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O15519 (CFLAR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 145. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
CASP8 and FADD-like apoptosis regulator
Alternative name(s):
Caspase homolog
Short name=CASH
Caspase-eight-related protein
Short name=Casper
Caspase-like apoptosis regulatory protein
Short name=CLARP
Cellular FLICE-like inhibitory protein
Short name=c-FLIP
FADD-like antiapoptotic molecule 1
Short name=FLAME-1
Inhibitor of FLICE
Short name=I-FLICE
MACH-related inducer of toxicity
Short name=MRIT
Usurpin
Gene names
Name:CFLAR
Synonyms:CASH, CASP8AP1, CLARP, MRIT
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length480 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Apoptosis regulator protein which may function as a crucial link between cell survival and cell death pathways in mammalian cells. Acts as an inhibitor of TNFRSF6 mediated apoptosis. A proteolytic fragment (p43) is likely retained in the death-inducing signaling complex (DISC) thereby blocking further recruitment and processing of caspase-8 at the complex. Full length and shorter isoforms have been shown either to induce apoptosis or to reduce TNFRSF-triggered apoptosis. Lacks enzymatic (caspase) activity. Ref.16

Subunit structure

TNFRSF6 stimulation triggers recruitment to the death-inducing signaling complex (DISC) formed by TNFRSF6, FADD and caspase-8. A proteolytic fragment (p43) stays associated with the DISC. Also interacts with caspase-10, caspase-3, TRAF1, TRAF2 and Bcl-X(L) (in vitro). Interacts with HBV protein X. Ref.18

Tissue specificity

Widely expressed. Higher expression in skeletal muscle, pancreas, heart, kidney, placenta, and peripheral blood leukocytes. Also detected in diverse cell lines. Isoform 8 is predominantly expressed in testis and skeletal muscle.

Induction

Repressed by IL2/interleukin-2 after TCR stimulation, during progression to the S phase of the cell cycle. Ref.17

Domain

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

Post-translational modification

Proteolytically processed; probably by caspase-8. Processing likely occurs at the DISC and generates subunit p43 and p12.

Sequence similarities

Belongs to the peptidase C14A family.

Contains 2 DED (death effector) domains.

Ontologies

Keywords
   Biological processApoptosis
Host-virus interaction
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic signaling pathway

Traceable author statement. Source: Reactome

negative regulation of apoptotic process

Traceable author statement Ref.3. Source: ProtInc

negative regulation of extrinsic apoptotic signaling pathway via death domain receptors

Inferred from mutant phenotype PubMed 18202225. Source: BHF-UCL

negative regulation of myoblast fusion

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from expression pattern PubMed 12761501. Source: UniProtKB

positive regulation of NF-kappaB transcription factor activity

Inferred from sequence or structural similarity. Source: BHF-UCL

proteolysis

Inferred from electronic annotation. Source: InterPro

regulation of extrinsic apoptotic signaling pathway in absence of ligand

Traceable author statement. Source: Reactome

regulation of necroptotic process

Inferred from direct assay PubMed 21737330. Source: UniProtKB

regulation of satellite cell proliferation

Inferred from sequence or structural similarity. Source: BHF-UCL

skeletal muscle atrophy

Inferred from sequence or structural similarity. Source: BHF-UCL

skeletal muscle tissue development

Inferred from sequence or structural similarity. Source: BHF-UCL

skeletal muscle tissue regeneration

Inferred from sequence or structural similarity. Source: BHF-UCL

skeletal myofibril assembly

Inferred from sequence or structural similarity. Source: BHF-UCL

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentCD95 death-inducing signaling complex

Inferred from electronic annotation. Source: Ensembl

cytosol

Traceable author statement. Source: Reactome

death-inducing signaling complex

Inferred from direct assay PubMed 21803845. Source: UniProtKB

ripoptosome

Inferred from direct assay PubMed 21737330. Source: UniProtKB

   Molecular_functioncysteine-type endopeptidase activity

Inferred from electronic annotation. Source: InterPro

enzyme activator activity

Inferred from direct assay Ref.1. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 15 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O15519-1)

Also known as: FLIP-L; CLARP1; MRIT alpha-1; CASH alpha; I-FLICE 1; FLAME-1 gamma; Usurpin alpha;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O15519-2)

Also known as: FLIP-S; CLARP2; MRIT beta-1; CASH beta;

