| IED ID | IndEnz0002009714 |
| Enzyme Type ID | protease009714 |
| Protein Name |
Tumor necrosis factor ligand superfamily member 6 Apoptosis antigen ligand APTL CD95 ligand CD95-L Fas antigen ligand Fas ligand FasL CD antigen CD178 Cleaved into: Tumor necrosis factor ligand superfamily member 6, membrane form; Tumor necrosis factor ligand superfamily member 6, soluble form Receptor-binding FasL ectodomain Soluble Fas ligand sFasL ; ADAM10-processed FasL form APL ; FasL intracellular domain FasL ICD SPPL2A-processed FasL form SPA |
| Gene Name | FASLG APT1LG1 CD95L FASL TNFSF6 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MQQPFNYPYPQIYWVDSSASSPWAPPGTVLPCPTSVPRRPGQRRPPPPPPPPPLPPPPPPPPLPPLPLPPLKKRGNHSTGLCLLVMFFMVLVALVGLGLGMFQLFHLQKELAELRESTSQMHTASSLEKQIGHPSPPPEKKELRKVAHLTGKSNSRSMPLEWEDTYGIVLLSGVKYKKGGLVINETGLYFVYSKVYFRGQSCNNLPLSHKVYMRNSKYPQDLVMMEGKMMSYCTTGQMWARSSYLGAVFNLTSADHLYVNVSELSLVNFEESQTFFGLYKL |
| Enzyme Length | 281 |
| Uniprot Accession Number | P48023 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells (PubMed:26334989, PubMed:9228058). Involved in cytotoxic T-cell-mediated apoptosis, natural killer cell-mediated apoptosis and in T-cell development (PubMed:9228058, PubMed:7528780, PubMed:9427603). Initiates fratricidal/suicidal activation-induced cell death (AICD) in antigen-activated T-cells contributing to the termination of immune responses (By similarity). TNFRSF6/FAS-mediated apoptosis has also a role in the induction of peripheral tolerance (By similarity). Binds to TNFRSF6B/DcR3, a decoy receptor that blocks apoptosis (PubMed:27806260). {ECO:0000250|UniProtKB:P41047, ECO:0000269|PubMed:17557115, ECO:0000269|PubMed:27806260, ECO:0000269|PubMed:7528780, ECO:0000269|PubMed:9228058, ECO:0000269|PubMed:9427603}.; FUNCTION: [Tumor necrosis factor ligand superfamily member 6, soluble form]: Induces FAS-mediated activation of NF-kappa-B, initiating non-apoptotic signaling pathways (By similarity). Can induce apoptosis but does not appear to be essential for this process (PubMed:27806260). {ECO:0000250|UniProtKB:P41047, ECO:0000269|PubMed:27806260}.; FUNCTION: [FasL intracellular domain]: Cytoplasmic form induces gene transcription inhibition. {ECO:0000269|PubMed:17557115}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (2); Beta strand (12); Chain (4); Compositional bias (1); Disulfide bond (1); Glycosylation (3); Helix (2); Mutagenesis (3); Natural variant (2); Region (2); Site (2); Topological domain (2); Transmembrane (1); Turn (1) |
| Keywords | 3D-structure;Alternative splicing;Apoptosis;Cell membrane;Cytokine;Cytoplasmic vesicle;Disulfide bond;Glycoprotein;Lysosome;Membrane;Nucleus;Reference proteome;Repressor;Secreted;Signal-anchor;Transcription;Transcription regulation;Transmembrane;Transmembrane helix;Ubl conjugation |
| Interact With | Q14790; A8MQ03; Q16610; Q13158; P25445; Q96RU3; P06241; Q8IYA8; Q08881; Q14525; Q6A162; Q8IUC1; P60328; A0A0S2Z4D7; P16333-1; O43639; Q7Z3S9; Q9BY11; Q9UNF0; Q9UKS6; P27986; O43586; O76081; O76081-6; Q15436; Q8WV41; Q9Y5X1; O75044; Q63HR2; Q15642; Q15654; Q9DBG3; Q91ZR2 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17557115, ECO:0000269|PubMed:9427603}; Single-pass type II membrane protein {ECO:0000255}. Cytoplasmic vesicle lumen {ECO:0000269|PubMed:17164290}. Lysosome lumen {ECO:0000269|PubMed:17164290}. Note=Is internalized into multivesicular bodies of secretory lysosomes after phosphorylation by FGR and monoubiquitination (PubMed:17164290). Colocalizes with the SPPL2A protease at the cell membrane (PubMed:17557115). {ECO:0000269|PubMed:17164290, ECO:0000269|PubMed:17557115}.; SUBCELLULAR LOCATION: [Tumor necrosis factor ligand superfamily member 6, soluble form]: Secreted {ECO:0000269|PubMed:9427603}. Note=May be released into the extracellular fluid by cleavage from the cell surface. {ECO:0000269|PubMed:9427603}.; SUBCELLULAR LOCATION: [FasL intracellular domain]: Nucleus {ECO:0000269|PubMed:17557115}. Note=The FasL ICD cytoplasmic form is translocated into the nucleus. {ECO:0000269|PubMed:17557115}. |
| Modified Residue | |
| Post Translational Modification | PTM: The soluble form derives from the membrane form by proteolytic processing. The membrane-bound form undergoes two successive intramembrane proteolytic cleavages. The first one is processed by ADAM10 producing an N-terminal fragment, which lacks the receptor-binding extracellular domain. This ADAM10-processed FasL (FasL APL) remnant form is still membrane anchored and further processed by SPPL2A that liberates the FasL intracellular domain (FasL ICD). FasL shedding by ADAM10 is a prerequisite for subsequent intramembrane cleavage by SPPL2A in T-cells. {ECO:0000269|PubMed:17557115, ECO:0000269|PubMed:9427603}.; PTM: N-glycosylated (PubMed:9228058). Glycosylation enhances apoptotic activity (PubMed:27806260). {ECO:0000269|PubMed:27806260, ECO:0000269|PubMed:9228058}.; PTM: Phosphorylated by FGR on tyrosine residues; this is required for ubiquitination and subsequent internalization. {ECO:0000269|PubMed:17164290}.; PTM: Monoubiquitinated. {ECO:0000269|PubMed:17164290}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (3) |
| Cross Reference PDB | 4MSV; 5L19; 5L36; |
| Mapped Pubmed ID | 10102273; 10837247; 11036836; 11384965; 11438180; 11463377; 11463813; 11500835; 11716959; 11717445; 11739488; 11751256; 11786482; 11788891; 11801650; 11809905; 11830480; 11845233; 11856352; 11882326; 11895550; 11908702; 11909874; 11925103; 11961305; 11965496; 11994542; 12009596; 12021072; 12021310; 12100038; 12113885; 12137598; 12161534; 12198154; 12208869; 12215447; 12372468; 12414525; 12414956; 12421989; 12454289; 12464266; 12482410; 12482505; 12490654; 12507389; 12513781; 12515623; 12557947; 12559631; 12583439; 12594300; 12618758; 12620240; 12629150; 12637505; 12651606; 12698366; 12700199; 12707034; 12717632; 12742662; 12783210; 12787425; 12794109; 12803240; 12807917; 12849704; 12854132; 12867600; 12887920; 12912912; 12918731; 12923319; 12928375; 12930319; 14514471; 14534535; 14560009; 14576824; 14602201; 14625471; 14634098; 14642527; 14668794; 14669310; 14698859; 14701673; 14705811; 14739003; 14739407; 14739535; 14962292; 14967838; 14977837; 14988839; 14996347; 15019279; 15024054; 15042330; 15073283; 15093732; 15138553; 15173177; 15178561; 15183989; 15195700; 15218339; 15240787; 15272306; 15277733; 15287856; 15289496; 15302589; 15314293; 15337758; 15339846; 15358139; 15480896; 15492869; 15542843; 15557763; 15579659; 15653751; 15674374; 15686714; 15694838; 15791651; 15795317; 15803113; 15806311; 15814666; 15816832; 15833141; 15849828; 15870081; 15870181; 15907374; 15928037; 15937082; 15938782; 15962391; 15968727; 15975999; 15991293; 15996722; 16000573; 16081306; 16087126; 16124644; 16133992; 16155003; 16157125; 16157266; 16158329; 16163374; 16181301; 16186185; 16204241; 16212902; 16273638; 16282344; 16298578; 16306044; 16313826; 16318909; 16332967; 16332972; 16364925; 16474169; 16487513; 16498403; 16512757; 16514159; 16538171; 16538172; 16595635; 16595663; 16601838; 16691186; 16736614; 16767155; 16770006; 16808908; 16858424; 16868256; 16902496; 16972019; 16987075; 16990614; 17000697; 17008914; 17014925; 17053166; 17056762; 17071607; 17101499; 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19278658; 19305072; 19332441; 19337311; 19390575; 19403301; 19416807; 19434529; 19458913; 19505222; 19524512; 19527514; 19531476; 19535642; 19538867; 19542541; 19565204; 19572057; 19573080; 19614955; 19625176; 19641134; 19683492; 19692168; 19773279; 19779494; 19789190; 19810143; 19826071; 19854829; 19890662; 19926197; 19937732; 19941645; 19960225; 20013612; 20074157; 20101459; 20106900; 20150914; 20165911; 20190752; 20193111; 20204402; 20219325; 20222173; 20237496; 20308068; 20353032; 20359312; 20371612; 20378615; 20379197; 20379614; 20385987; 20393600; 20394629; 20406899; 20408337; 20438363; 20501759; 20533543; 20568250; 20572163; 20602615; 20618494; 20624652; 20650551; 20673483; 20675370; 20696707; 20842669; 20959405; 21087335; 21107701; 21122378; 21152963; 21159039; 21227011; 21235526; 21270445; 21271302; 21285513; 21286777; 21354149; 21368861; 21466843; 21516345; 21528407; 21605112; 21691772; 21695404; 21725926; 21729539; 21737330; 21746966; 21803845; 21807637; 21808135; 21864388; 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33862353; 34127318; 7530336; 7536190; 7536672; 8521815; 8681376; 9396774; 9405425; 9721089; 9880531; |
| Motif | |
| Gene Encoded By | |
| Mass | 31,485 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |