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Protein

CASP8 and FADD-like apoptosis regulator

Gene

CFLAR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

  • cysteine-type endopeptidase activity involved in apoptotic signaling pathway Source: GO_Central
  • death effector domain binding Source: GO_Central
  • enzyme activator activity Source: UniProtKB
  • protease binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Apoptosis, Host-virus interaction

Enzyme and pathway databases

ReactomeiREACT_164011. Regulation by c-FLIP.
REACT_355311. CASP8 activity is inhibited.
REACT_355409. RIPK1-mediated regulated necrosis.
REACT_402. TRAIL signaling.
REACT_832. Dimerization of procaspase-8.
SignaLinkiO15519.

Protein family/group databases

MEROPSiC14.971.

Names & Taxonomyi

Protein namesi
Recommended 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
Cleaved into the following 2 chains:
Gene namesi
Name:CFLAR
Synonyms:CASH, CASP8AP1, CLARP, MRIT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:1876. CFLAR.

Subcellular locationi

GO - Cellular componenti

  • CD95 death-inducing signaling complex Source: Ensembl
  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • death-inducing signaling complex Source: UniProtKB
  • membrane raft Source: Ensembl
  • ripoptosome Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi360 – 3601Y → F: Decreases apoptosis-inducing activity. Reduces interaction with caspase-3 and proteolytic processing. 1 Publication
Mutagenesisi376 – 3761D → N or A: Abolishes proteolytic processing. 1 Publication

Organism-specific databases

PharmGKBiPA26425.

Polymorphism and mutation databases

BioMutaiCFLAR.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 376376CASP8 and FADD-like apoptosis regulator subunit p43PRO_0000004678Add
BLAST
Chaini377 – 480104CASP8 and FADD-like apoptosis regulator subunit p12Sequence AnalysisPRO_0000004679Add
BLAST

Post-translational modificationi

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

Proteomic databases

MaxQBiO15519.
PaxDbiO15519.
PRIDEiO15519.

PTM databases

PhosphoSiteiO15519.

Expressioni

Tissue specificityi

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.

Inductioni

Repressed by IL2/interleukin-2 after TCR stimulation, during progression to the S phase of the cell cycle.1 Publication

Gene expression databases

BgeeiO15519.
ExpressionAtlasiO15519. baseline and differential.
GenevestigatoriO15519.

Organism-specific databases

HPAiCAB022157.
CAB025216.
HPA019044.

Interactioni

Subunit structurei

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.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CASP10Q928513EBI-514941,EBI-495095
CASP10Q92851-43EBI-4478097,EBI-6621134
CASP8Q147909EBI-514941,EBI-78060
MAP2K1Q027503EBI-4567563,EBI-492564
MAP2K7O147332EBI-4567563,EBI-492605
TRAF1Q130773EBI-514941,EBI-359224

Protein-protein interaction databases

BioGridi114364. 39 interactions.
DIPiDIP-27629N.
IntActiO15519. 29 interactions.
MINTiMINT-1529273.

Structurei

Secondary structure

1
480
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi239 – 2413Combined sources
Beta strandi249 – 26012Combined sources
Helixi266 – 2749Combined sources
Beta strandi276 – 2838Combined sources
Helixi286 – 29712Combined sources
Helixi300 – 3045Combined sources
Beta strandi306 – 31712Combined sources
Helixi333 – 3408Combined sources
Turni342 – 3443Combined sources
Helixi346 – 3483Combined sources
Beta strandi353 – 3619Combined sources
Beta strandi400 – 40910Combined sources
Helixi410 – 4123Combined sources
Helixi422 – 43312Combined sources
Helixi439 – 45416Combined sources
Helixi459 – 4613Combined sources
Beta strandi463 – 4697Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3H11X-ray1.90A209-480[»]
3H13X-ray2.20A209-480[»]
ProteinModelPortaliO15519.
SMRiO15519. Positions 4-169, 237-480.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO15519.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 7373DED 1PROSITE-ProRule annotationAdd
BLAST
Domaini92 – 17079DED 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 435435Not proteolytically processed and involved in apoptosis inhibitionAdd
BLAST
Regioni1 – 305305Interaction with caspase-8 propeptideAdd
BLAST
Regioni1 – 227227Interaction with FADDAdd
BLAST
Regioni1 – 195195Interaction with caspase-8Add
BLAST
Regioni192 – 480289Interaction with TRAF1 and TRAF2Add
BLAST
Regioni192 – 435244Interaction with caspase-3Add
BLAST
Regioni217 – 480264Interaction with caspase-8 subunits p18 and p10Add
BLAST
Regioni263 – 35896CaspaseAdd
BLAST
Regioni370 – 480111Interaction with caspase-8Add
BLAST

Domaini

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

Sequence similaritiesi

Belongs to the peptidase C14A family.Curated
Contains 2 DED (death effector) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiNOG331323.
GeneTreeiENSGT00530000064199.
HOGENOMiHOG000069972.
HOVERGENiHBG050918.
InParanoidiO15519.
KOiK04724.
OMAiKLFFIQN.
OrthoDBiEOG74N5GK.
PhylomeDBiO15519.
TreeFamiTF352765.

Family and domain databases

Gene3Di1.10.533.10. 3 hits.
3.40.50.1460. 1 hit.
InterProiIPR029030. Caspase-like_dom.
IPR011029. DEATH-like_dom.
IPR001875. DED.
IPR011600. Pept_C14_caspase.
IPR001309. Pept_C14_ICE_p20.
IPR015917. Pept_C14A_p45_core.
[Graphical view]
PfamiPF01335. DED. 2 hits.
PF00656. Peptidase_C14. 1 hit.
[Graphical view]
SMARTiSM00115. CASc. 1 hit.
SM00031. DED. 2 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 2 hits.
PROSITEiPS50208. CASPASE_P20. 1 hit.
PS50168. DED. 2 hits.
[Graphical view]

Sequences (15)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 15 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O15519-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSAEVIHQVE EALDTDEKEM LLFLCRDVAI DVVPPNVRDL LDILRERGKL
60 70 80 90 100
SVGDLAELLY RVRRFDLLKR ILKMDRKAVE THLLRNPHLV SDYRVLMAEI
110 120 130 140 150
GEDLDKSDVS SLIFLMKDYM GRGKISKEKS FLDLVVELEK LNLVAPDQLD
160 170 180 190 200
LLEKCLKNIH RIDLKTKIQK YKQSVQGAGT SYRNVLQAAI QKSLKDPSNN
210 220 230 240 250
FRLHNGRSKE QRLKEQLGAQ QEPVKKSIQE SEAFLPQSIP EERYKMKSKP
260 270 280 290 300
LGICLIIDCI GNETELLRDT FTSLGYEVQK FLHLSMHGIS QILGQFACMP
310 320 330 340 350
EHRDYDSFVC VLVSRGGSQS VYGVDQTHSG LPLHHIRRMF MGDSCPYLAG
360 370 380 390 400
KPKMFFIQNY VVSEGQLEDS SLLEVDGPAM KNVEFKAQKR GLCTVHREAD
410 420 430 440 450
FFWSLCTADM SLLEQSHSSP SLYLQCLSQK LRQERKRPLL DLHIELNGYM
460 470 480
YDWNSRVSAK EKYYVWLQHT LRKKLILSYT
Length:480
Mass (Da):55,344
Last modified:January 1, 1998 - v1
Checksum:i8C6D7E92AE1EB672
GO
Isoform 2 (identifier: O15519-2) [UniParc]FASTAAdd to basket

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.

Show »
Length:221
Mass (Da):25,379
Checksum:i12774D7AB3E53263
GO
Isoform 3 (identifier: O15519-3) [UniParc]FASTAAdd to basket

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

Show »
Length:366
Mass (Da):41,319
Checksum:iB5DB6C8A18608582
GO
Isoform 4 (identifier: O15519-4) [UniParc]FASTAAdd to basket

Also known as: I-FLICE 2

The sequence of this isoform differs from the canonical sequence as follows:
     1-245: Missing.

Show »
Length:235
Mass (Da):27,055
Checksum:i1B34FA73556DC390
GO
Isoform 5 (identifier: O15519-5) [UniParc]FASTAAdd to basket

Also known as: I-FLICE 3

The sequence of this isoform differs from the canonical sequence as follows:
     449-480: YMYDWNSRVSAKEKYYVWLQHTLRKKLILSYT → L

Show »
Length:449
Mass (Da):51,390
Checksum:i8AC8D85BA2F72F7E
GO
Isoform 6 (identifier: O15519-6) [UniParc]FASTAAdd to basket

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

Show »
Length:442
Mass (Da):50,661
Checksum:iB20A318B728B2543
GO
Isoform 7 (identifier: O15519-7) [UniParc]FASTAAdd to basket

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

Show »
Length:348
Mass (Da):39,245
Checksum:iE9F524387399F9CA
GO
Isoform 8 (identifier: O15519-8) [UniParc]FASTAAdd to basket

Also known as: FLAME-1 alpha

The sequence of this isoform differs from the canonical sequence as follows:
     203-237: Missing.

Show »
Length:445
Mass (Da):51,330
Checksum:i91CD549119606DB2
GO
Isoform 9 (identifier: O15519-9) [UniParc]FASTAAdd to basket

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.

Show »
Length:270
Mass (Da):30,399
Checksum:i230E9C0C0ADD1003
GO
Isoform 10 (identifier: O15519-10) [UniParc]FASTAAdd to basket

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.

Show »
Length:300
Mass (Da):34,384
Checksum:iF6A777C2BA1469EF
GO
Isoform 11 (identifier: O15519-11) [UniParc]FASTAAdd to basket

Also known as: Usurpin beta

The sequence of this isoform differs from the canonical sequence as follows:
     436-480: KRPLLDLHIELNGYMYDWNSRVSAKEKYYVWLQHTLRKKLILSYT → GTIPGSGITESKDMHFSSLGCILLDVL

Show »
Length:462
Mass (Da):52,551
Checksum:iD4E0109CBA47EAA3
GO
Isoform 12 (identifier: O15519-12) [UniParc]FASTAAdd to basket

Also known as: Usurpin gamma

The sequence of this isoform differs from the canonical sequence as follows:
     265-292: ELLRDTFTSLGYEVQKFLHLSMHGISQI → GWSAMAQSQLTAISTSQVQAILLPQPPE
     293-480: Missing.

Show »
Length:292
Mass (Da):33,273
Checksum:i542E30BD5169F336
GO
Isoform 13 (identifier: O15519-13) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     203-480: Missing.

Show »
Length:202
Mass (Da):23,289
Checksum:i67D3C756AFD14F94
GO
Isoform 14 (identifier: O15519-14) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     436-480: Missing.

Show »
Length:435
Mass (Da):49,778
Checksum:iB37ED523D7738376
GO
Isoform 15 (identifier: O15519-15) [UniParc]FASTAAdd to basket

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

Show »
Length:384
Mass (Da):44,112
Checksum:i846E6372DB81F0F6
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti130 – 1323SFL → ISW in AAC15825 (PubMed:9380701).Curated
Sequence conflicti130 – 1323SFL → ISW in AAC15826 (PubMed:9380701).Curated
Sequence conflicti343 – 3431D → E in AAC15825 (PubMed:9380701).Curated
Sequence conflicti364 – 3641E → D in AAB99794 (Ref. 6) Curated
Sequence conflicti366 – 3683QLE → PAG in AAC15825 (PubMed:9380701).Curated
Sequence conflicti369 – 3691D → N in CAA74366 (PubMed:9289491).Curated
Sequence conflicti372 – 3721L → F in AAB99793 (Ref. 6) Curated
Sequence conflicti373 – 3742LE → WR in AAC15825 (PubMed:9380701).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti203 – 2031L → I.
Corresponds to variant rs13424615 [ dbSNP | Ensembl ].
VAR_048619

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 245245Missing in isoform 4. 1 PublicationVSP_000825Add
BLAST
Alternative sequencei1 – 9696Missing in isoform 3, isoform 7 and isoform 15. 3 PublicationsVSP_000824Add
BLAST
Alternative sequencei2 – 3029SAEVI…RDVAI → LERPPVCSKV in isoform 6. 1 PublicationVSP_000826Add
BLAST
Alternative sequencei203 – 480278Missing in isoform 13. 1 PublicationVSP_000831Add
BLAST
Alternative sequencei203 – 23735Missing in isoform 8 and isoform 9. 1 PublicationVSP_000830Add
BLAST
Alternative sequencei203 – 22119LHNGR…LGAQQ → MITPYAHCPDLKILGNCSM in isoform 2. 4 PublicationsVSP_000828Add
BLAST
Alternative sequencei203 – 22119LHNGR…LGAQQ → E in isoform 7. 1 PublicationVSP_000827Add
BLAST
Alternative sequencei222 – 480259Missing in isoform 2. 4 PublicationsVSP_000829Add
BLAST
Alternative sequencei265 – 29228ELLRD…GISQI → GWSAMAQSQLTAISTSQVQA ILLPQPPE in isoform 12. 1 PublicationVSP_000832Add
BLAST
Alternative sequencei266 – 30035LLRDT…FACMP → NAHSWIFTLNSMATCMIGTA EFLPRRNIMFGCSTL in isoform 10. 1 PublicationVSP_000834Add
BLAST
Alternative sequencei267 – 30539LRDTF…EHRDY → CGVRGPAGGQQPLGGGWASD EECGIQGSEARAVHSSPRS in isoform 9. 1 PublicationVSP_000836Add
BLAST
Alternative sequencei293 – 480188Missing in isoform 12. 1 PublicationVSP_000833Add
BLAST
Alternative sequencei301 – 480180Missing in isoform 10. 1 PublicationVSP_000835Add
BLAST
Alternative sequencei306 – 480175Missing in isoform 9. 1 PublicationVSP_000837Add
BLAST
Alternative sequencei436 – 48045KRPLL…ILSYT → GTIPGSGITESKDMHFSSLG CILLDVL in isoform 11, isoform 7 and isoform 3. 4 PublicationsVSP_000838Add
BLAST
Alternative sequencei436 – 48045Missing in isoform 14. 1 PublicationVSP_000839Add
BLAST
Alternative sequencei449 – 48032YMYDW…ILSYT → L in isoform 5. 1 PublicationVSP_000840Add
BLAST
Alternative sequencei453 – 48028WNSRV…ILSYT → SLEHTGGRY in isoform 6. 1 PublicationVSP_000841Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS2337.1. [O15519-1]
CCDS46487.1. [O15519-2]
CCDS56157.1. [O15519-8]
CCDS56158.1. [O15519-15]
CCDS59436.1. [O15519-3]
RefSeqiNP_001120655.1. NM_001127183.2. [O15519-1]
NP_001120656.1. NM_001127184.2. [O15519-2]
NP_001189444.1. NM_001202515.1. [O15519-4]
NP_001189445.1. NM_001202516.1. [O15519-8]
NP_001189446.1. NM_001202517.1. [O15519-15]
NP_001189447.1. NM_001202518.1. [O15519-3]
NP_001189448.1. NM_001202519.1. [O15519-3]
NP_003870.4. NM_003879.5. [O15519-1]
XP_005246994.1. XM_005246937.3. [O15519-11]
UniGeneiHs.390736.
Hs.731912.

