LRAT

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0047173 phosphatidylcholine-retinol O-acyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) annotation to the precise molecular function phosphatidylcholine-retinol O-acyltransferase activity. This is exactly the LRAT reaction (acyl transfer from the sn-1 position of lecithin to all-trans-retinol, EC 2.3.1.135) and is independently supported by direct experimental evidence (IDA, PMID:10819989/PMID:9920938). Core function. Supporting Evidence: file:human/LRAT/LRAT-uniprot.txt Transfers the acyl group from the sn-1 position of
GO:0042572 retinol metabolic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) annotation to retinol metabolic process. This is the correct core biological process: LRAT esterifies all-trans-retinol to retinyl esters, the committed storage/entry step of retinol (vitamin A) metabolism. Independently supported by IDA (PMID:10819989) and by the UniProt PATHWAY statement. Supporting Evidence: file:human/LRAT/LRAT-uniprot.txt PATHWAY: Cofactor metabolism; retinol metabolism.
GO:0006776 vitamin A metabolic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic (IBA) annotation to vitamin A metabolic process. Retinol is vitamin A, and LRAT generates the retinyl-ester storage form of vitamin A, so this is a correct process annotation. It is a broader sibling of the more specific retinol metabolic process; retained as non-core relative to GO:0042572. Reason: Correct but a broader retinoid/vitamin A metabolic term; the more specific GO:0042572 retinol metabolic process captures the core role. Supporting Evidence: PMID:10819989 Lecithin retinol acyltransferase (LRAT) is an essential enzyme in vitamin A
GO:0005791 rough endoplasmic reticulum	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic (IBA) annotation (is_active_in) to rough endoplasmic reticulum. LRAT is an ER membrane enzyme and rough ER localization is documented (by similarity, in hepatic stellate cells). This is a biologically reasonable specific compartment, but the functionally central and better-supported location is the ER membrane (GO:0005789); retained as non-core. Reason: Correct sub-compartment observed in rodent stellate cells; ER membrane (GO:0005789) is the core catalytic location. Supporting Evidence: file:human/LRAT/LRAT-uniprot.txt Rough endoplasmic reticulum
GO:0005771 multivesicular body	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Electronic annotation to multivesicular body, transferred from rodent orthologs (UniProtKB:Q9JI61). LRAT was observed in the multivesicular body of retinoid-storing hepatic stellate cells (by similarity). This is a peripheral, non-core localization relative to the ER membrane where the enzyme acts. Reason: By-similarity localization from rodent stellate-cell data; peripheral to the core ER-membrane catalytic site. Supporting Evidence: file:human/LRAT/LRAT-uniprot.txt Endosome, multivesicular body
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: Electronic annotation (UniProt Subcellular Location keyword mapping) to endoplasmic reticulum membrane. This is the correct, specific, and functionally central compartment for LRAT, a single-pass ER membrane enzyme. Core localization. Supporting Evidence: file:human/LRAT/LRAT-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005791 rough endoplasmic reticulum	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Electronic annotation to rough endoplasmic reticulum, transferred from rodent orthologs. Consistent with the by-similarity UniProt location, but a sub-compartment relative to the core ER membrane annotation (GO:0005789). Reason: Correct sub-compartment (by similarity); ER membrane is the core location. Supporting Evidence: file:human/LRAT/LRAT-uniprot.txt Rough endoplasmic reticulum
GO:0042572 retinol metabolic process	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation (ARBA / UniPathway UPA00912) to retinol metabolic process. Correct core biological process, redundant with the experimental IDA and phylogenetic IBA annotations to the same term. Supporting Evidence: file:human/LRAT/LRAT-uniprot.txt PATHWAY: Cofactor metabolism; retinol metabolism.
GO:0047173 phosphatidylcholine-retinol O-acyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation (ARBA / RHEA:17469 / EC:2.3.1.135) to the precise molecular function phosphatidylcholine-retinol O-acyltransferase activity. This exactly matches the LRAT catalytic reaction and the experimental IDA annotation. Core function. Supporting Evidence: file:human/LRAT/LRAT-uniprot.txt phosphatidylcholine to all-trans retinol, producing all-trans retinyl
GO:0048471 perinuclear region of cytoplasm	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Electronic annotation to perinuclear region of cytoplasm, transferred from rodent orthologs (observed in endothelial cells by similarity). A peripheral localization relative to the core ER membrane; retained as non-core. Reason: By-similarity localization; peripheral to the core ER-membrane site. Supporting Evidence: file:human/LRAT/LRAT-uniprot.txt perinuclear region
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: IPI "protein binding" from the HuRI systematic binary-interactome map (interactor BLCAP, UniProtKB:P62952). This is a high-throughput binary-interaction hit with no functional characterization and the bare GO:0005515 term is uninformative about LRAT's molecular function. Retained (experimental IPI, not removed) but flagged as an over-annotation. Reason: Bare "protein binding" from a large-scale interactome screen; not informative about molecular function.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: IPI "protein binding" from the HuRI systematic binary-interactome map (interactor HSD17B13, UniProtKB:Q7Z5P4, an ER/lipid-droplet enzyme). Uninformative bare GO:0005515; retained as an experimental IPI but flagged as an over-annotation. Reason: Bare "protein binding" from a large-scale interactome screen; not informative about molecular function.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: IPI "protein binding" from the HuRI systematic binary-interactome map (interactor TMX2, UniProtKB:Q9Y320, an ER thioredoxin-related membrane protein). Uninformative bare GO:0005515; retained as an experimental IPI but flagged as an over-annotation. Reason: Bare "protein binding" from a large-scale interactome screen; not informative about molecular function.
GO:0001972 retinoic acid binding	IEA GO_REF:0000107	REMOVE	Summary: Electronic annotation (Ensembl Compara transfer from rat) to retinoic acid binding. LRAT's characterized substrate is all-trans-retinol (not retinoic acid), and there is no experimental evidence that human LRAT is a retinoic-acid-binding protein; retinoic acid instead acts upstream to induce LRAT expression. This binding term is a mispropagated electronic inference rather than a molecular function of the enzyme. Reason: Unsupported IEA transferred from ortholog; LRAT acts on retinol, not retinoic acid, and no evidence supports retinoic-acid binding as a molecular function.
GO:0005783 endoplasmic reticulum	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Electronic annotation to endoplasmic reticulum. Correct but a general parent of the specific and better-supported endoplasmic reticulum membrane (GO:0005789); retained as non-core. Reason: General parent of the specific core term GO:0005789 endoplasmic reticulum membrane. Supporting Evidence: file:human/LRAT/LRAT-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0006776 vitamin A metabolic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronic annotation (Ensembl Compara transfer) to vitamin A metabolic process. Correct, redundant with the IBA/ISS annotations to the same term; a broader sibling of the specific retinol metabolic process. Retained as non-core. Reason: Correct broader term; GO:0042572 retinol metabolic process is the more specific core process. Supporting Evidence: PMID:10819989 Lecithin retinol acyltransferase (LRAT) is an essential enzyme in vitamin A
GO:0019841 retinol binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronic annotation (Ensembl Compara transfer from rat) to retinol binding. LRAT binds all-trans-retinol transiently as a catalytic substrate (indeed it preferentially uses retinol presented by cellular retinol-binding protein), so it necessarily interacts with retinol; but the standalone "retinol binding" molecular-function term normally denotes a soluble retinoid-carrier/transport function (e.g. CRBP/RBP) rather than an enzyme's substrate handling. The catalytic activity term GO:0047173 already captures the retinol-utilizing function, so this binding term is retained as non-core rather than as an independent molecular function. Reason: Reflects substrate binding subsumed by the catalytic MF (GO:0047173); not an independent carrier/binding function.
GO:0032526 response to retinoic acid	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronic annotation (Ensembl Compara transfer) to response to retinoic acid. This reflects transcriptional regulation of LRAT (its expression is induced by retinoic acid under vitamin A depletion) rather than the enzyme's own molecular activity. It is a regulatory/physiological context annotation, not a core function. Reason: Captures upstream regulation of LRAT expression by retinoic acid, not the enzyme's core catalytic role. Supporting Evidence: file:human/LRAT/LRAT-uniprot.txt induced by retinoic acid