The sequence of this isoform differs from the canonical sequence as follows:
     203-221: LHNGRSKEQRLKEQLGAQQ → MITPYAHCPDLKILGNCSM
     222-480: Missing.
Isoform 3 (identifier: O15519-3)

Also known as: MRIT alpha-2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-96: Missing.
     436-480: KRPLLDLHIELNGYMYDWNSRVSAKEKYYVWLQHTLRKKLILSYT → GTIPGSGITESKDMHFSSLGCILLDVL
Isoform 4 (identifier: O15519-4)

Also known as: I-FLICE 2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-245: Missing.
Isoform 5 (identifier: O15519-5)

Also known as: I-FLICE 3;

The sequence of this isoform differs from the canonical sequence as follows:
     449-480: YMYDWNSRVSAKEKYYVWLQHTLRKKLILSYT → L
Isoform 6 (identifier: O15519-6)

Also known as: I-FLICE 4;

The sequence of this isoform differs from the canonical sequence as follows:
     2-30: SAEVIHQVEEALDTDEKEMLLFLCRDVAI → LERPPVCSKV
     453-480: WNSRVSAKEKYYVWLQHTLRKKLILSYT → SLEHTGGRY
Isoform 7 (identifier: O15519-7)

Also known as: I-FLICE 5;

The sequence of this isoform differs from the canonical sequence as follows:
     1-96: Missing.
     203-221: LHNGRSKEQRLKEQLGAQQ → E
     436-480: KRPLLDLHIELNGYMYDWNSRVSAKEKYYVWLQHTLRKKLILSYT → GTIPGSGITESKDMHFSSLGCILLDVL
Isoform 8 (identifier: O15519-8)

Also known as: FLAME-1 alpha;

The sequence of this isoform differs from the canonical sequence as follows:
     203-237: Missing.
Isoform 9 (identifier: O15519-9)

Also known as: FLAME-1 beta;

The sequence of this isoform differs from the canonical sequence as follows:
     203-237: Missing.
     267-305: LRDTFTSLGY...FACMPEHRDY → CGVRGPAGGQ...ARAVHSSPRS
     306-480: Missing.
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Isoform 10 (identifier: O15519-10)

Also known as: FLAME-1 delta;

The sequence of this isoform differs from the canonical sequence as follows:
     266-300: LLRDTFTSLGYEVQKFLHLSMHGISQILGQFACMP → NAHSWIFTLNSMATCMIGTAEFLPRRNIMFGCSTL
     301-480: Missing.
Isoform 11 (identifier: O15519-11)

Also known as: Usurpin beta;

The sequence of this isoform differs from the canonical sequence as follows:
     436-480: KRPLLDLHIELNGYMYDWNSRVSAKEKYYVWLQHTLRKKLILSYT → GTIPGSGITESKDMHFSSLGCILLDVL
Isoform 12 (identifier: O15519-12)

Also known as: Usurpin gamma;

The sequence of this isoform differs from the canonical sequence as follows:
     265-292: ELLRDTFTSLGYEVQKFLHLSMHGISQI → GWSAMAQSQLTAISTSQVQAILLPQPPE
     293-480: Missing.
Isoform 13 (identifier: O15519-13)

The sequence of this isoform differs from the canonical sequence as follows:
     203-480: Missing.
Isoform 14 (identifier: O15519-14)

The sequence of this isoform differs from the canonical sequence as follows:
     436-480: Missing.
Isoform 15 (identifier: O15519-15)

The sequence of this isoform differs from the canonical sequence as follows:
     1-96: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 376376CASP8 and FADD-like apoptosis regulator subunit p43
PRO_0000004678
Chain377 – 480104CASP8 and FADD-like apoptosis regulator subunit p12 Potential
PRO_0000004679

Regions

Domain1 – 7373DED 1
Domain92 – 17079DED 2
Region1 – 435435Not proteolytically processed and involved in apoptosis inhibition
Region1 – 305305Interaction with caspase-8 propeptide
Region1 – 227227Interaction with FADD
Region1 – 195195Interaction with caspase-8
Region192 – 480289Interaction with TRAF1 and TRAF2
Region192 – 435244Interaction with caspase-3
Region217 – 480264Interaction with caspase-8 subunits p18 and p10
Region263 – 35896Caspase
Region370 – 480111Interaction with caspase-8

Natural variations

Alternative sequence1 – 245245Missing in isoform 4.
VSP_000825
Alternative sequence1 – 9696Missing in isoform 3, isoform 7 and isoform 15.
VSP_000824
Alternative sequence2 – 3029SAEVI…RDVAI → LERPPVCSKV in isoform 6.
VSP_000826
Alternative sequence203 – 480278Missing in isoform 13.
VSP_000831
Alternative sequence203 – 23735Missing in isoform 8 and isoform 9.
VSP_000830
Alternative sequence203 – 22119LHNGR…LGAQQ → MITPYAHCPDLKILGNCSM in isoform 2.
VSP_000828
Alternative sequence203 – 22119LHNGR…LGAQQ → E in isoform 7.
VSP_000827
Alternative sequence222 – 480259Missing in isoform 2.
VSP_000829
Alternative sequence265 – 29228ELLRD…GISQI → GWSAMAQSQLTAISTSQVQA ILLPQPPE in isoform 12.
VSP_000832
Alternative sequence266 – 30035LLRDT…FACMP → NAHSWIFTLNSMATCMIGTA EFLPRRNIMFGCSTL in isoform 10.
VSP_000834
Alternative sequence267 – 30539LRDTF…EHRDY → CGVRGPAGGQQPLGGGWASD EECGIQGSEARAVHSSPRS in isoform 9.
VSP_000836
Alternative sequence293 – 480188Missing in isoform 12.
VSP_000833
Alternative sequence301 – 480180Missing in isoform 10.
VSP_000835
Alternative sequence306 – 480175Missing in isoform 9.
VSP_000837
Alternative sequence436 – 48045KRPLL…ILSYT → GTIPGSGITESKDMHFSSLG CILLDVL in isoform 11, isoform 7 and isoform 3.
VSP_000838
Alternative sequence436 – 48045Missing in isoform 14.
VSP_000839
Alternative sequence449 – 48032YMYDW…ILSYT → L in isoform 5.
VSP_000840
Alternative sequence453 – 48028WNSRV…ILSYT → SLEHTGGRY in isoform 6.
VSP_000841
Natural variant2031L → I.
Corresponds to variant rs13424615 [ dbSNP | Ensembl ].
VAR_048619

Experimental info

Mutagenesis3601Y → F: Decreases apoptosis-inducing activity. Reduces interaction with caspase-3 and proteolytic processing. Ref.1
Mutagenesis3761D → N or A: Abolishes proteolytic processing. Ref.4
Sequence conflict130 – 1323SFL → ISW in AAC15825. Ref.8
Sequence conflict130 – 1323SFL → ISW in AAC15826. Ref.8
Sequence conflict3431D → E in AAC15825. Ref.8
Sequence conflict3641E → D in AAB99794. Ref.6
Sequence conflict366 – 3683QLE → PAG in AAC15825. Ref.8
Sequence conflict3691D → N in CAA74366. Ref.7
Sequence conflict3721L → F in AAB99793. Ref.6
Sequence conflict373 – 3742LE → WR in AAC15825. Ref.8

Secondary structure

.................................. 480
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (FLIP-L) (CLARP1) (MRIT alpha-1) (CASH alpha) (I-FLICE 1) (FLAME-1 gamma) (Usurpin alpha) [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 8C6D7E92AE1EB672

FASTA48055,344
        10         20         30         40         50         60 
MSAEVIHQVE EALDTDEKEM LLFLCRDVAI DVVPPNVRDL LDILRERGKL SVGDLAELLY 

        70         80         90        100        110        120 
RVRRFDLLKR ILKMDRKAVE THLLRNPHLV SDYRVLMAEI GEDLDKSDVS SLIFLMKDYM 

       130        140        150        160        170        180 
GRGKISKEKS FLDLVVELEK LNLVAPDQLD LLEKCLKNIH RIDLKTKIQK YKQSVQGAGT 

       190        200        210        220        230        240 
SYRNVLQAAI QKSLKDPSNN FRLHNGRSKE QRLKEQLGAQ QEPVKKSIQE SEAFLPQSIP 

       250        260        270        280        290        300 
EERYKMKSKP LGICLIIDCI GNETELLRDT FTSLGYEVQK FLHLSMHGIS QILGQFACMP 

       310        320        330        340        350        360 
EHRDYDSFVC VLVSRGGSQS VYGVDQTHSG LPLHHIRRMF MGDSCPYLAG KPKMFFIQNY 

       370        380        390        400        410        420 
VVSEGQLEDS SLLEVDGPAM KNVEFKAQKR GLCTVHREAD FFWSLCTADM SLLEQSHSSP 

       430        440        450        460        470        480 
SLYLQCLSQK LRQERKRPLL DLHIELNGYM YDWNSRVSAK EKYYVWLQHT LRKKLILSYT 

« Hide

Isoform 2 (FLIP-S) (CLARP2) (MRIT beta-1) (CASH beta) [UniParc].

Checksum: 12774D7AB3E53263
Show »

FASTA22125,379
Isoform 3 (MRIT alpha-2) [UniParc].

Checksum: B5DB6C8A18608582
Show »

FASTA36641,319
Isoform 4 (I-FLICE 2) [UniParc].

Checksum: 1B34FA73556DC390
Show »

FASTA23527,055
Isoform 5 (I-FLICE 3) [UniParc].

Checksum: 8AC8D85BA2F72F7E
Show »

FASTA44951,390
Isoform 6 (I-FLICE 4) [UniParc].

Checksum: B20A318B728B2543
Show »

FASTA44250,661
Isoform 7 (I-FLICE 5) [UniParc].

Checksum: E9F524387399F9CA
Show »

FASTA34839,245
Isoform 8 (FLAME-1 alpha) [UniParc].

Checksum: 91CD549119606DB2
Show »

FASTA44551,330
Isoform 9 (FLAME-1 beta) [UniParc].

Checksum: 230E9C0C0ADD1003
Show »

FASTA27030,399
Isoform 10 (FLAME-1 delta) [UniParc].

Checksum: F6A777C2BA1469EF
Show »

FASTA30034,384
Isoform 11 (Usurpin beta) [UniParc].

Checksum: D4E0109CBA47EAA3
Show »

FASTA46252,551
Isoform 12 (Usurpin gamma) [UniParc].

Checksum: 542E30BD5169F336
Show »

FASTA29233,273
Isoform 13 [UniParc].

Checksum: 67D3C756AFD14F94
Show »

FASTA20223,289
Isoform 14 [UniParc].

Checksum: B37ED523D7738376
Show »

FASTA43549,778
Isoform 15 [UniParc].

Checksum: 846E6372DB81F0F6
Show »

