CFLAR
CASP8 and FADD-like apoptosis regulator
Also known as: c-FLIP, CASH, CASP8AP1, Casper, CFLAR_HUMAN, cFLIP, CLARP, FLAME, FLIP, I-FLICE, MRIT
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- O15519
- Gene
- CFLAR
- Ensembl
- ENSG00000003402
- Chromosome
- 2
- Canonical length
- 480 aa
- Protein class
- Cancer-related genes, Enzymes, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm,Nuclear bodies,Plasma membrane,Cytosol
OverviewNCBI Gene
The protein encoded by this gene is a regulator of apoptosis and is structurally similar to caspase-8. However, the encoded protein lacks caspase activity and appears to be itself cleaved into two peptides by caspase-8. Several transcript variants encoding different isoforms have been found for this gene, and partial evidence for several more variants exists. [provided by RefSeq, Feb 2011]
Canonical amino-acid sequenceUniProt
480 residues, UniProt reviewed canonical sequence.
>O15519|CFLAR
1 MSAEVIHQVE EALDTDEKEM LLFLCRDVAI DVVPPNVRDL LDILRERGKL SVGDLAELLY
61 RVRRFDLLKR ILKMDRKAVE THLLRNPHLV SDYRVLMAEI GEDLDKSDVS SLIFLMKDYM
121 GRGKISKEKS FLDLVVELEK LNLVAPDQLD LLEKCLKNIH RIDLKTKIQK YKQSVQGAGT
181 SYRNVLQAAI QKSLKDPSNN FRLHNGRSKE QRLKEQLGAQ QEPVKKSIQE SEAFLPQSIP
241 EERYKMKSKP LGICLIIDCI GNETELLRDT FTSLGYEVQK FLHLSMHGIS QILGQFACMP
301 EHRDYDSFVC VLVSRGGSQS VYGVDQTHSG LPLHHIRRMF MGDSCPYLAG KPKMFFIQNY
361 VVSEGQLEDS SLLEVDGPAM KNVEFKAQKR GLCTVHREAD FFWSLCTADM SLLEQSHSSP
421 SLYLQCLSQK LRQERKRPLL DLHIELNGYM YDWNSRVSAK EKYYVWLQHT LRKKLILSYTLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CFLAR can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.33
- Highest tissue expression
- 234 nTPM
Expression across tissuesHPA
Tissue
- bone marrow: 234 nTPM
- skeletal muscle: 201 nTPM
- heart muscle: 169 nTPM
- lung: 161 nTPM
- adipose tissue: 115 nTPM
- tonsil: 101 nTPM
Single-cell type
- neutrophils: 2,589 nCPM
- neutrophil progenitors: 824 nCPM
- platelets: 789 nCPM
- alveolar cells type 1: 787 nCPM
- myonuclei: 754 nCPM
- monocytes: 711 nCPM
Immune cell
- neutrophil: 394 nTPM
- basophil: 92 nTPM
- eosinophil: 71 nTPM
- non-classical monocyte: 69 nTPM
- intermediate monocyte: 62 nTPM
- T-reg: 61 nTPM
Brain region
- choroid plexus: 169 nTPM
- thalamus: 124 nTPM
- cerebellum: 119 nTPM
- cerebral cortex: 112 nTPM
- medulla oblongata: 110 nTPM
- white matter: 104 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.17
- gnomAD pLI
- 1
- gnomAD missense Z
- 2.19
- DepMap mean gene effect
- -0.66
- DepMap dependency class
- common
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- apoptotic process
- cellular response to dexamethasone stimulus
- cellular response to epidermal growth factor stimulus
- cellular response to estradiol stimulus
- cellular response to hypoxia
- cellular response to insulin stimulus
- cellular response to nitric oxide
- extrinsic apoptotic signaling pathway via death domain receptors
- macrophage differentiation
- negative regulation of apoptotic process
- negative regulation of cardiac muscle cell apoptotic process
- negative regulation of cellular response to transforming growth factor beta stimulus
- negative regulation of extrinsic apoptotic signaling pathway
- negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
- negative regulation of hepatocyte apoptotic process
- negative regulation of myoblast fusion
- negative regulation of reactive oxygen species biosynthetic process
- positive regulation of canonical NF-kappaB signal transduction
- positive regulation of ERK1 and ERK2 cascade
- positive regulation of extracellular matrix organization
- positive regulation of glomerular mesangial cell proliferation
- positive regulation of hepatocyte proliferation
- positive regulation of neuron apoptotic process
- positive regulation of neuron projection development
- proteolysis
- regulation of necroptotic process
- regulation of skeletal muscle satellite cell proliferation
- response to testosterone
- skeletal muscle atrophy
- skeletal muscle tissue development
- skeletal muscle tissue regeneration
- skeletal myofibril assembly
Molecular functions
- cysteine-type endopeptidase activity
- death receptor binding
- enzyme activator activity
- protease binding
- protein-containing complex binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CFLAR in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads CFLAR as an antibody target. Whether an autoantibody or antibody against CFLAR could matter depends on whether native CFLAR is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CFLAR is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label CFLAR as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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