GO:0033189 response to vitamin A	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronic annotation (Ensembl Compara transfer) to response to vitamin A. LRAT activity/expression is up-regulated by dietary vitamin A, so this is a correct regulatory/physiological response annotation, but not the enzyme's core catalytic function. Reason: Captures regulation of LRAT by dietary vitamin A, not the core catalytic function. Supporting Evidence: file:human/LRAT/LRAT-uniprot.txt LRAT activity is up-regulated by dietary vitamin A
GO:0001523 retinoid metabolic process	TAS Reactome:R-HSA-2453902	KEEP AS NON CORE	Summary: Reactome TAS annotation (canonical retinoid cycle in rods) to retinoid metabolic process. LRAT esterifies all-trans-retinol to retinyl esters, the entry step of the retinoid cycle, so this is a correct process. It is the broad parent of the more specific retinol metabolic process (GO:0042572); retained as non-core relative to that specific term. Reason: Correct but broader parent of GO:0042572 retinol metabolic process (which is the specific core process).
GO:0001523 retinoid metabolic process	TAS Reactome:R-HSA-975634	KEEP AS NON CORE	Summary: Reactome TAS annotation (Retinoid metabolism and transport) to retinoid metabolic process. Correct broad process for LRAT's role in retinoid esterification/storage; broader parent of the specific GO:0042572. Retained as non-core. Reason: Correct but broader parent of the specific core process GO:0042572.
GO:0047173 phosphatidylcholine-retinol O-acyltransferase activity	TAS Reactome:R-HSA-975608	ACCEPT	Summary: Reactome TAS annotation (reaction "LRAT esterifies RBP2:atROL and FACYLs to atREs") to the precise molecular function phosphatidylcholine-retinol O-acyltransferase activity. This matches the enzyme's core catalytic function and the experimental IDA. Core function. Supporting Evidence: file:human/LRAT/LRAT-uniprot.txt Transfers the acyl group from the sn-1 position of
GO:0016416 O-palmitoyltransferase activity	TAS Reactome:R-HSA-2404137	MARK AS OVER ANNOTATED	Summary: Reactome TAS annotation to O-palmitoyltransferase activity. Palmitoyl is one of the acyl groups LRAT transfers (retinyl palmitate is the major product), so this is not wrong, but GO:0016416 is a less informative sibling of the precise GO:0047173 phosphatidylcholine-retinol O-acyltransferase activity and does not capture that the acyl donor is lecithin or that the acceptor is retinol. Over-annotation relative to the specific term. Reason: Generic O-palmitoyltransferase term; the specific and mechanistically accurate MF is GO:0047173 (lecithin as acyl donor, retinol as acceptor).
GO:0016416 O-palmitoyltransferase activity	TAS Reactome:R-HSA-2453855	MARK AS OVER ANNOTATED	Summary: Reactome TAS annotation to O-palmitoyltransferase activity (duplicate of the R-HSA-2404137 annotation). Palmitoyl transfer is part of the LRAT reaction but this generic term is less informative than the specific GO:0047173. Over-annotation relative to the specific term. Reason: Generic term; the specific MF GO:0047173 better captures the lecithin-to-retinol acyl transfer.
GO:0016416 O-palmitoyltransferase activity	TAS Reactome:R-HSA-2466710	MARK AS OVER ANNOTATED	Summary: Reactome TAS annotation to O-palmitoyltransferase activity (from the "Defective LRAT" reaction). Same generic palmitoyltransferase term; less informative than the specific GO:0047173. Over-annotation relative to the specific term. Reason: Generic term; superseded in specificity by GO:0047173.
GO:0005783 endoplasmic reticulum	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS annotation (sequence-similarity transfer from mouse Q9JI60) to endoplasmic reticulum. Correct general compartment but a parent of the specific, better-supported endoplasmic reticulum membrane (GO:0005789); retained as non-core. Reason: General parent of the specific core term GO:0005789 endoplasmic reticulum membrane. Supporting Evidence: file:human/LRAT/LRAT-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0006776 vitamin A metabolic process	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS annotation (sequence-similarity transfer from mouse Q9JI60) to vitamin A metabolic process. Correct, redundant with the IBA/IEA annotations to the same term; broader sibling of the specific retinol metabolic process. Retained as non-core. Reason: Correct broader term; GO:0042572 retinol metabolic process is the specific core process. Supporting Evidence: PMID:10819989 Lecithin retinol acyltransferase (LRAT) is an essential enzyme in vitamin A
GO:0042572 retinol metabolic process	IDA PMID:10819989 Lecithin retinol acyltransferase contains cysteine residues ...	ACCEPT	Summary: Direct experimental (IDA) annotation to retinol metabolic process. Mondal et al. biochemically characterized the LRAT-catalyzed acyl transfer from lecithin to vitamin A (retinol) to generate retinyl esters, the core retinol metabolic reaction. Core biological process, experimentally grounded. Supporting Evidence: PMID:10819989 an acyl group from the sn-1 position of lecithin to vitamin A to generate
GO:0047173 phosphatidylcholine-retinol O-acyltransferase activity	IDA PMID:10819989 Lecithin retinol acyltransferase contains cysteine residues ...	ACCEPT	Summary: Direct experimental (IDA) annotation to phosphatidylcholine-retinol O-acyltransferase activity. Mondal et al. characterized the LRAT catalytic mechanism (thiol acyltransferase; essential Cys161 nucleophile forming an acyl-thioester intermediate) via site-directed mutagenesis, establishing the enzyme's molecular function. This is the definitive experimental support for the core molecular function. Supporting Evidence: PMID:10819989 an acyl group from the sn-1 position of lecithin to vitamin A to generate PMID:10819989 C161 may be the essential nucleophilic residue critical for catalysis.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-2466710	ACCEPT	Summary: Reactome TAS annotation to endoplasmic reticulum membrane. Correct and functionally central compartment for LRAT; consistent with the UniProt subcellular location and the IEA annotation to the same term. Core localization. Supporting Evidence: file:human/LRAT/LRAT-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-2404137	ACCEPT	Summary: Reactome TAS annotation to endoplasmic reticulum membrane (duplicate). Correct core compartment for LRAT. Supporting Evidence: file:human/LRAT/LRAT-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-2453855	ACCEPT	Summary: Reactome TAS annotation to endoplasmic reticulum membrane (duplicate). Correct core compartment for LRAT. Supporting Evidence: file:human/LRAT/LRAT-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-975608	ACCEPT	Summary: Reactome TAS annotation to endoplasmic reticulum membrane (duplicate). Correct core compartment for LRAT. Supporting Evidence: file:human/LRAT/LRAT-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005771 multivesicular body	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS annotation (sequence-similarity transfer from rat Q9JI61) to multivesicular body. Observed in retinoid-storing hepatic stellate cells by similarity; a peripheral localization relative to the core ER membrane. Retained as non-core. Reason: By-similarity localization from rodent stellate-cell data; peripheral to the core ER-membrane catalytic site. Supporting Evidence: file:human/LRAT/LRAT-uniprot.txt Endosome, multivesicular body
GO:0005791 rough endoplasmic reticulum	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS annotation (sequence-similarity transfer from rat Q9JI61) to rough endoplasmic reticulum. Consistent with the by-similarity UniProt location; a sub-compartment relative to the core ER membrane annotation. Retained as non-core. Reason: Correct sub-compartment (by similarity); ER membrane (GO:0005789) is the core location. Supporting Evidence: file:human/LRAT/LRAT-uniprot.txt Rough endoplasmic reticulum
GO:0048471 perinuclear region of cytoplasm	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS annotation (sequence-similarity transfer from rat Q9JI61) to perinuclear region of cytoplasm. Observed in endothelial cells by similarity; peripheral to the core ER membrane localization. Retained as non-core. Reason: By-similarity localization; peripheral to the core ER-membrane site. Supporting Evidence: file:human/LRAT/LRAT-uniprot.txt perinuclear region
GO:0016746 acyltransferase activity	TAS PMID:9920938 Molecular and biochemical characterization of lecithin retin...	KEEP AS NON CORE	Summary: TAS annotation (from the original molecular characterization, PMID:9920938) to the very general term acyltransferase activity. LRAT is indeed an acyltransferase, but this high-level parent is far less informative than the specific and experimentally supported GO:0047173 phosphatidylcholine-retinol O-acyltransferase activity. Retained as non-core. Reason: Correct but very general parent of the specific core MF GO:0047173. Supporting Evidence: PMID:9920938 The enzyme responsible for conversion of all-trans-retinol into retinyl esters,

Gene Description

Existing Annotations Review

Core Functions

Catalyzes the committed storage/entry step of retinol (vitamin A) metabolism and the visual (retinoid) cycle: esterification of all-trans-retinol to retinyl esters provides the vitamin A storage form and the substrate for the RPE65 isomerohydrolase in the retinal pigment epithelium.

References

📚 Additional Documentation

Notes

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