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HMDB Protein ID HMDBP00069
Secondary Accession Numbers
  • 5298
Name Phosphatidylcholine-sterol acyltransferase
  1. Lecithin-cholesterol acyltransferase
  2. Phospholipid-cholesterol acyltransferase
Gene Name LCAT
Protein Type Enzyme
Biological Properties
General Function Involved in phosphatidylcholine-sterol O-acyltransferase activity
Specific 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. Has a preference for plasma 16:0-18:2 or 18:O-18:2 phosphatidylcholines. 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.
  • Glycerophospholipid metabolism
Phosphatidylcholine + a sterol → 1-acylglycerophosphocholine + a sterol ester details
Phosphatidylcholine + Sterol → 1-Acyl-sn-glycero-3-phosphocholine + Steryl ester details
GO Classification
Biological Process
cholesterol esterification
high-density lipoprotein particle remodeling
lipoprotein biosynthetic process
lipoprotein metabolic process
regulation of high-density lipoprotein particle assembly
reverse cholesterol transport
very-low-density lipoprotein particle remodeling
phosphatidylcholine biosynthetic process
cholesterol metabolic process
response to glucocorticoid stimulus
cholesterol homeostasis
response to copper ion
Cellular Component
high-density lipoprotein particle
catalytic activity
transferase activity
transferase activity, transferring acyl groups
transferase activity, transferring acyl groups other than amino-acyl groups
acyltransferase activity
o-acyltransferase activity
phosphatidylcholine-sterol o-acyltransferase activity
Molecular Function
phospholipase A2 activity
phosphatidylcholine-sterol O-acyltransferase activity
metabolic process
primary metabolic process
lipid metabolic process
Cellular Location
  1. Secreted
Gene Properties
Chromosome Location 16
Locus 16q22.1
Gene Sequence
>1323 bp
Protein Properties
Number of Residues 440
Molecular Weight 49577.545
Theoretical pI 6.11
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Phosphatidylcholine-sterol acyltransferase
GenBank ID Protein 15928623
UniProtKB/Swiss-Prot ID P04180
UniProtKB/Swiss-Prot Entry Name LCAT_HUMAN
PDB IDs Not Available
GenBank Gene ID BC014781
GeneCard ID LCAT
GenAtlas ID LCAT
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. McLean J, Fielding C, Drayna D, Dieplinger H, Baer B, Kohr W, Henzel W, Lawn R: Cloning and expression of human lecithin-cholesterol acyltransferase cDNA. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2335-9. [PubMed:3458198 ]
  3. McLean J, Wion K, Drayna D, Fielding C, Lawn R: Human lecithin-cholesterol acyltransferase gene: complete gene sequence and sites of expression. Nucleic Acids Res. 1986 Dec 9;14(23):9397-406. [PubMed:3797244 ]
  4. Tata F, Chaves ME, Markham AF, Scrace GD, Waterfield MD, McIntyre N, Williamson R, Humphries SE: The isolation and characterisation of cDNA and genomic clones for human lecithin: cholesterol acyltransferase. Biochim Biophys Acta. 1987 Nov 20;910(2):142-8. [PubMed:2823898 ]
  5. Rogne S, Skretting G, Larsen F, Myklebost O, Mevag B, Carlson LA, Holmquist L, Gjone E, Prydz H: The isolation and characterisation of a cDNA clone for human lecithin:cholesterol acyl transferase and its use to analyse the genes in patients with LCAT deficiency and fish eye disease. Biochem Biophys Res Commun. 1987 Oct 14;148(1):161-9. [PubMed:2823801 ]
  6. Yang CY, Manoogian D, Pao Q, Lee FS, Knapp RD, Gotto AM Jr, Pownall HJ: Lecithin:cholesterol acyltransferase. Functional regions and a structural model of the enzyme. J Biol Chem. 1987 Mar 5;262(7):3086-91. [PubMed:2880847 ]
  7. Schindler PA, Settineri CA, Collet X, Fielding CJ, Burlingame AL: Site-specific detection and structural characterization of the glycosylation of human plasma proteins lecithin:cholesterol acyltransferase and apolipoprotein D using HPLC/electrospray mass spectrometry and sequential glycosidase digestion. Protein Sci. 1995 Apr;4(4):791-803. [PubMed:7613477 ]
  8. Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, Smith RD: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res. 2005 Nov-Dec;4(6):2070-80. [PubMed:16335952 ]
  9. Skretting G, Prydz H: An amino acid exchange in exon I of the human lecithin: cholesterol acyltransferase (LCAT) gene is associated with fish eye disease. Biochem Biophys Res Commun. 1992 Jan 31;182(2):583-7. [PubMed:1571050 ]
  10. Klein HG, Lohse P, Pritchard PH, Bojanovski D, Schmidt H, Brewer HB Jr: Two different allelic mutations in the lecithin-cholesterol acyltransferase gene associated with the fish eye syndrome. Lecithin-cholesterol acyltransferase (Thr123----Ile) and lecithin-cholesterol acyltransferase (Thr347----Met). J Clin Invest. 1992 Feb;89(2):499-506. [PubMed:1737840 ]
  11. Taramelli R, Pontoglio M, Candiani G, Ottolenghi S, Dieplinger H, Catapano A, Albers J, Vergani C, McLean J: Lecithin cholesterol acyl transferase deficiency: molecular analysis of a mutated allele. Hum Genet. 1990 Jul;85(2):195-9. [PubMed:2370048 ]
  12. Gotoda T, Yamada N, Murase T, Sakuma M, Murayama N, Shimano H, Kozaki K, Albers JJ, Yazaki Y, Akanuma Y: Differential phenotypic expression by three mutant alleles in familial lecithin:cholesterol acyltransferase deficiency. Lancet. 1991 Sep 28;338(8770):778-81. [PubMed:1681161 ]
  13. Skretting G, Blomhoff JP, Solheim J, Prydz H: The genetic defect of the original Norwegian lecithin:cholesterol acyltransferase deficiency families. FEBS Lett. 1992 Sep 14;309(3):307-10. [PubMed:1516702 ]
  14. Maeda E, Naka Y, Matozaki T, Sakuma M, Akanuma Y, Yoshino G, Kasuga M: Lecithin-cholesterol acyltransferase (LCAT) deficiency with a missense mutation in exon 6 of the LCAT gene. Biochem Biophys Res Commun. 1991 Jul 31;178(2):460-6. [PubMed:1859405 ]
  15. Funke H, von Eckardstein A, Pritchard PH, Hornby AE, Wiebusch H, Motti C, Hayden MR, Dachet C, Jacotot B, Gerdes U, et al.: Genetic and phenotypic heterogeneity in familial lecithin: cholesterol acyltransferase (LCAT) deficiency. Six newly identified defective alleles further contribute to the structural heterogeneity in this disease. J Clin Invest. 1993 Feb;91(2):677-83. [PubMed:8432868 ]
  16. Hill JS, O K, Wang X, Pritchard PH: Lecithin:cholesterol acyltransferase deficiency: identification of a causative gene mutation and a co-inherited protein polymorphism. Biochim Biophys Acta. 1993 Jun 19;1181(3):321-3. [PubMed:8318557 ]
  17. Steyrer E, Haubenwallner S, Horl G, Giessauf W, Kostner GM, Zechner R: A single G to A nucleotide transition in exon IV of the lecithin: cholesterol acyltransferase (LCAT) gene results in an Arg140 to His substitution and causes LCAT-deficiency. Hum Genet. 1995 Jul;96(1):105-9. [PubMed:7607641 ]
  18. Wiebusch H, Cullen P, Owen JS, Collins D, Sharp PS, Funke H, Assmann G: Deficiency of lecithin:cholesterol acyltransferase due to compound heterozygosity of two novel mutations (Gly33Arg and 30 bp ins) in the LCAT gene. Hum Mol Genet. 1995 Jan;4(1):143-5. [PubMed:7711728 ]
  19. Kuivenhoven JA, Stalenhoef AF, Hill JS, Demacker PN, Errami A, Kastelein JJ, Pritchard PH: Two novel molecular defects in the LCAT gene are associated with fish eye disease. Arterioscler Thromb Vasc Biol. 1996 Feb;16(2):294-303. [PubMed:8620346 ]
  20. Owen JS, Wiebusch H, Cullen P, Watts GF, Lima VL, Funke H, Assmann G: Complete deficiency of plasma lecithin-cholesterol acyltransferase (LCAT) activity due to a novel homozygous mutation (Gly-30-Ser) in the LCAT gene. Hum Mutat. 1996;8(1):79-82. [PubMed:8807342 ]
  21. Okubo M, Aoyama Y, Shio H, Albers JJ, Murase T: A novel missense mutation (Asn5-->Ile) in lecithin: cholesterol acyltransferase (LCAT) gene in a Japanese patient with LCAT deficiency. Int J Clin Lab Res. 1996;26(4):250-4. [PubMed:9007616 ]
  22. Blanco-Vaca F, Qu SJ, Fiol C, Fan HZ, Pao Q, Marzal-Casacuberta A, Albers JJ, Hurtado I, Gracia V, Pinto X, Marti T, Pownall HJ: Molecular basis of fish-eye disease in a patient from Spain. Characterization of a novel mutation in the LCAT gene and lipid analysis of the cornea. Arterioscler Thromb Vasc Biol. 1997 Jul;17(7):1382-91. [PubMed:9261271 ]
  23. Argyropoulos G, Jenkins A, Klein RL, Lyons T, Wagenhorst B, St Armand J, Marcovina SM, Albers JJ, Pritchard PH, Garvey WT: Transmission of two novel mutations in a pedigree with familial lecithin:cholesterol acyltransferase deficiency: structure-function relationships and studies in a compound heterozygous proband. J Lipid Res. 1998 Sep;39(9):1870-6. [PubMed:9741700 ]
  24. Sessa A, Battini G, Meroni M, Daidone G, Carnera I, Brambilla PL, Vigano G, Giordano F, Pallotti F, Torri Tarelli L, Calabresi L, Rolleri M, Bertolini S: Hypocomplementemic type II membranoproliferative glomerulonephritis in a male patient with familial lecithin-cholesterol acyltransferase deficiency due to two different allelic mutations. Nephron. 2001 Jul;88(3):268-72. [PubMed:11423760 ]
  25. Nanjee MN, Stocks J, Cooke CJ, Molhuizen HO, Marcovina S, Crook D, Kastelein JP, Miller NE: A novel LCAT mutation (Phe382-->Val) in a kindred with familial LCAT deficiency and defective apolipoprotein B-100. Atherosclerosis. 2003 Sep;170(1):105-13. [PubMed:12957688 ]
  26. Morabia A, Cayanis E, Costanza MC, Ross BM, Flaherty MS, Alvin GB, Das K, Gilliam TC: Association of extreme blood lipid profile phenotypic variation with 11 reverse cholesterol transport genes and 10 non-genetic cardiovascular disease risk factors. Hum Mol Genet. 2003 Nov 1;12(21):2733-43. Epub 2003 Sep 9. [PubMed:12966036 ]
  27. Calabresi L, Pisciotta L, Costantin A, Frigerio I, Eberini I, Alessandrini P, Arca M, Bon GB, Boscutti G, Busnach G, Frasca G, Gesualdo L, Gigante M, Lupattelli G, Montali A, Pizzolitto S, Rabbone I, Rolleri M, Ruotolo G, Sampietro T, Sessa A, Vaudo G, Cantafora A, Veglia F, Calandra S, Bertolini S, Franceschini G: The molecular basis of lecithin:cholesterol acyltransferase deficiency syndromes: a comprehensive study of molecular and biochemical findings in 13 unrelated Italian families. Arterioscler Thromb Vasc Biol. 2005 Sep;25(9):1972-8. Epub 2005 Jun 30. [PubMed:15994445 ]
  28. Idzior-Walus B, Sieradzki J, Kostner G, Malecki MT, Klupa T, Wesolowska T, Rostworowski W, Hartwich J, Walus M, Kiec AD, Naruszewicz M: Familial lecithin-cholesterol acyltransferase deficiency: biochemical characteristics and molecular analysis of a new LCAT mutation in a Polish family. Atherosclerosis. 2006 Apr;185(2):413-20. Epub 2005 Jul 26. [PubMed:16051254 ]
  29. Horl G, Kroisel PM, Wagner E, Tiran B, Petek E, Steyrer E: Compound heterozygosity (G71R/R140H) in the lecithin:cholesterol acyltransferase (LCAT) gene results in an intermediate phenotype between LCAT-deficiency and fish-eye disease. Atherosclerosis. 2006 Jul;187(1):101-9. Epub 2005 Oct 10. [PubMed:16216249 ]
  30. Gigante M, Ranieri E, Cerullo G, Calabresi L, Iolascon A, Assmann G, Morrone L, Pisciotta L, Schena FP, Gesualdo L: LCAT deficiency: molecular and phenotypic characterization of an Italian family. J Nephrol. 2006 May-Jun;19(3):375-81. [PubMed:16874701 ]