CFLAR (Danio rerio)
Description [+]
- Synonyms: CFLAR, CASP8 AND FADD-LIKE APOPTOSIS REGULATOR, CLARP1, FLIP
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Pisces; Danio rerio
- Short gene description: CASP8 and FADD-like apoptosis regulator [Source:RefSeq_peptide;Acc:NP_919380]
- Family: Caspase
- Process: apoptosis,
- Pathways: extrinsic pathway,
- Criteria: manually curated
- Curator comment: Cflar contains N-terminal death effector domains (DEDs) and an enzymatically inactive caspase cataltic domain [16888647]. Ectopic expression of Cflar in zebrafish embryos prevents induction of apoptosis by the Apo2L/TRAIL orthologs [16888647].
- Human ortholog(s): CFLAR
- WIKI: CFLAR-D_rerio
References [+]
- Delineation of the cell-extrinsic apoptosis pathway in the zebrafish.
- Eimon PM, Kratz E, Varfolomeev E, Hymowitz SG, Stern H, Zha J, Ashkenazi A
- The mammalian extrinsic apoptosis pathway is triggered by Fas ligand (FasL) and Apo2 ligand/tumor necrosis factor (TNF)-related apoptosis-inducing ligand (Apo2L/TRAIL). Ligand binding to cognate receptors activates initiator caspases directly in a death-inducing signaling complex. In Drosophila, TNF ligand binding activates initiator caspases indirectly, through JNK. We characterized the extrinsic pathway in zebrafish to determine how it operates in a nonmammalian vertebrate. We identified homologs of FasL and Apo2L/TRAIL, their receptors, and other components of the cell death machinery. Studies with three Apo2L/TRAIL homologs demonstrated that they bind the receptors zHDR (previously linked to hematopoiesis) and ovarian TNFR (zOTR). Ectopic expression of these ligands during embryogenesis induced apoptosis in erythroblasts and notochord cells. Inhibition of zHDR, zOTR, the adaptor zFADD, or caspase-8-like proteases blocked ligand-induced apoptosis, as did antiapoptotic Bcl-2 family members. Thus, the extrinsic apoptosis pathway in zebrafish closely resembles its mammalian counterpart and cooperates with the intrinsic pathway to trigger tissue-specific apoptosis during embryogenesis in response to ectopic Apo2L/TRAIL expression. Cell Death Differ. 2006 Oct;13(10):1619-30. Epub 2006 Aug 4.
- References from Human ortholog(s):
- 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.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | DED | 5 | 89 |
| PFAM A | DED | 102 | 185 |
| PFAM A | Peptidase_C14 | 249 | 461 |
Protein sequence [+]
cflar | Danio rerio | 7955 | length:461
MADGFSTLVNKVTASLSSDESKILLYLCTDLFNNSCVEELRGDLLAFAQQNPNQAGQPHS
GNALLMELMFQMKRYDLLRKVFGTNKQQVEGILRKERVISDYRVLMADVSENLDKEDLQS
LIFLLSSILPKERSTRATSFLDVVVELEKLNEVSCEKLDFLEKCLKNIRRNDLVKKIQAY
RNRGQNMPCAAPNTFKFTPMQCQPFEKQVRQSQCFNHEFNKLKLSVPETGIHYQQAITEE
YQMNPEQRGLCVIIDCVGYDGEMLKHTFECLGFKVVFHSLLGLKETQKVLEDLSLNRILQ
RVRCFVCCLISRGTNTHLLATDSNRLGINLKDLKQLFNATKCPKIFFTQLYRITEAPVMP
SMDDEYLETDAPASRQCSNTGSVPMPADVLWSVCTAEVKLLEESGHQSVYLNALNNALLK
GHERNVPILDVMKEVQRNVLSHDSDNYQLQQSHTLQKKLYL
GNALLMELMFQMKRYDLLRKVFGTNKQQVEGILRKERVISDYRVLMADVSENLDKEDLQS
LIFLLSSILPKERSTRATSFLDVVVELEKLNEVSCEKLDFLEKCLKNIRRNDLVKKIQAY
RNRGQNMPCAAPNTFKFTPMQCQPFEKQVRQSQCFNHEFNKLKLSVPETGIHYQQAITEE
YQMNPEQRGLCVIIDCVGYDGEMLKHTFECLGFKVVFHSLLGLKETQKVLEDLSLNRILQ
RVRCFVCCLISRGTNTHLLATDSNRLGINLKDLKQLFNATKCPKIFFTQLYRITEAPVMP
SMDDEYLETDAPASRQCSNTGSVPMPADVLWSVCTAEVKLLEESGHQSVYLNALNNALLK
GHERNVPILDVMKEVQRNVLSHDSDNYQLQQSHTLQKKLYL
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 | Human |
| 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 |
| CFLAR | orthology | Zebra finch |
| CASP7 | paralogy | Chicken |
| NP_001038154.1 | paralogy | Chicken |
| NP_989923.1 | paralogy | Chicken |
| CASP10 | paralogy | Chicken |
| NP_990056.1 | paralogy | Chicken |
| CASP3_PANTR | paralogy | Chimpanzee |
| XR_025516.1 | paralogy | Chimpanzee |
| CASP7 | paralogy | Chimpanzee |
| CASP8 | paralogy | Chimpanzee |
| CASP6 | paralogy | Chimpanzee |
| C_intestinalis_ENSCINP00000011493 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000011503 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000024485 | paralogy | Ciona |
| CASP6_BOVIN | paralogy | Cow |
| CASP3_BOVIN | paralogy | Cow |
| NP_001039435.1 | paralogy | Cow |
| IPI00689801.3 | paralogy | Cow |
| IPI00700977.3 | paralogy | Cow |
| CASP10 | paralogy | Dog |
| Q38JA9_CANFA | paralogy | Dog |
| CASP7 | paralogy | Dog |
| T_rubripes_ENSTRUP00000024467 | paralogy | Fugu |
| CASP7 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000044662 | paralogy | Fugu |
| CASP7 | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000016969 | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000005791 | paralogy | Gasterosteus |
| CASP3 (2 of 4) | paralogy | Gasterosteus |
| CASP8 | paralogy | Gorilla |
| CASP7 | paralogy | Gorilla |
| CASP10 | paralogy | Horse |
| CASP7 | paralogy | Horse |
| CASP8 | paralogy | Horse |
| CASP6 | paralogy | Human |
| CASP3 | paralogy | Human |
| CASP10 | paralogy | Human |
| CASP7 | paralogy | Human |
| CASP8 | paralogy | Human |
| CASP7 | paralogy | Lyzard |
| CASP10 | paralogy | Lyzard |
| CASP3 | paralogy | Lyzard |
| CASP10 | paralogy | Macaca |
| CASP7 | paralogy | Macaca |
| CASP8 | paralogy | Macaca |
| Q56VC9_ORYLA | paralogy | Medaka |
| Q8JIS9_ORYLA | paralogy | Medaka |
| CASP2 | paralogy | Medaka |
| NP_001033059.1 | paralogy | Monodelphis |
| NP_001033061.1 | paralogy | Monodelphis |
| CASP10 | paralogy | Monodelphis |
| CASP8 | paralogy | Monodelphis |
| Casp8 | paralogy | Mouse |
| Casp6 | paralogy | Mouse |
| Casp7 | paralogy | Mouse |
| Q5RCR7_PONPY | paralogy | Orangutan |
| CASP6 | paralogy | Orangutan |
| CASP7 | paralogy | Orangutan |
| Q5RB11_PONPY | paralogy | Orangutan |
| CASP7 | paralogy | Ornithorhynchus |
| CASP8 | paralogy | Ornithorhynchus |
| CASP3 | paralogy | Ornithorhynchus |
| O_anatinus_ENSOANP00000001054 | paralogy | Ornithorhynchus |
| CASP8 | paralogy | Rabbit |
| CASP7 | paralogy | Rabbit |
| Casp7 | paralogy | Rat |
| Casp8 | paralogy | Rat |
| T_nigroviridis_ENSTNIP00000001216 | paralogy | Tetraodon |
| T_nigroviridis_ENSTNIP00000010722 | paralogy | Tetraodon |
| casp7 | paralogy | Xenopus |
| casp10 | paralogy | Xenopus |
| CASP3 | paralogy | Zebra finch |
| CASP10 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000011206 | paralogy | Zebra finch |
| CASP8 | paralogy | Zebra finch |
| A2BGE2_DANRE | paralogy | Zebrafish |
| casp3b | paralogy | Zebrafish |
| casp8l2 | paralogy | Zebrafish |
| casp8l2 | paralogy | Zebrafish |
| casp8l1 | paralogy | Zebrafish |
| casp7 | paralogy | Zebrafish |
| casp8 | paralogy | Zebrafish |
| casp8l2 | 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:0006915 | apoptosis | biological_proccess | IEA |
| GO:0004197 | cysteine-type endopeptidase activity | mollecular_function | IEA |
| GO:0005515 | protein binding | mollecular_function | IEA |
| GO:0008234 | cysteine-type peptidase activity | mollecular_function | IEA |
Check GO Evidence Codes here
KEGG Pathways [+]
Information from other databases [+]
- Gene info from ZFIN [?] ZDB-GENE-030826-3
- Ensembl genome browser [?] : ENSDARG00000055966
- Expression info from Arrayexpress [?] : ENSDARG00000055966
- Protein expression from Protein Atlas: [?] ENSDARG00000055966
- Community gene edition from Wikigenes: [?] 373114
Click on [?] for more information.
