FAS

Protein identityUniProt · HPA

UniProt accession

P25445

Gene

FAS

Ensembl

ENSG00000026103

Chromosome

10

Canonical length

335 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, CD markers, Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins, Predicted secreted proteins

Subcellular location

Nuclear bodies,Plasma membrane,Cytosol

Secretome location

Secreted to blood

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

335 residues, UniProt reviewed canonical sequence.

>P25445|FAS
     1  MLGIWTLLPL VLTSVARLSS KSVNAQVTDI NSKGLELRKT VTTVETQNLE GLHHDGQFCH
    61  KPCPPGERKA RDCTVNGDEP DCVPCQEGKE YTDKAHFSSK CRRCRLCDEG HGLEVEINCT
   121  RTQNTKCRCK PNFFCNSTVC EHCDPCTKCE HGIIKECTLT SNTKCKEEGS RSNLGWLCLL
   181  LLPIPLIVWV KRKEVQKTCR KHRKENQGSH ESPTLNPETV AINLSDVDLS KYITTIAGVM
   241  TLSQVKGFVR KNGVNEAKID EIKNDNVQDT AEQKVQLLRN WHQLHGKKEA YDTLIKDLKK
   301  ANLCTLAEKI QTIILKDITS DSENSNFRNE IQSLV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FAS can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.43

Highest tissue expression

16 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FAS.

Disease | AllUniProt

Conditions FAS is implicated in, by any mechanism.

• Autoimmune lymphoproliferative syndrome 1A (ALPS1A) MIM:601859

Disease | GeneticClinVar

119 pathogenic / likely-pathogenic of 518 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autoimmune lymphoproliferative syndrome type 1
• FAS-related autoimmune lymphoproliferative syndrome
• SQUAMOUS CELL CARCINOMA, BURN SCAR-RELATED, SOMATIC
• FAS-related disorder
• Autoimmune lymphoproliferative syndrome with defective apoptosis

ReferencesPubMed · IEDB

Publications for FAS from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.44

gnomAD pLI

0.81

gnomAD missense Z

1.23

DepMap mean gene effect

-0.13

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• activation-induced cell death of T cells
• apoptotic process
• cellular response to amino acid starvation
• cellular response to hyperoxia
• cellular response to mechanical stimulus
• extrinsic apoptotic signaling pathway
• extrinsic apoptotic signaling pathway via death domain receptors
• Fas signaling pathway
• immune response
• motor neuron apoptotic process
• necroptotic signaling pathway
• negative regulation of apoptotic process
• positive regulation of apoptotic process
• positive regulation of apoptotic signaling pathway
• positive regulation of reactive oxygen species biosynthetic process
• protein-containing complex assembly
• regulation of apoptotic process
• regulation of stress-activated MAPK cascade
• signal transduction

Molecular functions

• calmodulin binding
• identical protein binding
• kinase binding
• signaling receptor activity
• tumor necrosis factor receptor activity

Cellular components

• CD95 death-inducing signaling complex
• cell surface
• cytosol
• death-inducing signaling complex
• external side of plasma membrane
• extracellular exosome
• membrane raft
• nuclear body
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Death domain
• TNFR/NGFR cysteine-rich region
• Death-like domain superfamily
• TNFR/NGFR cysteine-rich region
• Death domain
• Fas receptor
• Fas receptor, death domain
• Fas receptor, N-terminal

KeywordsUniProt

• Apoptosis
• Calmodulin-binding
• Cell membrane
• Disulfide bond
• Glycoprotein
• Lipoprotein
• Membrane
• Palmitate
• Phosphoprotein
• Receptor
• Repeat
• Secreted
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of FAS in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• BABAM2
• BIRC2
• CALM
• DDX3X
• FEM1B
• GSK3B
• HIPK3
• CASP8
• DAXX
• FADD
• FASLG
• MAP3K5