Cflar CASP8 and FADD-like apoptosis regulator [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Cflarprovided by MGI
Official Full Name: CASP8 and FADD-like apoptosis regulatorprovided by MGI
Primary source: MGI:MGI:1336166
See related: Ensembl:ENSMUSG00000026031 AllianceGenome:MGI:1336166
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Cash; Flip; MRIT; CLARP; FLAME; Casper; Gm9845; c-Flip; FLAME-1; I-FLICE; 2310024N18Rik; A430105C05Rik
Summary: Enables peptidase activator activity. Involved in several processes, including negative regulation of myoblast fusion; positive regulation of NF-kappaB transcription factor activity; and skeletal muscle atrophy. Acts upstream of or within negative regulation of programmed cell death and response to bacterium. Located in cytoplasm. Is expressed in several structures, including central nervous system; gut; heart; peripheral nervous system ganglion; and retina. Orthologous to human CFLAR (CASP8 and FADD like apoptosis regulator). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Ubiquitous expression in lung adult (RPKM 9.2), kidney adult (RPKM 7.4) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 1 C1.3; 1 29.16 cM

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	1	NC_000067.7 (58750353..58798043)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	1	NC_000067.6 (58711311..58758884)

Chromosome 1 - NC_000067.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The Regulatory Impact of CFLAR Methylation Modification on Liver Lipid Metabolism.
Title: The Regulatory Impact of CFLAR Methylation Modification on Liver Lipid Metabolism.
cFLIP in the molecular regulation of astroglia-driven neuroinflammation in experimental glaucoma.
Title: cFLIP in the molecular regulation of astroglia-driven neuroinflammation in experimental glaucoma.
Cleavage of cFLIP restrains cell death during viral infection and tissue injury and favors tissue repair.
Title: Cleavage of cFLIP restrains cell death during viral infection and tissue injury and favors tissue repair.
Bclaf1 regulates c-FLIP expression and protects cells from TNF-induced apoptosis and tissue injury.
Title: Bclaf1 regulates c-FLIP expression and protects cells from TNF-induced apoptosis and tissue injury.
Oncogenic signaling inhibits c-FLIPL expression and its non-apoptotic function during ECM-detachment.
Title: Oncogenic signaling inhibits c-FLIP(L) expression and its non-apoptotic function during ECM-detachment.
c-FLIP regulates autophagy by interacting with Beclin-1 and influencing its stability.
Title: c-FLIP regulates autophagy by interacting with Beclin-1 and influencing its stability.
Honokiol Alleviates Methionine-Choline Deficient Diet-Induced Hepatic Steatosis and Oxidative Stress in C57BL/6 Mice by Regulating CFLAR-JNK Pathway.
Title: Honokiol Alleviates Methionine-Choline Deficient Diet-Induced Hepatic Steatosis and Oxidative Stress in C57BL/6 Mice by Regulating CFLAR-JNK Pathway.
hnRNPK knockdown alleviates NLRP3 inflammasome priming by repressing FLIP expression in Raw264.7 macrophages.
Title: hnRNPK knockdown alleviates NLRP3 inflammasome priming by repressing FLIP expression in Raw264.7 macrophages.
TNF Is Partially Required for Cell-Death-Triggered Skin Inflammation upon Acute Loss of cFLIP.
Title: TNF Is Partially Required for Cell-Death-Triggered Skin Inflammation upon Acute Loss of cFLIP.
The data demonstrate a non-redundant function of c-FLIP for the generation of NKp46(+) innate lymphoid cells, which protect T/B lymphocyte-sufficient mice from intestinal inflammation.
Title: c-FLIP is crucial for IL-7/IL-15-dependent NKp46(+) ILC development and protection from intestinal inflammation in mice.

Submit: New GeneRIF Correction See all GeneRIFs (85)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (2)
Spontaneous (1) 1 citation
Targeted (6) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AU021929 (e-PCR)
- UniSTS:207162

D9Mit34.1 (e-PCR), detects polymorphism
- UniSTS:131903

PMC305633P2 (e-PCR)
- UniSTS:272554

AI646576 (e-PCR)
- UniSTS:178400

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables cysteine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables cysteine-type endopeptidase activity	IEA Inferred from Electronic Annotation more info
enables death receptor binding	ISO Inferred from Sequence Orthology more info
enables enzyme activator activity	ISO Inferred from Sequence Orthology more info
enables peptidase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables protease binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in apoptotic process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in cellular response to nitric oxide	ISO Inferred from Sequence Orthology more info
involved_in extrinsic apoptotic signaling pathway via death domain receptors	IBA Inferred from Biological aspect of Ancestor more info
involved_in macrophage differentiation	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of necroptotic process	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cardiac muscle cell apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cellular response to transforming growth factor beta stimulus	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of cysteine-type endopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of epithelial cell apoptotic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of extrinsic apoptotic signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
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	PubMed
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	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of myoblast fusion	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of necroptotic process	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of reactive oxygen species biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of ERK1 and ERK2 cascade	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of NF-kappaB transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of extracellular matrix organization	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of glomerular mesangial cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of hepatocyte proliferation	ISO Inferred from Sequence Orthology more info
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	ISO Inferred from Sequence Orthology more info
involved_in proteolysis	IEA Inferred from Electronic Annotation more info
involved_in regulation of necroptotic process	ISO Inferred from Sequence Orthology more info
involved_in regulation of skeletal muscle satellite cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to bacterium	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to testosterone	ISO Inferred from Sequence Orthology more info
involved_in skeletal muscle atrophy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in skeletal muscle tissue development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in skeletal muscle tissue regeneration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in skeletal myofibril assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in wound healing	IMP Inferred from Mutant Phenotype more info	PubMed

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

Names: FADD-like antiapoptotic molecule 1; MACH-related inducer of toxicity; caspase homolog; caspase-eight-related protein; caspase-like apoptosis regulatory protein; cellular FLICE-like inhibitory protein; inhibitor of FLICE; usurpin

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_001289704.3 → NP_001276633.1 CASP8 and FADD-like apoptosis regulator isoform 1

See identical proteins and their annotated locations for NP_001276633.1

Status: VALIDATED

Source sequence(s)

AC112968

Consensus CDS

CCDS14978.1

UniProtKB/Swiss-Prot

D3Z0W6, O35707, O35732, O35733

UniProtKB/TrEMBL

A0A2C9F2D9, Q812G4

Related

ENSMUSP00000109952.2, ENSMUST00000114313.8

Conserved Domains (3) summary

smart00115
Location:246 → 480

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues

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
NM_001293804.2 → NP_001280733.1 CASP8 and FADD-like apoptosis regulator isoform 4

See identical proteins and their annotated locations for NP_001280733.1

Status: VALIDATED

Source sequence(s)

AC112968, AK152515

Conserved Domains (1) summary

smart00115
Location:60 → 294

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues
NM_001293805.2 → NP_001280734.1 CASP8 and FADD-like apoptosis regulator isoform 4

See identical proteins and their annotated locations for NP_001280734.1

Status: VALIDATED

Source sequence(s)

AC112968, AK161120

Conserved Domains (1) summary

smart00115
Location:60 → 294

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues
NM_001355056.1 → NP_001341985.1 CASP8 and FADD-like apoptosis regulator isoform 4

Status: VALIDATED

Source sequence(s)

AC112968

Conserved Domains (1) summary

smart00115
Location:60 → 294

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues
NM_009805.4 → NP_033935.2 CASP8 and FADD-like apoptosis regulator isoform 2

See identical proteins and their annotated locations for NP_033935.2

Status: VALIDATED

Source sequence(s)

BB856464, BC085105

Consensus CDS

CCDS35582.1

UniProtKB/TrEMBL

Q5U4G3

Related

ENSMUSP00000109948.2, ENSMUST00000114309.8

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
NM_207653.6 → NP_997536.1 CASP8 and FADD-like apoptosis regulator isoform 1

See identical proteins and their annotated locations for NP_997536.1

Status: VALIDATED

Source sequence(s)

AC112968

Consensus CDS

CCDS14978.1

UniProtKB/Swiss-Prot

D3Z0W6, O35707, O35732, O35733

UniProtKB/TrEMBL

A0A2C9F2D9, Q812G4

Related

ENSMUSP00000065107.8, ENSMUST00000069333.8

Conserved Domains (3) summary

smart00115
Location:246 → 480

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues

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

RNA

NR_149255.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AC112968
NR_149256.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AC112968

Related

ENSMUST00000156870.2
NR_149257.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AC112968, BX524743

Related

ENSMUST00000124567.2
NR_149258.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AC112968

Related

ENSMUST00000149874.8

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000067.7 Reference GRCm39 C57BL/6J

Range

58750353..58798043

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011238421.4 → XP_011236723.1 CASP8 and FADD-like apoptosis regulator isoform X1

See identical proteins and their annotated locations for XP_011236723.1

UniProtKB/Swiss-Prot

D3Z0W6, O35707, O35732, O35733

UniProtKB/TrEMBL

A0A2C9F2D9, Q812G4

Related

ENSMUSP00000095329.3, ENSMUST00000097722.9

Conserved Domains (3) summary

smart00115
Location:246 → 480

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues

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
XM_011238420.4 → XP_011236722.1 CASP8 and FADD-like apoptosis regulator isoform X1

See identical proteins and their annotated locations for XP_011236722.1

UniProtKB/Swiss-Prot

D3Z0W6, O35707, O35732, O35733

UniProtKB/TrEMBL

A0A2C9F2D9, Q812G4

Conserved Domains (3) summary

smart00115
Location:246 → 480

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues

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
XM_030244988.2 → XP_030100848.1 CASP8 and FADD-like apoptosis regulator isoform X1

UniProtKB/Swiss-Prot

D3Z0W6, O35707, O35732, O35733

UniProtKB/TrEMBL

A0A2C9F2D9, Q812G4

Conserved Domains (3) summary

smart00115
Location:246 → 480

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues

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
XM_011238422.1 → XP_011236724.1 CASP8 and FADD-like apoptosis regulator isoform X1

See identical proteins and their annotated locations for XP_011236724.1

UniProtKB/Swiss-Prot

D3Z0W6, O35707, O35732, O35733

UniProtKB/TrEMBL

A0A2C9F2D9, Q812G4

Conserved Domains (3) summary

smart00115
Location:246 → 480

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues

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
XM_011238423.4 → XP_011236725.1 CASP8 and FADD-like apoptosis regulator isoform X1

See identical proteins and their annotated locations for XP_011236725.1

UniProtKB/Swiss-Prot

D3Z0W6, O35707, O35732, O35733

UniProtKB/TrEMBL

A0A2C9F2D9, Q812G4

Conserved Domains (3) summary

smart00115
Location:246 → 480

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues

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
XM_006495635.5 → XP_006495698.1 CASP8 and FADD-like apoptosis regulator isoform X1

See identical proteins and their annotated locations for XP_006495698.1

UniProtKB/Swiss-Prot

D3Z0W6, O35707, O35732, O35733

UniProtKB/TrEMBL

A0A2C9F2D9, Q812G4

Conserved Domains (3) summary

smart00115
Location:246 → 480

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues

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
XM_036156889.1 → XP_036012782.1 CASP8 and FADD-like apoptosis regulator isoform X2

Conserved Domains (1) summary

smart00115
Location:60 → 294

CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues