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O35732 (CFLAR_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended 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:

  1. CASP8 and FADD-like apoptosis regulator subunit p43
  2. 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 › Mus

Protein attributes

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

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. Ref.3 Ref.4

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.

Ontologies

Keywords
   Biological processApoptosis
   Coding sequence diversityAlternative splicing
   DomainRepeat
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological processnegative regulation of cysteine-type endopeptidase activity involved in apoptotic process

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

Complete GO annotation...

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.

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 in AAC53281. Ref.2

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) [UniParc].

Checksum: 3C3850C808606725
Show »

FASTA22225,287

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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		Y14041 mRNA. Translation: CAA74368.1.
Y14042 mRNA. Translation: CAA74369.1.
U97076 mRNA. Translation: AAC53281.1.
IPIIPI00133915.
IPI00230112.
RefSeqNP_997536.1. NM_207653.3.
UniGeneMm.336848.

3D structure databases

ProteinModelPortalO35732.
SMRO35732. Positions 8-180, 242-484.
ModBaseSearch...

Protein-protein interaction databases

IntActO35732. 3 interactions.
STRINGO35732.

Protein family/group databases

MEROPSC14.974.

PTM databases

PhosphoSiteO35732.

Proteomic databases

PRIDEO35732.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID12633.
KEGGmmu:12633.

Organism-specific databases

CTD8837.
MGIMGI:1336166. Cflar.

Phylogenomic databases

eggNOGroNOG12806.
HOVERGENHBG050918.

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. 2 hits.
KOK04724.
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]
SUPFAMSSF47986. DEATH_like. 2 hits.
PROSITEPS50208. CASPASE_P20. 1 hit.
PS50168. DED. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio281824.
SOURCESearch...

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: January 25, 2012
This is version 109 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

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

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents