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Reviewed, UniProtKB/Swiss-Prot O35732 (CFLAR_MOUSE)

Last modified October 13, 2009. Version 92. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    CASP8 and FADD-like apoptosis regulator
Alternative name(s):
    Cellular FLICE-like inhibitory protein
      Short name=c-FLIP
    Caspase-eight-related protein
      Short name=Casper
    Caspase-like apoptosis regulatory protein
      Short name=CLARP
    MACH-related inducer of toxicity
      Short name=MRIT
    Caspase homolog
      Short name=CASH
    Inhibitor of FLICE
      Short name=I-FLICE
    FADD-like antiapoptotic molecule 1
      Short name=FLAME-1
    Usurpin
Cleaved into the following 2 chains:
    1- Recommended name:
            CASP8 and FADD-like apoptosis regulator subunit p43
    2- Recommended name:
            CASP8 and FADD-like apoptosis regulator subunit p12
Gene names
Name: Cflar
Synonyms: Cash
OrganismMus musculus (Mouse)
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

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Protein attributes

Sequence length484 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

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.

Subunit structure

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.

Tissue specificity

Highly expressed in heart.

Developmental stage

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

Induction

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

Domain

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

Post-translational modification

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

Sequence similarities

Belongs to the peptidase C14A family.

Contains 2 DED (death effector) domains.

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Ontologies

Keywords
   Biological processApoptosis
   Coding sequence diversityAlternative splicing
   DomainRepeat
Gene Ontology (GO)
   Biological processnegative regulation of caspase activity

Inferred from mutant phenotype. Source: MGI

proteolysis

Inferred from electronic annotation. Source: InterPro

   Cellular componentcytoplasm

Inferred from direct assay. Source: MGI

   Molecular functioncysteine-type endopeptidase activity

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction. Source: IntAct

Complete GO annotation...

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

FaddQ611601EBI-851729,EBI-524415
ItchQ8C8631EBI-851729,EBI-851782

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O35732-1)

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.
Isoform 2 (identifier: O35732-2)

Also known as: FLIP-S; CASH beta;

The sequence of this isoform differs from the canonical sequence as follows:
     208-218: LQNGRSKEPRF → VSLEPVYGVPA
     219-480: Missing.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 380380CASP8 and FADD-like apoptosis regulator subunit p43 By similarity
PRO_0000004680
Chain381 – 484104CASP8 and FADD-like apoptosis regulator subunit p12 By similarity
PRO_0000004681

Regions

Domain6 – 7873DED 1
Domain97 – 17579DED 2
Region268 – 36396Caspase
Compositional bias421 – 4255Poly-Ser

Natural variations

Alternative sequence208 – 21811LQNGRSKEPRF → VSLEPVYGVPA in isoform 2.
VSP_000842
Alternative sequence219 – 480262Missing in isoform 2.
VSP_000843

Experimental info

Sequence conflict123 – 1253Missing Ref.2

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (FLIP-L) (CASH alpha) [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 0BF7A92CB09F5F1F

FASTA48455,245
        10         20         30         40         50         60 
MAQSPVSAEV IHQVEECLDE DEKEMMLFLC RDVTENLAAP NVRDLLDSLS ERGQLSFATL 

        70         80         90        100        110        120 
AELLYRVRRF DLLKRILKTD KATVEDHLRR NPHLVSDYRV LLMEIGESLD QNDVSSLVFL 

       130        140        150        160        170        180 
TRITRDYTGR GKIAKDKSFL DLVIELEKLN LIASDQLNLL EKCLKNIHRI DLNTKIQKYT 

       190        200        210        220        230        240 
QSSQGARSNM NTLQASLPKL SIKYNSRLQN GRSKEPRFVE YRDSQRTLVK TSIQESGAFL 

       250        260        270        280        290        300 
PPHIREETYR MQSKPLGICL IIDCIGNDTK YLQETFTSLG YHIQLFLFPK SHDITQIVRR 

       310        320        330        340        350        360 
YASMAQHQDY DSFACVLVSL GGSQSMMGRD QVHSGFSLDH VKNMFTGDTC PSLRGKPKLF 

       370        380        390        400        410        420 
FIQNYESLGS QLEDSSLEVD GPSIKNVDSK PLQPRHCTTH PEADIFWSLC TADVSHLEKP 

       430        440        450        460        470        480 
SSSSSVYLQK LSQQLKQGRR RPLVDLHVEL MDKVYAWNSG VSSKEKYSLS LQHTLRKKLI 


LAPT

« Hide

Isoform 2 (FLIP-S) (CASH beta).

Checksum: 3C3850C808606725
Show »

FASTA22225,287

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References

[1]"CASH, a novel caspase homologue with death effector domains."
Goltsev Y.V., Kovalenko A.V., Arnold E., Varfolomeev E.E., Brodianskii V.M., Wallach D.
J. Biol. Chem. 272:19641-19644(1997) [PubMed: 9289491] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
Tissue: Liver.
[2]"Inhibition of death receptor signals by cellular FLIP."
Irmler M., Thome M., Hahne M., Schneider P., Hofmann K., Steiner V., Bodmer J.-L., Schroeter M., Burns K., Mattmann C., Rimoldi D., French L.E., Tschopp J.
Nature 388:190-195(1997) [PubMed: 9217161] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Heart.
[3]"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: 10894163] [Abstract]
Cited for: FUNCTION.
[4]"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: 10602037] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

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Cross-references

Sequence databases

Y14041 mRNA. Translation: CAA74368.1.
Y14042 mRNA. Translation: CAA74369.1.
U97076 mRNA. Translation: AAC53281.1.
IPIIPI00133915.
IPI00230112.
RefSeqNP_997536.1.
UniGeneMm.336848

3D structure databases

HSSPHSSP built from PDB template 1QTN based on UniProtKB Q9C0K4.
ModBaseSearch...

Protein-protein interaction databases

IntActO35732. 3 interactions.
STRINGO35732.

Protein family/group databases

MEROPSC14.974.

PTM databases

PhosphoSiteO35732.

Proteomic databases

PRIDEO35732.

Genome annotation databases

EnsemblENSMUST00000069333; ENSMUSP00000065107; ENSMUSG00000026031; Mus musculus. [Genome view]
ENSMUST00000097722; ENSMUSP00000095329; ENSMUSG00000026031; Mus musculus. [Genome view]
ENSMUST00000114313; ENSMUSP00000109952; ENSMUSG00000026031; Mus musculus. [Genome view]
GeneID12633.

Organism-specific databases

CTD12633.
MGIMGI:1336166. Cflar.

Phylogenomic databases

HOGENOMO35732.
HOVERGENO35732.

Gene expression databases

ArrayExpressO35732.
BgeeO35732.
CleanExMM_CFLAR.
GenevestigatorO35732.
GermOnlineENSMUSG00000026031. Mus musculus.

Family and domain databases

InterProIPR011029. DEATH-like.
IPR001875. DED.
IPR011600. Pept_C14_cat.
IPR001309. Pept_C14_ICE_p20.
IPR002398. Pept_C14_p45.
IPR015917. Pept_C14_p45_core.
[Graphical view]
Gene3DG3DSA:1.10.533.10. DEATH_like. 1 hit.
PANTHERPTHR10454. Pept_C14_p45. 1 hit.
PfamPF01335. DED. 2 hits.
PF00656. Peptidase_C14. 1 hit.
[Graphical view]
SMARTSM00115. CASc. 1 hit.
SM00031. DED. 2 hits.
[Graphical view]
PROSITEPS50208. CASPASE_P20. 1 hit.
PS50168. DED. 2 hits.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio281824.
SOURCESearch...

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Entry information

Entry nameCFLAR_MOUSE
AccessionPrimary (citable) accession number: O35732
Secondary accession number(s): O35707, O35733
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 1, 1998
Last modified: October 13, 2009
This is version 92 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents