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Tbio Lecithin retinol acyltransferase

Transfers the acyl group from the sn-1 position of phosphatidylcholine to all-trans retinol, producing all-trans retinyl esters. Retinyl esters are storage forms of vitamin A. LRAT plays a critical role in vision. It provides the all-trans retinyl ester substrates for the isomerohydrolase which processes the esters into 11-cis-retinol in the retinal pigment epithelium; due to a membrane-associated alcohol dehydrogenase, 11 cis-retinol is oxidized and converted into 11-cis-retinaldehyde which is the chromophore for rhodopsin and the cone photopigments.

The protein encoded by this gene localizes to the endoplasmic reticulum, where it catalyzes the esterification of all-trans-retinol into all-trans-retinyl ester. This reaction is an important step in vitamin A metabolism in the visual system. Mutations in this gene have been associated with early-onset severe retinal dystrophy and Leber congenital amaurosis 14. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2014]

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Property Summary

NCBI Gene PubMed Count 45
PubMed Score 25.61
PubTator Score 77.63

Knowledge Summary

Patent

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TINX Plot

  Disease (5)

Disease Target Count P-value
atypical teratoid/rhabdoid tumor 1095 9.6e-03
Disease Target Count Z-score Confidence
Alzheimer's disease 644 0.0 1.0
Disease Target Count Z-score Confidence
Fundus dystrophy 77 4.581 2.3
Cone dystrophy 59 3.301 1.7
Blindness 84 3.007 1.5

Expression

  Differential Expression (1)

Disease log2 FC p
atypical teratoid/rhabdoid tumor 2.200 9.6e-03

Synonym

Accession O95237 A8K983 Q8N716
Symbols LCA14

Gene

LRAT

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

 UniProt Keyword (15)

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 GO Function (6)

 GO Component (5)

 GO Process (7)

 Compartment GO Term (28)

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 IMPC Phenotype (1)

 OMIM Phenotype (3)

 MGI Phenotype (6)

 GWAS Trait (1)

 HCA RNA Cell Line (54)

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Pathway (19)

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Protein-protein Interaction (3)

RPE65   RDH11   NME2P1  

Gene RIF (26)

PMID Text
25383759 These findings reveal structural adaptation that facilitates selective catalysis and mechanism responsible for diverse substrate specificity within the LRAT-like enzyme family
25260806 LRAT hypermethylation was associated with decreased mRNA levels in colorectal cancer clinical specimens.
25236354 lecithin retinol acyltransferase affects all-trans retinoic acid levels and has a role in retinoid sensitivity in malignant melanoma cells.
24613493 Lecithin-retinol acyltransferase is a thermostable and highly active enzyme with a likely mode of interfacial activation.
24433184 high LRAT expression in melanoma might be important in removing retinol as substrate for RA production, thereby inducing signalling pathways leading to dedifferentiation, proliferation and anti-apoptosis
23890161 Functional hepatic stellate cells coexpressing both LRAT and CRBP-1, that continue to maintain the ability to store vitamin A, contribute in part to the development of portal and parenchymal fibrogenesis in patients with viral hepatitis.
22605381 Data show that acyl-modified forms of HRAS-like tumor suppressors HRASLS2 and HRASLS3 mimicking lipolytic activity of lecithin retinol acyltransferase LRAT.
22570351 LRAT mutations cause a severe, early childhood onset, progressive retinal dystrophy.
22559933 A genetic defect was identified in LRAT as a novel cause of retinitis punctata albescens.
21465477 This study showed that malignant melanoma cells are able to esterify all-trans retinol and subsequently isomerize all-trans retinyl esters (RE) into 11-cis retinol, whereas their benign counterparts-melanocytes are not able to catalyze these reactions.
20801516 Observational study of genetic testing. (HuGE Navigator)
20591486 Observational study of genetic testing. (HuGE Navigator)
20574532 Observational study of gene-disease association. (HuGE Navigator)
19665987 proximal region together with basal transcription factors may be sufficient to drive Lrat expression.
19471114 Data show that overexpression of human LRAT specifically in mice oral basal epithelial cells makes these cells more sensitive to carcinogen induced tumorigenesis.
18823527 Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
18652909 transcriptional regulation is aberrant in human prostate cancer and involves GATA transcription factors in normal prostate epithelial cells
18544127 Lecithin: retinol acyltransferase protein is distributed in both hepatic stellate cells and endothelial cells of normal rodent and human liver.
17438524 LRAT mutations are likely a rare cause of Leber congenital amaurosis among patients from North America.
17011878 The phenotype of patients with mutations in LRAT is similar to that of patients with mutations in RPE65, suggesting the need to systematically screen both genes in case of typical phenotype.
16939223 These experiments are consistent with an expanded role for LRAT function as a protein palmitoyl transferase.
16115871 LRAT has a role in retinoid absorption and storage
15474300 Results provide evidence that multiple LRAT mRNA transcripts, which are expressed in a tissue-specific manner, may result from differential splicing of the 5'UTR region and the use of multiple polyadenylation signals in the 3'UTR.
15161698 LRAT has a role in preventing progression of invasive bladder cancer
14596594 Conserved residues Cys-161 and His-60 form the essential catalytic dyad of LRAT that represents a novel thiol protease motif, which functions in an acyltransferase reaction.
14581364 LRAT expression is higher in renal tumors with an indolent biological behavior

