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Protein

Lecithin retinol acyltransferase

Gene

LRAT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

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

Enzyme regulationi

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

Pathway:iretinol metabolism

This protein is involved in the pathway retinol metabolism, which is part of Cofactor metabolism.
View all proteins of this organism that are known to be involved in the pathway retinol metabolism and in Cofactor metabolism.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei161 – 1611Acyl-thioester intermediateBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Acyltransferase, Transferase

Keywords - Biological processi

Sensory transduction, Vision

Enzyme and pathway databases

BioCyciMetaCyc:HS04474-MONOMER.
BRENDAi2.3.1.135. 2681.
ReactomeiREACT_160130. Retinoid cycle disease events.
REACT_160156. The canonical retinoid cycle in rods (twilight vision).
REACT_24968. Retinoid metabolism and transport.
UniPathwayiUPA00912.

Names & Taxonomyi

Protein namesi
Recommended name:
Lecithin retinol acyltransferase (EC:2.3.1.135)
Alternative name(s):
Phosphatidylcholine--retinol O-acyltransferase
Gene namesi
Name:LRAT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:6685. LRAT.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 194194CytoplasmicBy similarityAdd
BLAST
Transmembranei195 – 21521HelicalSequence AnalysisAdd
BLAST
Topological domaini216 – 23015LumenalBy similarityAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Endosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Leber congenital amaurosis 14 (LCA14)3 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:613341
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti175 – 1751S → R in LCA14; loss of function. 1 Publication
VAR_018386

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi161 – 1611C → A or S: Loss of activity. 1 Publication
Mutagenesisi168 – 1681C → A: Loss of activity. 1 Publication
Mutagenesisi168 – 1681C → S: Does not affect activity. 1 Publication
Mutagenesisi182 – 1821C → A: Does not affect activity. 1 Publication
Mutagenesisi208 – 2081C → A: Does not affect activity. 1 Publication

Keywords - Diseasei

Disease mutation, Leber congenital amaurosis

Organism-specific databases

MIMi613341. phenotype.
Orphaneti65. Leber congenital amaurosis.
791. Retinitis pigmentosa.
364055. Severe early-childhood-onset retinal dystrophy.
PharmGKBiPA30443.

Chemistry

DrugBankiDB00162. Vitamin A.

Polymorphism and mutation databases

BioMutaiLRAT.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 230230Lecithin retinol acyltransferasePRO_0000152478Add
BLAST

Proteomic databases

MaxQBiO95237.
PaxDbiO95237.
PRIDEiO95237.

PTM databases

PhosphoSiteiO95237.

Expressioni

Tissue specificityi

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.2 Publications

Inductioni

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).By similarity

Gene expression databases

BgeeiO95237.
CleanExiHS_LRAT.
ExpressionAtlasiO95237. baseline and differential.
GenevisibleiO95237. HS.

Organism-specific databases

HPAiHPA008397.

Interactioni

Protein-protein interaction databases

BioGridi114658. 2 interactions.
STRINGi9606.ENSP00000337224.

Structurei

3D structure databases

ProteinModelPortaliO95237.
SMRiO95237. Positions 48-177.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the H-rev107 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG40588.
GeneTreeiENSGT00510000047351.
HOGENOMiHOG000013187.
HOVERGENiHBG047861.
InParanoidiO95237.
KOiK00678.
OMAiIPFCLWM.
PhylomeDBiO95237.
TreeFamiTF330836.

Family and domain databases

InterProiIPR007053. LRAT-like_dom.
[Graphical view]
PfamiPF04970. LRAT. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O95237-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKNPMLEVVS LLLEKLLLIS NFTLFSSGAA GEDKGRNSFY ETSSFHRGDV
60 70 80 90 100
LEVPRTHLTH YGIYLGDNRV AHMMPDILLA LTDDMGRTQK VVSNKRLILG
110 120 130 140 150
VIVKVASIRV DTVEDFAYGA NILVNHLDES LQKKALLNEE VARRAEKLLG
160 170 180 190 200
FTPYSLLWNN CEHFVTYCRY GTPISPQSDK FCETVKIIIR DQRSVLASAV
210 220 230
LGLASIVCTG LVSYTTLPAI FIPFFLWMAG
Length:230
Mass (Da):25,703
Last modified:April 26, 2004 - v2
Checksum:iDCB7F5A1C3FF7689
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti32 – 321E → K in AAD13529 (PubMed:9920938).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti173 – 1731P → L.1 Publication
VAR_063559
Natural varianti175 – 1751S → R in LCA14; loss of function. 1 Publication
VAR_018386

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3789.1.
RefSeqiNP_001288574.1. NM_001301645.1.
NP_004735.2. NM_004744.4.
XP_006714475.1. XM_006714412.2.
UniGeneiHs.658427.
Hs.736130.

Genome annotation databases

EnsembliENST00000336356; ENSP00000337224; ENSG00000121207.
ENST00000507827; ENSP00000426761; ENSG00000121207.
GeneIDi9227.
KEGGihsa:9227.
UCSCiuc003iom.1. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3789.1.
RefSeqiNP_001288574.1. NM_001301645.1.
NP_004735.2. NM_004744.4.
XP_006714475.1. XM_006714412.2.
UniGeneiHs.658427.
Hs.736130.

3D structure databases

ProteinModelPortaliO95237.
SMRiO95237. Positions 48-177.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114658. 2 interactions.
STRINGi9606.ENSP00000337224.

Chemistry

BindingDBiO95237.
ChEMBLiCHEMBL2202.
DrugBankiDB00162. Vitamin A.

PTM databases

PhosphoSiteiO95237.

Polymorphism and mutation databases

BioMutaiLRAT.

Proteomic databases

MaxQBiO95237.
PaxDbiO95237.
PRIDEiO95237.

Protocols and materials databases

DNASUi9227.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000336356; ENSP00000337224; ENSG00000121207.
ENST00000507827; ENSP00000426761; ENSG00000121207.
GeneIDi9227.
KEGGihsa:9227.
UCSCiuc003iom.1. human.

Organism-specific databases

CTDi9227.
GeneCardsiGC04P155549.
GeneReviewsiLRAT.
HGNCiHGNC:6685. LRAT.
HPAiHPA008397.
MIMi604863. gene.
613341. phenotype.
neXtProtiNX_O95237.
Orphaneti65. Leber congenital amaurosis.
791. Retinitis pigmentosa.
364055. Severe early-childhood-onset retinal dystrophy.
PharmGKBiPA30443.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG40588.
GeneTreeiENSGT00510000047351.
HOGENOMiHOG000013187.
HOVERGENiHBG047861.
InParanoidiO95237.
KOiK00678.
OMAiIPFCLWM.
PhylomeDBiO95237.
TreeFamiTF330836.

Enzyme and pathway databases

UniPathwayiUPA00912.
BioCyciMetaCyc:HS04474-MONOMER.
BRENDAi2.3.1.135. 2681.
ReactomeiREACT_160130. Retinoid cycle disease events.
REACT_160156. The canonical retinoid cycle in rods (twilight vision).
REACT_24968. Retinoid metabolism and transport.

Miscellaneous databases

ChiTaRSiLRAT. human.
GeneWikiiLecithin_retinol_acyltransferase.
GenomeRNAii9227.
NextBioi34583.
PROiO95237.
SOURCEiSearch...

Gene expression databases

BgeeiO95237.
CleanExiHS_LRAT.
ExpressionAtlasiO95237. baseline and differential.
GenevisibleiO95237. HS.

Family and domain databases

InterProiIPR007053. LRAT-like_dom.
[Graphical view]
PfamiPF04970. LRAT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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 cDNA from human liver."
    Zolfaghari R., Ross A.C.
    Gene 341:181-188(2004) [PubMed] [Europe PMC] [Abstract]
    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.
    , 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. 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.

Entry informationi

Entry nameiLRAT_HUMAN
AccessioniPrimary (citable) accession number: O95237
Secondary accession number(s): A8K983, Q8N716
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: April 26, 2004
Last modified: June 24, 2015
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.