far-1

Gene Description

FAR-1 (Bm-FAR-1, also known as Bm20) is a small (~20 kDa), helix-rich, secreted fatty-acid- and retinol-binding protein of the filarial nematode Brugia malayi, belonging to the nematode-specific fatty-acid and retinol-binding protein (FARBP/Gp-FAR-1) family. It is synthesized with an N-terminal signal peptide and released into the extracellular environment (excretory-secretory product). Biochemically it binds all-trans-retinol and long-chain fatty acids: in fluorescence-based assays it binds the fluorescent fatty-acid analogue DAUDA and produces a characteristic blue-shift in DAUDA emission, and bound DAUDA and retinol are competitively displaced by the long-chain fatty acid oleic acid. Unlike the orthologous proteins of some other filariae, Bm-FAR-1 is not glycosylated. As a secreted lipid carrier, FAR proteins are thought to scavenge and transport host-derived lipids (retinoids and fatty acids) that the parasite cannot synthesize de novo, and may sequester lipid signalling molecules at the host-parasite interface.

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005576 extracellular region	IEA GO_REF:0000044	ACCEPT	Summary: Localization to the extracellular region is well supported: the protein carries a cleaved N-terminal signal peptide and FAR proteins are released into culture medium by all filarial species and developmental stages tested. This IEA assignment (from the UniProt subcellular-location keyword mapping) agrees with the experimentally/ISS-supported "Secreted" location.
GO:0008289 lipid binding	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Correct but general. This InterPro2GO mapping (from the Gp-FAR-1 domain, IPR008632) captures the lipid-binding activity of the family. It is subsumed by the more specific, experimentally supported fatty acid binding and retinol binding annotations, so it is accurate but not the most informative term for the core function.
GO:0005504 fatty acid binding	IDA PMID:12106870 The FAR proteins of filarial nematodes: secretion, glycosyla...	ACCEPT	Summary: Strongly supported experimental annotation. Recombinant Bm-FAR-1 was shown by fluorescence-based ligand-binding assays to bind the fatty-acid analogue DAUDA and the long-chain fatty acid oleic acid (by competition), producing a dramatic blue-shift in DAUDA emission. This is a core molecular function of the protein.
GO:0005576 extracellular region	ISS PMID:12106870 The FAR proteins of filarial nematodes: secretion, glycosyla...	ACCEPT	Summary: Accept. Consistent with the cleaved signal peptide and the demonstration that FAR proteins are released into the culture medium by all species and stages investigated; the ISS is propagated from the secreted ortholog Q25619.
GO:0019841 retinol binding	IDA PMID:12106870 The FAR proteins of filarial nematodes: secretion, glycosyla...	ACCEPT	Summary: Strongly supported experimental annotation. Recombinant Bm-FAR-1 was shown to bind all-trans-retinol in fluorescence-based assays, with bound retinol competitively displaceable by oleic acid. Together with fatty acid binding, this defines the core lipid/retinoid-carrier function of the protein.

Core Functions

Secreted retinol-binding activity; Bm-FAR-1 binds all-trans-retinol in a site shared with fatty-acid ligands (oleic acid competes off bound retinol).

Molecular Function:

retinol binding

Supporting Evidence:

PMID:12106870
Both were found to bind all-trans-retinol, (dansylamino) undecanoic acid (DAUDA), and oleic acid by competition.

Secreted long-chain fatty-acid binding; binds the fluorescent fatty-acid analogue DAUDA (with a characteristic emission blue-shift) and oleic acid.