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O35732 (CFLAR_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

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
Gene names
Name:Cflar
Synonyms:Cash
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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.4 Ref.5

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.

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
     219-484: 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 – 17276DED 2
Region268 – 36396Caspase
Compositional bias421 – 4255Poly-Ser

Natural variations

Alternative sequence208 – 21811LQNGRSKEPRF → VSLEPVYGVPA in isoform 2.
VSP_000842
Alternative sequence219 – 484266Missing in isoform 2.
VSP_000843

Experimental info

Sequence conflict1211T → TRIT in CAA74369. Ref.1
Sequence conflict1211T → TRIT in CAA74368. Ref.1
Sequence conflict201 – 2077PSVLYLK → YNSR in CAA74368. Ref.1
Sequence conflict201 – 2077PSVLYLK → YNSR in AAC53281. Ref.2

Sequences

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

Last modified October 3, 2012. Version 2.
Checksum: B272DE6DB2861C86

FASTA48455,155
        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 
TRDYTGRGKI AKDKSFLDLV IELEKLNLIA SDQLNLLEKC LKNIHRIDLN TKIQKYTQSS 

       190        200        210        220        230        240 
QGARSNMNTL QASLPKLSIK PSVLYLKLQN 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: E42F32F27C66C337
Show »

FASTA21824,815

References

« Hide 'large scale' 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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Heart.
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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.
+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.
AC112968 Genomic DNA. No translation available.
RefSeqNP_001276633.1. NM_001289704.1.
NP_997536.1. NM_207653.4.
XP_006495698.1. XM_006495635.1.
UniGeneMm.336848.
Mm.486313.

3D structure databases

ProteinModelPortalO35732.
SMRO35732. Positions 12-182, 244-484.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198686. 7 interactions.
IntActO35732. 2 interactions.

Protein family/group databases

MEROPSC14.974.

PTM databases

PhosphoSiteO35732.

Proteomic databases

PRIDEO35732.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000097722; ENSMUSP00000095329; ENSMUSG00000026031. [O35732-1]
GeneID12633.
KEGGmmu:12633.
UCSCuc007bco.1. mouse. [O35732-1]

Organism-specific databases

CTD8837.
MGIMGI:1336166. Cflar.

Phylogenomic databases

eggNOGNOG331323.
GeneTreeENSGT00530000064199.
HOGENOMHOG000069972.
HOVERGENHBG050918.
KOK04724.
OMAYDWNSRV.
OrthoDBEOG74N5GK.

Gene expression databases

ArrayExpressO35732.
BgeeO35732.
CleanExMM_CFLAR.
GenevestigatorO35732.

Family and domain databases

Gene3D1.10.533.10. 3 hits.
3.40.50.1460. 1 hit.
InterProIPR029030. 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]
PfamPF01335. DED. 2 hits.
PF00656. Peptidase_C14. 1 hit.
[Graphical view]
SMARTSM00115. CASc. 1 hit.
SM00031. DED. 2 hits.
[Graphical view]
SUPFAMSSF47986. SSF47986. 2 hits.
PROSITEPS50208. CASPASE_P20. 1 hit.
PS50168. DED. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCFLAR. mouse.
NextBio281824.
PROO35732.
SOURCESearch...

Entry information

Entry nameCFLAR_MOUSE
AccessionPrimary (citable) accession number: O35732
Secondary accession number(s): D3Z0W6, O35707, O35733
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: October 3, 2012
Last modified: June 11, 2014
This is version 132 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

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