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O15519

- CFLAR_HUMAN

UniProt

O15519 - CFLAR_HUMAN

Protein

CASP8 and FADD-like apoptosis regulator

Gene

CFLAR

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 151 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      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.1 Publication

    GO - Molecular functioni

    1. cysteine-type peptidase activity Source: InterPro
    2. death effector domain binding Source: RefGenome
    3. enzyme activator activity Source: UniProtKB
    4. protease binding Source: UniProtKB
    5. protein binding Source: IntAct

    GO - Biological processi

    1. apoptotic process Source: UniProtKB
    2. apoptotic signaling pathway Source: Reactome
    3. negative regulation of apoptotic process Source: ProtInc
    4. negative regulation of extrinsic apoptotic signaling pathway Source: UniProtKB
    5. negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: BHF-UCL
    6. negative regulation of myoblast fusion Source: BHF-UCL
    7. positive regulation of catalytic activity Source: GOC
    8. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
    9. positive regulation of NF-kappaB transcription factor activity Source: BHF-UCL
    10. regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: Reactome
    11. regulation of necroptotic process Source: UniProtKB
    12. regulation of satellite cell proliferation Source: BHF-UCL
    13. skeletal muscle atrophy Source: BHF-UCL
    14. skeletal muscle tissue development Source: BHF-UCL
    15. skeletal muscle tissue regeneration Source: BHF-UCL
    16. skeletal myofibril assembly Source: BHF-UCL
    17. viral process Source: UniProtKB-KW

    Keywords - Biological processi

    Apoptosis, Host-virus interaction

    Enzyme and pathway databases

    ReactomeiREACT_164011. Regulation by c-FLIP.
    REACT_402. TRAIL signaling.
    REACT_832. Dimerization of procaspase-8.
    SignaLinkiO15519.

    Protein family/group databases

    MEROPSiC14.971.

    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, CASP8AP1, CLARP, MRIT
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:1876. CFLAR.

    Subcellular locationi

    GO - Cellular componenti

    1. CD95 death-inducing signaling complex Source: Ensembl
    2. cytoplasm Source: UniProtKB
    3. cytosol Source: Reactome
    4. death-inducing signaling complex Source: UniProtKB
    5. ripoptosome Source: UniProtKB

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi360 – 3601Y → F: Decreases apoptosis-inducing activity. Reduces interaction with caspase-3 and proteolytic processing. 1 Publication
    Mutagenesisi376 – 3761D → N or A: Abolishes proteolytic processing. 1 Publication

    Organism-specific databases

    PharmGKBiPA26425.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 376376CASP8 and FADD-like apoptosis regulator subunit p43PRO_0000004678Add
    BLAST
    Chaini377 – 480104CASP8 and FADD-like apoptosis regulator subunit p12Sequence AnalysisPRO_0000004679Add
    BLAST

    Post-translational modificationi

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

    Proteomic databases

    MaxQBiO15519.
    PaxDbiO15519.
    PRIDEiO15519.

    PTM databases

    PhosphoSiteiO15519.

    Expressioni

    Tissue specificityi

    Widely expressed. Higher expression in skeletal muscle, pancreas, heart, kidney, placenta, and peripheral blood leukocytes. Also detected in diverse cell lines. Isoform 8 is predominantly expressed in testis and skeletal muscle.

    Inductioni

    Repressed by IL2/interleukin-2 after TCR stimulation, during progression to the S phase of the cell cycle.1 Publication

    Gene expression databases

    ArrayExpressiO15519.
    BgeeiO15519.
    GenevestigatoriO15519.

    Organism-specific databases

    HPAiCAB022157.
    CAB025216.
    HPA019044.

    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. Also interacts with caspase-10, caspase-3, TRAF1, TRAF2 and Bcl-X(L) (in vitro). Interacts with HBV protein X.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CASP10Q928513EBI-514941,EBI-495095
    CASP10Q92851-43EBI-4478097,EBI-6621134
    CASP8Q147909EBI-514941,EBI-78060
    MAP2K1Q027503EBI-4567563,EBI-492564
    MAP2K7O147332EBI-4567563,EBI-492605

    Protein-protein interaction databases

    BioGridi114364. 36 interactions.
    DIPiDIP-27629N.
    IntActiO15519. 28 interactions.
    MINTiMINT-1529273.

    Structurei

    Secondary structure

    1
    480
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi239 – 2413
    Beta strandi249 – 26012
    Helixi266 – 2749
    Beta strandi276 – 2838
    Helixi286 – 29712
    Helixi300 – 3045
    Beta strandi306 – 31712
    Helixi333 – 3408
    Turni342 – 3443
    Helixi346 – 3483
    Beta strandi353 – 3619
    Beta strandi400 – 40910
    Helixi410 – 4123
    Helixi422 – 43312
    Helixi439 – 45416
    Helixi459 – 4613
    Beta strandi463 – 4697

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3H11X-ray1.90A209-480[»]
    3H13X-ray2.20A209-480[»]
    ProteinModelPortaliO15519.
    SMRiO15519. Positions 4-169, 237-480.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO15519.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini1 – 7373DED 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini92 – 17079DED 2PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 435435Not proteolytically processed and involved in apoptosis inhibitionAdd
    BLAST
    Regioni1 – 305305Interaction with caspase-8 propeptideAdd
    BLAST
    Regioni1 – 227227Interaction with FADDAdd
    BLAST
    Regioni1 – 195195Interaction with caspase-8Add
    BLAST
    Regioni192 – 480289Interaction with TRAF1 and TRAF2Add
    BLAST
    Regioni192 – 435244Interaction with caspase-3Add
    BLAST
    Regioni217 – 480264Interaction with caspase-8 subunits p18 and p10Add
    BLAST
    Regioni263 – 35896CaspaseAdd
    BLAST
    Regioni370 – 480111Interaction with caspase-8Add
    BLAST

    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.
    HOVERGENiHBG050918.
    InParanoidiO15519.
    KOiK04724.
    OMAiYDWNSRV.
    OrthoDBiEOG74N5GK.
    PhylomeDBiO15519.
    TreeFamiTF352765.

    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 (15)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 15 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O15519-1) [UniParc]FASTAAdd to Basket

    Also known as: FLIP-L, CLARP1, MRIT alpha-1, CASH alpha, I-FLICE 1, FLAME-1 gamma, Usurpin 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

    MSAEVIHQVE EALDTDEKEM LLFLCRDVAI DVVPPNVRDL LDILRERGKL    50
    SVGDLAELLY RVRRFDLLKR ILKMDRKAVE THLLRNPHLV SDYRVLMAEI 100
    GEDLDKSDVS SLIFLMKDYM GRGKISKEKS FLDLVVELEK LNLVAPDQLD 150
    LLEKCLKNIH RIDLKTKIQK YKQSVQGAGT SYRNVLQAAI QKSLKDPSNN 200
    FRLHNGRSKE QRLKEQLGAQ QEPVKKSIQE SEAFLPQSIP EERYKMKSKP 250
    LGICLIIDCI GNETELLRDT FTSLGYEVQK FLHLSMHGIS QILGQFACMP 300
    EHRDYDSFVC VLVSRGGSQS VYGVDQTHSG LPLHHIRRMF MGDSCPYLAG 350
    KPKMFFIQNY VVSEGQLEDS SLLEVDGPAM KNVEFKAQKR GLCTVHREAD 400
    FFWSLCTADM SLLEQSHSSP SLYLQCLSQK LRQERKRPLL DLHIELNGYM 450
    YDWNSRVSAK EKYYVWLQHT LRKKLILSYT 480
    Length:480
    Mass (Da):55,344
    Last modified:January 1, 1998 - v1
    Checksum:i8C6D7E92AE1EB672
    GO
    Isoform 2 (identifier: O15519-2) [UniParc]FASTAAdd to Basket

    Also known as: FLIP-S, CLARP2, MRIT beta-1, CASH beta

    The sequence of this isoform differs from the canonical sequence as follows:
         203-221: LHNGRSKEQRLKEQLGAQQ → MITPYAHCPDLKILGNCSM
         222-480: Missing.

