CFLAR (Homo sapiens)
Description [+]
- Synonyms: CFLAR, CASH, CASPER, CLARP, FLAME, FLIP, I-FLICE, MRIT
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: CASP8 and FADD-like apoptosis regulator Precursor (Cellular FLICE-like inhibitory protein)(c-FLIP)(Caspase-eight-related protein)(Casper)(Caspase-like apoptosis regulatory protein)(CLARP)(MACH-related inducer of toxicity)(MRIT)(Caspase homolog)(CASH)(Inhibitor of FLICE)(I-FLICE)(FADD-like antiapoptotic molecule 1)(FLAME-1)(Usurpin) [Contains CASP8 and FADD-like apoptosis regulator subunit p43;CASP8 and FADD-like apoptosis regulator subunit p12] [Source:UniProtKB/Swiss-Prot;Acc:O15519]
- Family: caspase Death effector domain-containing protein : other
- Process: apoptosis,
- Pathways: extrinsic pathway,
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): Cflar
- WIKI: CFLAR-H_sapiens
References [+]
- Inhibition of death receptor signals by cellular FLIP.
- Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V, Bodmer JL, Schroter M, Burns K, Mattmann C, Rimoldi D, French LE, Tschopp J
- The widely expressed protein Fas is a member of the tumour necrosis factor receptor family which can trigger apoptosis. However, Fas surface expression does not necessarily render cells susceptible to Fas ligand-induced death signals, indicating that inhibitors of the apoptosis-signalling pathway must exist. Here we report the characterization of an inhibitor of apoptosis, designated FLIP (for FLICE-inhibitory protein), which is predominantly expressed in muscle and lymphoid tissues. The short form, FLIPs, contains two death effector domains and is structurally related to the viral FLIP inhibitors of apoptosis, whereas the long form, FLIP(L), contains in addition a caspase-like domain in which the active-centre cysteine residue is substituted by a tyrosine residue. FLIPs and FLIP(L) interact with the adaptor protein FADD and the protease FLICE, and potently inhibit apoptosis induced by all known human death receptors. FLIP(L) is expressed during the early stage of T-cell activation, but disappears when T cells become susceptible to Fas ligand-mediated apoptosis. High levels of FLIP(L) protein are also detectable in melanoma cell lines and malignant melanoma tumours. Thus FLIP may be implicated in tissue homeostasis as an important regulator of apoptosis. Nature. 1997 Jul 10;388(6638):190-5.
- References from Mouse ortholog(s):
- Requirement for Casper (c-FLIP) in regulation of death receptor-induced apoptosis and embryonic development.
- Yeh WC, Itie A, Elia AJ, Ng M, Shu HB, Wakeham A, Mirtsos C, Suzuki N, Bonnard M, Goeddel DV, Mak TW
- Casper (c-FLIP) associates with FADD and caspase-8 in signaling complexes downstream of death receptors like Fas. We generated Casper-deficient mice and cells and noted a duality in the physiological functions of this molecule. casper-/- embryos do not survive past day 10.5 of embryogenesis and exhibit impaired heart development. This phenotype is reminiscent of that reported for FADD-/- and caspase-8-/- embryos. However, unlike FADD-/- and caspase-8-/- cells, casper-/- embryonic fibroblasts are highly sensitive to FasL- or TNF-induced apoptosis and show rapid induction of caspase activities. NF-kappaB and JNK/SAPK activation is intact in TNF-stimulated casper-/- cells. These results suggest that Casper has two distinct roles: to cooperate with FADD and caspase-8 during embryonic development and to mediate cytoprotection against death factor-induced apoptosis. Immunity. 2000 Jun;12(6):633-42.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | DED | 2 | 79 |
| PFAM A | DED | 93 | 176 |
| PFAM A | Peptidase_C14 | 252 | 477 |
Protein sequence [+]
CFLAR | Homo sapiens | 9606 | length:480
MSAEVIHQVEEALDTDEKEMLLFLCRDVAIDVVPPNVRDLLDILRERGKLSVGDLAELLY
RVRRFDLLKRILKMDRKAVETHLLRNPHLVSDYRVLMAEIGEDLDKSDVSSLIFLMKDYM
GRGKISKEKSFLDLVVELEKLNLVAPDQLDLLEKCLKNIHRIDLKTKIQKYKQSVQGAGT
SYRNVLQAAIQKSLKDPSNNFRLHNGRSKEQRLKEQLGAQQEPVKKSIQESEAFLPQSIP
EERYKMKSKPLGICLIIDCIGNETELLRDTFTSLGYEVQKFLHLSMHGISQILGQFACMP
EHRDYDSFVCVLVSRGGSQSVYGVDQTHSGLPLHHIRRMFMGDSCPYLAGKPKMFFIQNY
VVSEGQLEDSSLLEVDGPAMKNVEFKAQKRGLCTVHREADFFWSLCTADMSLLEQSHSSP
SLYLQCLSQKLRQERKRPLLDLHIELNGYMYDWNSRVSAKEKYYVWLQHTLRKKLILSYT
RVRRFDLLKRILKMDRKAVETHLLRNPHLVSDYRVLMAEIGEDLDKSDVSSLIFLMKDYM
GRGKISKEKSFLDLVVELEKLNLVAPDQLDLLEKCLKNIHRIDLKTKIQKYKQSVQGAGT
SYRNVLQAAIQKSLKDPSNNFRLHNGRSKEQRLKEQLGAQQEPVKKSIQESEAFLPQSIP
EERYKMKSKPLGICLIIDCIGNETELLRDTFTSLGYEVQKFLHLSMHGISQILGQFACMP
EHRDYDSFVCVLVSRGGSQSVYGVDQTHSGLPLHHIRRMFMGDSCPYLAGKPKMFFIQNY
VVSEGQLEDSSLLEVDGPAMKNVEFKAQKRGLCTVHREADFFWSLCTADMSLLEQSHSSP
SLYLQCLSQKLRQERKRPLLDLHIELNGYMYDWNSRVSAKEKYYVWLQHTLRKKLILSYT
Structure links:
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| CFLAR | orthology | Chicken |
| CFLAR | orthology | Chimpanzee |
| NP_001012281.1 | orthology | Cow |
| CFLAR | orthology | Dog |
| CFLAR | orthology | Fugu |
| CFLAR | orthology | Gasterosteus |
| CFLAR | orthology | Gorilla |
| CFLAR | orthology | Horse |
| CFLAR | orthology | Lyzard |
| Q8MJ18_MACMU | orthology | Macaca |
| CFLAR | orthology | Medaka |
| CFLAR | orthology | Monodelphis |
| Cflar | orthology | Mouse |
| CFLAR_PONPY | orthology | Orangutan |
| CFLAR | orthology | Ornithorhynchus |
| CFLAR | orthology | Rabbit |
| Cflar | orthology | Rat |
| CFLAR | orthology | Tetraodon |
| X_tropicalis_ENSXETP00000017024 | orthology | Xenopus |
| CFLAR | orthology | Zebra finch |
| cflar | orthology | Zebrafish |
| A_aegypti_AAEL003444-PA | paralogy | Aedes |
| A_aegypti_AAEL003439-PA | paralogy | Aedes |
| CASPS3 | paralogy | Anopheles |
| CASPS8 | paralogy | Anopheles |
| NP_990056.1 | paralogy | Chicken |
| NP_989923.1 | paralogy | Chicken |
| NP_001038154.1 | paralogy | Chicken |
| Q90WU0_CHICK | paralogy | Chicken |
| CASP7 | paralogy | Chicken |
| NP_990057.1 | paralogy | Chicken |
| CASP10 | paralogy | Chicken |
| CASP3_PANTR | paralogy | Chimpanzee |
| CASP6 | paralogy | Chimpanzee |
| XR_025516.1 | paralogy | Chimpanzee |
| CASP8 | paralogy | Chimpanzee |
| CASP7 | paralogy | Chimpanzee |
| C_intestinalis_ENSCINP00000002956 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000025743 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000024485 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000003204 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000011493 | paralogy | Ciona |
| NP_001039435.1 | paralogy | Cow |
| CASP3_BOVIN | paralogy | Cow |
| IPI00689801.3 | paralogy | Cow |
| Q38JA9_CANFA | paralogy | Dog |
| CASP7 | paralogy | Dog |
| CASP10 | paralogy | Dog |
| CASP3_CANFA | paralogy | Dog |
| CASP6 | paralogy | Dog |
| Dcp-1 | paralogy | Fly |
| CASP6 | paralogy | Fugu |
| CASP7 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000024164 | paralogy | Fugu |
| NP_001027871.1 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000044662 | paralogy | Fugu |
| CASP2 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000024467 | paralogy | Fugu |
| CASP7 | paralogy | Gasterosteus |
| CASP3 (2 of 4) | paralogy | Gasterosteus |
| CASP3 (1 of 4) | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000016969 | paralogy | Gasterosteus |
| CASP6 | paralogy | Gasterosteus |
| CASP3 (4 of 4) | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000005791 | paralogy | Gasterosteus |
| CASP3 (3 of 4) | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000016983 | paralogy | Gasterosteus |
| CASP8 | paralogy | Gorilla |
| CASP7 | paralogy | Gorilla |
| Q3S2Z5_HORSE | paralogy | Horse |
| CASP7 | paralogy | Horse |
| CASP8 | paralogy | Horse |
| CASP10 | paralogy | Horse |
| CASP10 | paralogy | Human |
| CASP8 | paralogy | Human |
| CASP6 | paralogy | Human |
| CASP3 | paralogy | Human |
| CASP7 | paralogy | Human |
| CASP10 | paralogy | Lyzard |
| CASP6 | paralogy | Lyzard |
| CASP3 | paralogy | Lyzard |
| CASP7 | paralogy | Lyzard |
| CASP2 | paralogy | Lyzard |
| CASP7 | paralogy | Macaca |
| CASP10 | paralogy | Macaca |
| CASP8 | paralogy | Macaca |
