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O35732

- CFLAR_MOUSE

UniProt

O35732 - CFLAR_MOUSE

Protein

CASP8 and FADD-like apoptosis regulator

Gene

Cflar

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 134 (01 Oct 2014)
      Sequence version 2 (03 Oct 2012)
      Previous versions | rss
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    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

    Keywords - Biological processi

    Apoptosis

    Enzyme and pathway databases

    ReactomeiREACT_215122. Regulation by c-FLIP.

    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

    ArrayExpressiO35732.
    BgeeiO35732.
    CleanExiMM_CFLAR.
    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.
    KOiK04724.
    OMAiYDWNSRV.
    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

    MAQSPVSAEV IHQVEECLDE DEKEMMLFLC RDVTENLAAP NVRDLLDSLS    50
    ERGQLSFATL AELLYRVRRF DLLKRILKTD KATVEDHLRR NPHLVSDYRV 100
    LLMEIGESLD QNDVSSLVFL TRDYTGRGKI AKDKSFLDLV IELEKLNLIA 150
    SDQLNLLEKC LKNIHRIDLN TKIQKYTQSS QGARSNMNTL QASLPKLSIK 200
    PSVLYLKLQN GRSKEPRFVE YRDSQRTLVK TSIQESGAFL PPHIREETYR 250
    MQSKPLGICL IIDCIGNDTK YLQETFTSLG YHIQLFLFPK SHDITQIVRR 300
    YASMAQHQDY DSFACVLVSL GGSQSMMGRD QVHSGFSLDH VKNMFTGDTC 350
    PSLRGKPKLF FIQNYESLGS QLEDSSLEVD GPSIKNVDSK PLQPRHCTTH 400
    PEADIFWSLC TADVSHLEKP SSSSSVYLQK LSQQLKQGRR RPLVDLHVEL 450
    MDKVYAWNSG VSSKEKYSLS LQHTLRKKLI LAPT 484
    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:
    EMBL
    GenBank
    DDBJ
    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_001289704.1.
    NP_997536.1. NM_207653.4.
    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y14041 mRNA. Translation: CAA74368.1 .
    Y14042 mRNA. Translation: CAA74369.1 .
    U97076 mRNA. Translation: AAC53281.1 .
    AC112968 Genomic DNA. No translation available.
    RefSeqi NP_001276633.1. NM_001289704.1.
    NP_997536.1. NM_207653.4.
    XP_006495698.1. XM_006495635.1.
    UniGenei Mm.336848.
    Mm.486313.

    3D structure databases

    ProteinModelPortali O35732.
    SMRi O35732. Positions 12-182, 244-484.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 198686. 7 interactions.
    IntActi O35732. 2 interactions.

    Protein family/group databases

    MEROPSi C14.974.

    PTM databases

    PhosphoSitei O35732.

    Proteomic databases

    PRIDEi O35732.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000097722 ; ENSMUSP00000095329 ; ENSMUSG00000026031 . [O35732-1 ]
    GeneIDi 12633.
    KEGGi mmu:12633.
    UCSCi uc007bco.1. mouse. [O35732-1 ]

    Organism-specific databases

    CTDi 8837.
    MGIi MGI:1336166. Cflar.

    Phylogenomic databases

    eggNOGi NOG331323.
    GeneTreei ENSGT00530000064199.
    HOGENOMi HOG000069972.
    HOVERGENi HBG050918.
    KOi K04724.
    OMAi YDWNSRV.
    OrthoDBi EOG74N5GK.

    Enzyme and pathway databases

    Reactomei REACT_215122. Regulation by c-FLIP.

    Miscellaneous databases

    ChiTaRSi CFLAR. mouse.
    NextBioi 281824.
    PROi O35732.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O35732.
    Bgeei O35732.
    CleanExi MM_CFLAR.
    Genevestigatori O35732.

    Family and domain databases

    Gene3Di 1.10.533.10. 3 hits.
    3.40.50.1460. 1 hit.
    InterProi IPR029030. 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 ]
    Pfami PF01335. DED. 2 hits.
    PF00656. Peptidase_C14. 1 hit.
    [Graphical view ]
    SMARTi SM00115. CASc. 1 hit.
    SM00031. DED. 2 hits.
    [Graphical view ]
    SUPFAMi SSF47986. SSF47986. 2 hits.
    PROSITEi PS50208. CASPASE_P20. 1 hit.
    PS50168. DED. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 134 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