    Show »
    Length:221
    Mass (Da):25,379
    Checksum:i12774D7AB3E53263
    GO
    Isoform 3 (identifier: O15519-3) [UniParc]FASTAAdd to Basket

    Also known as: MRIT alpha-2

    The sequence of this isoform differs from the canonical sequence as follows:
         1-96: Missing.
         436-480: KRPLLDLHIELNGYMYDWNSRVSAKEKYYVWLQHTLRKKLILSYT → GTIPGSGITESKDMHFSSLGCILLDVL

    Show »
    Length:366
    Mass (Da):41,319
    Checksum:iB5DB6C8A18608582
    GO
    Isoform 4 (identifier: O15519-4) [UniParc]FASTAAdd to Basket

    Also known as: I-FLICE 2

    The sequence of this isoform differs from the canonical sequence as follows:
         1-245: Missing.

    Show »
    Length:235
    Mass (Da):27,055
    Checksum:i1B34FA73556DC390
    GO
    Isoform 5 (identifier: O15519-5) [UniParc]FASTAAdd to Basket

    Also known as: I-FLICE 3

    The sequence of this isoform differs from the canonical sequence as follows:
         449-480: YMYDWNSRVSAKEKYYVWLQHTLRKKLILSYT → L

    Show »
    Length:449
    Mass (Da):51,390
    Checksum:i8AC8D85BA2F72F7E
    GO
    Isoform 6 (identifier: O15519-6) [UniParc]FASTAAdd to Basket

    Also known as: I-FLICE 4

    The sequence of this isoform differs from the canonical sequence as follows:
         2-30: SAEVIHQVEEALDTDEKEMLLFLCRDVAI → LERPPVCSKV
         453-480: WNSRVSAKEKYYVWLQHTLRKKLILSYT → SLEHTGGRY

    Show »
    Length:442
    Mass (Da):50,661
    Checksum:iB20A318B728B2543
    GO
    Isoform 7 (identifier: O15519-7) [UniParc]FASTAAdd to Basket

    Also known as: I-FLICE 5

    The sequence of this isoform differs from the canonical sequence as follows:
         1-96: Missing.
         203-221: LHNGRSKEQRLKEQLGAQQ → E
         436-480: KRPLLDLHIELNGYMYDWNSRVSAKEKYYVWLQHTLRKKLILSYT → GTIPGSGITESKDMHFSSLGCILLDVL

    Show »
    Length:348
    Mass (Da):39,245
    Checksum:iE9F524387399F9CA
    GO
    Isoform 8 (identifier: O15519-8) [UniParc]FASTAAdd to Basket

    Also known as: FLAME-1 alpha

    The sequence of this isoform differs from the canonical sequence as follows:
         203-237: Missing.

    Show »
    Length:445
    Mass (Da):51,330
    Checksum:i91CD549119606DB2
    GO
    Isoform 9 (identifier: O15519-9) [UniParc]FASTAAdd to Basket

    Also known as: FLAME-1 beta

    The sequence of this isoform differs from the canonical sequence as follows:
         203-237: Missing.
         267-305: LRDTFTSLGY...FACMPEHRDY → CGVRGPAGGQ...ARAVHSSPRS
         306-480: Missing.

    Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

    Show »
    Length:270
    Mass (Da):30,399
    Checksum:i230E9C0C0ADD1003
    GO
    Isoform 10 (identifier: O15519-10) [UniParc]FASTAAdd to Basket

    Also known as: FLAME-1 delta

    The sequence of this isoform differs from the canonical sequence as follows:
         266-300: LLRDTFTSLGYEVQKFLHLSMHGISQILGQFACMP → NAHSWIFTLNSMATCMIGTAEFLPRRNIMFGCSTL
         301-480: Missing.

    Show »
    Length:300
    Mass (Da):34,384
    Checksum:iF6A777C2BA1469EF
    GO
    Isoform 11 (identifier: O15519-11) [UniParc]FASTAAdd to Basket

    Also known as: Usurpin beta

    The sequence of this isoform differs from the canonical sequence as follows:
         436-480: KRPLLDLHIELNGYMYDWNSRVSAKEKYYVWLQHTLRKKLILSYT → GTIPGSGITESKDMHFSSLGCILLDVL

    Show »
    Length:462
    Mass (Da):52,551
    Checksum:iD4E0109CBA47EAA3
    GO
    Isoform 12 (identifier: O15519-12) [UniParc]FASTAAdd to Basket

    Also known as: Usurpin gamma

    The sequence of this isoform differs from the canonical sequence as follows:
         265-292: ELLRDTFTSLGYEVQKFLHLSMHGISQI → GWSAMAQSQLTAISTSQVQAILLPQPPE
         293-480: Missing.

    Show »
    Length:292
    Mass (Da):33,273
    Checksum:i542E30BD5169F336
    GO
    Isoform 13 (identifier: O15519-13) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         203-480: Missing.

    Show »
    Length:202
    Mass (Da):23,289
    Checksum:i67D3C756AFD14F94
    GO
    Isoform 14 (identifier: O15519-14) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         436-480: Missing.

    Show »
    Length:435
    Mass (Da):49,778
    Checksum:iB37ED523D7738376
    GO
    Isoform 15 (identifier: O15519-15) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-96: Missing.

    Show »
    Length:384
    Mass (Da):44,112
    Checksum:i846E6372DB81F0F6
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti130 – 1323SFL → ISW in AAC15825. (PubMed:9380701)Curated
    Sequence conflicti130 – 1323SFL → ISW in AAC15826. (PubMed:9380701)Curated
    Sequence conflicti343 – 3431D → E in AAC15825. (PubMed:9380701)Curated
    Sequence conflicti364 – 3641E → D in AAB99794. 1 PublicationCurated
    Sequence conflicti366 – 3683QLE → PAG in AAC15825. (PubMed:9380701)Curated
    Sequence conflicti369 – 3691D → N in CAA74366. (PubMed:9289491)Curated
    Sequence conflicti372 – 3721L → F in AAB99793. 1 PublicationCurated
    Sequence conflicti373 – 3742LE → WR in AAC15825. (PubMed:9380701)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti203 – 2031L → I.
    Corresponds to variant rs13424615 [ dbSNP | Ensembl ].
    VAR_048619

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 245245Missing in isoform 4. 1 PublicationVSP_000825Add
    BLAST
    Alternative sequencei1 – 9696Missing in isoform 3, isoform 7 and isoform 15. 3 PublicationsVSP_000824Add
    BLAST
    Alternative sequencei2 – 3029SAEVI…RDVAI → LERPPVCSKV in isoform 6. 1 PublicationVSP_000826Add
    BLAST
    Alternative sequencei203 – 480278Missing in isoform 13. 1 PublicationVSP_000831Add
    BLAST
    Alternative sequencei203 – 23735Missing in isoform 8 and isoform 9. 1 PublicationVSP_000830Add
    BLAST
    Alternative sequencei203 – 22119LHNGR…LGAQQ → MITPYAHCPDLKILGNCSM in isoform 2. 4 PublicationsVSP_000828Add
    BLAST
    Alternative sequencei203 – 22119LHNGR…LGAQQ → E in isoform 7. 1 PublicationVSP_000827Add
    BLAST
    Alternative sequencei222 – 480259Missing in isoform 2. 4 PublicationsVSP_000829Add
    BLAST
    Alternative sequencei265 – 29228ELLRD…GISQI → GWSAMAQSQLTAISTSQVQA ILLPQPPE in isoform 12. 1 PublicationVSP_000832Add
    BLAST
    Alternative sequencei266 – 30035LLRDT…FACMP → NAHSWIFTLNSMATCMIGTA EFLPRRNIMFGCSTL in isoform 10. 1 PublicationVSP_000834Add
    BLAST
    Alternative sequencei267 – 30539LRDTF…EHRDY → CGVRGPAGGQQPLGGGWASD EECGIQGSEARAVHSSPRS in isoform 9. 1 PublicationVSP_000836Add
    BLAST
    Alternative sequencei293 – 480188Missing in isoform 12. 1 PublicationVSP_000833Add
    BLAST
    Alternative sequencei301 – 480180Missing in isoform 10. 1 PublicationVSP_000835Add
    BLAST
    Alternative sequencei306 – 480175Missing in isoform 9. 1 PublicationVSP_000837Add
    BLAST
    Alternative sequencei436 – 48045KRPLL…ILSYT → GTIPGSGITESKDMHFSSLG CILLDVL in isoform 11, isoform 7 and isoform 3. 4 PublicationsVSP_000838Add
    BLAST
    Alternative sequencei436 – 48045Missing in isoform 14. 1 PublicationVSP_000839Add
    BLAST
    Alternative sequencei449 – 48032YMYDW…ILSYT → L in isoform 5. 1 PublicationVSP_000840Add
    BLAST
    Alternative sequencei453 – 48028WNSRV…ILSYT → SLEHTGGRY in isoform 6. 1 PublicationVSP_000841Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF010127 mRNA. Translation: AAB64110.1.
    U85059 mRNA. Translation: AAB82648.1.
    U97074 mRNA. Translation: AAC51622.1.
    U97075 mRNA. Translation: AAC51623.1.
    AF009616 mRNA. Translation: AAB70909.1.
    AF009617 mRNA. Translation: AAB70910.1.
    AF009618 mRNA. Translation: AAB70911.1.
    AF009619 mRNA. Translation: AAB70912.1.
    AF041458 mRNA. Translation: AAB99790.1.
    AF041459 mRNA. Translation: AAB99791.1.
    AF041462 mRNA. Translation: AAB99794.1.
    AF041461 mRNA. Translation: AAB99793.1.
    AF041460 mRNA. Translation: AAB99792.1.
    Y14039 mRNA. Translation: CAA74366.1.
    Y14040 mRNA. Translation: CAA74367.1.
    AF005774 mRNA. Translation: AAC15825.1.
    AF005775 mRNA. Translation: AAC15826.1.
    AF015450 mRNA. Translation: AAC16439.1.
    AF015451 mRNA. Translation: AAC16440.1.
    AF015452 mRNA. Translation: AAC16441.1.
    AB038972 Genomic DNA. Translation: BAB32551.1.
    AB038972 Genomic DNA. Translation: BAB32552.1.
    BT006751 mRNA. Translation: AAP35397.1.
    AK289913 mRNA. Translation: BAF82602.1.
    AK296036 mRNA. Translation: BAG58802.1.
    AK315208 mRNA. Translation: BAG37645.1.
    AK315924 mRNA. Translation: BAH14295.1.
    AC007283 Genomic DNA. Translation: AAY24290.1.
    CH471063 Genomic DNA. Translation: EAW70237.1.
    CH471063 Genomic DNA. Translation: EAW70244.1.
    BC001602 mRNA. Translation: AAH01602.1.
    CCDSiCCDS2337.1. [O15519-1]
    CCDS46487.1. [O15519-2]
    CCDS56157.1. [O15519-8]
    CCDS56158.1. [O15519-15]
    CCDS59436.1. [O15519-3]
    RefSeqiNP_001120655.1. NM_001127183.2. [O15519-1]
    NP_001120656.1. NM_001127184.2. [O15519-2]
    NP_001189444.1. NM_001202515.1. [O15519-4]
    NP_001189445.1. NM_001202516.1. [O15519-8]
    NP_001189446.1. NM_001202517.1. [O15519-15]
    NP_001189447.1. NM_001202518.1. [O15519-3]
    NP_001189448.1. NM_001202519.1. [O15519-3]
    NP_003870.4. NM_003879.5. [O15519-1]
    XP_005246992.1. XM_005246935.2. [O15519-1]
    XP_005246993.1. XM_005246936.2. [O15519-1]
    XP_005246994.1. XM_005246937.2. [O15519-11]
    UniGeneiHs.390736.
    Hs.731912.

    Genome annotation databases

    EnsembliENST00000309955; ENSP00000312455; ENSG00000003402. [O15519-1]
    ENST00000340870; ENSP00000339326; ENSG00000003402. [O15519-11]
    ENST00000341222; ENSP00000339335; ENSG00000003402. [O15519-2]
    ENST00000341582; ENSP00000345807; ENSG00000003402. [O15519-8]
    ENST00000342795; ENSP00000342809; ENSG00000003402. [O15519-12]
    ENST00000423241; ENSP00000399420; ENSG00000003402. [O15519-1]
    ENST00000440180; ENSP00000406775; ENSG00000003402. [O15519-2]
    ENST00000443227; ENSP00000413270; ENSG00000003402. [O15519-15]
    ENST00000457277; ENSP00000411535; ENSG00000003402. [O15519-11]
    ENST00000479953; ENSP00000471805; ENSG00000003402. [O15519-3]
    GeneIDi8837.
    KEGGihsa:8837.
    UCSCiuc002uwz.3. human. [O15519-2]
    uc002uxb.4. human. [O15519-1]
    uc002uxc.4. human. [O15519-8]
    uc002uxf.3. human. [O15519-11]
    uc002uxg.3. human. [O15519-4]
    uc010fsw.3. human. [O15519-3]
    uc010fsz.3. human. [O15519-7]
    uc021vuw.1. human. [O15519-12]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF010127 mRNA. Translation: AAB64110.1 .
    U85059 mRNA. Translation: AAB82648.1 .
    U97074 mRNA. Translation: AAC51622.1 .
    U97075 mRNA. Translation: AAC51623.1 .
    AF009616 mRNA. Translation: AAB70909.1 .
    AF009617 mRNA. Translation: AAB70910.1 .
    AF009618 mRNA. Translation: AAB70911.1 .
    AF009619 mRNA. Translation: AAB70912.1 .
    AF041458 mRNA. Translation: AAB99790.1 .
    AF041459 mRNA. Translation: AAB99791.1 .
    AF041462 mRNA. Translation: AAB99794.1 .
    AF041461 mRNA. Translation: AAB99793.1 .
    AF041460 mRNA. Translation: AAB99792.1 .
    Y14039 mRNA. Translation: CAA74366.1 .
    Y14040 mRNA. Translation: CAA74367.1 .
    AF005774 mRNA. Translation: AAC15825.1 .
    AF005775 mRNA. Translation: AAC15826.1 .
    AF015450 mRNA. Translation: AAC16439.1 .
    AF015451 mRNA. Translation: AAC16440.1 .
    AF015452 mRNA. Translation: AAC16441.1 .
    AB038972 Genomic DNA. Translation: BAB32551.1 .
    AB038972 Genomic DNA. Translation: BAB32552.1 .
    BT006751 mRNA. Translation: AAP35397.1 .
    AK289913 mRNA. Translation: BAF82602.1 .
    AK296036 mRNA. Translation: BAG58802.1 .
    AK315208 mRNA. Translation: BAG37645.1 .
    AK315924 mRNA. Translation: BAH14295.1 .
    AC007283 Genomic DNA. Translation: AAY24290.1 .
    CH471063 Genomic DNA. Translation: EAW70237.1 .
    CH471063 Genomic DNA. Translation: EAW70244.1 .
    BC001602 mRNA. Translation: AAH01602.1 .
    CCDSi CCDS2337.1. [O15519-1 ]
    CCDS46487.1. [O15519-2 ]
    CCDS56157.1. [O15519-8 ]
    CCDS56158.1. [O15519-15 ]
    CCDS59436.1. [O15519-3 ]
    RefSeqi NP_001120655.1. NM_001127183.2. [O15519-1 ]
    NP_001120656.1. NM_001127184.2. [O15519-2 ]
    NP_001189444.1. NM_001202515.1. [O15519-4 ]
    NP_001189445.1. NM_001202516.1. [O15519-8 ]
    NP_001189446.1. NM_001202517.1. [O15519-15 ]
    NP_001189447.1. NM_001202518.1. [O15519-3 ]
    NP_001189448.1. NM_001202519.1. [O15519-3 ]
    NP_003870.4. NM_003879.5. [O15519-1 ]
    XP_005246992.1. XM_005246935.2. [O15519-1 ]
    XP_005246993.1. XM_005246936.2. [O15519-1 ]
    XP_005246994.1. XM_005246937.2. [O15519-11 ]
    UniGenei Hs.390736.
    Hs.731912.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3H11 X-ray 1.90 A 209-480 [» ]
    3H13 X-ray 2.20 A 209-480 [» ]
    ProteinModelPortali O15519.
    SMRi O15519. Positions 4-169, 237-480.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114364. 36 interactions.
    DIPi DIP-27629N.
    IntActi O15519. 28 interactions.
    MINTi MINT-1529273.

