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

Gene ID: 355, updated on 28-Jun-2020

Summary

Official Symbol
FASprovided by HGNC
Official Full Name
Fas cell surface death receptorprovided by HGNC
Primary source
HGNC:HGNC:11920
See related
Ensembl:ENSG00000026103 MIM:134637
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]
Annotation information
Note: FAS (Gene ID: 355) and FASN (Gene ID: 2194) share the FAS symbol/alias in common. FAS is a widely used alternative name for fatty acid synthase (FASN), which can be confused with the official symbol for FAS (Fas cell surface death receptor, GeneID 355). [01 Jun 2018]
Expression
Ubiquitous expression in colon (RPKM 4.3), lymph node (RPKM 4.0) and 24 other tissues See more
Orthologs

Genomic context

See FAS in Genome Data Viewer
Location:
10q23.31
Exon count:
15
Annotation release Status Assembly Chr Location
109.20200522 current GRCh38.p13 (GCF_000001405.39) 10 NC_000010.11 (88968429..89017059)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (90750288..90775542)

Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105379869 Neighboring gene ACTA2 antisense RNA 1 Neighboring gene actin alpha 2, smooth muscle Neighboring gene FAS antisense RNA 1 Neighboring gene microRNA 4679-2 Neighboring gene microRNA 4679-1 Neighboring gene zinc finger RNA binding protein pseudogene

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Autoimmune lymphoproliferative syndrome Compare labs

NHGRI GWAS Catalog

Description
A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia.
NHGRI GWA Catalog
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

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120 binds and signals through CD4, which leads to T cell activation with upregulation of the CXCR5, PD-1, Fas, and FasL expression 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 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 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-induced neuron apoptosis requires the upregulation of the death receptor Fas and its associated death proteins, FADD and CASP8 PubMed
env At high concentrations, HIV-1 gp120 enhances expression of Fas and FasL and promotes apoptosis in human mesangial cells (HMC) 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 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
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 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 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
Envelope surface glycoprotein gp160, precursor env The calmodulin-binding domains in HIV-1 gp160 are involved in Fas-mediated apoptosis PubMed
Nef nef HIV-1 Nef specifically incorporates CSF2, PPBP (NAP2), CCL5, TNF, FAS, CXCL1, IL12B, MIF and OSM into plasma extracellular vesicles from HIV-1 infected patient samples 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
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
Tat 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 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 vpu Increased susceptibility of HIV-infected cells to Fas killing has been mapped to the HIV-1 vpu gene PubMed
integrase gag-pol IL-7 and CD95 synergistically promote survival and proliferation of HIV-1-latently infected CD4+ T-cells measured by increased levels of integrated HIV-1 DNA, suggesting that HIV-1 IN interacts with IL-7 and CD95 in latently infected CD4+ T-cells PubMed
matrix gag HIV-1 MA increases FAS mRNA expression in HepG2 cells and primary hepatocytes PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
calmodulin binding IDA
Inferred from Direct Assay
more info
PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
kinase binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
signaling receptor activity NAS
Non-traceable Author Statement
more info
PubMed 
tumor necrosis factor-activated receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Process Evidence Code Pubs
Fas signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
activation of cysteine-type endopeptidase activity involved in apoptotic process TAS
Traceable Author Statement
more info
 
activation-induced cell death of T cells IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
apoptotic signaling pathway TAS
Traceable Author Statement
more info
 
cellular response to amino acid starvation IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to hyperoxia IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to mechanical stimulus IEP
Inferred from Expression Pattern
more info
PubMed 
extrinsic apoptotic signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
extrinsic apoptotic signaling pathway in absence of ligand IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
immune response IEA
Inferred from Electronic Annotation
more info
 
motor neuron apoptotic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
necroptotic signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
necroptotic signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of apoptotic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors TAS
Traceable Author Statement
more info
 
positive regulation of apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of apoptotic signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of protein phosphorylation IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein-containing complex assembly TAS
Traceable Author Statement
more info
PubMed 
regulation of apoptotic process NAS
Non-traceable Author Statement
more info
PubMed 
regulation of apoptotic process TAS
Traceable Author Statement
more info
 
regulation of extrinsic apoptotic signaling pathway via death domain receptors TAS
Traceable Author Statement
more info
 
regulation of stress-activated MAPK cascade IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
regulation of stress-activated MAPK cascade IMP
Inferred from Mutant Phenotype
more info
PubMed 
signal transduction TAS
Traceable Author Statement
more info
PubMed 
tumor necrosis factor-mediated signaling pathway IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
CD95 death-inducing signaling complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
CD95 death-inducing signaling complex IDA
Inferred from Direct Assay
more info
PubMed 
cell surface IDA
Inferred from Direct Assay
more info
PubMed 
cytosol 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 IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
extracellular exosome HDA PubMed 
integral component of membrane IEA
Inferred from Electronic Annotation
more info
 
membrane raft IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
membrane raft IDA
Inferred from Direct Assay
more info
PubMed 
nuclear body 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
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
tumor necrosis factor receptor superfamily member 6
Names
APO-1 cell surface antigen
CD95 antigen
FASLG receptor
Fas (TNF receptor superfamily, member 6)
Fas AMA
TNF receptor superfamily member 6
apoptosis antigen 1
apoptosis signaling receptor FAS
apoptosis-mediating surface antigen FAS
mutant tumor necrosis receptor superfamily member 6
tumor necrosis factor receptor superfamily, member 6

NCBI Reference Sequences (RefSeq)

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_000043.6NP_000034.1  tumor necrosis factor receptor superfamily member 6 isoform 1 precursor

    See identical proteins and their annotated locations for NP_000034.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    AK026195, AK290978, AL157394, BC012479, BU620333
    Consensus CDS
    CCDS7393.1
    UniProtKB/Swiss-Prot
    P25445
    Related
    ENSP00000498466.1, ENST00000652046.1
    Conserved Domains (2) summary
    cd08316
    Location:226319
    Death_FAS_TNFRSF6; Death domain of FAS or TNF receptor superfamily member 6
    cd10579
    Location:39167
    TNFRSF6; Tumor necrosis factor receptor superfamily member 6 (TNFRSF6), also known as fas cell surface death receptor (Fas)
  2. NM_001320619.2NP_001307548.1  tumor necrosis factor receptor superfamily member 6 isoform 4 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8) lacks an alternate exon in the 3' coding region resulting in a frameshift compared to variant 1. The encoded isoform (4) has a shorter and distinct C-terminus compared to isoform 1.
    Source sequence(s)
    AK026195, AK290978, AL157394, BC012479, BU620333, DA699562, FJ200481
    UniProtKB/Swiss-Prot
    P25445
    UniProtKB/TrEMBL
    K9J972
    Related
    ENSP00000347979.3, ENST00000355740.7
    Conserved Domains (1) summary
    cd10579
    Location:39167
    TNFRSF6; Tumor necrosis factor receptor superfamily member 6 (TNFRSF6), also known as fas cell surface death receptor (Fas)
  3. NM_152871.4NP_690610.1  tumor necrosis factor receptor superfamily member 6 isoform 2 precursor

    See identical proteins and their annotated locations for 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)
    AK026195, AK290978, AL157394, BC012479, BU620333, DA699562, Z47993
    Consensus CDS
    CCDS7394.1
    UniProtKB/Swiss-Prot
    P25445
    Related
    ENSP00000349896.2, ENST00000357339.6
    Conserved Domains (2) summary
    cd08316
    Location:205298
    Death_FAS_TNFRSF6; Death domain of FAS or TNF receptor superfamily member 6
    cd10579
    Location:39167
    TNFRSF6; Tumor necrosis factor receptor superfamily member 6 (TNFRSF6), also known as fas cell surface death receptor (Fas)
  4. NM_152872.4NP_690611.1  tumor necrosis factor receptor superfamily member 6 isoform 3 precursor

    See identical proteins and their annotated locations for 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)
    AK026195, AL157394, BC012479, BU620333, DA699562, Z66556
    Consensus CDS
    CCDS7395.1
    UniProtKB/Swiss-Prot
    P25445
    Related
    ENSP00000347426.2, ENST00000355279.2
    Conserved Domains (1) summary
    cd10579
    Location:39167
    TNFRSF6; Tumor necrosis factor receptor superfamily member 6 (TNFRSF6), also known as fas cell surface death receptor (Fas)

RNA

  1. NR_028033.4 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)
    AK026195, AK290978, AL157394, BC012479, BU620333, DA699562, Z70520
  2. NR_028034.4 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) lacks three alternate 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)
    AK026195, AK290978, AL157394, BC012479, BU620333, DA699562, Z47995
  3. NR_028035.4 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) lacks two alternate 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)
    AK026195, AK290978, AL157394, BC012479, BU620333, DA699562, Z47994
  4. NR_028036.4 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)
    AK026195, AK290978, AL157394, BC012479, BU620333, DA699562, Z70519
  5. NR_135313.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AK026195, AK290978, AL157394, BC012479, BU620333, DA699562, X83492
  6. NR_135314.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AK026195, AK290978, AK311424, AL157394, BC012479, BU620333, DA040126
  7. NR_135315.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AK026195, AK290978, AK311424, AL157394, AV715411, BC012479, BU620333

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000010.11 Reference GRCh38.p13 Primary Assembly

    Range
    88968429..89017059
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006717819.3XP_006717882.1  tumor necrosis factor receptor superfamily member 6 isoform X3

    See identical proteins and their annotated locations for XP_006717882.1

    UniProtKB/TrEMBL
    Q59FU8
    Conserved Domains (2) summary
    cd08316
    Location:253346
    Death_FAS_TNFRSF6; Death domain of FAS or TNF receptor superfamily member 6
    cd10579
    Location:66194
    TNFRSF6; Tumor necrosis factor receptor superfamily member 6 (TNFRSF6), also known as fas cell surface death receptor (Fas)
  2. XM_011539764.2XP_011538066.1  tumor necrosis factor receptor superfamily member 6 isoform X1

    Conserved Domains (2) summary
    cd08316
    Location:280373
    Death_FAS_TNFRSF6; Death domain of FAS or TNF receptor superfamily member 6
    cd10579
    Location:93221
    TNFRSF6; Tumor necrosis factor receptor superfamily member 6 (TNFRSF6), also known as fas cell surface death receptor (Fas)
  3. XM_011539765.2XP_011538067.1  tumor necrosis factor receptor superfamily member 6 isoform X2

    Conserved Domains (2) summary
    cd08316
    Location:259352
    Death_FAS_TNFRSF6; Death domain of FAS or TNF receptor superfamily member 6
    cd10579
    Location:93221
    TNFRSF6; Tumor necrosis factor receptor superfamily member 6 (TNFRSF6), also known as fas cell surface death receptor (Fas)
  4. XM_011539766.2XP_011538068.1  tumor necrosis factor receptor superfamily member 6 isoform X3

    See identical proteins and their annotated locations for XP_011538068.1

    UniProtKB/TrEMBL
    Q59FU8
    Conserved Domains (2) summary
    cd08316
    Location:253346
    Death_FAS_TNFRSF6; Death domain of FAS or TNF receptor superfamily member 6
    cd10579
    Location:66194
    TNFRSF6; Tumor necrosis factor receptor superfamily member 6 (TNFRSF6), also known as fas cell surface death receptor (Fas)
  5. XM_011539767.3XP_011538069.1  tumor necrosis factor receptor superfamily member 6 isoform X4

    Conserved Domains (2) summary
    cd08316
    Location:241334
    Death_FAS_TNFRSF6; Death domain of FAS or TNF receptor superfamily member 6
    cd10579
    Location:54182
    TNFRSF6; Tumor necrosis factor receptor superfamily member 6 (TNFRSF6), also known as fas cell surface death receptor (Fas)

RNA

  1. XR_945733.2 RNA Sequence

  2. XR_945732.3 RNA Sequence

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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