FAR1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005778 peroxisomal membrane	IBA GO_REF:0000033	ACCEPT	Summary: FAR1 is a single-pass peroxisomal membrane protein; the phylogenetic (IBA) assignment of peroxisomal membrane as its active-in location is correct and represents a core aspect of the gene. Directly supported by experimental data (tail-anchored peroxisomal membrane protein). Supporting Evidence: PMID:24108123 Far1 is shown to be a peroxisomal tail-anchored protein
GO:0080019 alcohol-forming very long-chain fatty acyl-CoA reductase activity	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: The alcohol-forming acyl-CoA reductase activity type is correct, but the chain-length specialization is wrong for human FAR1: this term is for VERY long-chain (>22C) substrates, whereas FAR1 preferentially reduces C16/C18 (long-chain, 13-22C) fatty acyl-CoA. The very-long-chain term is a family-level (phylogenetic) over-annotation; the correct, experimentally supported term is GO:0102965 (alcohol-forming long-chain fatty acyl-CoA reductase activity). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH WRONG ORTHOLOG OR PARALOG Sources checked: PANTHER:PTN000110226 · fatty acyl-CoA reductase family node (includes plant/insect FARs acting on very-long-chain substrates) SUPPORTS SOURCE BUT NOT TARGET Proposed replacements: alcohol-forming long-chain fatty acyl-CoA reductase activity Supporting Evidence: file:human/FAR1/FAR1-uniprot.txt Catalyzes the reduction of saturated and unsaturated C16 or
GO:0035336 long-chain fatty-acyl-CoA metabolic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: FAR1 consumes long-chain (C16/C18) fatty acyl-CoA as its substrate, so participation in long-chain fatty-acyl-CoA metabolic process is correct. This is a somewhat generic process descriptor; the core biological role is better captured by ether lipid biosynthesis, but the annotation is valid. Supporting Evidence: PMID:15220348 FAR1 preferred saturated
GO:0005777 peroxisome	IEA GO_REF:0000117	ACCEPT	Summary: Peroxisome localization is the correct, experimentally established location of FAR1. This electronic annotation is redundant with, and supported by, the IDA/HPA peroxisome annotations; accept as a core cellular component. Supporting Evidence: PMID:15220348 were localized in the peroxisome
GO:0005778 peroxisomal membrane	IEA GO_REF:0000044	ACCEPT	Summary: Peroxisomal membrane is the correct location of this single-pass tail-anchored membrane protein. This Subcellular-Location-mapping IEA is redundant with the IDA/HDA evidence; accept as a core cellular component. Supporting Evidence: file:human/FAR1/FAR1-uniprot.txt Single-pass membrane protein
GO:0008610 lipid biosynthetic process	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: A very high-level parent term. FAR1 does participate in lipid biosynthesis, but this generic ARBA-derived annotation is uninformative and redundant with the specific ether-lipid / wax / glycerophospholipid biosynthetic process annotations.
GO:0016620 oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: This term describes oxidation of an aldehyde/oxo donor with NAD(P) as acceptor. The physiological FAR1 reaction reduces fatty acyl-CoA (with NADPH as donor) to a fatty alcohol; the aldehyde is a transient intermediate and the acceptor/donor direction of this generic term does not accurately capture the enzyme's function. Better captured by the specific alcohol-forming acyl-CoA reductase term (GO:0102965). Generic ARBA over-annotation. Proposed replacements: alcohol-forming long-chain fatty acyl-CoA reductase activity
GO:0080019 alcohol-forming very long-chain fatty acyl-CoA reductase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Same issue as the IBA assignment of this term: the InterPro family maps to alcohol-forming acyl-CoA reductase activity, but human FAR1 prefers C16/C18 (long-chain) rather than very-long-chain (>22C) substrates. The correct term is GO:0102965. Proposed replacements: alcohol-forming long-chain fatty acyl-CoA reductase activity Supporting Evidence: file:human/FAR1/FAR1-uniprot.txt Catalyzes the reduction of saturated and unsaturated C16 or
