P16301 (LCAT_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phosphatidylcholine-sterol acyltransferase
EC=2.3.1.43

Alternative name(s):
Lecithin-cholesterol acyltransferase
Phospholipid-cholesterol acyltransferase

Gene names

Name:

Lcat

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	438 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Cholesterol metabolism Lipid metabolism Steroid metabolism Sterol metabolism
Cellular component	Secreted
Domain	Signal
Molecular function	Acyltransferase Transferase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cholesterol esterification Inferred from electronic annotation. Source: Compara cholesterol homeostasis Inferred from electronic annotation. Source: Compara 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: Compara lipoprotein biosynthetic process Inferred from direct assay PubMed 16245952. Source: MGI phosphatidylcholine biosynthetic process Inferred from electronic annotation. Source: Compara regulation of high-density lipoprotein particle assembly Inferred from direct assay Ref.11. Source: UniProtKB reverse cholesterol transport Inferred from electronic annotation. Source: Compara very-low-density lipoprotein particle remodeling Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular space Inferred from direct assay PubMed 10549415. Source: MGI high-density lipoprotein particle Inferred from electronic annotation. Source: Compara
Molecular_function	phosphatidylcholine-sterol O-acyltransferase activity Inferred from direct assay PubMed 10549415PubMed 16245952PubMed 9300780. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24
	Chain	25 – 438	414	Phosphatidylcholine-sterol acyltransferase		PRO_0000017804
Regions
	Compositional bias	425 – 437	13	Pro-rich
Sites
	Active site	205	1	Charge relay system By similarity
	Site	173	1	Determinant for substrate specificity
Amino acid modifications
	Glycosylation	44	1	N-linked (GlcNAc...) Potential
	Glycosylation	108	1	N-linked (GlcNAc...) Potential
	Glycosylation	296	1	N-linked (GlcNAc...) Potential
	Glycosylation	397	1	N-linked (GlcNAc...) Ref.10
	Glycosylation	408	1	N-linked (GlcNAc...) Ref.10
	Disulfide bond	74 ↔ 98		By similarity
	Disulfide bond	337 ↔ 380		By similarity
Experimental info
	Sequence conflict	411	1	L → M in AAA39419. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P16301 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 2FDD571853523136	FASTA	438	49,747
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY. 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.
IPI	IPI00133500.
PIR	XXMSN. A34158.
RefSeq	NP_032516.2. NM_008490.2.
UniGene	Mm.1593.
3D structure databases
ProteinModelPortal	P16301.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000038232.
PTM databases
PhosphoSite	P16301.
Proteomic databases
PaxDb	P16301.
PRIDE	P16301.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000038896; ENSMUSP00000038232; ENSMUSG00000035237.
GeneID	16816.
KEGG	mmu:16816.
Organism-specific databases
CTD	3931.
MGI	MGI:96755. Lcat.
Phylogenomic databases
eggNOG	NOG322613.
GeneTree	ENSGT00390000004902.
HOVERGEN	HBG017055.
InParanoid	Q8K139.
KO	K00650.
OMA	DWRLEPS.
OrthoDB	EOG479F77.
Gene expression databases
Bgee	P16301.
CleanEx	MM_LCAT.
Genevestigator	P16301.
GermOnline	ENSMUSG00000035237. Mus musculus.
Family and domain databases
InterPro	IPR003386. LACT/PDAT_acylTrfase. [Graphical view]
PANTHER	PTHR11440. PTHR11440. 1 hit.
Pfam	PF02450. LACT. 1 hit. [Graphical view]
PROSITE	PS00120. LIPASE_SER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	290700.
SOURCE	Search...

Entry information

Entry name

LCAT_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 101 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program