Cflar CASP8 and FADD-like apoptosis regulator [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Cflarprovided by RGD
Official Full Name: CASP8 and FADD-like apoptosis regulatorprovided by RGD
Primary source: RGD:620847
See related: Ensembl:ENSRNOG00000012473 AllianceGenome:RGD:620847
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: Flip
Summary: Enables death receptor binding activity and protease binding activity. Involved in several processes, including cellular response to hormone stimulus; negative regulation of apoptotic process; and positive regulation of cell population proliferation. Located in membrane raft. Part of CD95 death-inducing signaling complex. Orthologous to human CFLAR (CASP8 and FADD like apoptosis regulator). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in Kidney (RPKM 156.3), Lung (RPKM 134.8) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 9q31

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	9	NC_086027.1 (67679502..67747226)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	9	NC_051344.1 (60185338..60236173)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	9	NC_005108.4 (65534608..65586395)

Chromosome 9 - NC_086027.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

c-FLIP expression was significantly decreased in organs of septic rats compared with control rats, and that c-FLIP overexpression protected HUVECs from LPS+CHX-induced apoptosis in vitro.
Title: Expression of c-FLIP in a rat model of sepsis and its effects on endothelial apoptosis.
Estradiol increased c-FLIPlong expression in anterior pituitary cells but not in GH3 cells.
Title: Estradiol Upregulates c-FLIPlong Expression in Anterior Pituitary Cells.
Our results also suggest that emodin regulates cFLIP expression in transcriptional level.
Title: Emodin suppresses hyperglycemia-induced proliferation and fibronectin expression in mesangial cells via inhibiting cFLIP.
data suggest that caspase-8 does not become activated through an extrinsic but an "intrinsic/intracellular" apoptotic pathway unleashed by the down-regulation of c-FLIP by c-Myc
Title: Caspase-8, c-FLIP, and caspase-9 in c-Myc-induced apoptosis of fibroblasts.
we uncover a new role for FLIP-L as an unexpected critical player in neurotrophin-induced mitogen-activated protein kinase/ERK- and NF-B-mediated control of neurite growth in developing neurons
Title: The death receptor antagonist FLIP-L interacts with Trk and is necessary for neurite outgrowth induced by neurotrophins.
Androgenic protection from TRAIL-induced apoptosis is via enhanced transcription of FLIP in prostate cancer cells. Loss of androgen-sensitivity in androgen-depletion-independent prostate cancer cells. Potential target for therapy of prostate cancer.
Title: Induction of FLIP expression by androgens protects prostate cancer cells from TRAIL-mediated apoptosis.
Data show that cAMP antagonizes UV-induced apoptosis through JNK activation by CREB-mediated induction of c-FLIP(L) and MKP-1.
Title: Cyclic AMP inhibits JNK activation by CREB-mediated induction of c-FLIP(L) and MKP-1, thereby antagonizing UV-induced apoptosis.
FLIP plays a crucial role as a negative regulator of Fas-induced apoptosis in lung epithelial cells.
Title: The Fas death signaling pathway connecting reactive oxygen species generation and FLICE inhibitory protein down-regulation.
FLIP levels decline with TGFbeta1 treatment, suggesting that apoptosis is mediated by caspase-8 and indeed the caspase inhibitor crmA blocks TGFbeta1-induced apoptosis.
Title: FLICE-like inhibitory protein blocks transforming growth factor beta 1-induced caspase activation and apoptosis in prostate epithelial cells.
Cytoprotective effect of bis(1-oxy-2-pyridinethiolato)oxovanadium(IV)was mediated by increased FLIP expression and decreased Fas ligand and Bim expression via activation of Akt.
Title: Cytoprotective effect of bis(1-oxy-2-pyridinethiolato)oxovanadiun(IV) on myocardial ischemia/reperfusion injury elicits inhibition of Fas ligand and Bim expression and elevation of FLIP expression.

Submit: New GeneRIF Correction See all GeneRIFs (15)

General gene information

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Markers

BE112005 (e-PCR)
- UniSTS:246057

RH133639 (e-PCR)
- UniSTS:216922

AI169244 (e-PCR)
- UniSTS:250240

RH133684 (e-PCR)
- UniSTS:216967

AA946075 (e-PCR)
- UniSTS:250327

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables cysteine-type endopeptidase activity involved in apoptotic signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
enables cysteine-type endopeptidase activity involved in execution phase of apoptosis	IBA Inferred from Biological aspect of Ancestor more info
enables death receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables enzyme activator activity	IBA Inferred from Biological aspect of Ancestor more info
enables enzyme activator activity	ISO Inferred from Sequence Orthology more info
enables peptidase activator activity	ISO Inferred from Sequence Orthology more info
enables protease binding	IPI Inferred from Physical Interaction more info	PubMed
enables protease binding	ISO Inferred from Sequence Orthology more info
enables protein-containing complex binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in apoptotic process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in apoptotic signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in cellular response to dexamethasone stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to epidermal growth factor stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to estradiol stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to hypoxia	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to insulin stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to nitric oxide	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in erythrocyte differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in execution phase of apoptosis	IBA Inferred from Biological aspect of Ancestor more info
involved_in keratinocyte differentiation	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of necroptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cardiac muscle cell apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cellular response to transforming growth factor beta stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of epithelial cell apoptotic process	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of extrinsic apoptotic signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of extrinsic apoptotic signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of hepatocyte apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of myoblast fusion	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of necroptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of reactive oxygen species biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuron differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of ERK1 and ERK2 cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of canonical NF-kappaB signal transduction	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of extracellular matrix organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of glomerular mesangial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of hepatocyte proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of neuron apoptotic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of neuron projection development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proteolysis	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of necroptotic process	ISO Inferred from Sequence Orthology more info
involved_in regulation of skeletal muscle satellite cell proliferation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within response to bacterium	ISO Inferred from Sequence Orthology more info
involved_in response to hypoxia	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to testosterone	IDA Inferred from Direct Assay more info	PubMed
involved_in skeletal muscle atrophy	ISO Inferred from Sequence Orthology more info
involved_in skeletal muscle tissue development	ISO Inferred from Sequence Orthology more info
involved_in skeletal muscle tissue regeneration	ISO Inferred from Sequence Orthology more info
involved_in skeletal myofibril assembly	ISO Inferred from Sequence Orthology more info
involved_in wound healing	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
part_of CD95 death-inducing signaling complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
part_of death-inducing signaling complex	IBA Inferred from Biological aspect of Ancestor more info
part_of death-inducing signaling complex	IDA Inferred from Direct Assay more info	PubMed
part_of death-inducing signaling complex	ISO Inferred from Sequence Orthology more info
part_of ripoptosome	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: CASP8 and FADD-like apoptosis regulator

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001033864.5 → NP_001029036.1 CASP8 and FADD-like apoptosis regulator isoform 1

See identical proteins and their annotated locations for NP_001029036.1

Status: VALIDATED

Source sequence(s)

JAXUCZ010000009

UniProtKB/TrEMBL

C0H5Y5, F7FBZ4

Related

ENSRNOP00000016730.3, ENSRNOT00000016730.6

Conserved Domains (3) summary

cd08337
Location:6 → 85

DED_c-FLIP_r1; Death Effector Domain, repeat 1, of cellular FLICE-Inhibitory Protein

cd08340
Location:96 → 176

DED_c-FLIP_r2; Death Effector Domain, repeat 2, of cellular FLICE-Inhibitory Protein

cl00042
Location:249 → 479

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
NM_057138.3 → NP_476479.1 CASP8 and FADD-like apoptosis regulator isoform 2

See identical proteins and their annotated locations for NP_476479.1

Status: VALIDATED

Source sequence(s)

JAXUCZ010000009

UniProtKB/TrEMBL

Q99MZ5

Conserved Domains (2) summary

cd08337
Location:6 → 85

DED_c-FLIP_r1; Death Effector Domain, repeat 1, of cellular FLICE-Inhibitory Protein

cd08340
Location:96 → 176

DED_c-FLIP_r2; Death Effector Domain, repeat 2, of cellular FLICE-Inhibitory Protein

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCr8

Genomic

NC_086027.1 Reference GRCr8

Range

67679502..67747226

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_063266581.1 → XP_063122651.1 CASP8 and FADD-like apoptosis regulator isoform X1

UniProtKB/TrEMBL

C0H5Y5, F7FBZ4
XM_039082962.2 → XP_038938890.1 CASP8 and FADD-like apoptosis regulator isoform X3

Conserved Domains (3) summary

cd08337
Location:6 → 85

DED_c-FLIP_r1; Death Effector Domain, repeat 1, of cellular FLICE-Inhibitory Protein

cd08340
Location:96 → 176

DED_c-FLIP_r2; Death Effector Domain, repeat 2, of cellular FLICE-Inhibitory Protein

cl00042
Location:249 → 268

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
XM_039082957.2 → XP_038938885.1 CASP8 and FADD-like apoptosis regulator isoform X1

UniProtKB/TrEMBL

C0H5Y5, F7FBZ4

Conserved Domains (3) summary

cd08337
Location:6 → 85

DED_c-FLIP_r1; Death Effector Domain, repeat 1, of cellular FLICE-Inhibitory Protein

cd08340
Location:96 → 176

DED_c-FLIP_r2; Death Effector Domain, repeat 2, of cellular FLICE-Inhibitory Protein

cl00042
Location:249 → 479

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
XM_006244949.5 → XP_006245011.1 CASP8 and FADD-like apoptosis regulator isoform X1

See identical proteins and their annotated locations for XP_006245011.1

UniProtKB/TrEMBL

C0H5Y5, F7FBZ4

Conserved Domains (3) summary

cd08337
Location:6 → 85

DED_c-FLIP_r1; Death Effector Domain, repeat 1, of cellular FLICE-Inhibitory Protein

cd08340
Location:96 → 176

DED_c-FLIP_r2; Death Effector Domain, repeat 2, of cellular FLICE-Inhibitory Protein

cl00042
Location:249 → 479

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
XM_063266584.1 → XP_063122654.1 CASP8 and FADD-like apoptosis regulator isoform X3
XM_063266582.1 → XP_063122652.1 CASP8 and FADD-like apoptosis regulator isoform X1

UniProtKB/TrEMBL

C0H5Y5, F7FBZ4
XM_039082958.2 → XP_038938886.1 CASP8 and FADD-like apoptosis regulator isoform X1

UniProtKB/TrEMBL

C0H5Y5, F7FBZ4

Conserved Domains (3) summary

cd08337
Location:6 → 85

DED_c-FLIP_r1; Death Effector Domain, repeat 1, of cellular FLICE-Inhibitory Protein

cd08340
Location:96 → 176

DED_c-FLIP_r2; Death Effector Domain, repeat 2, of cellular FLICE-Inhibitory Protein

cl00042
Location:249 → 479

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
XM_039082959.2 → XP_038938887.1 CASP8 and FADD-like apoptosis regulator isoform X1

UniProtKB/TrEMBL

C0H5Y5, F7FBZ4

Conserved Domains (3) summary

cd08337
Location:6 → 85

DED_c-FLIP_r1; Death Effector Domain, repeat 1, of cellular FLICE-Inhibitory Protein

cd08340
Location:96 → 176

DED_c-FLIP_r2; Death Effector Domain, repeat 2, of cellular FLICE-Inhibitory Protein

cl00042
Location:249 → 479

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
XM_063266583.1 → XP_063122653.1 CASP8 and FADD-like apoptosis regulator isoform X2