GO:0102965 alcohol-forming long-chain fatty acyl-CoA reductase activity	IEA GO_REF:0000120	ACCEPT	Summary: This is the correct core molecular function of FAR1: alcohol-forming long-chain (C16/C18) fatty acyl-CoA reductase activity (EC 1.2.1.84). This electronic (RHEA/EC-based) annotation agrees with the experimental IDA annotations; accept as the core function. Supporting Evidence: file:human/FAR1/FAR1-uniprot.txt Reaction=a long-chain fatty acyl-CoA + 2 NADPH + 2 H(+) = a long-chain
GO:1901568 fatty acid derivative metabolic process	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Generic high-level process term. FAR1's product (fatty alcohol) is a fatty acid derivative, so the annotation is not wrong, but it is uninformative and redundant with the specific biosynthetic-process annotations. Generic ARBA over-annotation.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: Bare 'protein binding' from a large-scale yeast two-hybrid interactome (IntAct records with KLF11, a BAG6 isoform, and a COL26A1 isoform). These high-throughput interactions have no established biological role for FAR1 and the term is uninformative. Retained per policy (IPI protein binding), but marked as over-annotated. The functionally meaningful interaction (PEX19, for peroxisomal targeting) is a distinct, literature-curated interaction (PMID:24108123).
GO:0010025 wax biosynthetic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: FAR1's fatty-alcohol product is a precursor for wax monoester synthesis; wax biosynthetic process is a valid downstream role, largely inferred from the mouse ortholog and Reactome. It is not the primary (ether-lipid) role in human, so keep as non-core. Supporting Evidence: file:human/FAR1/FAR1-uniprot.txt also required for wax monoesters
GO:0010025 wax biosynthetic process	TAS Reactome:R-HSA-9640463	KEEP AS NON CORE	Summary: Same wax biosynthetic role, asserted by Reactome. Valid downstream use of the fatty-alcohol product; keep as non-core (the principal human role is ether-lipid/plasmalogen biosynthesis). Supporting Evidence: Reactome:R-HSA-9640463 FAR1 and FAR2 catalyze the reduction of fatty acids to fatty alcohols
GO:0005777 peroxisome	IDA GO_REF:0000052	ACCEPT	Summary: Immunofluorescence (HPA) localization to the peroxisome; consistent with confocal microscopy in the original characterization and with the membrane-topology study. Core cellular component. Supporting Evidence: PMID:15220348 were localized in the peroxisome
GO:0102965 alcohol-forming long-chain fatty acyl-CoA reductase activity	IDA PMID:15220348 Mammalian wax biosynthesis. I. Identification of two fatty a...	ACCEPT	Summary: Direct experimental demonstration that FAR1 reduces C16/C18 fatty acyl-CoA to fatty alcohols in an NADPH-dependent manner. This is the core molecular function of the gene. Supporting Evidence: PMID:15220348 FAR1 preferred saturated
GO:0102965 alcohol-forming long-chain fatty acyl-CoA reductase activity	IDA PMID:20071337 Posttranslational regulation of fatty acyl-CoA reductase 1, ...	ACCEPT	Summary: Direct evidence supporting the alcohol-forming long-chain fatty acyl-CoA reductase activity of FAR1 (fatty-alcohol supply for ether-bond formation). Core molecular function. Supporting Evidence: PMID:20071337 supplies the fatty alcohols used in the
GO:0102965 alcohol-forming long-chain fatty acyl-CoA reductase activity	IDA PMID:24108123 Topogenesis and homeostasis of fatty acyl-CoA reductase 1.	ACCEPT	Summary: Direct evidence for FAR1's alcohol-forming fatty acyl-CoA reductase activity (Far1 expression increases plasmalogen synthesis; rate-limiting enzyme). Core molecular function. Supporting Evidence: PMID:24108123 Far1 is a rate-limiting enzyme for plasmalogen synthesis
GO:0016491 oxidoreductase activity	TAS Reactome:R-HSA-390425	KEEP AS NON CORE	Summary: FAR1 is an oxidoreductase; this Reactome-asserted parent term is correct but very generic. The specific molecular function (GO:0102965) is preferred; keep this general term as non-core. Supporting Evidence: Reactome:R-HSA-390425 FAR1 catalyzes the reaction of palmitoyl-CoA (PalmCoA) and 2 NADPH
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-390425	ACCEPT	Summary: Peroxisomal membrane localization asserted by Reactome; correct and consistent with the experimental topology data. Core cellular component. Supporting Evidence: PMID:24108123 Far1 is shown to be a peroxisomal tail-anchored protein
GO:0010025 wax biosynthetic process	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Wax biosynthetic role inferred by sequence similarity from the mouse ortholog (Q922J9). Valid downstream use of the fatty-alcohol product; keep as non-core (ether-lipid biosynthesis is the primary human role). Supporting Evidence: file:human/FAR1/FAR1-uniprot.txt also required for wax monoesters
GO:0005778 peroxisomal membrane	IDA PMID:24108123 Topogenesis and homeostasis of fatty acyl-CoA reductase 1.	ACCEPT	Summary: Direct experimental evidence that FAR1 is a peroxisomal tail-anchored, single-pass membrane protein targeted via PEX19. Core cellular component. Supporting Evidence: PMID:24108123 Far1 is shown to be a peroxisomal tail-anchored protein
GO:0008611 ether lipid biosynthetic process	IDA PMID:24108123 Topogenesis and homeostasis of fatty acyl-CoA reductase 1.	ACCEPT	Summary: Direct evidence that FAR1 is required for and rate-limiting in ether lipid/plasmalogen biosynthesis (Far1 supplies the fatty alcohols for ether-bond formation; its expression increases plasmalogen synthesis). This is the core biological process of the gene. Supporting Evidence: PMID:24108123 Peroxisomal fatty acyl-CoA reductase 1 (Far1) is essential for supplying fatty alcohols required for ether bond formation in ether glycerophospholipid synthesis
GO:0008611 ether lipid biosynthetic process	IMP PMID:20071337 Posttranslational regulation of fatty acyl-CoA reductase 1, ...	ACCEPT	Summary: Manipulation of Far1 (levels/activity modulated by plasmalogen feedback) controls ether glycerophospholipid synthesis, supporting involvement in ether lipid biosynthesis. Core biological process. Supporting Evidence: PMID:20071337 supplies the fatty alcohols used in the
GO:0035336 long-chain fatty-acyl-CoA metabolic process	IDA PMID:15220348 Mammalian wax biosynthesis. I. Identification of two fatty a...	KEEP AS NON CORE	Summary: FAR1 acts on long-chain (C16/C18) fatty acyl-CoA substrates, consistent with participation in long-chain fatty-acyl-CoA metabolic process. Correct but generic process descriptor; keep as non-core relative to ether-lipid biosynthesis. Supporting Evidence: PMID:15220348 FAR1 preferred saturated
GO:0046474 glycerophospholipid biosynthetic process	IDA PMID:20071337 Posttranslational regulation of fatty acyl-CoA reductase 1, ...	KEEP AS NON CORE	Summary: Ether glycerophospholipids (plasmalogens) are glycerophospholipids, so this annotation is correct; it is a more general parent of the ether-lipid-specific process. Keep as non-core; the specific term GO:0008611 better captures the role. Supporting Evidence: PMID:20071337 supplies the fatty alcohols used in the
GO:0005777 peroxisome	IDA PMID:20071337 Posttranslational regulation of fatty acyl-CoA reductase 1, ...	ACCEPT	Summary: Direct experimental localization of Far1 to the peroxisome. Core cellular component. Supporting Evidence: PMID:15220348 were localized in the peroxisome
GO:0005778 peroxisomal membrane	HDA PMID:21525035 PEX14 is required for microtubule-based peroxisome motility ...	ACCEPT	Summary: FAR1 was identified in native peroxisomal membrane protein complexes isolated from human cells by proteomics, corroborating its peroxisomal membrane localization. Core cellular component. Supporting Evidence: PMID:21525035 isolating native peroxisomal membrane

Gene Description

Existing Annotations Review

Core Functions

NADPH-dependent reduction of long-chain (C16/C18) fatty acyl-CoA to the corresponding primary fatty alcohol (EC 1.2.1.84), the committed step that supplies fatty alcohols for ether-lipid biosynthesis.

As the rate-limiting enzyme supplying fatty alcohols, FAR1 drives ether-lipid (plasmalogen) biosynthesis, acting at the peroxisomal membrane; its product is used by AGPS to form the ether bond.

References

📚 Additional Documentation

Notes

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