AA Sequence 

MKNPMLEVVSLLLEKLLLISNFTLFSSGAAGEDKGRNSFYETSSFHRGDVLEVPRTHLTHYGIYLGDNRV      1 - 70
AHMMPDILLALTDDMGRTQKVVSNKRLILGVIVKVASIRVDTVEDFAYGANILVNHLDESLQKKALLNEE     71 - 140
VARRAEKLLGFTPYSLLWNNCEHFVTYCRYGTPISPQSDKFCETVKIIIRDQRSVLASAVLGLASIVCTG    141 - 210
LVSYTTLPAIFIPFFLWMAG                                                      211 - 230
//

Text Mined References (43)

PMID Year Title
25383759 2015 LRAT-specific domain facilitates vitamin A metabolism by domain swapping in HRASLS3.
25260806 2014 High incidence of LRAT promoter hypermethylation in colorectal cancer correlates with tumor stage.
25236354 2014 Knockdown of lecithin retinol acyltransferase increases all-trans retinoic acid levels and restores retinoid sensitivity in malignant melanoma cells.
24613493 2014 Enzymatic activity of Lecithin:retinol acyltransferase: a thermostable and highly active enzyme with a likely mode of interfacial activation.
24433184 2013 Lecithin retinol acyltransferase as a potential prognostic marker for malignant melanoma.
24036882 2014 The retinol esterifying enzyme LRAT supports cell signaling by retinol-binding protein and its receptor STRA6.
23890161 2014 Hepatic stellate cells that coexpress LRAT and CRBP-1 partially contribute to portal fibrogenesis in patients with human viral hepatitis.
22605381 2012 Structural basis for the acyltransferase activity of lecithin:retinol acyltransferase-like proteins.
22570351 2012 Early onset retinal dystrophy due to mutations in LRAT: molecular analysis and detailed phenotypic study.
22559933 2012 A homozygous frameshift mutation in LRAT causes retinitis punctata albescens.
21465477 2012 Vitamin A metabolism in benign and malignant melanocytic skin cells: importance of lecithin/retinol acyltransferase and RPE65.
20801516 2011 Simultaneous mutation detection in 90 retinal disease genes in multiple patients using a custom-designed 300-kb retinal resequencing chip.
20591486 2010 Development of a diagnostic genetic test for simplex and autosomal recessive retinitis pigmentosa.
20574532 2010 Intermediate phenotypes identify divergent pathways to Alzheimer's disease.
20356843 2010 FATP1 inhibits 11-cis retinol formation via interaction with the visual cycle retinoid isomerase RPE65 and lecithin:retinol acyltransferase.
19665987 2009 An essential set of basic DNA response elements is required for receptor-dependent transcription of the lecithin:retinol acyltransferase (Lrat) gene.
19471114 2009 Overexpression of lecithin:retinol acyltransferase in the epithelial basal layer makes mice more sensitive to oral cavity carcinogenesis induced by a carcinogen.
18823527 2008 A genome-wide association study for late-onset Alzheimer's disease using DNA pooling.
18652909 2009 Retinoic acid receptors and GATA transcription factors activate the transcription of the human lecithin:retinol acyltransferase gene.
18544127 2009 Lecithin: retinol acyltransferase protein is distributed in both hepatic stellate cells and endothelial cells of normal rodent and human liver.
18055821 2007 Identification of novel mutations in patients with Leber congenital amaurosis and juvenile RP by genome-wide homozygosity mapping with SNP microarrays.
17438524 2007 Low prevalence of lecithin retinol acyltransferase mutations in patients with Leber congenital amaurosis and autosomal recessive retinitis pigmentosa.
17011878 2006 Screening genes of the retinoid metabolism: novel LRAT mutation in leber congenital amaurosis.
16939223 2006 Palmitoyl transferase activity of lecithin retinol acyl transferase.
16115871 2005 Retinoid absorption and storage is impaired in mice lacking lecithin:retinol acyltransferase (LRAT).
15583024 2004 Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15474300 2004 Cloning, gene organization and identification of an alternative splicing process in lecithin:retinol acyltransferase cDNA from human liver.
15186777 2004 A palmitoylation switch mechanism in the regulation of the visual cycle.
15161698 2004 Reduced lecithin: retinol acyltransferase expression correlates with increased pathologic tumor stage in bladder cancer.
14704332 2004 Regulation of hepatic retinol metabolism: perspectives from studies on vitamin A status.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14596594 2003 Lecithin retinol acyltransferase is a founder member of a novel family of enzymes.
14581364 2003 Differential expression of the enzyme that esterifies retinol, lecithin:retinol acyltransferase, in subtypes of human renal cancer and normal kidney.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12009892 2002 Lecithin retinol acyltransferase forms functional homodimers.
11381255 2001 Mutations in the gene encoding lecithin retinol acyltransferase are associated with early-onset severe retinal dystrophy.
11162450 2000 Expression of a smaller lecithin:retinol acyl transferase transcript and reduced retinol esterification in MCF-7 cells.
11133845 2001 Genomic organization and mutation analysis of the gene encoding lecithin retinol acyltransferase in human retinal pigment epithelium.
10819989 2000 Lecithin retinol acyltransferase contains cysteine residues essential for catalysis.
9920938 1999 Molecular and biochemical characterization of lecithin retinol acyltransferase.
9767084 1998 Distribution of 11-cis LRAT, 11-cis RD and 11-cis REH in bovine retinal pigment epithelium membranes.
1322170 1992 Differential interaction of lecithin-retinol acyltransferase with cellular retinol binding proteins.