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O95237 (LRAT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Lecithin retinol acyltransferase

EC=2.3.1.135
Alternative name(s):
Phosphatidylcholine--retinol O-acyltransferase
Gene names
Name:LRAT
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length230 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1

Catalytic activity

Phosphatidylcholine + retinol--[cellular-retinol-binding-protein] = 2-acylglycerophosphocholine + retinyl-ester--[cellular-retinol-binding-protein].

Enzyme regulation

Inhibited by all-trans-retinyl alpha-bromoacetate and N-boc-L-biocytinyl-11-aminoundecane chloro-methyl ketone (BACMK). Ref.1

Pathway

Cofactor metabolism; retinol metabolism.

Subcellular location

Endoplasmic reticulum membrane; Single-pass membrane protein By similarity. Rough endoplasmic reticulum By similarity. Endosomemultivesicular body By similarity. Cytoplasmperinuclear region By similarity. Note: Present in the rough endoplasmic reticulum and multivesicular body in hepatic stellate cells. Present in the rough endoplasmic reticulum and perinuclear region in endothelial cells By similarity.

Tissue specificity

Hepatic stellate cells and endothelial cells (at protein level). Found at high levels in testis and liver, followed by retinal pigment epithelium, small intestine, prostate, pancreas and colon. Low expression observed in brain. In fetal tissues, expressed in retinal pigment epithelium and liver, and barely in the brain. Ref.1 Ref.8

Induction

LRAT activity is up-regulated by dietary vitamin A. Under conditions of vitamin A depletion, LRAT expression in the liver is induced by retinoic acid By similarity. Ref.1

Involvement in disease

Leber congenital amaurosis 14 (LCA14) [MIM:613341]: A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.9 Ref.10

Sequence similarities

Belongs to the H-rev107 family.

Ontologies

Keywords
   Biological processSensory transduction
Vision
   Cellular componentCytoplasm
Endoplasmic reticulum
Endosome
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Leber congenital amaurosis
   DomainTransmembrane
Transmembrane helix
   Molecular functionAcyltransferase
Transferase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processembryo development

Inferred from electronic annotation. Source: Ensembl

phototransduction, visible light

Traceable author statement. Source: Reactome

retinoic acid metabolic process

Inferred from electronic annotation. Source: Ensembl

retinoid metabolic process

Traceable author statement. Source: Reactome

retinol metabolic process

Inferred from electronic annotation. Source: UniProtKB-UniPathway

visual perception

Inferred from electronic annotation. Source: UniProtKB-KW

vitamin A metabolic process

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentendoplasmic reticulum membrane

Traceable author statement. Source: Reactome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

multivesicular body

Inferred from sequence or structural similarity. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

rough endoplasmic reticulum

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionphosphatidylcholine-retinol O-acyltransferase activity

Inferred from electronic annotation. Source: UniProtKB-EC

retinoic acid binding

Inferred from electronic annotation. Source: Ensembl

retinol binding

Inferred from electronic annotation. Source: Ensembl

transferase activity, transferring acyl groups

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 230230Lecithin retinol acyltransferase
PRO_0000152478

Regions

Topological domain1 – 194194Cytoplasmic By similarity
Transmembrane195 – 21521Helical; Potential
Topological domain216 – 23015Lumenal By similarity

Sites

Active site1611Acyl-thioester intermediate By similarity

Natural variations

Natural variant1731P → L. Ref.10
VAR_063559
Natural variant1751S → R in LCA14; loss of function. Ref.9
VAR_018386

Experimental info

Mutagenesis1611C → A or S: Loss of activity. Ref.6
Mutagenesis1681C → A: Loss of activity. Ref.6
Mutagenesis1681C → S: Does not affect activity. Ref.6
Mutagenesis1821C → A: Does not affect activity. Ref.6
Mutagenesis2081C → A: Does not affect activity. Ref.6
Sequence conflict321E → K in AAD13529. Ref.1

Sequences

Sequence LengthMass (Da)Tools
O95237 [UniParc].

Last modified April 26, 2004. Version 2.
Checksum: DCB7F5A1C3FF7689

FASTA23025,703
        10         20         30         40         50         60 
MKNPMLEVVS LLLEKLLLIS NFTLFSSGAA GEDKGRNSFY ETSSFHRGDV LEVPRTHLTH 

        70         80         90        100        110        120 
YGIYLGDNRV AHMMPDILLA LTDDMGRTQK VVSNKRLILG VIVKVASIRV DTVEDFAYGA 

       130        140        150        160        170        180 
NILVNHLDES LQKKALLNEE VARRAEKLLG FTPYSLLWNN CEHFVTYCRY GTPISPQSDK 

       190        200        210        220        230 
FCETVKIIIR DQRSVLASAV LGLASIVCTG LVSYTTLPAI FIPFFLWMAG 

« Hide

References

« Hide 'large scale' references
[1]"Molecular and biochemical characterization of lecithin retinol acyltransferase."
Ruiz A., Winston A., Lim Y.-H., Gilbert B.A., Rando R.R., Bok D.
J. Biol. Chem. 274:3834-3841(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ENZYME REGULATION, TISSUE SPECIFICITY.
[2]"Cloning, gene organization and identification of an alternative splicing process in lecithin:retinol acyltransferase (LRAT) cDNA from human liver."
Zolfaghari R., Ross A.C.
Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[6]"Lecithin retinol acyltransferase contains cysteine residues essential for catalysis."
Mondal M.S., Ruiz A., Bok D., Rando R.R.
Biochemistry 39:5215-5220(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF CYS-161; CYS-168; CYS-182 AND CYS-208.
[7]"Identification of novel mutations in patients with Leber congenital amaurosis and juvenile RP by genome-wide homozygosity mapping with SNP microarrays."
den Hollander A.I., Lopez I., Yzer S., Zonneveld M.N., Janssen I.M., Strom T.M., Hehir-Kwa J.Y., Veltman J.A., Arends M.L., Meitinger T., Musarella M.A., van den Born L.I., Fishman G.A., Maumenee I.H., Rohrschneider K., Cremers F.P., Koenekoop R.K.
Invest. Ophthalmol. Vis. Sci. 48:5690-5698(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN LCA14.
[8]"Lecithin: retinol acyltransferase protein is distributed in both hepatic stellate cells and endothelial cells of normal rodent and human liver."
Nagatsuma K., Hayashi Y., Hano H., Sagara H., Murakami K., Saito M., Masaki T., Lu T., Tanaka M., Enzan H., Aizawa Y., Tajiri H., Matsuura T.
Liver Int. 29:47-54(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[9]"Mutations in the gene encoding lecithin retinol acyltransferase are associated with early-onset severe retinal dystrophy."
Thompson D.A., Li Y., McHenry C.L., Carlson T.J., Ding X., Sieving P.A., Apfelstedt-Sylla E., Gal A.
Nat. Genet. 28:123-124(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LCA14 ARG-175.
[10]"Screening genes of the retinoid metabolism: novel LRAT mutation in Leber congenital amaurosis."
Senechal A., Humbert G., Surget M.O., Bazalgette C., Bazalgette C., Arnaud B., Arndt C., Laurent E., Brabet P., Hamel C.P.
Am. J. Ophthalmol. 142:702-704(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LEU-173, INVOLVEMENT IN LCA14.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF071510 mRNA. Translation: AAD13529.1.
AY546085 mRNA. Translation: AAS49412.1.
AY546086 mRNA. Translation: AAS49413.1.
AK292598 mRNA. Translation: BAF85287.1.
CH471056 Genomic DNA. Translation: EAX04904.1.
BC031053 mRNA. Translation: AAH31053.1.
CCDSCCDS3789.1.
RefSeqNP_004735.2. NM_004744.3.
XP_006714475.1. XM_006714412.1.
UniGeneHs.658427.

3D structure databases

ProteinModelPortalO95237.
SMRO95237. Positions 48-171.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114658. 1 interaction.
STRING9606.ENSP00000337224.

Chemistry

BindingDBO95237.
ChEMBLCHEMBL2202.
DrugBankDB00162. Vitamin A.

PTM databases

PhosphoSiteO95237.

Proteomic databases

MaxQBO95237.
PaxDbO95237.
PRIDEO95237.

Protocols and materials databases

DNASU9227.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000336356; ENSP00000337224; ENSG00000121207.
ENST00000507827; ENSP00000426761; ENSG00000121207.
GeneID9227.
KEGGhsa:9227.
UCSCuc003iom.1. human.

Organism-specific databases

CTD9227.
GeneCardsGC04P155549.
GeneReviewsLRAT.
HGNCHGNC:6685. LRAT.
HPAHPA008397.
MIM604863. gene.
613341. phenotype.
neXtProtNX_O95237.
Orphanet65. Leber congenital amaurosis.
791. Retinitis pigmentosa.
364055. Severe early-childhood-onset retinal dystrophy.
PharmGKBPA30443.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG40588.
HOGENOMHOG000013187.
HOVERGENHBG047861.
InParanoidO95237.
KOK00678.
OMAAIFIPFC.
PhylomeDBO95237.
TreeFamTF330836.

Enzyme and pathway databases

BioCycMetaCyc:HS04474-MONOMER.
BRENDA2.3.1.135. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
UniPathwayUPA00912.

Gene expression databases

ArrayExpressO95237.
BgeeO95237.
CleanExHS_LRAT.
GenevestigatorO95237.

Family and domain databases

InterProIPR007053. LRAT-like_dom.
[Graphical view]
PfamPF04970. LRAT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSLRAT. human.
GeneWikiLecithin_retinol_acyltransferase.
GenomeRNAi9227.
NextBio34583.
PROO95237.
SOURCESearch...

Entry information

Entry nameLRAT_HUMAN
AccessionPrimary (citable) accession number: O95237
Secondary accession number(s): A8K983, Q8N716
Entry history
Integrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: April 26, 2004
Last modified: July 9, 2014
This is version 113 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM