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FAS Fas cell surface death receptor [ Homo sapiens (human) ]

Gene ID: 355, updated on 13-Apr-2014
Official Symbol
FASprovided by HGNC
Official Full Name
Fas cell surface death receptorprovided by HGNC
Primary source
HGNC:11920
Locus tag
RP11-399O19.7
See related
Ensembl:ENSG00000026103; HPRD:00609; MIM:134637; Vega:OTTHUMG00000018701
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
APT1; CD95; FAS1; APO-1; FASTM; ALPS1A; TNFRSF6
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]
Location :
10q24.1
Sequence :
Chromosome: 10; NC_000010.11 (88969796..89017059)

Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene STAM binding protein-like 1 Neighboring gene ACTA2 antisense RNA 1 Neighboring gene actin, alpha 2, smooth muscle, aorta Neighboring gene FAS antisense RNA 1 Neighboring gene microRNA 4679-2 Neighboring gene microRNA 4679-1 Neighboring gene zinc finger RNA binding protein pseudogene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Associated conditions

Description Tests
Autoimmune lymphoproliferative syndrome Compare labs

NHGRI GWAS Catalog

Description
Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency.
NHGRI GWA Catalog
Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia.
NHGRI GWA Catalog
Identification of genomic predictors of atrioventricular conduction: using electronic medical records as a tool for genome science.
NHGRI GWA Catalog
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
NHGRI GWA Catalog

Protein interactions

Protein Gene Interaction Pubs
Env, gp160, envelope glycoprotein env The calmodulin-binding domains in HIV-1 gp160 are involved in Fas-mediated apoptosis PubMed
Envelope surface glycoprotein gp120 env At high concentrations, HIV-1 gp120 enhances expression of Fas and FasL and promotes apoptosis in human mesangial cells (HMC) PubMed
env CXCR4-tropic and CXCR4/CCR5 dual-tropic HIV-1 gp120 induce the relocalization of cytoplasmic CD95 to the cellular plasma membrane and a 23% increase in CD95-mediated apoptosis PubMed
env HIV-1 gp120-induced neuron apoptosis requires the upregulation of the death receptor Fas and its associated death proteins, FADD and CASP8 PubMed
env Binding of HIV-1 gp120 to CD4 downregulates Bcl-2 protein in CD4+ T lymphocytes and facilitates Fas/Fas-ligand triggered apoptosis; addition of IL-2 rescues CD4+ T cells from CD4/gp120-induced Bcl-2 down modulation and apoptosis induction PubMed
env CD45 modulates HIV-1 gp120-induced apoptosis by regulating Fas ligand induction and activation of the phosphoinositide 3-kinase/Akt pathway PubMed
env HIV-1 gp120-mediated CD4 engagement is involved in the induction of susceptibility of primary human T lymphocytes to CD95-mediated apoptosis through ezrin phosphorylation and ezrin-to-CD95 association PubMed
env Antibodies reactive to a domain within the V3 region of HIV-1 gp120 are effective cross-linkers of Fas and increase apoptosis in peripheral T cells PubMed
env Preincubation of T cells with HIV-1 gp120 accelerates the apoptosis observed during CD2-pathway stimulation of the T cells; this process is mediated by Fas/Fas ligand interaction and related to an increased induction of Fas ligand mRNA by gp120 PubMed
env Apoptosis induced by HIV-1 gp120/CD4 cross-linking in Th1 clones is inhibited by anti-CD95 or anti-CD95L neutralizing monoclonal antibodies, as well as by a specific interleukin-1 beta converting enzyme (ICE) inhibitor PubMed
env HIV-1 gp120 induces CD4 association with lymphocyte surface molecules CD3, CD11a, CD27, CD45RA, CD45RB, CD45RO, CD49d, CD38, CD26, CD59, CD95 and class I MHC molecules PubMed
Nef, p27 nef Amino acid 106 of HIV-1 Nef is important for the inhibition of Fas-mediated apoptosis resulting from the interaction of Nef with ASK1 PubMed
nef HIV-1 Nef inhibits Fas-mediated apoptosis by binding to and inactivating the catalytic activity of ASK1, as well as through the downregulation of caspase-3 and caspase-8 PubMed
nef In a murine model of AIDS, CD4C/HIV transgenic (Tg) mice expressing HIV-1 Nef, it has been shown that Nef upregulates expression of Fas and FasL in CD4+ and CD8+ cells from the Tg mouse PubMed
nef HIV-1 Nef sensitizes CD4+ T lymphoid cells to apoptosis by upregulating the expression of both Fas and Fas ligand, an effect that requires the PxxP motif (amino acids 72-75) in the core region of Nef PubMed
Tat, p14 tat HIV-1 Tat sensitizes T cells to CD95 mediated apoptosis through the upregulation of CD95 ligand and caspase 8 PubMed
tat HIV-1 Tat activates B and T cells and upregulates expression of Fas (CD95) in these cells PubMed
Vpr, p15 vpr Virion-associated Vpr activates caspase 3/7, 8, and 9 in Fas-mediated apoptosis in Jurkat T cells and human activated PBMCs PubMed
Vpu, p16 vpu Increased susceptibility of HIV-infected cells to Fas killing has been mapped to the HIV-1 vpu gene PubMed

Go to the HIV-1, Human Protein Interaction Database

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    Direct p53 effectors, organism-specific biosystem
    Direct p53 effectors
  • Extrinsic Pathway for Apoptosis, organism-specific biosystem (from REACTOME)
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    FAS (CD95) signaling pathway, organism-specific biosystem
    FAS (CD95) signaling pathway
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  • FasL/ CD95L signaling, organism-specific biosystem (from REACTOME)
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  • Graft-versus-host disease, organism-specific biosystem (from KEGG)
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  • HIV-1 Nef: Negative effector of Fas and TNF-alpha, organism-specific biosystem (from Pathway Interaction Database)
    HIV-1 Nef: Negative effector of Fas and TNF-alpha, organism-specific biosystem
    HIV-1 Nef: Negative effector of Fas and TNF-alpha
  • Hepatitis B, organism-specific biosystem (from KEGG)
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  • Herpes simplex infection, organism-specific biosystem (from KEGG)
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  • Influenza A, organism-specific biosystem (from KEGG)
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  • Influenza A, conserved biosystem (from KEGG)
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    Pathways in cancer, organism-specific biosystem
    Pathways in cancer
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  • Regulation by c-FLIP, organism-specific biosystem (from REACTOME)
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  • TNF signaling pathway, organism-specific biosystem (from KEGG)
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  • TNF signaling pathway, conserved biosystem (from KEGG)
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Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
identical protein binding IPI
Inferred from Physical Interaction
more info
 
kinase binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
receptor activity NAS
Non-traceable Author Statement
more info
PubMed 
signal transducer activity TAS
Traceable Author Statement
more info
PubMed 
transmembrane signaling receptor activity IEA
Inferred from Electronic Annotation
more info
 
Process Evidence Code Pubs
B cell mediated immunity IEA
Inferred from Electronic Annotation
more info
 
activation of cysteine-type endopeptidase activity involved in apoptotic process TAS
Traceable Author Statement
more info
 
activation-induced cell death of T cells IEA
Inferred from Electronic Annotation
more info
 
apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
apoptotic process TAS
Traceable Author Statement
more info
 
apoptotic signaling pathway TAS
Traceable Author Statement
more info
 
cellular response to hyperoxia IMP
Inferred from Mutant Phenotype
more info
 
cellular response to lithium ion IEA
Inferred from Electronic Annotation
more info
 
cellular response to mechanical stimulus IEP
Inferred from Expression Pattern
more info
PubMed 
extrinsic apoptotic signaling pathway IMP
Inferred from Mutant Phenotype
more info
 
extrinsic apoptotic signaling pathway in absence of ligand IEA
Inferred from Electronic Annotation
more info
 
extrinsic apoptotic signaling pathway via death domain receptors IEA
Inferred from Electronic Annotation
more info
 
immunoglobulin production IEA
Inferred from Electronic Annotation
more info
 
inflammatory cell apoptotic process IEA
Inferred from Electronic Annotation
more info
 
motor neuron apoptotic process IEA
Inferred from Electronic Annotation
more info
 
necroptotic signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of B cell activation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of apoptotic process IEA
Inferred from Electronic Annotation
more info
 
negative thymic T cell selection IEA
Inferred from Electronic Annotation
more info
 
positive regulation of apoptotic process IDA
Inferred from Direct Assay
more info
 
positive regulation of apoptotic process IMP
Inferred from Mutant Phenotype
more info
 
positive regulation of extrinsic apoptotic signaling pathway in absence of ligand IEA
Inferred from Electronic Annotation
more info
 
positive regulation of protein homooligomerization IEA
Inferred from Electronic Annotation
more info
 
protein complex assembly TAS
Traceable Author Statement
more info
PubMed 
protein homooligomerization IEA
Inferred from Electronic Annotation
more info
 
regulation of apoptotic process NAS
Non-traceable Author Statement
more info
PubMed 
regulation of extrinsic apoptotic signaling pathway in absence of ligand TAS
Traceable Author Statement
more info
 
regulation of lymphocyte differentiation IEA
Inferred from Electronic Annotation
more info
 
regulation of myeloid cell differentiation IEA
Inferred from Electronic Annotation
more info
 
renal system process IEA
Inferred from Electronic Annotation
more info
 
response to glucocorticoid IEA
Inferred from Electronic Annotation
more info
 
response to toxic substance IEA
Inferred from Electronic Annotation
more info
 
signal transduction TAS
Traceable Author Statement
more info
PubMed 
spleen development IEA
Inferred from Electronic Annotation
more info
 
transformed cell apoptotic process IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
CD95 death-inducing signaling complex IDA
Inferred from Direct Assay
more info
 
cell surface IDA
Inferred from Direct Assay
more info
 
cytoplasm IDA
Inferred from Direct Assay
more info
 
cytosol NAS
Non-traceable Author Statement
more info
PubMed 
death-inducing signaling complex IDA
Inferred from Direct Assay
more info
PubMed 
external side of plasma membrane IEA
Inferred from Electronic Annotation
more info
 
extracellular vesicular exosome IDA
Inferred from Direct Assay
more info
 
integral component of membrane IEA
Inferred from Electronic Annotation
more info
 
membrane raft IDA
Inferred from Direct Assay
more info
 
nucleus IDA
Inferred from Direct Assay
more info
 
plasma membrane IDA
Inferred from Direct Assay
more info
 
plasma membrane IMP
Inferred from Mutant Phenotype
more info
 
plasma membrane TAS
Traceable Author Statement
more info
 
Preferred Names
tumor necrosis factor receptor superfamily member 6
Names
tumor necrosis factor receptor superfamily member 6
Fas AMA
FAS 827dupA
CD95 antigen
FASLG receptor
apoptosis antigen 1
Delta Fas/APO-1/CD95
FAS receptor variant 9
APO-1 cell surface antigen
TNF receptor superfamily member 6
apoptosis-mediating surface antigen FAS
Fas (TNF receptor superfamily, member 6)
tumor necrosis factor receptor superfamily, member 6

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_009089.2 RefSeqGene

    Range
    5001..30255
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_134

mRNA and Protein(s)

  1. NM_000043.4NP_000034.1  tumor necrosis factor receptor superfamily member 6 isoform 1 precursor

    See proteins identical to NP_000034.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    AK290978, BC012479, DB284727
    Consensus CDS
    CCDS7393.1
    UniProtKB/Swiss-Prot
    P25445
    Related
    ENSP00000347979, OTTHUMP00000020045, ENST00000355740, OTTHUMT00000049274
    Conserved Domains (2) summary
    cd00185
    Location:56147
    Blast Score: 235
    TNFR; Tumor necrosis factor receptor (TNFR) domain; superfamily of TNF-like receptor domains. When bound to TNF-like cytokines, TNFRs trigger multiple signal transduction pathways, they are involved in inflammation response, apoptosis, autoimmunity and ...
    cd08316
    Location:226319
    Blast Score: 377
    Death_FAS_TNFRSF6; Death domain of FAS or TNF receptor superfamily member 6
  2. NM_152871.2NP_690610.1  tumor necrosis factor receptor superfamily member 6 isoform 2 precursor

    See proteins identical to NP_690610.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2), also known as FasdeltaTM or soluble FAS, lacks an alternate in-frame exon in the 3' coding region, compared to variant 1. The resulting isoform (2) lacks an internal region, compared to isoform 1.
    Source sequence(s)
    AK290978, BC012479, DA759225, Z47993
    Consensus CDS
    CCDS7394.1
    UniProtKB/Swiss-Prot
    P25445
    Conserved Domains (2) summary
    cd00185
    Location:56147
    Blast Score: 233
    TNFR; Tumor necrosis factor receptor (TNFR) domain; superfamily of TNF-like receptor domains. When bound to TNF-like cytokines, TNFRs trigger multiple signal transduction pathways, they are involved in inflammation response, apoptosis, autoimmunity and ...
    cd08316
    Location:205298
    Blast Score: 375
    Death_FAS_TNFRSF6; Death domain of FAS or TNF receptor superfamily member 6
  3. NM_152872.2NP_690611.1  tumor necrosis factor receptor superfamily member 6 isoform 3 precursor

    See proteins identical to NP_690611.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3), also known as FASExo8Del, lacks a coding segment, which leads to a translation frameshift, compared to variant 1. The resulting isoform (3) contains a distinct and shorter C-terminus, as compared to isoform 1.
    Source sequence(s)
    AL157394, BC012479, DA759225, Z66556
    Consensus CDS
    CCDS7395.1
    UniProtKB/Swiss-Prot
    P25445
    Conserved Domains (1) summary
    cd00185
    Location:56147
    Blast Score: 201
    TNFR; Tumor necrosis factor receptor (TNFR) domain; superfamily of TNF-like receptor domains. When bound to TNF-like cytokines, TNFRs trigger multiple signal transduction pathways, they are involved in inflammation response, apoptosis, autoimmunity and ...

RNA

  1. NR_028033.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks two alternate coding exons compared to variant 1. The resulting transcript is a candidate for nonsense-mediated mRNA decay (NMD) and likely is not translated.
    Source sequence(s)
    AK290978, BC012479, DA759225, Z70520
  2. NR_028034.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) lacks three alternate coding exons compared to variant 1. The resulting transcript is a candidate for nonsense-mediated mRNA decay (NMD) and likely is not translated.
    Source sequence(s)
    AK290978, BC012479, DA759225, Z47995
  3. NR_028035.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) lacks two alternate coding exons compared to variant 1. The resulting transcript is a candidate for nonsense-mediated mRNA decay (NMD) and likely is not translated.
    Source sequence(s)
    AK290978, BC012479, DA759225, Z47994
  4. NR_028036.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) lacks an alternate coding exon compared to variant 1. The resulting transcript is a candidate for nonsense-mediated mRNA decay (NMD) and likely is not translated.
    Source sequence(s)
    AK290978, BC012479, DA759225, Z70519

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000010.11

    Range
    88969796..89017059
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006717819.1XP_006717882.1  

    See proteins identical to XP_006717882.1

    Conserved Domains (2) summary
    cd00185
    Location:83174
    Blast Score: 235
    TNFR; Tumor necrosis factor receptor (TNFR) domain; superfamily of TNF-like receptor domains. When bound to TNF-like cytokines, TNFRs trigger multiple signal transduction pathways, they are involved in inflammation response, apoptosis, autoimmunity and ...
    cd08316
    Location:253346
    Blast Score: 380
    Death_FAS_TNFRSF6; Death domain of FAS or TNF receptor superfamily member 6

Alternate HuRef

Genomic

  1. AC_000142.1 Alternate HuRef

    Range
    84384755..84410009
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018921.2 Alternate CHM1_1.1

    Range
    91032348..91057602
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_152873.1: Suppressed sequence

    Description
    NM_152873.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
  2. NM_152874.1: Suppressed sequence

    Description
    NM_152874.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
  3. NM_152875.1: Suppressed sequence

    Description
    NM_152875.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
  4. NM_152876.1: Suppressed sequence

    Description
    NM_152876.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
  5. NM_152877.1: Suppressed sequence

    Description
    NM_152877.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.

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