FOLR1 (P15328) — curation notes

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Protein and localization

Folate receptor alpha is GPI-anchored on the outer leaflet of the plasma membrane, so
the whole folate-binding domain is extracellular and accessible on intact cells.
PMID:2527252
[file:human/FOLR1/FOLR1-uniprot.txt "SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:2527252, ECO:0000269|PubMed:8033114, ECO:0000269|PubMed:8567728}; Lipid-anchor, GPI-anchor"]
It recycles through clathrin-coated vesicles and endosomes.
PMID:8567728
Polarised sorting is tissue-dependent: basolateral in retinal pigment epithelium, apical
elsewhere.
PMID:10787414

Localization conclusion: plasma membrane, GPI-anchored with the ligand-binding domain
extracellular, plus the endocytic recycling compartments. The 21 Reactome rows for ER
membrane, ERGIC, ER-to-Golgi vesicles, Golgi membrane and transport vesicles describe the
GPI-anchoring and secretory route and are kept as non-core; the extracellular-region row
reflects the shed soluble form; the single nucleus row is a surprising claim and is kept
as non-core.

Function

[file:human/FOLR1/FOLR1-uniprot.txt "Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells"]
[file:human/FOLR1/FOLR1-uniprot.txt "Exposure to slightly acidic pH after receptor endocytosis triggers a conformation change that strongly reduces its affinity for folates and mediates their release"]
PMID:23851396

Review decisions of note

• Both signaling receptor activity rows (IBA and TAS) were MODIFYed to
  GO:0061714 folic acid receptor activity. GO places that term under cargo receptor
  activity, and its definition — combining selectively with extracellular folic acid and
  delivering it into the cell via endocytosis — is precisely what FOLR1 does. The TAS row
  rests on co-residence with Lyn and G alpha i-3 in detergent-resistant membranes, which
  is typical of GPI-anchored proteins and does not show signal transduction by FOLR1.
• tetrahydrofolate biosynthetic process was marked as over-annotation: FOLR1 imports
  folates, while DHFR performs the reduction.
• Rodent-derived developmental rows (heart looping, neural crest migration, pharyngeal
  arch artery morphogenesis, anterior neural tube closure, axon regeneration, Wnt and
  TGF-beta regulation) are kept as non-core, since the receptor's contribution is folate
  supply.