Protein detail

CFLAR

CASP8 and FADD-like apoptosis regulator (Caspase homolog) (CASH) (Caspase-eight-related protein) (Casper) (Caspase-like apoptosis regulatory protein) (CLARP) (Cellular FLICE-like inhibitory protein) (c-FLIP) (FADD-like antiapoptotic molecule 1) (FLAME-1) (Inhibitor of FLICE) (I-FLICE) (MACH-related inducer of toxicity) (MRIT) (Usurpin) [Cleaved into: CASP8 and FADD-like apoptosis regulator subunit p43; CASP8 and FADD-like apoptosis regulator subunit p12]

Protein symbol CFLAR	UniProt ID O15519	EVMP score 0.38
Frequency 1	Transmembrane count	Protein classification Cancer-related genesEnzymesPredicted intracellular proteins

EVMP score: annotation confidence score.

Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40

Basic Information

Protein Names

Protein Class

Cancer-related genesEnzymesPredicted intracellular proteins

Protein Function

Peptidases:Cysteine-type peptidases
Enzymes
Cancer-related genes:Candidate cancer biomarkers
Predicted intracellular proteins

Ensembl

ENSG00000003402

Entrez Gene Symbol

CFLAR

Gene Synonym

c-FLIPCASHCASP8AP1CaspercFLIPCLARPFLAMEFLIPI-FLICEMRIT

Gene Description

CASP8 and FADD like apoptosis regulator

Chromosome

Position

201116154-201176687

Frequency

EVMP Score

0.38

Fluorescence & Localization

Tissue Specificbone marrowCell SpecificpDCsSingle-Nuclei Brain SpecificleukocyteBlood Cell Specificplasmacytoid DCBlood Lineage Specificdendritic cells

Function & Pathway

Protein Function

Peptidases:Cysteine-type peptidases
Enzymes
Cancer-related genes:Candidate cancer biomarkers
Predicted intracellular proteins

Cellular Component

Molecular Function

Biological Process

KEGG

Reactome

Canonical Pathways

M241 Pid rac1 reg pathway
M81 Pid cdc42 pathway
M164 Pid erbb1 downstream pathway

Mediation Categories

Fusion and delivery mediationImmune mediationMetabolism mediationReceptor-signaling mediation

Relations & Evidence

Enzyme-Mediated Modification

4 records.

Substrate Gene Symbol	Enzyme Gene Symbol	Enzyme UniProt ID	Residue Type	Residue Offset	Modification	Database	References
CFLAR	AKT1	P31749	S	273	phosphorylation	PhosphoSite_MIMPMIMPSIGNORProtMapperSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper	ProtMapper:19339247 SIGNOR:19339247
CFLAR	PRKCA	P17252	S	193	phosphorylation	PhosphoSite_MIMPMIMPProtMapperPhosphoSitePhosphoSite_ProtMapper
CFLAR	PRKCB	P05771	S	193	phosphorylation	PhosphoSite_MIMPMIMPProtMapperPhosphoSitePhosphoSite_ProtMapper
CFLAR	ROS1	P08922	T	166	phosphorylation	REACH_ProtMapperProtMapper	ProtMapper:25675293

Ligand-Receptor Signaling

3 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
intracellular	intracellular	ComPPI	No	No	No	No	No
intracellular	intracellular	GO_Intercell	No	No	No	No	No
intracellular	intracellular	OmniPath	No	No	No	No	No

Regulatory Interaction Network

9 records.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
ITCH	Q96J02	CFLAR	O15519	Yes	No	Yes	SIGNORBioGRIDACSNSPIKE_LCSPIKE	BioGRID:30736843 ACSN:16469705 SIGNOR:16469705 SPIKE_LC:18786561 SPIKE:18786561 BioGRID:19090833
CFLAR	O15519	CASP8	Q14790	Yes	No	Yes	WangKEGG-MEDICUSNetPathSIGNORHPRDCui2007HINTBioGRIDCA1IntActInnateDBDIPSPIKE_LCLit-BM-17SPIKE	Lit-BM-17:11741985 SPIKE_LC:17159907 Lit-BM-17:9228018 Lit-BM-17:9208847 SIGNOR:9794838 Lit-BM-17:17159907 Lit-BM-17:15280356 IntAct:19416807 Lit-BM-17:24438025 SPIKE_LC:17145710 InnateDB:22421964 InnateDB:9208847 InnateDB:9380701 Lit-BM-17:9289491 BioGRID:19710364 DIP:19416807 Lit-BM-17:19343040 HINT:19343040 HINT:12887920 HPRD:9208847 HINT:15024054 HPRD:9289491 InnateDB:15024054 HINT:9326610 Lit-BM-17:22864571 HPRD:12215447 SPIKE:9880531 SPIKE_LC:9880531 HINT:24438025 HPRD:17159907 Lit-BM-17:21737330 Lit-BM-17:9326610 Lit-BM-17:26186194 BioGRID:12215447 InnateDB:17047155 NetPath:12887920 HINT:9380701 InnateDB:12097160 Lit-BM-17:19710364 HINT:17047155 HINT:17159907 HPRD:12097160 HINT:33961781 Lit-BM-17:12215447 HINT:9228018 Lit-BM-17:17047155 CA1:9217161 HINT:19416807 SIGNOR:14585074 Lit-BM-17:21737329 Lit-BM-17:12887920 HPRD:9380701 HINT:12097160 HINT:9289491 IntAct:24438025 HINT:38710704
AKT1	P31749	CFLAR	O15519	Yes	No	Yes	PhosphoSite_MIMPMIMPiPTMnetSIGNORProtMapperSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper	PhosphoSite:19339247 ProtMapper:19339247 SIGNOR:19339247
CHIP	Q9UNE7	CFLAR	O15519	Yes	No	Yes	Lit-BM-17SIGNOR	SIGNOR:23256568 Lit-BM-17:23256568 Lit-BM-17:25036637
BIRC2	Q13490	CFLAR	O15519	Yes	No	Yes	NetPathWangSIGNOR	SIGNOR:22345097 NetPath:12887920
CBL	P22681	CFLAR	O15519	Yes	No	Yes	SIGNOR	SIGNOR:19597496
KPCB	P05771	CFLAR	O15519	Yes	Yes	No	PhosphoSite_MIMPMIMPiPTMnetSIGNORProtMapperPhosphoSite_ProtMapper	SIGNOR:19343040
MK14	Q16539	CFLAR	O15519	Yes	Yes	No	SIGNOR	SIGNOR:19597496
KPCA	P17252	CFLAR	O15519	Yes	Yes	No	PhosphoSite_MIMPMIMPPhosphoSite_norefSIGNORiPTMnetProtMapperPhosphoSitePhosphoSite_ProtMapper	SIGNOR:19343040 PhosphoSite:19343040

Protein Complex Composition

8 records.

Component Name	Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs	References
Death induced signaling complex II (FADDCASP8CFLAR)cytosolicCD95L induced	CASP8 CFLAR FADD	O15519 Q13158 Q14790	4:3:3	CompleatCORUMPDB	PDB:8yniCompleat:HC1309PDB:8ybxPDB:8yd8PDB:8yd7CORUM:5798	18635548
MRIT complex	BCL2L1 CASP8 CFLAR	O15519 Q07817 Q14790	1:1:1	CompleatCORUM	CORUM:5749Compleat:HC3429	9326610
	APAF1 CASP1 CASP10 CASP2 CASP3 CASP4 CASP6 CASP7 CASP8 CFLAR DSP HSPA5 KRT18 RB1 TNFSF10	O14727 O15519 P05783 P06400 P11021 P15924 P29466 P42574 P42575 P49662 P50591 P55210 P55212 Q14790 Q92851	1:1:1:1:1:1:1:1:1:1:1:1:1:1:1	CompleatCFinder	Compleat:HC6912
	CFLAR DEDD SMAD3 UBC	O15519 O75618 P0CG48 P84022	1:1:1:1	CompleatCFinder	Compleat:HC6627
	CFLAR FOS NFKB1 RELA TPR	O15519 P01100 P12270 P19838 Q04206	1:1:1:1:1	NetworkBlastCompleat	Compleat:HC7805
	CFLAR ITCH MAP2K4 UBC	O15519 P0CG48 P45985 Q96J02	1:1:1:1	CompleatCFinder	Compleat:HC6777
	CFLAR PLIN5	O15519 Q00G26	0:0	hu.MAP
	CASP8 CFLAR	O15519 Q14790	6:4	PDB	PDB:8ym4PDB:8ym5PDB:8ynnPDB:8ynkPDB:8ynmPDB:7deePDB:3h11PDB:8ym6PDB:8ynl

Isolation & Detection Technology

1 record.

EV Isolation Method	Detection Method	Number of References	References
Differential UltracentrifugationSize Exclusion Chromatography	Mass spectrometryR Sequencing	2	36394150 31382537

Sequence, Structure & Domains

Sequences

Length

480

Mass

55,344

Sequence

MSAEVIHQVEEALDTDEKEMLLFLCRDVAIDVVPPNVRDLLDILRERGKLSVGDLAELLYRVRRFDLLKRILKMDRKAVETHLLRNPHLVSDYRVLMAEIGEDLDKSDVSSLIFLMKDYMGRGKISKEKSFLDLVVELEKLNLVAPDQLDLLEKCLKNIHRIDLKTKIQKYKQSVQGAGTSYRNVLQAAIQKSLKDPSNNFRLHNGRSKEQRLKEQLGAQQEPVKKSIQESEAFLPQSIPEERYKMKSKPLGICLIIDCIGNETELLRDTFTSLGYEVQKFLHLSMHGISQILGQFACMPEHRDYDSFVCVLVSRGGSQSVYGVDQTHSGLPLHHIRRMFMGDSCPYLAGKPKMFFIQNYVVSEGQLEDSSLLEVDGPAMKNVEFKAQKRGLCTVHREADFFWSLCTADMSLLEQSHSSPSLYLQCLSQKLRQERKRPLLDLHIELNGYMYDWNSRVSAKEKYYVWLQHTLRKKLILSYT

Alternative Products

Event=Alternative splicing; Named isoforms=15; Name=1; Synonyms=FLIP-L, CLARP1, MRIT alpha-1, CASH alpha, I-FLICE 1, FLAME-1 gamma, Usurpin alpha; IsoId=O15519-1; Sequence=Displayed; Name=2; Synonyms=FLIP-S, CLARP2, MRIT beta-1, CASH beta; IsoId=O15519-2; Sequence=VSP_000828, VSP_000829; Name=3; Synonyms=MRIT alpha-2; IsoId=O15519-3; Sequence=VSP_000824, VSP_000838; Name=4; Synonyms=I-FLICE 2; IsoId=O15519-4; Sequence=VSP_000825; Name=5; Synonyms=I-FLICE 3; IsoId=O15519-5; Sequence=VSP_000840; Name=6; Synonyms=I-FLICE 4; IsoId=O15519-6; Sequence=VSP_000826, VSP_000841; Name=7; Synonyms=I-FLICE 5; IsoId=O15519-7; Sequence=VSP_000824, VSP_000827, VSP_000838; Name=8; Synonyms=FLAME-1 alpha; IsoId=O15519-8; Sequence=VSP_000830; Name=9; Synonyms=FLAME-1 beta; IsoId=O15519-9; Sequence=VSP_000830, VSP_000836, VSP_000837; Name=10; Synonyms=FLAME-1 delta; IsoId=O15519-10; Sequence=VSP_000834, VSP_000835; Name=11; Synonyms=Usurpin beta; IsoId=O15519-11; Sequence=VSP_000838; Name=12; Synonyms=Usurpin gamma; IsoId=O15519-12; Sequence=VSP_000832, VSP_000833; Name=13; IsoId=O15519-13; Sequence=VSP_000831; Name=14; IsoId=O15519-14; Sequence=VSP_000839; Name=15; IsoId=O15519-15; Sequence=VSP_000824

Alternative Sequence

1..245; Missing (in isoform 4); 1..96; Missing (in isoform 3, isoform 7 and isoform 15); 2..30; SAEVIHQVEEALDTDEKEMLLFLCRDVAI -> LERPPVCSKV (in isoform 6); 203..480; Missing (in isoform 13); 203..237; Missing (in isoform 8 and isoform 9); 203..221; LHNGRSKEQRLKEQLGAQQ -> MITPYAHCPDLKILGNCSM (in isoform 2); 203..221; LHNGRSKEQRLKEQLGAQQ -> E (in isoform 7); 222..480; Missing (in isoform 2); 265..292; ELLRDTFTSLGYEVQKFLHLSMHGISQI -> GWSAMAQSQLTAISTSQVQAILLPQPPE (in isoform 12); 266..300; LLRDTFTSLGYEVQKFLHLSMHGISQILGQFACMP -> NAHSWIFTLNSMATCMIGTAEFLPRRNIMFGCSTL (in isoform 10); 267..305; LRDTFTSLGYEVQKFLHLSMHGISQILGQFACMPEHRDY -> CGVRGPAGGQQPLGGGWASDEECGIQGSEARAVHSSPRS (in isoform 9); 293..480; Missing (in isoform 12); 301..480; Missing (in isoform 10); 306..480; Missing (in isoform 9); 436..480; KRPLLDLHIELNGYMYDWNSRVSAKEKYYVWLQHTLRKKLILSYT -> GTIPGSGITESKDMHFSSLGCILLDVL (in isoform 11, isoform 7 and isoform 3); 436..480; Missing (in isoform 14); 449..480; YMYDWNSRVSAKEKYYVWLQHTLRKKLILSYT -> L (in isoform 5); 453..480; WNSRVSAKEKYYVWLQHTLRKKLILSYT -> SLEHTGGRY (in isoform 6)

3D Structural Models

Turn

25..28; 342..344

Helix

3..12; 15..24; 37..46; 52..61; 65..70; 76..85; 92..102; 106..116; 117..119; 131..140; 150..158; 162..175; 266..274; 286..297; 300..304; 333..340; 346..348; 410..412; 422..433; 439..454; 459..461

Beta Strand

239..241; 249..260; 276..283; 306..317; 353..361; 400..409; 463..469

3D Structure

Electron microscopy (6); NMR spectroscopy (4); X-ray crystallography (7)

Domain & Motif Annotations

Domain (CC)

The caspase domain lacks the active site residues involved in catalysis.

Domain (FT)

1..73; DED 1; 92..170; DED 2

Region

1..435; Not proteolytically processed and involved in apoptosis inhibition; 1..305; Interaction with CASP8 propeptide; 1..227; Interaction with FADD; 1..195; Interaction with CASP8; 192..480; Interaction with TRAF1 and TRAF2; 192..435; Interaction with CASP3; 217..480; Interaction with CASP8 subunits p18 and p10; 263..358; Caspase; 370..480; Interaction with CASP8

Protein Families

Peptidase C14A family

Sequence Similarities

Belongs to the peptidase C14A family.

Clinical Relevance

Disease Involvement

Cancer-related genes

Drugs

ALLOPURINOL NINTEDANIB ESYLATE IDRONOXIL FINASTERIDE CABOZANTINIB S-MALATE DOVITINIB BAY-11-7085 BICALUTAMIDE

Antibody

HPA019044 CAB022157 CAB025216

Interaction Protein

ENSG00000003400ENSG00000056558ENSG00000064012

Interaction Count

Interaction Dataset

intact_biogrid