P04180 (LCAT_HUMAN) 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

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	440 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. 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. Ref.15
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.19
Subcellular location	Secreted. Note: Secreted into blood plasma. Produced in astrocytes and secreted into cerebral spinal fluid (CSF). Ref.19
Tissue specificity	Expressed mainly in brain, liver and testes. Secreted into plasma and cerebral spinal fluid. Expressed in Hep-G2 cell line. Ref.1 Ref.13
Post-translational modification	O- and N-glycosylated. O-glycosylation on Thr-431 and Ser-433 consists of sialylated galactose beta 1-->3N-acetylgalactosamine structures. N-glycosylated sites contain sialylated triantennary and/or biantennary complex structures. Ref.11
Involvement in disease	Lecithin-cholesterol acyltransferase deficiency (LCATD) [MIM:245900]: A disorder of lipoprotein metabolism characterized by inadequate esterification of plasmatic cholesterol. Two clinical forms are recognized: complete LCAT deficiency and fish-eye disease. LCATD is generally referred to the complete form which is associated with absence of both alpha and beta LCAT activities resulting in esterification anomalies involving both HDL (alpha-LCAT activity) and LDL (beta-LCAT activity). It causes a typical triad of diffuse corneal opacities, target cell hemolytic anemia, and proteinuria with renal failure. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.22 Ref.23 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.31 Ref.32 Ref.34 Ref.35 Ref.36 Ref.38 Ref.39 Ref.40 Fish-eye disease (FED) [MIM:136120]: A disorder of lipoprotein metabolism due to partial lecithin-cholesterol acyltransferase deficiency that affects only alpha-LCAT activity. FED is characterized by low plasma HDL and corneal opacities due to accumulation of cholesterol deposits in the cornea ('fish-eye'). Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.20 Ref.21 Ref.24 Ref.30 Ref.33 Ref.38 Ref.42
Miscellaneous	Levels of LCAT activity correlates inversely with leptin levels as well as with obesity for a wide range of BMI values.
Sequence similarities	Belongs to the AB hydrolase superfamily. Lipase family.
Biophysicochemical properties	Kinetic parameters: Affinity for LDL is 2.3 to 4-fold lower than for HDL. Relative reactivities are 16% for HDL3, 1.3% for HDL2 and 6.5% for LDL. KM=0.97 mM for LDL Ref.14 KM=0.4 mM for HDL2 KM=0.10 mM for HDL3 Vmax=8.3 mmol/min/mg enzyme with LDL as substrate Vmax=0.58 mmol/min/mg enzyme with HDL2 as substrate Vmax=2.0 mmol/min/mg enzyme with HDL3 as substrate

Ontologies

Keywords
Biological process	Cholesterol metabolism Lipid metabolism Steroid metabolism Sterol metabolism
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Corneal dystrophy Disease mutation
Domain	Signal
Molecular function	Acyltransferase Transferase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cholesterol esterification Inferred from direct assay Ref.2PubMed 4335615. Source: BHF-UCL cholesterol homeostasis Inferred from direct assay PubMed 4335615. Source: BHF-UCL cholesterol metabolic process Inferred from direct assay PubMed 4335615. Source: BHF-UCL high-density lipoprotein particle remodeling Inferred from direct assay Ref.15. Source: UniProtKB lipoprotein biosynthetic process Inferred from electronic annotation. Source: Compara lipoprotein metabolic process Traceable author statement. Source: Reactome phosphatidylcholine biosynthetic process Inferred from direct assay PubMed 11966470. Source: BHF-UCL regulation of high-density lipoprotein particle assembly Inferred from electronic annotation. Source: Compara reverse cholesterol transport Inferred from direct assay PubMed 4335615. Source: BHF-UCL very-low-density lipoprotein particle remodeling Inferred from direct assay PubMed 15654758. Source: BHF-UCL
Cellular_component	high-density lipoprotein particle Inferred from direct assay PubMed 3104518. Source: BHF-UCL
Molecular_function	phosphatidylcholine-sterol O-acyltransferase activity Non-traceable author statement PubMed 11966470. Source: UniProtKB
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 – 440	416	Phosphatidylcholine-sterol acyltransferase		PRO_0000017802
Regions
	Compositional bias	426 – 439	14	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...) (Complex) Ref.11 Ref.17
	Glycosylation	108	1	N-linked (GlcNAc...) (Complex) Ref.11
	Glycosylation	296	1	N-linked (GlcNAc...) (Complex) Ref.11 Ref.17
	Glycosylation	408	1	N-linked (GlcNAc...) (Complex) Ref.11
	Glycosylation	431	1	O-linked (GalNAc...) Ref.11
	Glycosylation	433	1	O-linked (GalNAc...) Ref.11
	Disulfide bond	74 ↔ 98		Ref.10
	Disulfide bond	337 ↔ 380		Ref.10
Natural variations
	Natural variant	17	1	L → LLLPPAAPFWL in LCATD.		VAR_004251
	Natural variant	29	1	N → I in LCATD. Ref.32		VAR_039020
	Natural variant	34	1	P → L in FED. Ref.20		VAR_004252
	Natural variant	34	1	P → Q in FED. Ref.30		VAR_039021
	Natural variant	37	1	T → M in LCATD. Ref.34		VAR_039022
	Natural variant	54	1	G → S in LCATD. Ref.31		VAR_004253
	Natural variant	57	1	G → R in LCATD. Ref.29		VAR_004254
	Natural variant	70	1	V → E in FED. Ref.38		VAR_039023
	Natural variant	95	1	G → R in a compound heterozygote carrying H-164; intermediate phenotype between LCATD and FED; reduction of activity. Ref.40		VAR_039024
	Natural variant	99	1	W → S in FED; loss of activity. Ref.42		VAR_066862
	Natural variant	115	1	S → P. Ref.38		VAR_039025
	Natural variant	117	1	A → T in LCATD. Ref.26 Ref.27 Corresponds to variant rs28940886 [ dbSNP | Ensembl ].		VAR_004255
	Natural variant	123	1	R → C in FED. Ref.33		VAR_039026
	Natural variant	134 – 135	2	EY → DN in a patient with low HDL-cholesterol levels; results in reduced activity.		VAR_066863
	Natural variant	147	1	T → I in FED. Ref.21		VAR_004256
	Natural variant	159	1	R → Q in FED. Ref.30		VAR_039027
	Natural variant	159	1	R → W in LCATD. Ref.26 Corresponds to variant rs28940887 [ dbSNP | Ensembl ].		VAR_004257
	Natural variant	164	1	R → C in LCATD. Ref.38		VAR_039028
	Natural variant	164	1	R → H in LCATD; also in a compound heterozygote carrying R-95 with intermediate phenotype between LCATD and FED; loss of activity. Ref.28 Ref.40		VAR_004258
	Natural variant	165	1	A → T. Ref.38		VAR_039029
	Natural variant	171	1	R → W in LCATD. Ref.22 Ref.38		VAR_004259
	Natural variant	180	1	Y → N in LCATD.		VAR_004260
	Natural variant	182	1	R → C. Ref.26 Ref.27		VAR_004261
	Natural variant	205	1	S → N in LCATD. Ref.38		VAR_039030
	Natural variant	232	1	S → T. Ref.36 Ref.37 Ref.41 Corresponds to variant rs4986970 [ dbSNP | Ensembl ].		VAR_017030
	Natural variant	233	1	L → P in LCATD. Ref.26 Corresponds to variant rs28942087 [ dbSNP | Ensembl ].		VAR_004262
	Natural variant	242	1	K → N in LCATD. Ref.38		VAR_039031
	Natural variant	246	1	V → F in a patient with low HDL-cholesterol levels; the mutant is hardly secreted and is catalytically inactive. Ref.42		VAR_066864
	Natural variant	252	1	N → K in LCATD. Ref.23		VAR_004263
	Natural variant	268	1	R → C in a patient with low HDL-cholesterol levels; the mutant is hardly secreted and is catalytically inactive. Ref.42		VAR_066865
	Natural variant	268	1	R → H in LCATD. Ref.38		VAR_039032
	Natural variant	276	1	M → K in FED. Ref.24		VAR_004264
	Natural variant	298	1	T → A in FED and LCATD. Ref.35 Ref.38		VAR_039033
	Natural variant	298	1	T → I in LCATD. Ref.38		VAR_039034
	Natural variant	317	1	M → I in LCATD; partially defective enzyme. Ref.23 Ref.25		VAR_004265
	Natural variant	322	1	R → C in a patient with low HDL-cholesterol levels; reduced protein secretion. Ref.42		VAR_066866
	Natural variant	331	1	P → S in LCATD. Ref.34		VAR_039035
	Natural variant	333	1	V → M in LCATD. Ref.38 Ref.39		VAR_039036
	Natural variant	338	1	L → F in FED; results in reduced protein secretion and activity. Ref.42		VAR_066867
	Natural variant	345	1	T → M in LCATD. Ref.26 Ref.36 Corresponds to variant rs28940888 [ dbSNP | Ensembl ].		VAR_004266
	Natural variant	347	1	R → C in FED; results in reduced activity. Ref.42		VAR_066868
	Natural variant	371	1	T → M in FED. Ref.21		VAR_004267
	Natural variant	396	1	L → R in a patient with LCATD. Ref.38 Ref.41		VAR_039037
	Natural variant	406	1	F → V in LCATD. Ref.36		VAR_039038
Experimental info
	Mutagenesis	173	1	E → A: Increased activity towards PAPC. Increased PAPC/POPC activity ratio. Ref.16
	Mutagenesis	173	1	E → D: Little change in enzyme specific activity nor in PAPC/POPC activity ratio. Ref.16
	Mutagenesis	173	1	E → K: Decreased enzyme specific activity. Increased PAPC/POPC activity ratio. Ref.16
	Mutagenesis	173	1	E → L: Increased activity towards PAPC. Increased PAPC/POPC activity ratio. Ref.16
	Mutagenesis	173	1	E → Q: Decreased enzyme specific activity. Increased PAPC/POPC activity ratio. Ref.16
	Sequence conflict	257	1	I → H in CAB56610. Ref.8
	Sequence conflict	257	1	I → H in AAA59499. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	P04180 [UniParc]. Last modified March 20, 1987. Version 1. Checksum: B315EF118AA7A378	FASTA	440	49,578
	10 20 30 40 50 60 MGPPGSPWQW VTLLLGLLLP PAAPFWLLNV LFPPHTTPKA ELSNHTRPVI LVPGCLGNQL 70 80 90 100 110 120 EAKLDKPDVV NWMCYRKTED FFTIWLDLNM FLPLGVDCWI DNTRVVYNRS SGLVSNAPGV 130 140 150 160 170 180 QIRVPGFGKT YSVEYLDSSK LAGYLHTLVQ NLVNNGYVRD ETVRAAPYDW RLEPGQQEEY 190 200 210 220 230 240 YRKLAGLVEE MHAAYGKPVF LIGHSLGCLH LLYFLLRQPQ AWKDRFIDGF ISLGAPWGGS 250 260 270 280 290 300 IKPMLVLASG DNQGIPIMSS IKLKEEQRIT TTSPWMFPSR MAWPEDHVFI STPSFNYTGR 310 320 330 340 350 360 DFQRFFADLH FEEGWYMWLQ SRDLLAGLPA PGVEVYCLYG VGLPTPRTYI YDHGFPYTDP 370 380 390 400 410 420 VGVLYEDGDD TVATRSTELC GLWQGRQPQP VHLLPLHGIQ HLNMVFSNLT LEHINAILLG 430 440 AYRQGPPASP TASPEPPPPE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human lecithin-cholesterol acyltransferase gene: complete gene sequence and sites of expression." McLean J., Wion K., Drayna D., Fielding C., Lawn R. Nucleic Acids Res. 14:9397-9406(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY.
[2]	"Cloning and expression of human lecithin-cholesterol acyltransferase cDNA." McLean J., Fielding C., Drayna D., Dieplinger H., Baer B., Kohr W., Henzel W., Lawn R. Proc. Natl. Acad. Sci. U.S.A. 83:2335-2339(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	Nickerson D.A., Smith J.D., Fullerton S.M., Clark A.G., Stengard J.H., Salomaa V., Boerwinkle E., Sing C.F., Weiss K.M. Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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: Brain.
[8]	"The isolation and characterisation of cDNA and genomic clones for human lecithin: cholesterol acyltransferase." Tata F., Chaves M.E., Markham A.F., Scrace G.D., Waterfield M.D., McIntyre N., Williamson R., Humphries S.E. Biochim. Biophys. Acta 910:142-148(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 17-440.
[9]	"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." Rogne S., Skretting G., Larsen F., Myklebost O., Mevag B., Carlson L.A., Holmquist L., Gjone E., Prydz H. Biochem. Biophys. Res. Commun. 148:161-169(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 13-440.
[10]	"Lecithin:cholesterol acyltransferase. Functional regions and a structural model of the enzyme." Yang C., Manoogian D., Pao Q., Lee F., Knapp R.D., Gotto A.M. Jr., Pownall H.J. J. Biol. Chem. 262:3086-3091(1987) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, DISULFIDE BONDS.
[11]	"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." Schindler P.A., Settineri C.A., Collet X., Fielding C.J., Burlingame A.L. Protein Sci. 4:791-803(1995) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-44; ASN-108; ASN-296; ASN-408; THR-431 AND SER-433, STRUCTURE OF CARBOHYDRATES, MASS SPECTROMETRY.
[12]	"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.
[13]	"Secretion of lecithin:cholesterol acyltransferase by brain neuroglial cell lines." Collet X., Francone O., Besnard F., Fielding C.J. Biochem. Biophys. Res. Commun. 258:73-76(1999) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[14]	"Binding affinity and reactivity of lecithin cholesterol acyltransferase with native lipoproteins." Kosek A.B., Durbin D., Jonas A. Biochem. Biophys. Res. Commun. 258:548-551(1999) [PubMed] [Europe PMC] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
[15]	"Formation of spherical, reconstituted high density lipoproteins containing both apolipoproteins A-I and A-II is mediated by lecithin:cholesterol acyltransferase." Clay M.A., Pyle D.H., Rye K.A., Barter P.J. J. Biol. Chem. 275:9019-9025(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN HIGH-DENSITY LIPOPROTEIN PARTICLE REMODELING.
[16]	"Negative charge at amino acid 149 is the molecular determinant for substrate specificity of lecithin: cholesterol acyltransferase for phosphatidylcholine containing 20-carbon sn-2 fatty acyl chains." Zhao Y., Wang J., Gebre A.K., Chisholm J.W., Parks J.S. Biochemistry 42:13941-13949(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBSTRATE SPECIFICITY, MUTAGENESIS OF GLU-173.
[17]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-44 AND ASN-296, MASS SPECTROMETRY. Tissue: Plasma.
[18]	"Relationship of endogenous hyperleptinemia to serum paraoxonase 1, cholesteryl ester transfer protein, and lecithin cholesterol acyltransferase in obese individuals." Bajnok L., Seres I., Varga Z., Jeges S., Peti A., Karanyi Z., Juhasz A., Csongradi E., Mezosi E., Nagy E.V., Paragh G. Metabolism 56:1542-1549(2007) [PubMed] [Europe PMC] [Abstract] Cited for: ASSOCIATION WITH OBESITY.
[19]	"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: ENZYME REGULATION, SUBCELLULAR LOCATION.
[20]	"An amino acid exchange in exon I of the human lecithin: cholesterol acyltransferase (LCAT) gene is associated with fish eye disease." Skretting G., Prydz H. Biochem. Biophys. Res. Commun. 182:583-587(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FED LEU-34.
[21]	"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)." Klein H.-G., Lohse P., Pritchard P.H., Bojanovski D., Schmidt H., Brewer H.B. Jr. J. Clin. Invest. 89:499-506(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS FED ILE-147 AND MET-371.
[22]	"Lecithin cholesterol acyl transferase deficiency: molecular analysis of a mutated allele." Taramelli R., Pontoglio M., Candiani G., Ottolenghi S., Dieplinger H., Catapano A., Albers J., Vergani C., McLean J. Hum. Genet. 85:195-199(1990) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LCATD TRP-171.
[23]	"Differential phenotypic expression by three mutant alleles in familial lecithin:cholesterol acyltransferase deficiency." Gotoda T., Yamada N., Murase T., Sakuma M., Murayama N., Shimano H., Kozaki K., Albers J.J., Yazaki Y., Akanuma Y. Lancet 338:778-781(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LCATD LYS-252 AND ILE-317.
[24]	"The genetic defect of the original Norwegian lecithin:cholesterol acyltransferase deficiency families." Skretting G., Blomhoff J.P., Solheim J., Prydz H. FEBS Lett. 309:307-310(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FED LYS-276.
[25]	"Lecithin-cholesterol acyltransferase (LCAT) deficiency with a missense mutation in exon 6 of the LCAT gene." Maeda E., Naka Y., Matozaki T., Sakuma M., Akanuma Y., Yoshino G., Kasuga M. Biochem. Biophys. Res. Commun. 178:460-466(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LCATD ILE-317.
[26]	"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." Funke H., von Eckardstein A., Pritchard P.H., Hornby A.E., Wiebusch H., Motti C., Hayden M.R., Dachet C., Jacotot B., Gerdes U., Faergeman O., Albers J.J., Colleoni N., Catapano A., Frohlich J., Assmann G. J. Clin. Invest. 91:677-683(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LCATD THR-117; TRP-159; PRO-233 AND MET-345, VARIANT CYS-182.
[27]	"Lecithin:cholesterol acyltransferase deficiency: identification of a causative gene mutation and a co-inherited protein polymorphism." Hill J.S., O K., Wang X., Pritchard P.H. Biochim. Biophys. Acta 1181:321-323(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LCATD THR-117, VARIANT CYS-182.
[28]	"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." Steyrer E., Haubenwallner S., Hoerl G., Giessauf W., Kostner G.M., Zechner R. Hum. Genet. 96:105-109(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LCATD HIS-164, CHARACTERIZATION OF VARIANT LCATD HIS-164.
[29]	"Deficiency of lecithin:cholesterol acyltransferase due to compound heterozygosity of two novel mutations (Gly33Arg and 30 bp ins) in the LCAT gene." Wiebusch H., Cullen P., Owen J.S., Collins D., Sharp P.S., Funke H., Assmann G. Hum. Mol. Genet. 4:143-145(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LCATD ARG-57 AND LEU-LEU-PRO-PRO-ALA-ALA-PRO-PHE-TRP-LEU-17 INS.
[30]	"Two novel molecular defects in the LCAT gene are associated with fish eye disease." Kuivenhoven J.A., Stalenhoef A.F., Hill J.S., Demacker P.N., Errami A., Kastelein J.J., Pritchard P.H. Arterioscler. Thromb. Vasc. Biol. 16:294-303(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS FED GLN-34 AND GLN-159.
[31]	"Complete deficiency of plasma lecithin-cholesterol acyltransferase (LCAT) activity due to a novel homozygous mutation (Gly-30-Ser) in the LCAT gene." Owen J.S., Wiebusch H., Cullen P., Watts G.F., Lima V.L.M., Funke H., Assmann G. Hum. Mutat. 8:79-82(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LCATD SER-54.
[32]	"A novel missense mutation (Asn5-->Ile) in lecithin: cholesterol acyltransferase (LCAT) gene in a Japanese patient with LCAT deficiency." Okubo M., Aoyama Y., Shio H., Albers J.J., Murase T. Int. J. Clin. Lab. Res. 26:250-254(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LCATD ILE-29.
[33]	"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." Blanco-Vaca F., Qu S.J., Fiol C., Fan H.Z., Pao Q., Marzal-Casacuberta A., Albers J.J., Hurtado I., Gracia V., Pinto X., Marti T., Pownall H.J. Arterioscler. Thromb. Vasc. Biol. 17:1382-1391(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FED CYS-123.
[34]	"Transmission of two novel mutations in a pedigree with familial lecithin:cholesterol acyltransferase deficiency: structure-function relationships and studies in a compound heterozygous proband." Argyropoulos G., Jenkins A., Klein R.L., Lyons T., Wagenhorst B., St Armand J., Marcovina S.M., Albers J.J., Pritchard P.H., Garvey W.T. J. Lipid Res. 39:1870-1876(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LCATD MET-37 AND SER-331.
[35]	"Hypocomplementemic type II membranoproliferative glomerulonephritis in a male patient with familial lecithin-cholesterol acyltransferase deficiency due to two different allelic mutations." Sessa A., Battini G., Meroni M., Daidone G., Carnera I., Brambilla P.L., Vigano G., Giordano F., Pallotti F., Torri Tarelli L., Calabresi L., Rolleri M., Bertolini S. Nephron 88:268-272(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LCATD ALA-298.
[36]	"A novel LCAT mutation (Phe382-->Val) in a kindred with familial LCAT deficiency and defective apolipoprotein B-100." Nanjee M.N., Stocks J., Cooke C.J., Molhuizen H.O., Marcovina S., Crook D., Kastelein J.P., Miller N.E. Atherosclerosis 170:105-113(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LCATD MET-345 AND VAL-406, VARIANT THR-232.
[37]	"Association of extreme blood lipid profile phenotypic variation with 11 reverse cholesterol transport genes and 10 non-genetic cardiovascular disease risk factors." Morabia A., Cayanis E., Costanza M.C., Ross B.M., Flaherty M.S., Alvin G.B., Das K., Gilliam T.C. Hum. Mol. Genet. 12:2733-2743(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT THR-232.
[38]	"The molecular basis of lecithin:cholesterol acyltransferase deficiency syndromes: a comprehensive study of molecular and biochemical findings in 13 unrelated Italian families." Calabresi L., Pisciotta L., Costantin A., Frigerio I., Eberini I., Alessandrini P., Arca M., Bon G.B., 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. Arterioscler. Thromb. Vasc. Biol. 25:1972-1978(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS FED GLU-70 AND ALA-298, VARIANTS LCATD CYS-164; TRP-171; ASN-205; ASN-242; HIS-268; ILE-298 AND MET-333, VARIANTS PRO-115; THR-165 AND ARG-396.
[39]	"Familial lecithin-cholesterol acyltransferase deficiency: biochemical characteristics and molecular analysis of a new LCAT mutation in a Polish family." Idzior-Walus B., Sieradzki J., Kostner G., Malecki M.T., Klupa T., Wesolowska T., Rostworowski W., Hartwich J., Walus M., Kiec A.D., Naruszewicz M. Atherosclerosis 185:413-420(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LCATD MET-333.
[40]	"Compound heterozygosity (G71R/R140H) in the lecithin:cholesterol acyltransferase (LCAT) gene results in an intermediate phenotype between LCAT-deficiency and fish-eye disease." Hoerl G., Kroisel P.M., Wagner E., Tiran B., Petek E., Steyrer E. Atherosclerosis 187:101-109(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ARG-95, VARIANT LCATD HIS-164, CHARACTERIZATION OF VARIANT ARG-95.
[41]	"LCAT deficiency: molecular and phenotypic characterization of an Italian family." Gigante M., Ranieri E., Cerullo G., Calabresi L., Iolascon A., Assmann G., Morrone L., Pisciotta L., Schena F.P., Gesualdo L. J. Nephrol. 19:375-381(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THR-232 AND ARG-396.
[42]	"High prevalence of mutations in LCAT in patients with low HDL cholesterol levels in The Netherlands: identification and characterization of eight novel mutations." Holleboom A.G., Kuivenhoven J.A., Peelman F., Schimmel A.W., Peter J., Defesche J.C., Kastelein J.J., Hovingh G.K., Stroes E.S., Motazacker M.M. Hum. Mutat. 32:1290-1298(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS 134-GLU-TYR-135 DELINS ASP-ASN; PHE-246; CYS-268 AND CYS-322, VARIANTS FED SER-99; PHE-338 AND CYS-347, CHARACTERIZATION OF VARIANTS 134-GLU-TYR-135 DELINS ASP-ASN; PHE-246; CYS-268 AND CYS-322, CHARACTERIZATION OF VARIANTS FED SER-99; PHE-338 CYS-347 AND CYS-347.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Lecithin-cholesterol acyltransferase entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	X04981 Genomic DNA. Translation: CAA28651.1. M12625 mRNA. Translation: AAA59498.1. AY422210 Genomic DNA. Translation: AAR03499.1. BT009748 mRNA. Translation: AAP88750.1. AC040162 Genomic DNA. No translation available. CH471092 Genomic DNA. Translation: EAW83190.1. BC014781 mRNA. Translation: AAH14781.1. M26268 mRNA. Translation: AAA59499.1. X06537 mRNA. Translation: CAB56610.1. M17959 Genomic DNA. Translation: AAA59500.1.
IPI	IPI00022331.
PIR	XXHUN. A00571.
RefSeq	NP_000220.1. NM_000229.1.
UniGene	Hs.387239.
3D structure databases
ProteinModelPortal	P04180.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29620N.
STRING	9606.ENSP00000264005.
PTM databases
GlycoSuiteDB	P04180.
PhosphoSite	P04180.
Polymorphism databases
DMDM	125993.
Proteomic databases
PaxDb	P04180.
PeptideAtlas	P04180.
PRIDE	P04180.
Protocols and materials databases
DNASU	3931.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264005; ENSP00000264005; ENSG00000213398.
GeneID	3931.
KEGG	hsa:3931.
UCSC	uc002euy.1. human.
Organism-specific databases
CTD	3931.
GeneCards	GC16M067973.
H-InvDB	HIX0134431.
HGNC	HGNC:6522. LCAT.
HPA	HPA044767.
MIM	136120. phenotype. 245900. phenotype. 606967. gene.
neXtProt	NX_P04180.
Orphanet	79293. Familial LCAT deficiency. 79292. Fish-eye disease.
PharmGKB	PA226.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG322613.
HOGENOM	HOG000238654.
HOVERGEN	HBG017055.
InParanoid	P04180.
KO	K00650.
OMA	DWRLEPS.
OrthoDB	EOG479F77.
Enzyme and pathway databases
BRENDA	2.3.1.43. 2681.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	P04180.
Bgee	P04180.
CleanEx	HS_LCAT.
Genevestigator	P04180.
GermOnline	ENSG00000124067. Homo sapiens.
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
ChEMBL	CHEMBL5942.
GenomeRNAi	3931.
NextBio	15437.
SOURCE	Search...

Entry information

Entry name

LCAT_HUMAN

Accession

Primary (citable) accession number: P04180
Secondary accession number(s): Q53XQ3

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 20, 1987
Last sequence update:	March 20, 1987
Last modified:	May 1, 2013
This is version 144 of the entry and version 1 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.