FGF1 (human, P05230) review notes

2026-09-30 initial review

Context: reviewed as the representative paracrine ligand of the FGFR signaling module
(modules/fgfr_signaling.yaml, modelled with GO:0005104). FGF8 review used as comparator.

Canonical extracellular ligand function

• Universal FGFR ligand: PMID:8663044
• Structural basis: PMID:10830168;
  FGFR2 complex PMID:10618369;
  FGFR3c complex PMID:14732692.
• Heparin binding: heparin-binding channel PMID:20145243;
  4xE charge reversal abolishes heparin binding PMID:18441324.
• Mitogen / angiogenic factor PMID:1693186;
  angiogenesis blocked by R50E PMID:23469107.
• Integrin alphaVbeta3 binding (Takada lab) PMID:18441324; treated as non-core (single-lab co-receptor model).

Non-classical secretion

• Cu2+/S100A13/Syt1 aggregate PMID:11432880.
• Stress release PMID:12746488; serum deprivation release in melanoma PMID:18400376.
• AHNAK2 PMID:25560297.

Intracellular / nuclear

• Endosome-to-cytosol translocation and nuclear import PMID:22321063.
• FGFR-independent anti-apoptotic activity, NLS not required PMID:35159330; requires p53, direct binding to p53 DBD PMID:37783936.
• Decision: intracellular CC terms kept as non-core. No NEW apoptosis-regulation term proposed: evidence comes from one laboratory and the mechanism (what FGF1 does to p53) is not defined; raised as a suggested question instead.

Physiology / metabolism

• Fgf1-null mice essentially normal PMID:10688672.
• High-fat-diet phenotype PMID:22522926.
• Pharmacological insulin sensitization via FGFR1 PMID:25043058.
• Decision: no NEW metabolic process terms; mouse phenotypes and pharmacology are downstream of FGFR signaling and the endogenous human role is not established.

Key annotation decisions

• 9 generic protein-binding rows with FGFR partners -> MODIFY to GO:0005104; VBP1 (HuRI) row -> REMOVE.
• Signal transduction (NAS, sequencing paper) -> MODIFY to GO:0008543.
• Anatomical structure morphogenesis (TAS, speculative) -> MARK_AS_OVER_ANNOTATED.
• Positive regulation of transcription by RNA Pol II (apoE/LXR in astrocytes) -> MARK_AS_OVER_ANNOTATED.
• PMID:16756958 (FGF16/18 paper, abstract-only) rows kept as non-core, deferring to curator's full-text reading.
• Ureteric bud rows (in vitro exogenous FGF1, PMID:11731227) non-core; no in vivo requirement.
• 157 Reactome TAS extracellular-region rows accepted.

Module relevance

• Supports modelling FGF1 as the paracrine FGFR ligand with GO:0005104 in the extracellular region, with heparin binding (GO:0008201) as the HS co-receptor contribution.
• Note: GO:0005615 extracellular space is obsolete in the current GO build; use GO:0005576.