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P16301 (LCAT_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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:
Phosphatidylcholine-sterol acyltransferase

EC=2.3.1.43
Alternative name(s):
Lecithin-cholesterol acyltransferase
Phospholipid-cholesterol acyltransferase
Gene names
Name:Lcat
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length438 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Central enzyme in the extracellular metabolism of plasma lipoproteins. Synthesized mainly in the liver and secreted into plasma where it converts cholesterol and phosphatidylcholines (lecithins) to cholesteryl esters and lysophosphatidylcholines on the surface of high and low density lipoproteins (HDLs and LDLs). The cholesterol ester is then transported back to the liver. Also produced in the brain by primary astrocytes, and esterifies free cholesterol on nascent APOE-containing lipoproteins secreted from glia and influences cerebral spinal fluid (CSF) APOE- and APOA1 levels. Together with APOE and the cholesterol transporter ABCA1, plays a key role in the maturation of glial-derived, nascent lipoproteins. Required for remodeling high-density lipoprotein particles into their spherical forms By similarity. Has a preference for plasma 16:0-18:2 or 18:O-18:2 phosphatidylcholines. Ref.7 Ref.8 Ref.9 Ref.11

Catalytic activity

Phosphatidylcholine + a sterol = 1-acylglycerophosphocholine + a sterol ester.

Enzyme regulation

APOA1 is the most potent activator in plasma. Also activated by APOE, APOC1 and APOA4. Ref.9 Ref.11

Subcellular location

Secreted. Note: Secreted into blood plasma. Produced in astrocytes and secreted into cerebral spinal fluid (CSF) By similarity.

Tissue specificity

Abundantly expressed in liver, brain and testis with highest levels in liver. In the brain, found in cerebellum, cerebral cortex, hippocampus and brain stem. Located to neurons and neuroglia. Ref.1 Ref.11

Developmental stage

In the testis, expressed days 4,8, 14, and 35 of postnatal life with highest levels at day 35. In the brain, expressed in fetal stages and levels begin to rise after day 4 after birth and continue to increase through suckling and weaning reaching a peak at postnatal day 24. In the liver, expressed in fetal life from day 16-21 of gestation with a 3-fold increase in the four final days of gestation. Ref.1

Disruption phenotype

Null mice exhibit a 7-fold increase in the cholesteryl ester fatty acid CEFA ratio of APOB lipoprotein CEs. There is also a 3.6 increase in vascular ring O2 production and plasma phospholipid (PL)-bound-F2-isoprostane levels. This effect is paradoxically reversed in the APOE knockout background. Ref.7 Ref.8 Ref.11

Sequence similarities

Belongs to the AB hydrolase superfamily. Lipase family.

Ontologies

Keywords
   Biological processCholesterol metabolism
Lipid metabolism
Steroid metabolism
Sterol metabolism
   Cellular componentSecreted
   DomainSignal
   Molecular functionAcyltransferase
Transferase
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcholesterol esterification

Inferred from electronic annotation. Source: Ensembl

cholesterol homeostasis

Inferred from electronic annotation. Source: Ensembl

cholesterol metabolic process

Inferred from direct assay PubMed 9300780. Source: MGI

cholesterol transport

Inferred from sequence orthology PubMed 10559507. Source: MGI

high-density lipoprotein particle remodeling

Inferred from electronic annotation. Source: Ensembl

lipoprotein biosynthetic process

Inferred from direct assay PubMed 16245952. Source: MGI

phosphatidylcholine biosynthetic process

Inferred from electronic annotation. Source: Ensembl

regulation of high-density lipoprotein particle assembly

Inferred from direct assay Ref.11. Source: UniProtKB

reverse cholesterol transport

Inferred from electronic annotation. Source: Ensembl

very-low-density lipoprotein particle remodeling

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentextracellular space

Inferred from direct assay PubMed 10549415. Source: MGI

high-density lipoprotein particle

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionphosphatidylcholine-sterol O-acyltransferase activity

Inferred from direct assay PubMed 10549415PubMed 16245952PubMed 9300780. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424
Chain25 – 438414Phosphatidylcholine-sterol acyltransferase
PRO_0000017804

Regions

Compositional bias425 – 43713Pro-rich

Sites

Active site2051Charge relay system By similarity
Site1731Determinant for substrate specificity

Amino acid modifications

Glycosylation441N-linked (GlcNAc...) Potential
Glycosylation1081N-linked (GlcNAc...) Potential
Glycosylation2961N-linked (GlcNAc...) Potential
Glycosylation3971N-linked (GlcNAc...) Ref.10
Glycosylation4081N-linked (GlcNAc...) Ref.10
Disulfide bond74 ↔ 98 By similarity
Disulfide bond337 ↔ 380 By similarity

Experimental info

Sequence conflict4111L → M in AAA39419. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P16301 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 2FDD571853523136

FASTA43849,747
        10         20         30         40         50         60 
MGLPGSPWQR VLLLLGLLLP PATPFWLLNV LFPPHTTPKA ELSNHTRPVI LVPGCLGNRL 

        70         80         90        100        110        120 
EAKLDKPDVV NWMCYRKTED FFTIWLDFNL FLPLGVDCWI DNTRIVYNHS SGRVSNAPGV 

       130        140        150        160        170        180 
QIRVPGFGKT ESVEYVDDNK LAGYLHTLVQ NLVNNGYVRD ETVRAAPYDW RLAPHQQDEY 

       190        200        210        220        230        240 
YKKLAGLVEE MYAAYGKPVF LIGHSLGCLH VLHFLLRQPQ SWKDHFIDGF ISLGAPWGGS 

       250        260        270        280        290        300 
IKAMRILASG DNQGIPILSN IKLKEEQRIT TTSPWMLPAP HVWPEDHVFI STPNFNYTVQ 

       310        320        330        340        350        360 
DFERFFTDLH FEEGWHMFLQ SRDLLERLPA PGVEVYCLYG VGRPTPHTYI YDHNFPYKDP 

       370        380        390        400        410        420 
VAALYEDGDD TVATRSTELC GQWQGRQSQP VHLLPMNETD HLNMVFSNKT LEHINAILLG 

       430 
AYRTPKSPAA SPSPPPPE 

« Hide

References

« Hide 'large scale' references
[1]"Tissue-specific expression, developmental regulation, and chromosomal mapping of the lecithin: cholesterol acyltransferase gene. Evidence for expression in brain and testes as well as liver."
Warden C.H., Langner C.A., Gordon J.I., Taylor B.A., McLean J.W., Lusis A.J.
J. Biol. Chem. 264:21573-21581(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Liver.
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[4]"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].
Strain: FVB/N.
Tissue: Liver.
[5]"Promoter and 5' flanking sequences of the mouse LCAT gene."
Meroni G., Malgaretti N., Magnaghi P., Taramelli R.
Submitted (MAY-1992) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-14.
[6]"Comparative studies on the substrate specificity of lecithin:cholesterol acyltransferase towards the molecular species of phosphatidylcholine in the plasma of 14 vertebrates."
Subbaiah P.V., Liu M.
J. Lipid Res. 37:113-122(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBSTRATE SPECIFICITY.
[7]"Oxidative stress is markedly elevated in lecithin:cholesterol acyltransferase-deficient mice and is paradoxically reversed in the apolipoprotein E knockout background in association with a reduction in atherosclerosis."
Ng D.S., Maguire G.F., Wylie J., Ravandi A., Xuan W., Ahmed Z., Eskandarian M., Kuksis A., Connelly P.W.
J. Biol. Chem. 277:11715-11720(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[8]"In vivo contribution of LCAT to apolipoprotein B lipoprotein cholesteryl esters in LDL receptor and apolipoprotein E knockout mice."
Furbee J.W. Jr., Francone O., Parks J.S.
J. Lipid Res. 43:428-437(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[9]"Apolipoprotein E is the major physiological activator of lecithin-cholesterol acyltransferase (LCAT) on apolipoprotein B lipoproteins."
Zhao Y., Thorngate F.E., Weisgraber K.H., Williams D.L., Parks J.S.
Biochemistry 44:1013-1025(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION.
[10]"Proteome-wide characterization of N-glycosylation events by diagonal chromatography."
Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.
J. Proteome Res. 5:2438-2447(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-397 AND ASN-408.
Strain: C57BL/6.
Tissue: Plasma.
[11]"LCAT synthesized by primary astrocytes esterifies cholesterol on glia-derived lipoproteins."
Hirsch-Reinshagen V., Donkin J., Stukas S., Chan J., Wilkinson A., Fan J., Parks J.S., Kuivenhoven J.A., Lutjohann D., Pritchard H., Wellington C.L.
J. Lipid Res. 50:885-893(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, ENZYME REGULATION, FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J05154 mRNA. Translation: AAA39419.1.
AK149476 mRNA. Translation: BAE28903.1.
AC159265 Genomic DNA. No translation available.
BC028861 mRNA. Translation: AAH28861.1.
X54095 Genomic DNA. Translation: CAA38029.1.
CCDSCCDS22622.1.
PIRXXMSN. A34158.
RefSeqNP_032516.2. NM_008490.2.
UniGeneMm.1593.

3D structure databases

ProteinModelPortalP16301.
SMRP16301. Positions 196-239.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10090.ENSMUSP00000038232.

PTM databases

PhosphoSiteP16301.

Proteomic databases

PaxDbP16301.
PRIDEP16301.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000038896; ENSMUSP00000038232; ENSMUSG00000035237.
GeneID16816.
KEGGmmu:16816.
UCSCuc009neq.2. mouse.

Organism-specific databases

CTD3931.
MGIMGI:96755. Lcat.

Phylogenomic databases

eggNOGNOG322613.
GeneTreeENSGT00390000004902.
HOVERGENHBG017055.
InParanoidQ8K139.
KOK00650.
OMALRQPQSW.
OrthoDBEOG73BVD0.
TreeFamTF313258.

Gene expression databases

BgeeP16301.
CleanExMM_LCAT.
GenevestigatorP16301.

Family and domain databases

Gene3D3.40.50.1820. 3 hits.
InterProIPR029058. AB_hydrolase.
IPR003386. LACT/PDAT_acylTrfase.
[Graphical view]
PfamPF02450. LCAT. 1 hit.
[Graphical view]
SUPFAMSSF53474. SSF53474. 2 hits.
PROSITEPS00120. LIPASE_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio290700.
PROP16301.
SOURCESearch...

Entry information

Entry nameLCAT_MOUSE
AccessionPrimary (citable) accession number: P16301
Secondary accession number(s): Q8K139
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 112 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot