FAS (Fas cell surface death receptor)

Gene

• Entrez ID: 355
• Gene name: Fas cell surface death receptor
• Gene symbol: FAS
• Synonyms: ALPS1A, APO-1, APT1, CD95, FAS1, FASTM, TNFRSF6
• Chromosome: 10
• Chromosome location: 10q23.31
• Summary: The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contains a death domain. It has been shown to play a central role in the physiological regulation of programmed cell death, and has been implicated in the pathogenesis of various malignancies and diseases of the immune system. The interaction of this receptor with its ligand allows the formation of a death-inducing signaling complex that includes Fas-associated death domain protein (FADD), caspase 8, and caspase 10. The autoproteolytic processing of the caspases in the complex triggers a downstream caspase cascade, and leads to apoptosis. This receptor has been also shown to activate NF-kappaB, MAPK3/ERK1, and MAPK8/JNK, and is found to be involved in transducing the proliferating signals in normal diploid fibroblast and T cells. Several alternatively spliced transcript variants have been described, some of which are candidates for nonsense-mediated mRNA decay (NMD). The isoforms lacking the transmembrane domain may negatively regulate the apoptosis mediated by the full length isoform. [provided by RefSeq, Mar 2011]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28929498	A>T	Pathogenic	Missense variant, coding sequence variant, 3 prime UTR variant, non coding transcript variant
rs56006128	G>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance, not-provided	Intron variant, coding sequence variant, missense variant, non coding transcript variant
rs121913076	A>C	Pathogenic	Non coding transcript variant, missense variant, 3 prime UTR variant, coding sequence variant
rs121913077	C>T	Pathogenic	Non coding transcript variant, stop gained, 3 prime UTR variant, coding sequence variant
rs121913078	C>T	Pathogenic	Intron variant, missense variant, non coding transcript variant, coding sequence variant
rs121913079	A>G	Pathogenic, uncertain-significance	Non coding transcript variant, missense variant, 3 prime UTR variant, coding sequence variant
rs121913080	G>C	Pathogenic, likely-pathogenic	Non coding transcript variant, missense variant, 3 prime UTR variant, coding sequence variant
rs121913081	C>T	Pathogenic	Non coding transcript variant, missense variant, 3 prime UTR variant, coding sequence variant
rs121913082	A>G	Pathogenic	Non coding transcript variant, missense variant, 3 prime UTR variant, coding sequence variant
rs121913083	A>G	Pathogenic	Intron variant, missense variant, non coding transcript variant, coding sequence variant
rs121913084	T>C	Pathogenic	Intron variant, missense variant, non coding transcript variant, coding sequence variant
rs121913085	G>C	Pathogenic	Non coding transcript variant, missense variant, 3 prime UTR variant, coding sequence variant
rs121913086	G>T	Pathogenic	Non coding transcript variant, missense variant, 3 prime UTR variant, coding sequence variant
rs267607122	T>A,C	Pathogenic	Splice donor variant, intron variant
rs483352683	T>A,C	Likely-pathogenic, uncertain-significance	Coding sequence variant, 3 prime UTR variant, non coding transcript variant, missense variant
rs606231361	G>-	Pathogenic	Coding sequence variant, intron variant, frameshift variant, non coding transcript variant
rs606231362	->T	Pathogenic	Intron variant, splice donor variant
rs606231363	A>C	Pathogenic	Intron variant, splice acceptor variant
rs606231364	G>A	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs606231365	->AAAATTCAAACTTCAGAAAT	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant, 3 prime UTR variant
rs606231366	->T	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant, 3 prime UTR variant
rs778993919	C>A,T	Pathogenic	Stop gained, coding sequence variant, non coding transcript variant, 3 prime UTR variant, synonymous variant
rs886039359	G>A	Pathogenic	Intron variant, splice donor variant
rs886039524	AT>-	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant, 3 prime UTR variant
rs1085307626	G>-	Likely-pathogenic	Frameshift variant, non coding transcript variant, intron variant, coding sequence variant
rs1554851356	C>-	Pathogenic	Non coding transcript variant, intron variant, coding sequence variant, frameshift variant
rs1554851718	T>G	Likely-pathogenic	Non coding transcript variant, intron variant, missense variant, coding sequence variant
rs1554852090	A>-	Likely-pathogenic	Intron variant, frameshift variant, non coding transcript variant, stop gained, coding sequence variant
rs1554852244	->CATG	Pathogenic	Non coding transcript variant, frameshift variant, 3 prime UTR variant, coding sequence variant
rs1564686301	T>A	Pathogenic	Non coding transcript variant, stop gained, coding sequence variant
rs1564691414	A>G	Likely-pathogenic	Intron variant, splice acceptor variant
rs1564692984	T>-,TT	Likely-pathogenic	Non coding transcript variant, intron variant, coding sequence variant, frameshift variant
rs1564696849	G>A,T	Pathogenic, pathogenic-likely-pathogenic	Intron variant, splice donor variant
rs1564699214	A>-	Pathogenic	Non coding transcript variant, frameshift variant, 3 prime UTR variant, coding sequence variant
rs1589465172	C>-	Pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant
rs1589465256	C>-	Likely-pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant
rs1589478691	G>-	Pathogenic	Frameshift variant, coding sequence variant, intron variant, non coding transcript variant
rs1589485636	->TGAAAT	Pathogenic	Intron variant, splice donor variant
rs1589488463	G>A	Pathogenic	Splice acceptor variant, intron variant
rs1589488494	AG>-	Pathogenic	Frameshift variant, coding sequence variant, intron variant, non coding transcript variant
rs1589488640	G>A	Pathogenic	Intron variant, splice donor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT002421	hsa-miR-21-5p	Microarray	20048743
MIRT005581	hsa-miR-146a-5p	Luciferase reporter assay, Western blot	20656888
MIRT005581	hsa-miR-146a-5p	Luciferase reporter assay	23645835
MIRT006331	hsa-miR-106a-5p	Luciferase reporter assay	22431000
MIRT006331	hsa-miR-106a-5p	Flow, Immunohistochemistry, In situ hybridization, Luciferase reporter assay, qRT-PCR, Western blot	27142596
MIRT016252	hsa-miR-504-5p	qRT-PCR	20542001
MIRT027598	hsa-miR-98-5p	Microarray	19088304
MIRT053338	hsa-miR-196b-5p	Immunohistochemistry, Luciferase reporter assay, Microarray, qRT-PCR, Western blot	22353710
MIRT053338	hsa-miR-196b-5p	Luciferase reporter assay, qRT-PCR, Western blot	25605245
MIRT053381	hsa-miR-23a-3p	Flow, Luciferase reporter assay, Microarray, Western blot	23804233
MIRT127441	hsa-miR-19a-3p	HITS-CLIP	22473208
MIRT127442	hsa-miR-19b-3p	HITS-CLIP	22473208
MIRT438784	hsa-miR-92a-2-5p	qRT-PCR	24955218
MIRT438785	hsa-miR-92a-1-5p	qRT-PCR	24955218
MIRT438786	hsa-miR-18a-5p	qRT-PCR	24955218
MIRT438787	hsa-miR-106b-5p	qRT-PCR	24955218
MIRT438788	hsa-miR-17-5p	qRT-PCR	24955218
MIRT731620	hsa-miR-133b	Luciferase reporter assay	26919791
MIRT735416	hsa-miR-320a	Luciferase reporter assay, qRT-PCR, Western blot	27277534

Transcription factors

Transcription factor	Regulation	Reference
ATF2	Unknown	19670268
ATM	Activation	19502594
EGR1	Repression	9300687
FOS	Activation	10903433
GLI1	Repression	21135115
GLI2	Repression	21135115
HDGF	Activation	19710540
JUN	Activation	10903433
JUN	Unknown	19670268
NFKB1	Activation	19628709;9733827
NFKB1	Repression	16784892
NFKB1	Unknown	10022897;10871852;16317104;7528667
NFKBIA	Repression	9733827
NFYA	Unknown	9261184
NFYB	Unknown	9261184
NFYC	Unknown	9261184
PURA	Repression	10903433
RELA	Activation	19628709;9733827
RELA	Repression	16784892
RELA	Unknown	10871852;16317104
SP1	Activation	22084312
SP1	Unknown	10022897;10871852;9261184;9300785
SREBF1	Activation	18420801
SREBF1	Unknown	12531699;20173757;9300785
SREBF2	Unknown	9300785
STAT1	Unknown	16317104
STAT3	Activation	15223310
STAT3	Repression	16651438;22313388
TFAP2A	Unknown	7528667
TP53	Activation	10101800;11313989
TP53	Unknown	16317104
YBX1	Repression	10903433
YY1	Repression	16784892;17530016

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001934	Process	Positive regulation of protein phosphorylation	IMP	11096076
GO:0005031	Function	Tumor necrosis factor-activated receptor activity	IBA	21873635
GO:0005515	Function	Protein binding	IPI	7536190, 7538907, 10918185, 11003656, 11495919, 11606059, 12724420, 12887920, 15465831, 16498403, 17047155, 17159907, 18328427, 18846110, 21109225, 21382479, 21625644, 21803845, 25241761
GO:0005516	Function	Calmodulin binding	IDA	24914971
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	NAS	7533181
GO:0005886	Component	Plasma membrane	IDA
GO:0005886	Component	Plasma membrane	IMP	21625644
GO:0005886	Component	Plasma membrane	TAS
GO:0006915	Process	Apoptotic process	IDA	9681877
GO:0006919	Process	Activation of cysteine-type endopeptidase activity involved in apoptotic process	TAS
GO:0006924	Process	Activation-induced cell death of T cells	IBA	21873635
GO:0006955	Process	Immune response	IEA
GO:0007165	Process	Signal transduction	TAS	9360929
GO:0009897	Component	External side of plasma membrane	IBA	21873635
GO:0009986	Component	Cell surface	IDA	22891283
GO:0016021	Component	Integral component of membrane	IEA
GO:0016604	Component	Nuclear body	IDA
GO:0019900	Function	Kinase binding	IPI	7538908
GO:0031264	Component	Death-inducing signaling complex	IDA	11101870, 21803845
GO:0031265	Component	CD95 death-inducing signaling complex	IBA	21873635
GO:0031265	Component	CD95 death-inducing signaling complex	IDA	20935634
GO:0032872	Process	Regulation of stress-activated MAPK cascade	IBA	21873635
GO:0032872	Process	Regulation of stress-activated MAPK cascade	IMP	11096076
GO:0033209	Process	Tumor necrosis factor-mediated signaling pathway	IEA
GO:0034198	Process	Cellular response to amino acid starvation	IMP	11096076
GO:0036337	Process	Fas signaling pathway	IMP	11096076
GO:0038023	Function	Signaling receptor activity	NAS	7533181
GO:0042802	Function	Identical protein binding	IPI	7536190, 7538908, 21382479
GO:0042981	Process	Regulation of apoptotic process	NAS	7533181
GO:0042981	Process	Regulation of apoptotic process	TAS
GO:0043065	Process	Positive regulation of apoptotic process	IDA	21625644
GO:0043065	Process	Positive regulation of apoptotic process	IMP	20935634
GO:0043066	Process	Negative regulation of apoptotic process	IBA	21873635
GO:0045121	Component	Membrane raft	IBA	21873635
GO:0045121	Component	Membrane raft	IDA	21382479
GO:0065003	Process	Protein-containing complex assembly	TAS	10875918
GO:0070062	Component	Extracellular exosome	HDA	20458337
GO:0071260	Process	Cellular response to mechanical stimulus	IEP	19593445
GO:0071455	Process	Cellular response to hyperoxia	IMP	21382479
GO:0097049	Process	Motor neuron apoptotic process	IBA	21873635
GO:0097190	Process	Apoptotic signaling pathway	TAS
GO:0097191	Process	Extrinsic apoptotic signaling pathway	IMP	22891283
GO:0097192	Process	Extrinsic apoptotic signaling pathway in absence of ligand	IBA	21873635
GO:0097527	Process	Necroptotic signaling pathway	IBA	21873635
GO:0097527	Process	Necroptotic signaling pathway	IMP	16507998
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:2001235	Process	Positive regulation of apoptotic signaling pathway	IMP	11096076
GO:2001269	Process	Positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway	IBA	21873635
GO:2001269	Process	Positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway	IMP	11096076

Other IDs

• MIM: 134637
• HGNC: 11920
• e!Ensembl: ENSG00000026103

Protein

• UniProt ID: P25445
• Protein name: Tumor necrosis factor receptor superfamily member 6 (Apo-1 antigen) (Apoptosis-mediating surface antigen FAS) (FASLG receptor) (CD antigen CD95)
• Protein function: Receptor for TNFSF6/FASLG. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both. The secreted isoforms 2 to 6 block apoptosis (in vitro).
• PDB: 1BZI, 1DDF, 2NA7, 3EWT, 3EZQ, 3THM, 3TJE
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00020	TNFR_c6	85 → 127	TNFR/NGFR cysteine-rich region	Domain
  PF00020	TNFR_c6	129 → 165	TNFR/NGFR cysteine-rich region	Domain
  PF00531	Death	230 → 314	Death domain	Domain

• Sequence:

  MLGIWTLLPLVLTSVARLSSKSVNAQVTDINSKGLELRKTVTTVETQNLEGLHHDGQFCH
  KPCPPGERKARDCTVNGDEPDCVPCQEGKEYTDKAHFSSKCRRCRLCDEGHGLEVEINCT
  RTQNTKCRCKPNFFCNSTVCEHCDPCTKCEHGIIKECTLTSNTKCKEEGSRSNLGWLCLL
  LLPIPLIVWVKRKEVQKTCRKHRKENQGSHESPTLNPETVAINLSDVDLSKYITTIAGVM
  TLSQVKGFVRKNGVNEAKIDEIKNDNVQDTAEQKVQLLRNWHQLHGKKEAYDTLIKDLKK
  ANLCTLAEKIQTIILKDITSDSENSNFRNEIQSLV

• Sequence length: 335