FASTA38444,112

References

« Hide 'large scale' references
[1]"Casper is a FADD- and caspase-related inducer of apoptosis."
Shu H.-B., Halpin D.R., Goeddel D.V.
Immunity 6:751-763(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 13 AND 14), MUTAGENESIS OF TYR-360.
Tissue: Embryonic kidney and Umbilical vein endothelial cell.
[2]"MRIT, a novel death-effector domain-containing protein, interacts with caspases and BclXL and initiates cell death."
Han D.K.M., Chaudhary P.M., Wright M.E., Friedman C., Trask B.J., Riedel R.T., Baskin D.G., Schwartz S.M., Hood L.
Proc. Natl. Acad. Sci. U.S.A. 94:11333-11338(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
[3]"Inhibition of death receptor signals by cellular FLIP."
Irmler M., Thome M., Hahne M., Schneider P., Hofmann K., Steiner V., Bodmer J.-L., Schroeter M., Burns K., Mattmann C., Rimoldi D., French L.E., Tschopp J.
Nature 388:190-195(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
Tissue: Peripheral blood lymphocyte.
[4]"FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis."
Srinivasula S.M., Ahmad M., Ottilie S., Bullrich F., Banks S., Wang Y., Fernandes-Alnemri T., Croce C.M., Litwack G., Tomaselli K.J., Armstrong R.C., Alnemri E.S.
J. Biol. Chem. 272:18542-18545(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 8; 9 AND 10), MUTAGENESIS OF ASP-376.
Tissue: T-cell.
[5]"I-FLICE, a novel inhibitor of tumor necrosis factor receptor-1- and CD-95-induced apoptosis."
Hu S., Vincenz C., Ni J., Gentz R., Dixit V.M.
J. Biol. Chem. 272:17255-17257(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Umbilical vein endothelial cell.
[6]Hu S., Dixit V.M.
Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4; 5; 6 AND 7).
[7]"CASH, a novel caspase homologue with death effector domains."
Goltsev Y.V., Kovalenko A.V., Arnold E., Varfolomeev E.E., Brodianskii V.M., Wallach D.
J. Biol. Chem. 272:19641-19644(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
Tissue: Skin fibroblast.
[8]"CLARP, a death effector domain-containing protein interacts with caspase-8 and regulates apoptosis."
Inohara N., Koseki T., Hu Y., Chen S., Nunez G.
Proc. Natl. Acad. Sci. U.S.A. 94:10717-10722(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
Tissue: Colon carcinoma.
[9]"Cell death attenuation by 'Usurpin', a mammalian DED-caspase homologue that precludes caspase-8 recruitment and activation by the CD-95 (Fas, APO-1) receptor complex."
Rasper D.M., Vaillancourt J.P., Hadano S., Houtzager V.M., Seiden I., Keen S.L.C., Tawa P., Xanthoudakis S., Nasir J., Martindale D., Koop B.F., Peterson E.P., Thornberry N.A., Huang J., MacPherson D.P., Black S.C., Hornung F., Lenardo M.J. expand/collapse author list , Hayden M.R., Roy S., Nicholson D.W.
Cell Death Differ. 5:271-288(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 11 AND 12).
Tissue: Kidney.
[10]"Cloning and characterization of three novel genes, ALS2CR1, ALS2CR2, and ALS2CR3, in the juvenile amyotrophic lateral sclerosis (ALS2) critical region at chromosome 2q33-q34: candidate genes for ALS2."
Hadano S., Yanagisawa Y., Skaug J., Fichter K., Nasir J., Martindale D., Koop B.F., Scherer S.W., Nicholson D.W., Rouleau G.A., Ikeda J.-E., Hayden M.R.
Genomics 71:200-213(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[11]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[12]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 15).
Tissue: Cerebellum, Corpus callosum and Subthalamic nucleus.
[13]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[14]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[15]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Lymph.
[16]"The role of c-FLIP in modulation of CD95-induced apoptosis."
Scaffidi C., Schmitz I., Krammer P.H., Peter M.E.
J. Biol. Chem. 274:1541-1548(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[17]"Cell cycle-dependent regulation of FLIP levels and susceptibility to Fas-mediated apoptosis."
Algeciras-Schimnich A., Griffith T.S., Lynch D.H., Paya C.V.
J. Immunol. 162:5205-5211(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[18]"Pro-apoptotic function of HBV X protein is mediated by interaction with c-FLIP and enhancement of death-inducing signal."
Kim K.H., Seong B.L.
EMBO J. 22:2104-2116(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HBV PROTEIN X.
[19]"An unappreciated role for RNA surveillance."
Hillman R.T., Green R.E., Brenner S.E.
Genome Biol. 5:R8.1-R8.16(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF010127 mRNA. Translation: AAB64110.1.
U85059 mRNA. Translation: AAB82648.1.
U97074 mRNA. Translation: AAC51622.1.
U97075 mRNA. Translation: AAC51623.1.
AF009616 mRNA. Translation: AAB70909.1.
AF009617 mRNA. Translation: AAB70910.1.
AF009618 mRNA. Translation: AAB70911.1.
AF009619 mRNA. Translation: AAB70912.1.
AF041458 mRNA. Translation: AAB99790.1.
AF041459 mRNA. Translation: AAB99791.1.
AF041462 mRNA. Translation: AAB99794.1.
AF041461 mRNA. Translation: AAB99793.1.
AF041460 mRNA. Translation: AAB99792.1.
Y14039 mRNA. Translation: CAA74366.1.
Y14040 mRNA. Translation: CAA74367.1.
AF005774 mRNA. Translation: AAC15825.1.
AF005775 mRNA. Translation: AAC15826.1.
AF015450 mRNA. Translation: AAC16439.1.
AF015451 mRNA. Translation: AAC16440.1.
AF015452 mRNA. Translation: AAC16441.1.
AB038972 Genomic DNA. Translation: BAB32551.1.
AB038972 Genomic DNA. Translation: BAB32552.1.
BT006751 mRNA. Translation: AAP35397.1.
AK289913 mRNA. Translation: BAF82602.1.
AK296036 mRNA. Translation: BAG58802.1.
AK315208 mRNA. Translation: BAG37645.1.
AK315924 mRNA. Translation: BAH14295.1.
AC007283 Genomic DNA. Translation: AAY24290.1.
CH471063 Genomic DNA. Translation: EAW70237.1.
CH471063 Genomic DNA. Translation: EAW70244.1.
BC001602 mRNA. Translation: AAH01602.1.
RefSeqNP_001120655.1. NM_001127183.2.
NP_001120656.1. NM_001127184.2.
NP_001189444.1. NM_001202515.1.
NP_001189445.1. NM_001202516.1.
NP_001189446.1. NM_001202517.1.
NP_001189447.1. NM_001202518.1.
NP_001189448.1. NM_001202519.1.
NP_003870.4. NM_003879.5.
XP_005246992.1. XM_005246935.1.
XP_005246993.1. XM_005246936.1.
XP_005246994.1. XM_005246937.1.
UniGeneHs.390736.
Hs.731912.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3H11X-ray1.90A209-480[»]
3H13X-ray2.20A209-480[»]
ProteinModelPortalO15519.
SMRO15519. Positions 4-169, 237-480.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114364. 36 interactions.
DIPDIP-27629N.
IntActO15519. 17 interactions.
MINTMINT-1529273.

Chemistry

ChEMBLCHEMBL1955713.

Protein family/group databases

MEROPSC14.971.

PTM databases

PhosphoSiteO15519.

Proteomic databases

PaxDbO15519.
PRIDEO15519.

Protocols and materials databases

DNASU8837.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000309955; ENSP00000312455; ENSG00000003402. [O15519-1]
ENST00000340870; ENSP00000339326; ENSG00000003402. [O15519-11]
ENST00000341222; ENSP00000339335; ENSG00000003402. [O15519-2]
ENST00000341582; ENSP00000345807; ENSG00000003402. [O15519-8]
ENST00000342795; ENSP00000342809; ENSG00000003402. [O15519-12]
ENST00000423241; ENSP00000399420; ENSG00000003402. [O15519-1]
ENST00000440180; ENSP00000406775; ENSG00000003402. [O15519-2]
ENST00000443227; ENSP00000413270; ENSG00000003402. [O15519-15]
ENST00000457277; ENSP00000411535; ENSG00000003402. [O15519-11]
ENST00000479953; ENSP00000471805; ENSG00000003402. [O15519-3]
GeneID8837.
KEGGhsa:8837.
UCSCuc002uwz.3. human. [O15519-2]
uc002uxb.4. human. [O15519-1]
uc002uxc.4. human. [O15519-8]
uc002uxf.3. human. [O15519-11]
uc002uxg.3. human. [O15519-4]
uc010fsw.3. human. [O15519-3]
uc010fsz.3. human. [O15519-7]
uc021vuw.1. human. [O15519-12]

Organism-specific databases

CTD8837.
GeneCardsGC02P201980.
HGNCHGNC:1876. CFLAR.
HPACAB022157.
CAB025216.
HPA019044.
MIM603599. gene.
neXtProtNX_O15519.
PharmGKBPA26425.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG331323.
HOVERGENHBG050918.
InParanoidO15519.
KOK04724.
OMAYDWNSRV.
OrthoDBEOG74N5GK.
PhylomeDBO15519.
TreeFamTF352765.

Enzyme and pathway databases

ReactomeREACT_578. Apoptosis.
SignaLinkO15519.

Gene expression databases

ArrayExpressO15519.
BgeeO15519.
GenevestigatorO15519.

Family and domain databases

Gene3D1.10.533.10. 3 hits.
InterProIPR011029. DEATH-like_dom.
IPR001875. DED.
IPR011600. Pept_C14_caspase.
IPR001309. Pept_C14_ICE_p20.
IPR015917. Pept_C14A_p45_core.
[Graphical view]
PfamPF01335. DED. 2 hits.
PF00656. Peptidase_C14. 1 hit.
[Graphical view]
SMARTSM00115. CASc. 1 hit.
SM00031. DED. 2 hits.
[Graphical view]
SUPFAMSSF47986. SSF47986. 2 hits.
PROSITEPS50208. CASPASE_P20. 1 hit.
PS50168. DED. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCFLAR. human.
EvolutionaryTraceO15519.
GeneWikiCFLAR.
GenomeRNAi8837.
NextBio33168.
PROO15519.
SOURCESearch...

Entry information

Entry nameCFLAR_HUMAN
AccessionPrimary (citable) accession number: O15519
Secondary accession number(s): B4DJE0 expand/collapse secondary AC list , B7Z9F9, O14673, O14674, O14675, O15137, O15138, O15356, O15510, O43618, O43619, O43620, O60458, O60459, Q53TS6, Q54AF1, Q96TE4, Q9UEW1
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 1, 1998
Last modified: March 19, 2014
This is version 145 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM