UniProt Accession

 CFLAR_HUMAN; O15519; B4DJE0; B7Z9F9; O14673; O14674; O14675; O15137; O15138; O15356; O15510; O43618; O43619; O43620; O60458; O60459; Q53TS6; Q54AF1; Q96TE4; Q9UEW1 

Genbank Protein ID

 AF010127; U85059; U97074; U97075; AF009616; AF009617; AF009618; AF009619; AF041458; AF041459; AF041462; AF041461; AF041460; Y14039; Y14040; AF005774; AF005775; AF015450; AF015451; AF015452; AB038972; AB038972; BT006751; AK289913; AK296036; AK315208; AK315924; AC007283; CH471063; CH471063; BC001602 

Genbank Nucleotide ID

 AAB64110.1; AAB82648.1; AAC51622.1; AAC51623.1; AAB70909.1; AAB70910.1; AAB70911.1; AAB70912.1; AAB99790.1; AAB99791.1; AAB99794.1; AAB99793.1; AAB99792.1; CAA74366.1; CAA74367.1; AAC15825.1; AAC15826.1; AAC16439.1; AAC16440.1; AAC16441.1; BAB32551.1; BAB32552.1; AAP35397.1; BAF82602.1; BAG58802.1; BAG37645.1; BAH14295.1; AAY24290.1; EAW70237.1; EAW70244.1; AAH01602.1 

Protein Name

 CASP8 and FADD-like apoptosis regulator 

Protein Synonyms/Alias

 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; CASP8 and FADD-like apoptosis regulator subunit p43; CASP8 and FADD-like apoptosis regulator subunit p12 

Gene Name

 CFLAR 

Gene Synonyms/Alias

 CASH; CASP8AP1; CLARP; MRIT 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
49	DILRERGKLSVGDLA	ubiquitination	[1]
154	DQLDLLEKCLKNIHR	ubiquitination	[1]
172	KTKIQKYKQSVQGAG	ubiquitination	[1]
192	VLQAAIQKSLKDPSN	ubiquitination	[1, 2, 3]
195	AAIQKSLKDPSNNFR	ubiquitination	[1]
214	RSKEQRLKEQLGAQQ	ubiquitination	[1]
225	GAQQEPVKKSIQESE	ubiquitination	[1]
226	AQQEPVKKSIQESEA	ubiquitination	[1]
386	AMKNVEFKAQKRGLC	ubiquitination	[1]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 1 73 DED 1.
 DOMAIN 92 170 DED 2.
 REGION 1 435 Not proteolytically processed and
 REGION 1 305 Interaction with caspase-8 propeptide.
 REGION 1 227 Interaction with FADD.
 REGION 1 195 Interaction with caspase-8.
 REGION 192 480 Interaction with TRAF1 and TRAF2.
 REGION 192 435 Interaction with caspase-3.
 REGION 217 480 Interaction with caspase-8 subunits p18
 REGION 263 358 Caspase.
 REGION 370 480 Interaction with caspase-8.  

Keyword

 3D-structure; Alternative splicing; Apoptosis; Complete proteome; Host-virus interaction; Polymorphism; Reference proteome; Repeat. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 480 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; IDA:UniProtKB.
 GO:0031264; C:death-inducing signaling complex; IDA:UniProtKB.
 GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro.
 GO:0008047; F:enzyme activator activity; IDA:UniProtKB.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc.
 GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IMP:BHF-UCL.
 GO:1901740; P:negative regulation of myoblast fusion; ISS:BHF-UCL.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IEP:UniProtKB.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:BHF-UCL.
 GO:0006508; P:proteolysis; IEA:InterPro.
 GO:0014842; P:regulation of satellite cell proliferation; ISS:BHF-UCL.
 GO:0014732; P:skeletal muscle atrophy; ISS:BHF-UCL.
 GO:0007519; P:skeletal muscle tissue development; ISS:BHF-UCL.
 GO:0043403; P:skeletal muscle tissue regeneration; ISS:BHF-UCL.
 GO:0014866; P:skeletal myofibril assembly; ISS:BHF-UCL.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 

Interpro

 IPR011029; DEATH-like_dom.
 IPR001875; DED.
 IPR011600; Pept_C14_cat.
 IPR001309; Pept_C14_ICE_p20.
 IPR002398; Pept_C14_p45.
 IPR015917; Pept_C14_p45_core. 

Pfam

 PF01335; DED
 PF00656; Peptidase_C14 

SMART

 SM00115; CASc
 SM00031; DED 

PROSITE

 PS50208; CASPASE_P20
 PS50168; DED 

PRINTS