FASLG (Fas ligand)

Gene

• Entrez ID: 356
• Gene name: Fas ligand
• Gene symbol: FASLG
• Synonyms: ALPS1B, APT1LG1, APTL, CD178, CD95-L, CD95L, FASL, TNFSF6, TNLG1A
• Chromosome: 1
• Chromosome location: 1q24.3
• Summary: This gene is a member of the tumor necrosis factor superfamily. The primary function of the encoded transmembrane protein is the induction of apoptosis triggered by binding to FAS. The FAS/FASLG signaling pathway is essential for immune system regulation, including activation-induced cell death (AICD) of T cells and cytotoxic T lymphocyte induced cell death. It has also been implicated in the progression of several cancers. Defects in this gene may be related to some cases of systemic lupus erythematosus (SLE). Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2014]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs763110	C>T	Risk-factor	Upstream transcript variant
rs56302117	T>G	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, missense variant
rs80358236	TGCCTCTGGAATGGGAAGACACCTATGGAATTGTCCTGCTTTCTGGAGTGAAGTATAAGAAGGGTGGCCTTGTGATCAATGAAA>-	Pathogenic	3 prime UTR variant, inframe deletion, coding sequence variant
rs140406512	C>A,T	Conflicting-interpretations-of-pathogenicity	Intron variant, coding sequence variant, missense variant
rs201525996	A>G	Benign, conflicting-interpretations-of-pathogenicity	Intron variant
rs587776450	T>-	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT006989	hsa-miR-21-5p	Luciferase reporter assay, Western blot	21820586
MIRT006989	hsa-miR-21-5p	Luciferase reporter assay, qRT-PCR, Western blot	23177026
MIRT006989	hsa-miR-21-5p	Reporter assay;Western blot;Other	20371612
MIRT006989	hsa-miR-21-5p	Luciferase reporter assay, Western blot	23504349
MIRT006989	hsa-miR-21-5p	Luciferase reporter assay, qRT-PCR, Western blot	24821435
MIRT006989	hsa-miR-21-5p	Luciferase reporter assay	25118289
MIRT029780	hsa-miR-26b-5p	Microarray	19088304
MIRT611039	hsa-miR-3941	HITS-CLIP	23824327
MIRT611040	hsa-miR-5195-5p	HITS-CLIP	23824327
MIRT611041	hsa-miR-603	HITS-CLIP	23824327
MIRT611042	hsa-miR-362-3p	HITS-CLIP	23824327
MIRT611043	hsa-miR-329-3p	HITS-CLIP	23824327
MIRT611044	hsa-miR-8485	HITS-CLIP	23824327
MIRT611045	hsa-miR-7849-3p	HITS-CLIP	23824327
MIRT629081	hsa-miR-4325	HITS-CLIP	23824327
MIRT629082	hsa-miR-7703	HITS-CLIP	23824327
MIRT629083	hsa-miR-32-5p	HITS-CLIP	23824327
MIRT629084	hsa-miR-363-3p	HITS-CLIP	23824327
MIRT629085	hsa-miR-25-3p	HITS-CLIP	23824327
MIRT629086	hsa-miR-92b-3p	HITS-CLIP	23824327
MIRT629087	hsa-miR-367-3p	HITS-CLIP	23824327
MIRT629088	hsa-miR-92a-3p	HITS-CLIP	23824327
MIRT658285	hsa-miR-539-3p	HITS-CLIP	23824327
MIRT658286	hsa-miR-485-3p	HITS-CLIP	23824327
MIRT731263	hsa-let-7e-5p	Luciferase reporter assay	26826505
MIRT733648	hsa-miR-21-3p	Luciferase reporter assay, Western blot	25394756
MIRT733810	hsa-miR-149-5p	Luciferase reporter assay, qRT-PCR, Western blot	28013316
MIRT734003	hsa-miR-34a-5p	PCR array	28097098

Transcription factors

Transcription factor	Regulation	Reference
ATF2	Unknown	19670268;9710625
CEBPB	Unknown	12496392
CIITA	Unknown	14563113
CREM	Repression	11754361
EGR1	Unknown	14563113
EGR2	Repression	19651900
FOXO3	Activation	11756562
IRF1	Unknown	14563113
JUN	Unknown	14563113;19670268;9710625
MAX	Unknown	10734130
MYC	Activation	12655294
MYC	Unknown	10734130;14563113
NFKB1	Activation	12655294;16770006
NFKB1	Unknown	10671224;14563113;15160330
NR4A1	Unknown	14563113
PDCD11	Unknown	14563113
PPARG	Activation	18293083
RELA	Activation	12655294;16770006
RELA	Unknown	10671224;14563113;15160330
SP1	Activation	12655294
SP1	Unknown	14563113;15004200

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IDA	17557115
GO:0005102	Function	Signaling receptor binding	TAS	7826947
GO:0005123	Function	Death receptor binding	IEA
GO:0005125	Function	Cytokine activity	IEA
GO:0005164	Function	Tumor necrosis factor receptor binding	IEA
GO:0005515	Function	Protein binding	IPI	12198154, 12887920, 16318909, 16498403, 16595635, 17761170, 19807924, 21803845, 24025841, 25241761, 25416956, 26871637, 28514442, 32296183
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IDA	18835034
GO:0005634	Component	Nucleus	IDA	17557115
GO:0005886	Component	Plasma membrane	IDA	12201652
GO:0005887	Component	Integral component of plasma membrane	TAS	7826947
GO:0005901	Component	Caveola	IEA
GO:0006915	Process	Apoptotic process	TAS	8787672
GO:0006919	Process	Activation of cysteine-type endopeptidase activity involved in apoptotic process	IGI	19364818
GO:0006919	Process	Activation of cysteine-type endopeptidase activity involved in apoptotic process	IMP	18293083
GO:0006919	Process	Activation of cysteine-type endopeptidase activity involved in apoptotic process	TAS
GO:0006925	Process	Inflammatory cell apoptotic process	IEA
GO:0007165	Process	Signal transduction	TAS	7826947
GO:0007267	Process	Cell-cell signaling	TAS	7826947
GO:0008284	Process	Positive regulation of cell population proliferation	IEA
GO:0008625	Process	Extrinsic apoptotic signaling pathway via death domain receptors	IBA	21873635
GO:0008625	Process	Extrinsic apoptotic signaling pathway via death domain receptors	IDA	18835034, 26582200
GO:0009897	Component	External side of plasma membrane	IEA
GO:0016525	Process	Negative regulation of angiogenesis	IDA	18835034
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0030644	Process	Cellular chloride ion homeostasis	IEA
GO:0032496	Process	Response to lipopolysaccharide	IEA
GO:0043065	Process	Positive regulation of apoptotic process	IDA	14749367, 21625644
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IBA	21873635
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IEP	12761501
GO:0043202	Component	Lysosomal lumen	IEA
GO:0043525	Process	Positive regulation of neuron apoptotic process	IEA
GO:0045742	Process	Positive regulation of epidermal growth factor receptor signaling pathway	IEA
GO:0046666	Process	Retinal cell programmed cell death	IEA
GO:0048388	Process	Endosomal lumen acidification	IEA
GO:0048471	Component	Perinuclear region of cytoplasm	IEA
GO:0060205	Component	Cytoplasmic vesicle lumen	IEA
GO:0070062	Component	Extracellular exosome	IDA	17076679
GO:0070231	Process	T cell apoptotic process	IDA	17076679
GO:0070266	Process	Necroptotic process	IDA	11101870
GO:0070848	Process	Response to growth factor	IEA
GO:0071346	Process	Cellular response to interferon-gamma	IEA
GO:0097190	Process	Apoptotic signaling pathway	IDA	11101870
GO:0097190	Process	Apoptotic signaling pathway	TAS
GO:0097191	Process	Extrinsic apoptotic signaling pathway	IDA	22891283
GO:0097527	Process	Necroptotic signaling pathway	IDA	11101870
GO:1902041	Process	Regulation of extrinsic apoptotic signaling pathway via death domain receptors	TAS
GO:1902042	Process	Negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	TAS
GO:1903514	Process	Release of sequestered calcium ion into cytosol by endoplasmic reticulum	IDA	26582200
GO:1905782	Process	Positive regulation of phosphatidylserine exposure on apoptotic cell surface	IDA	24904167
GO:2000353	Process	Positive regulation of endothelial cell apoptotic process	IDA	18835034

Other IDs

• MIM: 134638
• HGNC: 11936
• e!Ensembl: ENSG00000117560

Protein

• UniProt ID: P48023
• 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)]
• Protein 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). ; [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). ; [FasL intracellular domain]: Cytoplasmic form induces gene transcription inhibition.
• PDB: 1BZI, 4MSV, 5L19, 5L36
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00229	TNF	160 → 281	TNF(Tumour Necrosis Factor) family	Domain

• Sequence:

  MQQPFNYPYPQIYWVDSSASSPWAPPGTVLPCPTSVPRRPGQRRPPPPPPPPPLPPPPPP
  PPLPPLPLPPLKKRGNHSTGLCLLVMFFMVLVALVGLGLGMFQLFHLQKELAELRESTSQ
  MHTASSLEKQIGHPSPPPEKKELRKVAHLTGKSNSRSMPLEWEDTYGIVLLSGVKYKKGG
  LVINETGLYFVYSKVYFRGQSCNNLPLSHKVYMRNSKYPQDLVMMEGKMMSYCTTGQMWA
  RSSYLGAVFNLTSADHLYVNVSELSLVNFEESQTFFGLYKL

• Sequence length: 281