    Chemistry

    ChEMBLi CHEMBL1955713.

    Protein family/group databases

    MEROPSi C14.971.

    PTM databases

    PhosphoSitei O15519.

    Proteomic databases

    MaxQBi O15519.
    PaxDbi O15519.
    PRIDEi O15519.

    Protocols and materials databases

    DNASUi 8837.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000309955 ; ENSP00000312455 ; ENSG00000003402 . [O15519-1 ]
    ENST00000340870 ; ENSP00000339326 ; ENSG00000003402 . [O15519-11 ]
    ENST00000341222 ; ENSP00000339335 ; ENSG00000003402 . [O15519-2 ]
    ENST00000341582 ; ENSP00000345807 ; ENSG00000003402 . [O15519-8 ]
    ENST00000342795 ; ENSP00000342809 ; ENSG00000003402 . [O15519-12 ]
    ENST00000423241 ; ENSP00000399420 ; ENSG00000003402 . [O15519-1 ]
    ENST00000440180 ; ENSP00000406775 ; ENSG00000003402 . [O15519-2 ]
    ENST00000443227 ; ENSP00000413270 ; ENSG00000003402 . [O15519-15 ]
    ENST00000457277 ; ENSP00000411535 ; ENSG00000003402 . [O15519-11 ]
    ENST00000479953 ; ENSP00000471805 ; ENSG00000003402 . [O15519-3 ]
    GeneIDi 8837.
    KEGGi hsa:8837.
    UCSCi uc002uwz.3. human. [O15519-2 ]
    uc002uxb.4. human. [O15519-1 ]
    uc002uxc.4. human. [O15519-8 ]
    uc002uxf.3. human. [O15519-11 ]
    uc002uxg.3. human. [O15519-4 ]
    uc010fsw.3. human. [O15519-3 ]
    uc010fsz.3. human. [O15519-7 ]
    uc021vuw.1. human. [O15519-12 ]

    Organism-specific databases

    CTDi 8837.
    GeneCardsi GC02P201980.
    HGNCi HGNC:1876. CFLAR.
    HPAi CAB022157.
    CAB025216.
    HPA019044.
    MIMi 603599. gene.
    neXtProti NX_O15519.
    PharmGKBi PA26425.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG331323.
    HOVERGENi HBG050918.
    InParanoidi O15519.
    KOi K04724.
    OMAi YDWNSRV.
    OrthoDBi EOG74N5GK.
    PhylomeDBi O15519.
    TreeFami TF352765.

    Enzyme and pathway databases

    Reactomei REACT_164011. Regulation by c-FLIP.
    REACT_402. TRAIL signaling.
    REACT_832. Dimerization of procaspase-8.
    SignaLinki O15519.

    Miscellaneous databases

    ChiTaRSi CFLAR. human.
    EvolutionaryTracei O15519.
    GeneWikii CFLAR.
    GenomeRNAii 8837.
    NextBioi 33168.
    PROi O15519.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O15519.
    Bgeei O15519.
    Genevestigatori O15519.

    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. "Casper is a FADD- and caspase-related inducer of apoptosis."
      Shu H.-B., Halpin D.R., Goeddel D.V.
      Immunity 6:751-763(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 13 AND 14), MUTAGENESIS OF TYR-360.
      Tissue: Embryonic kidney and Umbilical vein endothelial cell.
    2. "MRIT, a novel death-effector domain-containing protein, interacts with caspases and BclXL and initiates cell death."
      Han D.K.M., Chaudhary P.M., Wright M.E., Friedman C., Trask B.J., Riedel R.T., Baskin D.G., Schwartz S.M., Hood L.
      Proc. Natl. Acad. Sci. U.S.A. 94:11333-11338(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
    3. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
      Tissue: Peripheral blood lymphocyte.
    4. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 8; 9 AND 10), MUTAGENESIS OF ASP-376.
      Tissue: T-cell.
    5. "I-FLICE, a novel inhibitor of tumor necrosis factor receptor-1- and CD-95-induced apoptosis."
      Hu S., Vincenz C., Ni J., Gentz R., Dixit V.M.
      J. Biol. Chem. 272:17255-17257(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Umbilical vein endothelial cell.
    6. Hu S., Dixit V.M.
      Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4; 5; 6 AND 7).
    7. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
      Tissue: Skin fibroblast.
    8. "CLARP, a death effector domain-containing protein interacts with caspase-8 and regulates apoptosis."
      Inohara N., Koseki T., Hu Y., Chen S., Nunez G.
      Proc. Natl. Acad. Sci. U.S.A. 94:10717-10722(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
      Tissue: Colon carcinoma.
    9. "Cell death attenuation by 'Usurpin', a mammalian DED-caspase homologue that precludes caspase-8 recruitment and activation by the CD-95 (Fas, APO-1) receptor complex."
      Rasper D.M., Vaillancourt J.P., Hadano S., Houtzager V.M., Seiden I., Keen S.L.C., Tawa P., Xanthoudakis S., Nasir J., Martindale D., Koop B.F., Peterson E.P., Thornberry N.A., Huang J., MacPherson D.P., Black S.C., Hornung F., Lenardo M.J.
      , Hayden M.R., Roy S., Nicholson D.W.
      Cell Death Differ. 5:271-288(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 11 AND 12).
      Tissue: Kidney.
    10. "Cloning and characterization of three novel genes, ALS2CR1, ALS2CR2, and ALS2CR3, in the juvenile amyotrophic lateral sclerosis (ALS2) critical region at chromosome 2q33-q34: candidate genes for ALS2."
      Hadano S., Yanagisawa Y., Skaug J., Fichter K., Nasir J., Martindale D., Koop B.F., Scherer S.W., Nicholson D.W., Rouleau G.A., Ikeda J.-E., Hayden M.R.
      Genomics 71:200-213(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    11. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    12. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 15).
      Tissue: Cerebellum, Corpus callosum and Subthalamic nucleus.
    13. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
      Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
      , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
      Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    14. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    15. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Lymph.
    16. "The role of c-FLIP in modulation of CD95-induced apoptosis."
      Scaffidi C., Schmitz I., Krammer P.H., Peter M.E.
      J. Biol. Chem. 274:1541-1548(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    17. "Cell cycle-dependent regulation of FLIP levels and susceptibility to Fas-mediated apoptosis."
      Algeciras-Schimnich A., Griffith T.S., Lynch D.H., Paya C.V.
      J. Immunol. 162:5205-5211(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.
    18. "Pro-apoptotic function of HBV X protein is mediated by interaction with c-FLIP and enhancement of death-inducing signal."
      Kim K.H., Seong B.L.
      EMBO J. 22:2104-2116(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HBV PROTEIN X.
    19. Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).

    Entry informationi

    Entry nameiCFLAR_HUMAN
    AccessioniPrimary (citable) accession number: O15519
    Secondary accession number(s): B4DJE0
    , B7Z9F9, O14673, O14674, O14675, O15137, O15138, O15356, O15510, O43618, O43619, O43620, O60458, O60459, Q53TS6, Q54AF1, Q96TE4, Q9UEW1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: January 1, 1998
    Last modified: October 1, 2014
    This is version 151 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Peptidase families
      Classification of peptidase families and list of entries
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3