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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 similarity

GO - Molecular functioni

  1. cysteine-type endopeptidase activity Source: InterPro

GO - Biological processi

  1. apoptotic process Source: UniProtKB-KW
  2. negative regulation of myoblast fusion Source: BHF-UCL
  3. positive regulation of NF-kappaB transcription factor activity Source: BHF-UCL
  4. regulation of apoptotic process Source: InterPro
  5. regulation of satellite cell proliferation Source: BHF-UCL
  6. skeletal muscle atrophy Source: BHF-UCL
  7. skeletal muscle tissue development Source: BHF-UCL
  8. skeletal muscle tissue regeneration Source: BHF-UCL
  9. skeletal myofibril assembly Source: BHF-UCL
Complete GO annotation...

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

ReactomeiREACT_215122. Regulation by c-FLIP.
REACT_243608. Dimerization of procaspase-8.
REACT_253999. 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
ProteomesiUP000000589: Chromosome 1

Organism-specific databases

MGIiMGI:1336166. Cflar.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 380380CASP8 and FADD-like apoptosis regulator subunit p43By similarityPRO_0000004680Add
BLAST
Chaini381 – 484104CASP8 and FADD-like apoptosis regulator subunit p12By similarityPRO_0000004681Add
BLAST

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

PRIDEiO35732.

PTM databases

PhosphoSiteiO35732.

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

BgeeiO35732.
CleanExiMM_CFLAR.
ExpressionAtlasiO35732. baseline and differential.
GenevestigatoriO35732.

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

Protein-protein interaction databases

BioGridi198686. 7 interactions.
IntActiO35732. 2 interactions.

Structurei

3D structure databases

ProteinModelPortaliO35732.
SMRiO35732. Positions 12-182, 244-484.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini6 – 7873DED 1PROSITE-ProRule annotationAdd
BLAST
Domaini97 – 17276DED 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni268 – 36396CaspaseAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi421 – 4255Poly-Ser

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

eggNOGiNOG331323.
GeneTreeiENSGT00530000064199.
HOGENOMiHOG000069972.
HOVERGENiHBG050918.
InParanoidiO35732.
KOiK04724.
OMAiKLFFIQN.
OrthoDBiEOG74N5GK.

Family and domain databases

Gene3Di1.10.533.10. 3 hits.
3.40.50.1460. 1 hit.
InterProiIPR029030. Caspase-like_dom.
IPR011029. DEATH-like_dom.
IPR001875. DED.
IPR011600. Pept_C14_caspase.
IPR001309. Pept_C14_ICE_p20.
IPR015917. Pept_C14A_p45_core.
[Graphical view]
PfamiPF01335. DED. 2 hits.
PF00656. Peptidase_C14. 1 hit.
[Graphical view]
SMARTiSM00115. CASc. 1 hit.
SM00031. DED. 2 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 2 hits.
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. Align

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti121 – 1211T → TRIT in CAA74369. (PubMed:9289491)Curated
Sequence conflicti121 – 1211T → TRIT in CAA74368. (PubMed:9289491)Curated
Sequence conflicti201 – 2077PSVLYLK → YNSR in CAA74368. (PubMed:9289491)Curated
Sequence conflicti201 – 2077PSVLYLK → YNSR in AAC53281. (PubMed:9217161)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei208 – 21811LQNGRSKEPRF → VSLEPVYGVPA in isoform 2. 1 PublicationVSP_000842Add
BLAST
Alternative sequencei219 – 484266Missing in isoform 2. 1 PublicationVSP_000843Add
BLAST

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_006495635.1.
UniGeneiMm.336848.
Mm.486313.

Genome annotation databases

EnsembliENSMUST00000097722; ENSMUSP00000095329; ENSMUSG00000026031. [O35732-1]
GeneIDi12633.
KEGGimmu:12633.
UCSCiuc007bco.1. mouse. [O35732-1]

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_006495635.1.
UniGeneiMm.336848.
Mm.486313.

3D structure databases

ProteinModelPortaliO35732.
SMRiO35732. Positions 12-182, 244-484.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198686. 7 interactions.
IntActiO35732. 2 interactions.

Protein family/group databases

MEROPSiC14.974.

PTM databases

PhosphoSiteiO35732.

Proteomic databases

PRIDEiO35732.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000097722; ENSMUSP00000095329; ENSMUSG00000026031. [O35732-1]
GeneIDi12633.
KEGGimmu:12633.
UCSCiuc007bco.1. mouse. [O35732-1]

Organism-specific databases

CTDi8837.
MGIiMGI:1336166. Cflar.

Phylogenomic databases

eggNOGiNOG331323.
GeneTreeiENSGT00530000064199.
HOGENOMiHOG000069972.
HOVERGENiHBG050918.
InParanoidiO35732.
KOiK04724.
OMAiKLFFIQN.
OrthoDBiEOG74N5GK.

Enzyme and pathway databases

ReactomeiREACT_215122. Regulation by c-FLIP.
REACT_243608. Dimerization of procaspase-8.
REACT_253999. TRAIL signaling.

Miscellaneous databases

ChiTaRSiCflar. mouse.
NextBioi281824.
PROiO35732.
SOURCEiSearch...

Gene expression databases

BgeeiO35732.
CleanExiMM_CFLAR.
ExpressionAtlasiO35732. baseline and differential.
GenevestigatoriO35732.

Family and domain databases

Gene3Di1.10.533.10. 3 hits.
3.40.50.1460. 1 hit.
InterProiIPR029030. Caspase-like_dom.
IPR011029. DEATH-like_dom.
IPR001875. DED.
IPR011600. Pept_C14_caspase.
IPR001309. Pept_C14_ICE_p20.
IPR015917. Pept_C14A_p45_core.
[Graphical view]
PfamiPF01335. DED. 2 hits.
PF00656. Peptidase_C14. 1 hit.
[Graphical view]
SMARTiSM00115. CASc. 1 hit.
SM00031. DED. 2 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 2 hits.
PROSITEiPS50208. CASPASE_P20. 1 hit.
PS50168. DED. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
    Tissue: Liver.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Heart.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. "Requirement for Casper (c-FLIP) in regulation of death receptor-induced apoptosis and embryonic development."
    Yeh W.-C., Itie A., Elia A.J., Ng M., Shu H.-B., Wakeham A., Mirtsos C., Suzuki N., Bonnard M., Goeddel D.V., Mak T.W.
    Immunity 12:633-642(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  5. "Inhibition of Fas-mediated apoptosis by the B cell antigen receptor through c-FLIP."
    Wang J., Lobito A.A., Shen F., Hornung F., Winoto A., Lenardo M.J.
    Eur. J. Immunol. 30:155-163(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

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: January 7, 2015
This is version 137 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

External Data

Dasty 3

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 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.