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Protein

CASP8 and FADD-like apoptosis regulator

Gene

Cflar

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Apoptosis regulator protein which may function as a crucial link between cell survival and cell death pathways in mammalian cells. Acts as an inhibitor of TNFRSF6 mediated apoptosis. A proteolytic fragment (p43) is likely retained in the death-inducing signaling complex (DISC) thereby blocking further recruitment and processing of caspase-8 at the complex. Full length and shorter isoforms have been shown either to induce apoptosis or to reduce TNFRSF-triggered apoptosis. Lacks enzymatic (caspase) activity (By similarity).By similarity2 Publications

GO - Molecular functioni

GO - Biological processi

  • apoptotic process Source: MGI
  • execution phase of apoptosis Source: GO_Central
  • negative regulation of apoptotic process Source: MGI
  • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
  • negative regulation of extrinsic apoptotic signaling pathway Source: MGI
  • negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: MGI
  • negative regulation of myoblast fusion Source: BHF-UCL
  • negative regulation of necroptotic process Source: MGI
  • positive regulation of NF-kappaB transcription factor activity Source: BHF-UCL
  • regulation of necroptotic process Source: MGI
  • regulation of skeletal muscle satellite cell proliferation Source: BHF-UCL
  • skeletal muscle atrophy Source: BHF-UCL
  • skeletal muscle tissue development Source: BHF-UCL
  • skeletal muscle tissue regeneration Source: BHF-UCL
  • skeletal myofibril assembly Source: BHF-UCL
Complete GO annotation...

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

ReactomeiR-MMU-3371378. Regulation by c-FLIP.
R-MMU-5213460. RIPK1-mediated regulated necrosis.
R-MMU-5218900. CASP8 activity is inhibited.
R-MMU-69416. Dimerization of procaspase-8.
R-MMU-75158. TRAIL signaling.

Protein family/group databases

MEROPSiC14.974.

Names & Taxonomyi

Protein namesi
Recommended name:
CASP8 and FADD-like apoptosis regulator
Alternative name(s):
Caspase homolog
Short name:
CASH
Caspase-eight-related protein
Short name:
Casper
Caspase-like apoptosis regulatory protein
Short name:
CLARP
Cellular FLICE-like inhibitory protein
Short name:
c-FLIP
FADD-like antiapoptotic molecule 1
Short name:
FLAME-1
Inhibitor of FLICE
Short name:
I-FLICE
MACH-related inducer of toxicity
Short name:
MRIT
Usurpin
Cleaved into the following 2 chains:
Gene namesi
Name:Cflar
Synonyms:Cash
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:1336166. Cflar.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • death-inducing signaling complex Source: MGI
  • ripoptosome Source: MGI
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000046801 – 380CASP8 and FADD-like apoptosis regulator subunit p43By similarityAdd BLAST380
ChainiPRO_0000004681381 – 484CASP8 and FADD-like apoptosis regulator subunit p12By similarityAdd BLAST104

Post-translational modificationi

Proteolytically processed; probably by caspase-8. Processing likely occurs at the DISC and generates subunit p43 and p12 (By similarity).By similarity

Proteomic databases

PaxDbiO35732.
PRIDEiO35732.

PTM databases

iPTMnetiO35732.
PhosphoSitePlusiO35732.

Expressioni

Tissue specificityi

Highly expressed in heart.

Developmental stagei

At embryonic days E9.5 and E10.5 highest expression in developing heart.

Inductioni

Isoform 1 but not isoform 2 is activated by BCR cross-linking in primary B-cells.

Gene expression databases

BgeeiENSMUSG00000026031.
CleanExiMM_CFLAR.
ExpressionAtlasiO35732. baseline and differential.

Interactioni

Subunit structurei

TNFRSF6 stimulation triggers recruitment to the death-inducing signaling complex (DISC) formed by TNFRSF6, FADD and caspase-8. A proteolytic fragment (p43) stays associated with the DISC (By similarity).By similarity

GO - Molecular functioni

  • protease binding Source: MGI
  • protein heterodimerization activity Source: MGI

Protein-protein interaction databases

BioGridi198686. 7 interactors.
IntActiO35732. 2 interactors.
STRINGi10090.ENSMUSP00000065107.

Structurei

3D structure databases

ProteinModelPortaliO35732.
SMRiO35732.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini6 – 78DED 1PROSITE-ProRule annotationAdd BLAST73
Domaini97 – 172DED 2PROSITE-ProRule annotationAdd BLAST76

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni268 – 363CaspaseAdd BLAST96

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi421 – 425Poly-Ser5

Domaini

The caspase domain lacks the active sites residues involved in catalysis.

Sequence similaritiesi

Belongs to the peptidase C14A family.Curated
Contains 2 DED (death effector) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3573. Eukaryota.
ENOG410ZQIE. LUCA.
GeneTreeiENSGT00530000064199.
HOGENOMiHOG000069972.
HOVERGENiHBG050918.
InParanoidiO35732.
KOiK04724.
OMAiYDWNSRV.
OrthoDBiEOG091G05YD.

Family and domain databases

CDDicd00032. CASc. 1 hit.
Gene3Di1.10.533.10. 3 hits.
3.40.50.1460. 1 hit.
InterProiIPR029030. Caspase-like_dom.
IPR011029. DEATH-like_dom.
IPR001875. DED_dom.
IPR001309. Pept_C14_p20.
IPR015917. Pept_C14A.
[Graphical view]
PfamiPF01335. DED. 2 hits.
[Graphical view]
SMARTiSM00115. CASc. 1 hit.
SM00031. DED. 2 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 2 hits.
SSF52129. SSF52129. 1 hit.
PROSITEiPS50208. CASPASE_P20. 1 hit.
PS50168. DED. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O35732-1) [UniParc]FASTAAdd to basket
Also known as: FLIP-L, CASH alpha

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.

« Hide

        10         20         30         40         50
MAQSPVSAEV IHQVEECLDE DEKEMMLFLC RDVTENLAAP NVRDLLDSLS
60 70 80 90 100
ERGQLSFATL AELLYRVRRF DLLKRILKTD KATVEDHLRR NPHLVSDYRV
110 120 130 140 150
LLMEIGESLD QNDVSSLVFL TRDYTGRGKI AKDKSFLDLV IELEKLNLIA
160 170 180 190 200
SDQLNLLEKC LKNIHRIDLN TKIQKYTQSS QGARSNMNTL QASLPKLSIK
210 220 230 240 250
PSVLYLKLQN GRSKEPRFVE YRDSQRTLVK TSIQESGAFL PPHIREETYR
260 270 280 290 300
MQSKPLGICL IIDCIGNDTK YLQETFTSLG YHIQLFLFPK SHDITQIVRR
310 320 330 340 350
YASMAQHQDY DSFACVLVSL GGSQSMMGRD QVHSGFSLDH VKNMFTGDTC
360 370 380 390 400
PSLRGKPKLF FIQNYESLGS QLEDSSLEVD GPSIKNVDSK PLQPRHCTTH
410 420 430 440 450
PEADIFWSLC TADVSHLEKP SSSSSVYLQK LSQQLKQGRR RPLVDLHVEL
460 470 480
MDKVYAWNSG VSSKEKYSLS LQHTLRKKLI LAPT
Length:484
Mass (Da):55,155
Last modified:October 3, 2012 - v2
Checksum:iB272DE6DB2861C86
GO
Isoform 2 (identifier: O35732-2) [UniParc]FASTAAdd to basket
Also known as: FLIP-S, CASH beta

The sequence of this isoform differs from the canonical sequence as follows:
     208-218: LQNGRSKEPRF → VSLEPVYGVPA
     219-484: Missing.