| Q8SPP8_MACMU | paralogy | Macaca |
| Q8SPU2_MACMU | paralogy | Macaca |
| O_latipes_ENSORLP00000013993 | paralogy | Medaka |
| CASP2 | paralogy | Medaka |
| Q56VC9_ORYLA | paralogy | Medaka |
| Q8JIS8_ORYLA | paralogy | Medaka |
| Q8JIS9_ORYLA | paralogy | Medaka |
| CASP6 (1 of 2) | paralogy | Medaka |
| NP_001033059.1 | paralogy | Monodelphis |
| CASP10 | paralogy | Monodelphis |
| CASP8 | paralogy | Monodelphis |
| NP_001033061.1 | paralogy | Monodelphis |
| Casp8 | paralogy | Mouse |
| Casp7 | paralogy | Mouse |
| Casp6 | paralogy | Mouse |
| Casp3 | paralogy | Mouse |
| Q5RCR7_PONPY | paralogy | Orangutan |
| CASP3 | paralogy | Orangutan |
| CASP7 | paralogy | Orangutan |
| CASP6 | paralogy | Orangutan |
| Q5RB11_PONPY | paralogy | Orangutan |
| CASP7 | paralogy | Ornithorhynchus |
| O_anatinus_ENSOANP00000001054 | paralogy | Ornithorhynchus |
| CASP8 | paralogy | Ornithorhynchus |
| CASP3 | paralogy | Ornithorhynchus |
| CASP9 | paralogy | Ornithorhynchus |
| CASP10 | paralogy | Ornithorhynchus |
| CASP10 | paralogy | Rabbit |
| CASP7 | paralogy | Rabbit |
| CASP8 | paralogy | Rabbit |
| Casp3 | paralogy | Rat |
| Casp7 | paralogy | Rat |
| Casp8 | paralogy | Rat |
| T_nigroviridis_ENSTNIP00000010722 | paralogy | Tetraodon |
| T_nigroviridis_ENSTNIP00000001216 | paralogy | Tetraodon |
| CASP2 | paralogy | Tetraodon |
| CASP6 | paralogy | Tetraodon |
| CASP7 | paralogy | Tetraodon |
| CASP3 | paralogy | Tetraodon |
| casp6 | paralogy | Xenopus |
| CASP3 | paralogy | Xenopus |
| casp7 | paralogy | Xenopus |
| casp10 | paralogy | Xenopus |
| T_guttata_ENSTGUP00000004278 | paralogy | Zebra finch |
| CASP10 | paralogy | Zebra finch |
| CASP8 | paralogy | Zebra finch |
| CASP3 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000011206 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000013612 | paralogy | Zebra finch |
| LOC795066 | paralogy | Zebrafish |
| casp8l2 | paralogy | Zebrafish |
| casp6l1 | paralogy | Zebrafish |
| NP_001077331.1 | paralogy | Zebrafish |
| casp8l1 | paralogy | Zebrafish |
| A2BGE2_DANRE | paralogy | Zebrafish |
| casp2 | paralogy | Zebrafish |
| casp3b | paralogy | Zebrafish |
| casp7 | paralogy | Zebrafish |
| casp8 | paralogy | Zebrafish |
| casp8l2 | paralogy | Zebrafish |
| casp8l2 | paralogy | Zebrafish |
| casp3a | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0006508 | proteolysis | biological_proccess | IEA |
| GO:0042981 | regulation of apoptosis | biological_proccess | IEA |
| GO:0006916 | anti-apoptosis | biological_proccess | TAS |
| GO:0008624 | induction of apoptosis by extracellular signals | biological_proccess | TAS |
| GO:0044419 | interspecies interaction between organisms | biological_proccess | IEA |
| GO:0043123 | positive regulation of I-kappaB kinase/NF-kappaB cascade | biological_proccess | IEP |
| GO:0006915 | apoptosis | biological_proccess | IEA |
| GO:0006916 | anti-apoptosis | biological_proccess | IEA |
| GO:0004197 | cysteine-type endopeptidase activity | mollecular_function | IEA |
| GO:0005515 | protein binding | mollecular_function | IPI |
| GO:0008234 | cysteine-type peptidase activity | mollecular_function | IEA |
| GO:0005515 | protein binding | mollecular_function | IEA |
Check GO Evidence Codes here
KEGG Pathways [+]
Curated Isoforms [+]
Info from The Vertebrate Genome Annotation (VEGA) database.
(*) Canonical transcript and translation forms.
Information from other databases [+]
- Gene info from HGNC [?] :1876
- Gene related info from GeneCards [?] : CFLAR
- Ensembl genome browser [?] : ENSG00000003402
- Expression info from Arrayexpress [?] : ENSG00000003402
- Protein expression from Protein Atlas: [?] ENSG00000003402
- Community gene edition from Wikigenes: [?] 8837
- OMIM gene information: 603599
- OMIM disease information:
- entrezgene: 8837
- refseq_dna: NM_003879
- refseq_dna: NM_001127183
- refseq_dna: NM_001127184
- refseq_peptide: NP_001120655
- refseq_peptide: NP_003870
- refseq_peptide: NP_001120656
Click on [?] for more information.
