O95237 (LRAT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Lecithin retinol acyltransferase
EC=2.3.1.135

Alternative name(s):
Phosphatidylcholine--retinol O-acyltransferase

Gene names

Name:

LRAT

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	230 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Endosome › multivesicular body By similarity. Cytoplasm › perinuclear 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 process	Sensory transduction Vision
Cellular component	Cytoplasm Endoplasmic reticulum Endosome Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Leber congenital amaurosis
Domain	Transmembrane Transmembrane helix
Molecular function	Acyltransferase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	embryo development Inferred from electronic annotation. Source: Compara response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW retinoic acid metabolic process Inferred from electronic annotation. Source: Compara retinoid metabolic process Traceable author statement. Source: Reactome retinol metabolic process Inferred from electronic annotation. Source: UniProtKB-UniPathway small molecule metabolic process Traceable author statement. Source: Reactome steroid metabolic process Traceable author statement. Source: Reactome visual perception Inferred from electronic annotation. Source: UniProtKB-KW vitamin A metabolic process Inferred from electronic annotation. Source: Compara
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to 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_function	phosphatidylcholine-retinol O-acyltransferase activity Inferred from electronic annotation. Source: EC retinoic acid binding Inferred from electronic annotation. Source: Compara retinol binding Inferred from electronic annotation. Source: Compara transferase activity, transferring acyl groups Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 230	230	Lecithin retinol acyltransferase		PRO_0000152478
Regions
	Topological domain	1 – 194	194	Cytoplasmic By similarity
	Transmembrane	195 – 215	21	Helical; Potential
	Topological domain	216 – 230	15	Lumenal By similarity
Sites
	Active site	161	1	Acyl-thioester intermediate By similarity
Natural variations
	Natural variant	173	1	P → L. Ref.10		VAR_063559
	Natural variant	175	1	S → R in LCA14; loss of function. Ref.9		VAR_018386
Experimental info
	Mutagenesis	161	1	C → A or S: Loss of activity. Ref.6
	Mutagenesis	168	1	C → A: Loss of activity. Ref.6
	Mutagenesis	168	1	C → S: Does not affect activity. Ref.6
	Mutagenesis	182	1	C → A: Does not affect activity. Ref.6
	Mutagenesis	208	1	C → A: Does not affect activity. Ref.6
	Sequence conflict	32	1	E → K in AAD13529. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O95237 [UniParc]. Last modified April 26, 2004. Version 2. Checksum: DCB7F5A1C3FF7689	FASTA	230	25,703
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00006231.
RefSeq	NP_004735.2. NM_004744.3.
UniGene	Hs.658427.
3D structure databases
ProteinModelPortal	O95237.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000337224.
PTM databases
PhosphoSite	O95237.
Proteomic databases
PaxDb	O95237.
PRIDE	O95237.
Protocols and materials databases
DNASU	9227.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000336356; ENSP00000337224; ENSG00000121207. ENST00000507827; ENSP00000426761; ENSG00000121207.
GeneID	9227.
KEGG	hsa:9227.
UCSC	uc003iom.1. human.
Organism-specific databases
CTD	9227.
GeneCards	GC04P155549.
HGNC	HGNC:6685. LRAT.
HPA	HPA008397.
MIM	604863. gene. 613341. phenotype.
neXtProt	NX_O95237.
Orphanet	65. Leber congenital amaurosis. 791. Retinitis pigmentosa.
PharmGKB	PA30443.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG40588.
HOGENOM	HOG000013187.
HOVERGEN	HBG047861.
InParanoid	O95237.
KO	K00678.
OMA	IPFCLWM.
OrthoDB	EOG49S67G.
PhylomeDB	O95237.
Enzyme and pathway databases
BioCyc	MetaCyc:HS04474-MONOMER.
BRENDA	2.3.1.135. 2681.
Pathway_Interaction_DB	cone_pathway. Visual signal transduction: Cones. rhodopsin_pathway. Visual signal transduction: Rods.
Reactome	REACT_111217. Metabolism.
UniPathway	UPA00912.
Gene expression databases
ArrayExpress	O95237.
Bgee	O95237.
CleanEx	HS_LRAT.
Genevestigator	O95237.
GermOnline	ENSG00000121207. Homo sapiens.
Family and domain databases
InterPro	IPR007053. LRAT-like_dom. [Graphical view]
Pfam	PF04970. LRAT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	O95237.
ChEMBL	CHEMBL2202.
ChiTaRS	LRAT. human.
DrugBank	DB00162. Vitamin A.
GenomeRNAi	9227.
NextBio	34583.
SOURCE	Search...

Entry information

Entry name

LRAT_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 102 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.