Show »
Length:218
Mass (Da):24,815
Checksum:iE42F32F27C66C337
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti121T → TRIT in CAA74369 (PubMed:9289491).Curated1
Sequence conflicti121T → TRIT in CAA74368 (PubMed:9289491).Curated1
Sequence conflicti201 – 207PSVLYLK → YNSR in CAA74368 (PubMed:9289491).Curated7
Sequence conflicti201 – 207PSVLYLK → YNSR in AAC53281 (PubMed:9217161).Curated7

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_000842208 – 218LQNGRSKEPRF → VSLEPVYGVPA in isoform 2. 1 PublicationAdd BLAST11
Alternative sequenceiVSP_000843219 – 484Missing in isoform 2. 1 PublicationAdd BLAST266

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y14041 mRNA. Translation: CAA74368.1.
Y14042 mRNA. Translation: CAA74369.1.
U97076 mRNA. Translation: AAC53281.1.
AC112968 Genomic DNA. No translation available.
RefSeqiNP_001276633.1. NM_001289704.2.
NP_997536.1. NM_207653.5.
XP_006495698.1. XM_006495635.3.
XP_011236722.1. XM_011238420.2.
XP_011236723.1. XM_011238421.2.
XP_011236724.1. XM_011238422.1.
XP_011236725.1. XM_011238423.2.
XP_017169048.1. XM_017313559.1.
UniGeneiMm.336848.
Mm.486313.

Genome annotation databases

EnsembliENSMUST00000097722; ENSMUSP00000095329; ENSMUSG00000026031. [O35732-1]
GeneIDi12633.
KEGGimmu:12633.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y14041 mRNA. Translation: CAA74368.1.
Y14042 mRNA. Translation: CAA74369.1.
U97076 mRNA. Translation: AAC53281.1.
AC112968 Genomic DNA. No translation available.
RefSeqiNP_001276633.1. NM_001289704.2.
NP_997536.1. NM_207653.5.
XP_006495698.1. XM_006495635.3.
XP_011236722.1. XM_011238420.2.
XP_011236723.1. XM_011238421.2.
XP_011236724.1. XM_011238422.1.
XP_011236725.1. XM_011238423.2.
XP_017169048.1. XM_017313559.1.
UniGeneiMm.336848.
Mm.486313.

3D structure databases

ProteinModelPortaliO35732.
SMRiO35732.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198686. 7 interactors.
IntActiO35732. 2 interactors.
STRINGi10090.ENSMUSP00000065107.

Protein family/group databases

MEROPSiC14.974.

PTM databases

iPTMnetiO35732.
PhosphoSitePlusiO35732.

Proteomic databases

PaxDbiO35732.
PRIDEiO35732.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000097722; ENSMUSP00000095329; ENSMUSG00000026031. [O35732-1]
GeneIDi12633.
KEGGimmu:12633.

Organism-specific databases

CTDi8837.
MGIiMGI:1336166. Cflar.

Phylogenomic databases

eggNOGiKOG3573. Eukaryota.
ENOG410ZQIE. LUCA.
GeneTreeiENSGT00530000064199.
HOGENOMiHOG000069972.
HOVERGENiHBG050918.
InParanoidiO35732.
KOiK04724.
OMAiYDWNSRV.
OrthoDBiEOG091G05YD.

Enzyme and pathway databases

ReactomeiR-MMU-3371378. Regulation by c-FLIP.
R-MMU-5213460. RIPK1-mediated regulated necrosis.
R-MMU-5218900. CASP8 activity is inhibited.
R-MMU-69416. Dimerization of procaspase-8.
R-MMU-75158. TRAIL signaling.

Miscellaneous databases

ChiTaRSiCflar. mouse.
PROiO35732.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000026031.
CleanExiMM_CFLAR.
ExpressionAtlasiO35732. baseline and differential.

Family and domain databases

CDDicd00032. CASc. 1 hit.
Gene3Di1.10.533.10. 3 hits.
3.40.50.1460. 1 hit.
InterProiIPR029030. Caspase-like_dom.
IPR011029. DEATH-like_dom.
IPR001875. DED_dom.
IPR001309. Pept_C14_p20.
IPR015917. Pept_C14A.
[Graphical view]
PfamiPF01335. DED. 2 hits.
[Graphical view]
SMARTiSM00115. CASc. 1 hit.
SM00031. DED. 2 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 2 hits.
SSF52129. SSF52129. 1 hit.
PROSITEiPS50208. CASPASE_P20. 1 hit.
PS50168. DED. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCFLAR_MOUSE
AccessioniPrimary (citable) accession number: O35732
Secondary accession number(s): D3Z0W6, O35707, O35733
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: October 3, 2012
Last modified: November 30, 2016
This is version 154 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.