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O95237

- LRAT_HUMAN

UniProt

O95237 - LRAT_HUMAN

Protein

Lecithin retinol acyltransferase

Gene

LRAT

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 115 (01 Oct 2014)
      Sequence version 2 (26 Apr 2004)
      Previous versions | rss
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    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

    Pathwayi

    Sites

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

    GO - Molecular functioni

    1. phosphatidylcholine-retinol O-acyltransferase activity Source: UniProtKB-EC
    2. retinoic acid binding Source: Ensembl
    3. retinol binding Source: Ensembl
    4. transferase activity, transferring acyl groups Source: ProtInc

    GO - Biological processi

    1. embryo development Source: Ensembl
    2. phototransduction, visible light Source: Reactome
    3. retinoic acid metabolic process Source: Ensembl
    4. retinoid metabolic process Source: Reactome
    5. retinol metabolic process Source: UniProtKB-UniPathway
    6. visual perception Source: UniProtKB-KW
    7. vitamin A metabolic process Source: Ensembl

    Keywords - Molecular functioni

    Acyltransferase, Transferase

    Keywords - Biological processi

    Sensory transduction, Vision

    Enzyme and pathway databases

    BioCyciMetaCyc:HS04474-MONOMER.
    BRENDAi2.3.1.135. 2681.
    ReactomeiREACT_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: Chromosome 4

    Organism-specific databases

    HGNCiHGNC:6685. LRAT.

    Subcellular locationi

    Endoplasmic reticulum membrane By similarity; 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.By similarity

    GO - Cellular componenti

    1. endoplasmic reticulum membrane Source: Reactome
    2. integral component of membrane Source: UniProtKB-KW
    3. multivesicular body Source: UniProtKB
    4. perinuclear region of cytoplasm Source: UniProtKB
    5. rough endoplasmic reticulum Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Endoplasmic reticulum, Endosome, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    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.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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.

    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

    ArrayExpressiO95237.
    BgeeiO95237.
    CleanExiHS_LRAT.
    GenevestigatoriO95237.

    Organism-specific databases

    HPAiHPA008397.

    Interactioni

    Protein-protein interaction databases

    BioGridi114658. 1 interaction.
    STRINGi9606.ENSP00000337224.

    Structurei

    3D structure databases

    ProteinModelPortaliO95237.
    SMRiO95237. Positions 48-171.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

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

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei195 – 21521HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the H-rev107 family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG40588.
    HOGENOMiHOG000013187.
    HOVERGENiHBG047861.
    InParanoidiO95237.
    KOiK00678.
    OMAiAIFIPFC.
    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

    MKNPMLEVVS LLLEKLLLIS NFTLFSSGAA GEDKGRNSFY ETSSFHRGDV    50
    LEVPRTHLTH YGIYLGDNRV AHMMPDILLA LTDDMGRTQK VVSNKRLILG 100
    VIVKVASIRV DTVEDFAYGA NILVNHLDES LQKKALLNEE VARRAEKLLG 150
    FTPYSLLWNN CEHFVTYCRY GTPISPQSDK FCETVKIIIR DQRSVLASAV 200
    LGLASIVCTG LVSYTTLPAI FIPFFLWMAG 230
    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:
    EMBL
    GenBank
    DDBJ
    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_004735.2. NM_004744.3.
    XP_006714475.1. XM_006714412.1.
    UniGeneiHs.658427.

    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:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS3789.1.
    RefSeqi NP_004735.2. NM_004744.3.
    XP_006714475.1. XM_006714412.1.
    UniGenei Hs.658427.

    3D structure databases

    ProteinModelPortali O95237.
    SMRi O95237. Positions 48-171.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114658. 1 interaction.
    STRINGi 9606.ENSP00000337224.

    Chemistry

    BindingDBi O95237.
    ChEMBLi CHEMBL2202.
    DrugBanki DB00162. Vitamin A.

    PTM databases

    PhosphoSitei O95237.

    Proteomic databases

    MaxQBi O95237.
    PaxDbi O95237.
    PRIDEi O95237.

    Protocols and materials databases

    DNASUi 9227.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000336356 ; ENSP00000337224 ; ENSG00000121207 .
    ENST00000507827 ; ENSP00000426761 ; ENSG00000121207 .
    GeneIDi 9227.
    KEGGi hsa:9227.
    UCSCi uc003iom.1. human.

    Organism-specific databases

    CTDi 9227.
    GeneCardsi GC04P155549.
    GeneReviewsi LRAT.
    HGNCi HGNC:6685. LRAT.
    HPAi HPA008397.
    MIMi 604863. gene.
    613341. phenotype.
    neXtProti NX_O95237.
    Orphaneti 65. Leber congenital amaurosis.
    791. Retinitis pigmentosa.
    364055. Severe early-childhood-onset retinal dystrophy.
    PharmGKBi PA30443.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG40588.
    HOGENOMi HOG000013187.
    HOVERGENi HBG047861.
    InParanoidi O95237.
    KOi K00678.
    OMAi AIFIPFC.
    PhylomeDBi O95237.
    TreeFami TF330836.

    Enzyme and pathway databases

    UniPathwayi UPA00912 .
    BioCyci MetaCyc:HS04474-MONOMER.
    BRENDAi 2.3.1.135. 2681.
    Reactomei REACT_160156. The canonical retinoid cycle in rods (twilight vision).
    REACT_24968. Retinoid metabolism and transport.

    Miscellaneous databases

    ChiTaRSi LRAT. human.
    GeneWikii Lecithin_retinol_acyltransferase.
    GenomeRNAii 9227.
    NextBioi 34583.
    PROi O95237.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O95237.
    Bgeei O95237.
    CleanExi HS_LRAT.
    Genevestigatori O95237.

    Family and domain databases

    InterProi IPR007053. LRAT-like_dom.
    [Graphical view ]
    Pfami PF04970. LRAT. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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: October 1, 2014
    This is version 115 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