Genome annotation databases

EnsembliENST00000309955; ENSP00000312455; ENSG00000003402. [O15519-1]
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]
GeneIDi8837.
KEGGihsa:8837.
UCSCiuc002uwz.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]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS2337.1. [O15519-1]
CCDS46487.1. [O15519-2]
CCDS56157.1. [O15519-8]
CCDS56158.1. [O15519-15]
CCDS59436.1. [O15519-3]
RefSeqiNP_001120655.1. NM_001127183.2. [O15519-1]
NP_001120656.1. NM_001127184.2. [O15519-2]
NP_001189444.1. NM_001202515.1. [O15519-4]
NP_001189445.1. NM_001202516.1. [O15519-8]
NP_001189446.1. NM_001202517.1. [O15519-15]
NP_001189447.1. NM_001202518.1. [O15519-3]
NP_001189448.1. NM_001202519.1. [O15519-3]
NP_003870.4. NM_003879.5. [O15519-1]
XP_005246994.1. XM_005246937.3. [O15519-11]
UniGeneiHs.390736.
Hs.731912.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3H11X-ray1.90A209-480[»]
3H13X-ray2.20A209-480[»]
ProteinModelPortaliO15519.
SMRiO15519. Positions 4-169, 237-480.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114364. 39 interactions.
DIPiDIP-27629N.
IntActiO15519. 29 interactions.
MINTiMINT-1529273.

Chemistry

ChEMBLiCHEMBL1955713.

Protein family/group databases

MEROPSiC14.971.

PTM databases

PhosphoSiteiO15519.

Polymorphism and mutation databases

BioMutaiCFLAR.

Proteomic databases

MaxQBiO15519.
PaxDbiO15519.
PRIDEiO15519.

Protocols and materials databases

DNASUi8837.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000309955; ENSP00000312455; ENSG00000003402. [O15519-1]
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]
GeneIDi8837.
KEGGihsa:8837.
UCSCiuc002uwz.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

CTDi8837.
GeneCardsiGC02P201980.
HGNCiHGNC:1876. CFLAR.
HPAiCAB022157.
CAB025216.
HPA019044.
MIMi603599. gene.
neXtProtiNX_O15519.
PharmGKBiPA26425.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG331323.
GeneTreeiENSGT00530000064199.
HOGENOMiHOG000069972.
HOVERGENiHBG050918.
InParanoidiO15519.
KOiK04724.
OMAiKLFFIQN.
OrthoDBiEOG74N5GK.
PhylomeDBiO15519.
TreeFamiTF352765.

Enzyme and pathway databases

ReactomeiREACT_164011. Regulation by c-FLIP.
REACT_355311. CASP8 activity is inhibited.
REACT_355409. RIPK1-mediated regulated necrosis.
REACT_402. TRAIL signaling.
REACT_832. Dimerization of procaspase-8.
SignaLinkiO15519.

Miscellaneous databases

ChiTaRSiCFLAR. human.
EvolutionaryTraceiO15519.
GeneWikiiCFLAR.
GenomeRNAii8837.
NextBioi33168.
PROiO15519.
SOURCEiSearch...

Gene expression databases

BgeeiO15519.
ExpressionAtlasiO15519. baseline and differential.
GenevestigatoriO15519.

Family and domain databases

Gene3Di1.10.533.10. 3 hits.
3.40.50.1460. 1 hit.
InterProiIPR029030. Caspase-like_dom.
IPR011029. DEATH-like_dom.
IPR001875. DED.
IPR011600. Pept_C14_caspase.
IPR001309. Pept_C14_ICE_p20.
IPR015917. Pept_C14A_p45_core.
[Graphical view]
PfamiPF01335. DED. 2 hits.
PF00656. Peptidase_C14. 1 hit.
[Graphical view]
SMARTiSM00115. CASc. 1 hit.
SM00031. DED. 2 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 2 hits.
PROSITEiPS50208. CASPASE_P20. 1 hit.
PS50168. DED. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
    Tissue: Peripheral blood lymphocyte.
  4. 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. 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.
    , 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.
    , 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.
    , 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. 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. Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).

Entry informationi

Entry nameiCFLAR_HUMAN
AccessioniPrimary (citable) accession number: O15519
Secondary accession number(s): B4DJE0
, B7Z9F9, O14673, O14674, O14675, O15137, O15138, O15356, O15510, O43618, O43619, O43620, O60458, O60459, Q53TS6, Q54AF1, Q96TE4, Q9UEW1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 1, 1998
Last modified: May 27, 2015
This is version 159 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.