BLAST94

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei188PhosphoserineBy similarity1
Modified residuei213PhosphoserineBy similarity1
Modified residuei336PhosphotyrosineBy similarity1
Modified residuei390Phosphoserine; by CDK1By similarity1

Post-translational modificationi

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 (By similarity).By similarity
Phosphorylation on Ser-389 during mitosis by CDK1 inhibits activation by proteolysis and prevents apoptosis. This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes (By similarity).By similarity

Keywords - PTMi

Phosphoprotein, Zymogen

Proteomic databases

PaxDbiQ9JHX4
PRIDEiQ9JHX4

PTM databases

iPTMnetiQ9JHX4
PhosphoSitePlusiQ9JHX4

Expressioni

Gene expression databases

BgeeiENSRNOG00000012331
GenevisibleiQ9JHX4 RN

Interactioni

Subunit structurei

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. Interacts with RFFL and RNF34; negatively regulate CASP8 through proteasomal degradation (By similarity). Interacts with TNFAIP8L2. Interacts with CASP8AP2. Interacts with NOL3; decreases CASP8 activity in a mitochondria localization- and phosphorylation-dependent manner and this interaction is dissociated by calcium.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
FaddQ8R2E72EBI-4326675,EBI-4326723

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ9JHX4, 2 interactors
STRINGi10116.ENSRNOP00000016613

Structurei

3D structure databases

ProteinModelPortaliQ9JHX4
SMRiQ9JHX4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 80DED 1PROSITE-ProRule annotationAdd BLAST79
Domaini100 – 177DED 2PROSITE-ProRule annotationAdd BLAST78

Sequence similaritiesi

Belongs to the peptidase C14A family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3573 Eukaryota
ENOG410ZQIE LUCA
GeneTreeiENSGT00760000118912
HOGENOMiHOG000276884
HOVERGENiHBG050803
KOiK04398
OMAiIFIEMEK
PhylomeDBiQ9JHX4
TreeFamiTF102023

Family and domain databases

CDDicd00032 CASc, 1 hit
InterProiView protein in InterPro
IPR033170 Caspase-8
IPR029030 Caspase-like_dom_sf
IPR033139 Caspase_cys_AS
IPR016129 Caspase_his_AS
IPR011029 DEATH-like_dom_sf
IPR001875 DED_dom
IPR002138 Pept_C14_p10
IPR001309 Pept_C14_p20
IPR015917 Pept_C14A
PANTHERiPTHR10454:SF162 PTHR10454:SF162, 1 hit
PfamiView protein in Pfam
PF01335 DED, 2 hits
PRINTSiPR00376 IL1BCENZYME
SMARTiView protein in SMART
SM00115 CASc, 1 hit
SM00031 DED, 2 hits
SUPFAMiSSF47986 SSF47986, 2 hits
SSF52129 SSF52129, 1 hit
PROSITEiView protein in PROSITE
PS01122 CASPASE_CYS, 1 hit
PS01121 CASPASE_HIS, 1 hit
PS50207 CASPASE_P10, 1 hit
PS50208 CASPASE_P20, 1 hit
PS50168 DED, 2 hits

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9JHX4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDFHSCLYDI AERLGNEELA ALKFLCLDHI PQKKQESIND VLVLFQRLQE
60 70 80 90 100
EGMLEEDNLS FLKELLFHIS RRDLLSRVLK SSPEEMVREL QVLGKAQVSA
110 120 130 140 150
YRVMLFKLSE DMDKEDLKSF KFLLITEIPK CKLQDNSSLL DIFVEMEKRT
160 170 180 190 200
ILAENNLVTL KSICFRVNRS LLGRIDDYER SSTERRMSTE GGEELPVSVL
210 220 230 240 250
DEVTIKMQDM WDSPGEQESE SLNSDNVYQM KSKPRGYCLI FNNNNFSKAR
260 270 280 290 300
EDIPKLSNMR DRKGTNYDEE ALSKTFKELH FEIVSFSDCT ASQIHEVLVS
310 320 330 340 350
YQSKDHKGKD CFICCILSHG DKGIVYGTDG KEASIYELTS YFTGSKCPSL
360 370 380 390 400
AGKPKIFFIQ ACQGNNFQKA VPVPDETGLE QEHVLEEDSS SYKNYIPDEA
410 420 430 440 450
DFLLGMATVK NCVSYRDPTR GTWYIQSLCQ SLRERCPRGE DILSILTGVN
460 470 480
YDVSNKDNPR NMGKQMPQPI FTLRKKLFFP PN
Length:482
Mass (Da):55,339
Last modified:October 1, 2000 - v1
Checksum:i82B4A29330C53264
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF279308 mRNA Translation: AAF87778.1
AF288372 mRNA Translation: AAK83055.1
AABR06060567 Genomic DNA No translation available.
AABR06060568 Genomic DNA No translation available.
CH473965 Genomic DNA Translation: EDL98978.1
CH473965 Genomic DNA Translation: EDL98979.1
RefSeqiNP_071613.1, NM_022277.1
XP_006245077.1, XM_006245015.3
UniGeneiRn.54474

Genome annotation databases

EnsembliENSRNOT00000016613; ENSRNOP00000016613; ENSRNOG00000012331
ENSRNOT00000084498; ENSRNOP00000069982; ENSRNOG00000012331
GeneIDi64044
KEGGirno:64044
UCSCiRGD:620945 rat

Similar proteinsi

Entry informationi

Entry nameiCASP8_RAT
AccessioniPrimary (citable) accession number: Q9JHX4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 2015
Last sequence update: October 1, 2000
Last modified: May 23, 2018
This is version 135 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Cookie policy

We would like to use anonymized google analytics cookies to gather statistics on how uniprot.org is used in aggregate. Learn more

UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health