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Protein

CASP8 and FADD-like apoptosis regulator

Gene

Cflar

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Keywordsi

Biological processApoptosis

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:1336166 Cflar

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000046801 – 377CASP8 and FADD-like apoptosis regulator subunit p43By similarityAdd BLAST377
ChainiPRO_0000004681378 – 481CASP8 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 9.5 and 10.5 dpc, highly expressed 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

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

Protein-protein interaction databases

BioGridi198686, 6 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
Regioni265 – 360CaspaseAdd BLAST96

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi418 – 422Poly-Ser5

Domaini

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

Sequence similaritiesi

Belongs to the peptidase C14A family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3573 Eukaryota
ENOG410ZQIE LUCA
GeneTreeiENSGT00530000064199
HOGENOMiHOG000069972
HOVERGENiHBG050918
InParanoidiO35732
KOiK04724
OrthoDBiEOG091G05YD

Family and domain databases

CDDicd00032 CASc, 1 hit
InterProiView protein in InterPro
IPR029030 Caspase-like_dom_sf
IPR011029 DEATH-like_dom_sf
IPR001875 DED_dom
IPR001309 Pept_C14_p20
IPR015917 Pept_C14A
PfamiView protein in Pfam
PF01335 DED, 2 hits
SMARTiView protein in SMART
SM00115 CASc, 1 hit
SM00031 DED, 2 hits
SUPFAMiSSF47986 SSF47986, 2 hits
SSF52129 SSF52129, 1 hit
PROSITEiView protein in PROSITE
PS50208 CASPASE_P20, 1 hit
PS50168 DED, 2 hits

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
YNSRLQNGRS KEPRFVEYRD SQRTLVKTSI QESGAFLPPH IREETYRMQS
260 270 280 290 300
KPLGICLIID CIGNDTKYLQ ETFTSLGYHI QLFLFPKSHD ITQIVRRYAS
310 320 330 340 350
MAQHQDYDSF ACVLVSLGGS QSMMGRDQVH SGFSLDHVKN MFTGDTCPSL
360 370 380 390 400
RGKPKLFFIQ NYESLGSQLE DSSLEVDGPS IKNVDSKPLQ PRHCTTHPEA
410 420 430 440 450
DIFWSLCTAD VSHLEKPSSS SSVYLQKLSQ QLKQGRRRPL VDLHVELMDK
460 470 480
VYAWNSGVSS KEKYSLSLQH TLRKKLILAP T
Length:481
Mass (Da):54,875
Last modified:October 25, 2017 - v3
Checksum:i433E07E2E5FA5A05
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:
     205-215: LQNGRSKEPRF → VSLEPVYGVPA
     216-481: Missing.

Show »
Length:215
Mass (Da):24,534
Checksum:i3E13F936D5F21580
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti121T → TRIT in CAA74369 (PubMed:9289491).Curated1
Sequence conflicti121T → TRIT in CAA74368 (PubMed:9289491).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_000842205 – 215LQNGRSKEPRF → VSLEPVYGVPA in isoform 2. 1 PublicationAdd BLAST11
Alternative sequenceiVSP_000843216 – 481Missing 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.
CCDSiCCDS14978.1 [O35732-1]
CCDS35582.1 [O35732-2]
RefSeqiNP_001276633.1, NM_001289704.2 [O35732-1]
NP_997536.1, NM_207653.5 [O35732-1]
XP_006495698.1, XM_006495635.3 [O35732-1]
XP_011236722.1, XM_011238420.2 [O35732-1]
XP_011236723.1, XM_011238421.2 [O35732-1]
XP_011236724.1, XM_011238422.1 [O35732-1]
XP_011236725.1, XM_011238423.2 [O35732-1]
XP_017169048.1, XM_017313559.1 [O35732-1]
UniGeneiMm.336848
Mm.486313

Genome annotation databases

EnsembliENSMUST00000069333; ENSMUSP00000065107; ENSMUSG00000026031 [O35732-1]
ENSMUST00000114309; ENSMUSP00000109948; ENSMUSG00000026031 [O35732-2]
ENSMUST00000114313; ENSMUSP00000109952; ENSMUSG00000026031 [O35732-1]
GeneIDi12633
KEGGimmu:12633

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiCFLAR_MOUSE
AccessioniPrimary (citable) accession number: O35732
Secondary accession number(s): D3Z0W6, O35707, O35733
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: October 25, 2017
Last modified: June 20, 2018
This is version 168 of the entry and version 3 of the sequence. See 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

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