LRAT_MOUSE
ID LRAT_MOUSE Reviewed; 231 AA.
AC Q9JI60;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Lecithin retinol acyltransferase;
DE EC=2.3.1.135 {ECO:0000305|PubMed:20628054};
DE AltName: Full=Phosphatidylcholine--retinol O-acyltransferase;
DE AltName: Full=Phosphatidylcholine-retinol-O-acyltransferase;
GN Name=Lrat;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION BY RETINOIC ACID.
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=11108736;
RA Zolfaghari R., Ross A.C.;
RT "Lecithin:retinol acyltransferase from mouse and rat liver. cDNA cloning
RT and liver-specific regulation by dietary vitamin A and retinoic acid.";
RL J. Lipid Res. 41:2024-2034(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=17114808; DOI=10.1074/jbc.m608315200;
RA Moise A.R., Golczak M., Imanishi Y., Palczewski K.;
RT "Topology and membrane association of lecithin: retinol acyltransferase.";
RL J. Biol. Chem. 282:2081-2090(2007).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=18544127; DOI=10.1111/j.1478-3231.2008.01773.x;
RA Nagatsuma K., Hayashi Y., Hano H., Sagara H., Murakami K., Saito M.,
RA Masaki T., Lu T., Tanaka M., Enzan H., Aizawa Y., Tajiri H., Matsuura T.;
RT "Lecithin: retinol acyltransferase protein is distributed in both hepatic
RT stellate cells and endothelial cells of normal rodent and human liver.";
RL Liver Int. 29:47-54(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP ACTIVE SITE, IDENTIFICATION BY MASS SPECTROMETRY, AND CATALYTIC ACTIVITY.
RX PubMed=20628054; DOI=10.1074/jbc.m110.152314;
RA Golczak M., Palczewski K.;
RT "An acyl-covalent enzyme intermediate of lecithin:retinol
RT acyltransferase.";
RL J. Biol. Chem. 285:29217-29222(2010).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25416279; DOI=10.1093/hmg/ddu588;
RA Zhang T., Enemchukwu N.O., Jones A., Wang S., Dennis E., Watt C.B.,
RA Pugh E.N. Jr., Fu Y.;
RT "Genetic deletion of S-opsin prevents rapid cone degeneration in a mouse
RT model of Leber congenital amaurosis.";
RL Hum. Mol. Genet. 24:1755-1763(2015).
RN [8]
RP SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF
RP GLU-14.
RX PubMed=28758396; DOI=10.1021/acs.biochem.7b00451;
RA Chelstowska S., Widjaja-Adhi M.A.K., Silvaroli J.A., Golczak M.;
RT "Impact of LCA-Associated E14L LRAT Mutation on Protein Stability and
RT Retinoid Homeostasis.";
RL Biochemistry 56:4489-4499(2017).
CC -!- FUNCTION: Transfers the acyl group from the sn-1 position of
CC phosphatidylcholine to all-trans retinol, producing all-trans retinyl
CC esters. Retinyl esters are storage forms of vitamin A
CC (PubMed:28758396). LRAT plays a critical role in vision (By
CC similarity). It provides the all-trans retinyl ester substrates for the
CC isomerohydrolase which processes the esters into 11-cis-retinol in the
CC retinal pigment epithelium; due to a membrane-associated alcohol
CC dehydrogenase, 11 cis-retinol is oxidized and converted into 11-cis-
CC retinaldehyde which is the chromophore for rhodopsin and the cone
CC photopigments (By similarity). Required for the survival of cone
CC photoreceptors and correct rod photoreceptor cell morphology
CC (PubMed:25416279). {ECO:0000250|UniProtKB:O95237,
CC ECO:0000269|PubMed:25416279, ECO:0000269|PubMed:28758396}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + all-trans-retinol--
CC [retinol-binding protein] = a 2-acyl-sn-glycero-3-phosphocholine + an
CC all-trans-retinyl ester + apo--[retinol-binding protein];
CC Xref=Rhea:RHEA:17469, Rhea:RHEA-COMP:14426, Rhea:RHEA-COMP:14428,
CC ChEBI:CHEBI:17336, ChEBI:CHEBI:57643, ChEBI:CHEBI:57875,
CC ChEBI:CHEBI:63410, ChEBI:CHEBI:83228; EC=2.3.1.135;
CC Evidence={ECO:0000305|PubMed:20628054};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17470;
CC Evidence={ECO:0000305|PubMed:20628054};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-diheptanoyl-sn-glycero-3-phosphocholine + all-trans-
CC retinol--[retinol-binding protein] = 2-heptanoyl-sn-glycero-3-
CC phosphocholine + all-trans-retinyl heptanoate + apo--[retinol-binding
CC protein]; Xref=Rhea:RHEA:55320, Rhea:RHEA-COMP:14426, Rhea:RHEA-
CC COMP:14428, ChEBI:CHEBI:17336, ChEBI:CHEBI:83228, ChEBI:CHEBI:138195,
CC ChEBI:CHEBI:138266, ChEBI:CHEBI:138724;
CC Evidence={ECO:0000269|PubMed:20628054, ECO:0000269|PubMed:28758396};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55321;
CC Evidence={ECO:0000305|PubMed:20628054, ECO:0000305|PubMed:28758396};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dioctanoyl-sn-glycero-3-phosphocholine + all-trans-
CC retinol--[retinol-binding protein] = 2-octanoyl-sn-glycero-3-
CC phosphocholine + all-trans-retinyl octanoate + apo--[retinol-binding
CC protein]; Xref=Rhea:RHEA:56240, Rhea:RHEA-COMP:14426, Rhea:RHEA-
CC COMP:14428, ChEBI:CHEBI:17336, ChEBI:CHEBI:78228, ChEBI:CHEBI:83228,
CC ChEBI:CHEBI:140082, ChEBI:CHEBI:140084;
CC Evidence={ECO:0000269|PubMed:20628054};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:56241;
CC Evidence={ECO:0000305|PubMed:20628054};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + all-trans-
CC retinol--[retinol-binding protein] = 2-hexadecanoyl-sn-glycero-3-
CC phosphocholine + all-trans-retinyl hexadecanoate + apo--[retinol-
CC binding protein]; Xref=Rhea:RHEA:56244, Rhea:RHEA-COMP:14426,
CC Rhea:RHEA-COMP:14428, ChEBI:CHEBI:17336, ChEBI:CHEBI:17616,
CC ChEBI:CHEBI:72999, ChEBI:CHEBI:76078, ChEBI:CHEBI:83228;
CC Evidence={ECO:0000269|PubMed:20628054};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:56245;
CC Evidence={ECO:0000305|PubMed:20628054};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-didodecanoyl-sn-glycero-3-phosphocholine + all-trans-
CC retinol--[retinol-binding protein] = 2-dodecanoyl-sn-glycero-3-
CC phosphocholine + all-trans-retinyl dodecanoate + apo--[retinol-
CC binding protein]; Xref=Rhea:RHEA:56248, Rhea:RHEA-COMP:14426,
CC Rhea:RHEA-COMP:14428, ChEBI:CHEBI:17336, ChEBI:CHEBI:65211,
CC ChEBI:CHEBI:83228, ChEBI:CHEBI:140088, ChEBI:CHEBI:140089;
CC Evidence={ECO:0000269|PubMed:20628054};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:56249;
CC Evidence={ECO:0000305|PubMed:20628054};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + all-trans-
CC retinol = all-trans-retinyl hexadecanoate + hexadecanoyl-sn-glycero-
CC 3-phosphocholine; Xref=Rhea:RHEA:43904, ChEBI:CHEBI:17336,
CC ChEBI:CHEBI:17616, ChEBI:CHEBI:64563, ChEBI:CHEBI:72999;
CC Evidence={ECO:0000250|UniProtKB:O95237};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43905;
CC Evidence={ECO:0000250|UniProtKB:O95237};
CC -!- ACTIVITY REGULATION: Inhibited by all-trans-retinyl alpha-bromoacetate
CC and N-boc-L-biocytinyl-11-aminoundecane chloro-methyl ketone (BACMK).
CC {ECO:0000250}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.9 uM for all-trans-retinol--[retinol-binding protein]
CC {ECO:0000269|PubMed:28758396};
CC -!- PATHWAY: Cofactor metabolism; retinol metabolism.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:17114808, ECO:0000269|PubMed:28758396}; Single-pass
CC membrane protein {ECO:0000269|PubMed:17114808}. Rough endoplasmic
CC reticulum {ECO:0000250}. Endosome, multivesicular body {ECO:0000250}.
CC Cytoplasm, perinuclear region {ECO:0000250}. Note=Present in the rough
CC endoplasmic reticulum and multivesicular body in hepatic stellate
CC cells. Present in the rough endoplasmic reticulum and perinuclear
CC region in endothelial cells (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Hepatic stellate cells and endothelial cells (at
CC protein level). {ECO:0000269|PubMed:18544127}.
CC -!- INDUCTION: LRAT activity is up-regulated by dietary vitamin A (By
CC similarity). Under conditions of vitamin A depletion, LRAT expression
CC in the liver is induced by retinoic acid. {ECO:0000250,
CC ECO:0000269|PubMed:11108736}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice are viable (PubMed:25416279).
CC Knockout mice at one month of age show loss of nearly all cone
CC photoreceptors in the central and ventral retina (PubMed:25416279).
CC Surviving cone cells show severe degeneration, the dorsal retinal also
CC exhibits a significant reduction in cone photoreceptors
CC (PubMed:25416279). At one month of age rod photoreceptors show shorter
CC outer segments (PubMed:25416279). Nearly all cone photoreceptors are
CC lost by six months of age (PubMed:25416279). Remaining cone cells show
CC disrupted structures with the majority showing abnormal cell bodies or
CC lack of an outer segment (PubMed:25416279).
CC {ECO:0000269|PubMed:25416279}.
CC -!- SIMILARITY: Belongs to the H-rev107 family. {ECO:0000305}.
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DR EMBL; AF255061; AAF97787.1; -; mRNA.
DR EMBL; AK004953; BAB23696.1; -; mRNA.
DR CCDS; CCDS17430.1; -.
DR RefSeq; NP_076113.1; NM_023624.4.
DR PDB; 4Q95; X-ray; 2.20 A; A/B=76-106.
DR PDBsum; 4Q95; -.
DR AlphaFoldDB; Q9JI60; -.
DR SMR; Q9JI60; -.
DR STRING; 10090.ENSMUSP00000029632; -.
DR SwissLipids; SLP:000001899; -.
DR iPTMnet; Q9JI60; -.
DR PhosphoSitePlus; Q9JI60; -.
DR MaxQB; Q9JI60; -.
DR PaxDb; Q9JI60; -.
DR PRIDE; Q9JI60; -.
DR ProteomicsDB; 252503; -.
DR Antibodypedia; 2389; 279 antibodies from 30 providers.
DR DNASU; 79235; -.
DR Ensembl; ENSMUST00000029632; ENSMUSP00000029632; ENSMUSG00000028003.
DR GeneID; 79235; -.
DR KEGG; mmu:79235; -.
DR UCSC; uc012cqv.1; mouse.
DR CTD; 9227; -.
DR MGI; MGI:1891259; Lrat.
DR VEuPathDB; HostDB:ENSMUSG00000028003; -.
DR eggNOG; ENOG502QWSA; Eukaryota.
DR GeneTree; ENSGT00510000047351; -.
DR HOGENOM; CLU_105262_0_0_1; -.
DR InParanoid; Q9JI60; -.
DR OMA; ADKFCEY; -.
DR OrthoDB; 1602481at2759; -.
DR PhylomeDB; Q9JI60; -.
DR TreeFam; TF330836; -.
DR BRENDA; 2.3.1.135; 3474.
DR Reactome; R-MMU-2453902; The canonical retinoid cycle in rods (twilight vision).
DR Reactome; R-MMU-975634; Retinoid metabolism and transport.
DR UniPathway; UPA00912; -.
DR BioGRID-ORCS; 79235; 2 hits in 75 CRISPR screens.
DR PRO; PR:Q9JI60; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9JI60; protein.
DR Bgee; ENSMUSG00000028003; Expressed in pigmented layer of retina and 54 other tissues.
DR ExpressionAtlas; Q9JI60; baseline and differential.
DR Genevisible; Q9JI60; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005771; C:multivesicular body; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005791; C:rough endoplasmic reticulum; ISO:MGI.
DR GO; GO:0102279; F:lecithin:11-cis retinol acyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0008374; F:O-acyltransferase activity; IDA:MGI.
DR GO; GO:0047173; F:phosphatidylcholine-retinol O-acyltransferase activity; IMP:UniProtKB.
DR GO; GO:0001972; F:retinoic acid binding; ISO:MGI.
DR GO; GO:0019841; F:retinol binding; ISO:MGI.
DR GO; GO:0006653; P:1,2-diacyl-sn-glycero-3-phosphocholine metabolic process; TAS:MGI.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
DR GO; GO:0032370; P:positive regulation of lipid transport; IGI:MGI.
DR GO; GO:0009617; P:response to bacterium; IEP:MGI.
DR GO; GO:0032526; P:response to retinoic acid; IEA:Ensembl.
DR GO; GO:0033189; P:response to vitamin A; IEA:Ensembl.
DR GO; GO:0042572; P:retinol metabolic process; IMP:UniProtKB.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR GO; GO:0006776; P:vitamin A metabolic process; IDA:MGI.
DR InterPro; IPR042288; LRAT.
DR InterPro; IPR007053; LRAT_dom.
DR PANTHER; PTHR46678; PTHR46678; 1.
DR Pfam; PF04970; LRAT; 1.
DR PROSITE; PS51934; LRAT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Cytoplasm; Endoplasmic reticulum; Endosome;
KW Lipid metabolism; Membrane; Reference proteome; Sensory transduction;
KW Transferase; Transmembrane; Transmembrane helix; Vision.
FT CHAIN 1..231
FT /note="Lecithin retinol acyltransferase"
FT /id="PRO_0000152479"
FT TOPO_DOM 1..194
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:17114808"
FT TRANSMEM 195..215
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 216..231
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:17114808"
FT DOMAIN 50..177
FT /note="LRAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01283"
FT ACT_SITE 60
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01283"
FT ACT_SITE 72
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01283"
FT ACT_SITE 161
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01283,
FT ECO:0000269|PubMed:20628054"
FT MUTAGEN 14
FT /note="E->L: Increases degradation via the proteasomal
FT pathway. No effect on endoplasmic reticulum location.
FT Impairs vitamin A uptake. No effect on retinol
FT acyltransferase activity."
FT /evidence="ECO:0000269|PubMed:28758396"
FT STRAND 76..83
FT /evidence="ECO:0007829|PDB:4Q95"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:4Q95"
FT STRAND 98..106
FT /evidence="ECO:0007829|PDB:4Q95"
SQ SEQUENCE 231 AA; 25820 MW; A1AE72330ED972BC CRC64;
MKNPMLEAAS LLLEKLLLIS NFKLFSVSVP GGGTGKNRPY EISSFVRGDV LEVSRTHFIH
YGIYLGENRV AHLMPDILLA LTNDKERTQK VVSNKRLLLG VICKVASIRV DTVEDFAYGA
DILVNHLDGT LKKKSLLNEE VARRAEQQLG LTPYSLLWNN CEHFVTYCRY GSRISPQAEK
FYDTVKIIIR DQRSSLASAV LGLASIVYTG LASYMTLPAI CIPFCLWMMS G
