Fas (rat, UniProt Q63199) - manual literature synthesis

No deep-research API was available for this review. This file was compiled by hand from
the cached publications in publications/ (all PMIDs cited in the rat GOA file plus
PMID:16987298), the rat UniProt record (Fas-uniprot.txt) and the existing human FAS
review (genes/human/FAS/FAS-ai-review.yaml). Quotes are verbatim from the cached text.

Identity and architecture

• Rat Fas (TNFRSF6, CD95, APO-1) is a 324-aa single-pass type I membrane protein: signal
  peptide 1-21, extracellular 22-171 with three TNFR cysteine-rich repeats, TM 172-188,
  cytoplasmic 189-324 containing a death domain (219-303) [file:rat/Fas/Fas-uniprot.txt,
  "Contains a death domain involved in the binding of FADD, and maybe to other cytosolic
  adapter proteins."].
• UniProt function (by similarity to human P25445): "Receptor for TNFSF6/FASLG. The adapter
  molecule FADD recruits caspase CASP8 to the activated receptor." [file:rat/Fas/Fas-uniprot.txt]
• Fas does not bind TNF; GO:0005031 "tumor necrosis factor receptor activity" is defined as
  combining with tumor necrosis factor. The appropriate MF is GO:0005035 death receptor
  activity (as used in the human FAS review).

Rat experimental evidence for receptor / DISC function

• Spinal cord injury: "SCI resulted in FasL and Fas translocation into membrane raft
  microdomains where Fas associates with the adaptor proteins Fas-associated death domain
  (FADD), caspase-8, cellular FLIP long form (cFLIPL ), and caspase-3, forming a
  death-inducing signaling complex (DISC)." PMID:17518537
• Cortical neurons: "immunoprecipitation verified formation of the Fas/FasL complex after
  phenylalanine treatment" and anti-Fas neutralising antibody blocked apoptosis and
  caspase-8/3 activation PMID:23940767.
• Rat hepatocytes: intracellular CD95 is targeted to the plasma membrane after CD95L, with
  DISC formation and ROS generation PMID:18045865.
• Neonatal ventricular myocytes: Fas activation raised diastolic Ca2+ and caused
  arrhythmias without apoptosis under normoxia; hypoxia increased Fas and sensitised to
  rFasL-induced apoptosis PMID:12031707. Recombinant FasL activated AP-1 in
  cardiomyocytes, and Fas localised to the sarcolemma PMID:10715265.
• Fas knockdown (siRNA) in type II alveolar epithelial cells and in nucleus pulposus
  cells reduced apoptosis [PMID:19823951, PMID:19902128].
• Agonist anti-Fas antibody induced endplate chondrocyte apoptosis PMID:16582846;
  antagonist ZB4 antibody blocked CoCl2-induced caspase-8 activation in PC12 cells
  PMID:15519734.
• Non-apoptotic outputs: in gastric mucosal cells low-level Fas stimulation leads to
  cFLIP-ERK1/2-NF-kB proliferative signalling PMID:17991709; in PC12 cells Fas ligation
  supported neurite regrowth through JNKs (Fas-Fc ligand trap reduced regrowth)
  PMID:18692025.
• Soluble Fas: ectodomain shedding in hepatocytes after partial hepatectomy PMID:12522536;
  secretory-granule localisation and soluble Fas secretion in castrated prostate epithelium
  PMID:11332701; a rat variant mRNA encodes a 65-aa truncated extracellular fragment
  PMID:7507668.

Expression-only papers (IEP)

Many rat GOA rows are IEP annotations from papers reporting Fas mRNA/protein changes
(cycloheximide PMID:9253159, TRH PMID:16392621, doxorubicin PMID:16687611,
fluoride PMID:20568470, p,p'-DDE PMID:21384494, maternal food restriction
PMID:19616844, IL-10 [PMID:17105443, PMID:16609999], ethanol PMID:27939985, liver
regeneration PMID:10632538, oestrous cycle PMID:16461545, early embryos
PMID:11331665, etc.). These show regulation of Fas expression, not that Fas performs
the process. PMID:16987298 (n-butylidenephthalide in glioblastoma) likewise reports that
the compound "significantly induced Fas expression (from one to 41.3-fold vs. one to
7.7-fold in DBTRG-05MG and RG2 cells, respectively)"; it is an expression observation in a
rat glioma line, not a functional test of Fas.

Annotation attributed to the wrong gene

PMID:29970988 perturbs only the ligand gene Faslg (siRNA and overexpression) in Schwann
cells; Fas itself is not knocked down or measured as a variable. The two IMP rows on rat
Fas (negative regulation of Schwann cell proliferation / migration) appear to be a
ligand-to-receptor mis-attribution.