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P04180 (LCAT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 153. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length440 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. 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 processCholesterol metabolism
Lipid metabolism
Steroid metabolism
Sterol metabolism
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DiseaseCorneal dystrophy
Disease mutation
   DomainSignal
   Molecular functionAcyltransferase
Transferase
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcholesterol 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

cholesterol transport

Inferred from direct assay PubMed 10559507. Source: MGI

high-density lipoprotein particle remodeling

Inferred from direct assay Ref.15. Source: UniProtKB

lipoprotein biosynthetic process

Inferred from electronic annotation. Source: Ensembl

lipoprotein metabolic process

Traceable author statement. Source: Reactome

phosphatidylcholine biosynthetic process

Inferred from direct assay PubMed 11966470. Source: BHF-UCL

phospholipid metabolic process

Inferred from direct assay PubMed 4335615. Source: BHF-UCL

regulation of high-density lipoprotein particle assembly

Inferred from electronic annotation. Source: Ensembl

reverse cholesterol transport

Inferred from direct assay PubMed 4335615. Source: BHF-UCL

small molecule metabolic process

Traceable author statement. Source: Reactome

very-low-density lipoprotein particle remodeling

Inferred from direct assay PubMed 15654758. Source: BHF-UCL

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay Ref.2PubMed 4335615. Source: BHF-UCL

high-density lipoprotein particle

Inferred from direct assay PubMed 3104518. Source: BHF-UCL

   Molecular_functionapolipoprotein A-I binding

Inferred from physical interaction PubMed 1587806. Source: BHF-UCL

phosphatidylcholine-sterol O-acyltransferase activity

Non-traceable author statement PubMed 11966470. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424
Chain25 – 440416Phosphatidylcholine-sterol acyltransferase
PRO_0000017802

Regions

Compositional bias426 – 43914Pro-rich

Sites

Active site2051Charge relay system By similarity
Site1731Determinant for substrate specificity

Amino acid modifications

Glycosylation441N-linked (GlcNAc...) (complex) Ref.11 Ref.17
Glycosylation1081N-linked (GlcNAc...) (complex) Ref.11
Glycosylation2961N-linked (GlcNAc...) (complex) Ref.11 Ref.17
Glycosylation4081N-linked (GlcNAc...) (complex) Ref.11
Glycosylation4311O-linked (GalNAc...) Ref.11
Glycosylation4331O-linked (GalNAc...) Ref.11
Disulfide bond74 ↔ 98 Ref.10
Disulfide bond337 ↔ 380 Ref.10

Natural variations

Natural variant171L → LLLPPAAPFWL in LCATD.
VAR_004251
Natural variant291N → I in LCATD. Ref.32
VAR_039020
Natural variant341P → L in FED. Ref.20
VAR_004252
Natural variant341P → Q in FED. Ref.30
VAR_039021
Natural variant371T → M in LCATD. Ref.34
VAR_039022
Natural variant541G → S in LCATD. Ref.31
VAR_004253
Natural variant571G → R in LCATD. Ref.29
VAR_004254
Natural variant701V → E in FED. Ref.38
VAR_039023
Natural variant951G → R in a compound heterozygote carrying H-164; intermediate phenotype between LCATD and FED; reduction of activity. Ref.40
VAR_039024
Natural variant991W → S in FED; loss of activity. Ref.42
VAR_066862
Natural variant1151S → P. Ref.38
VAR_039025
Natural variant1171A → T in LCATD. Ref.26 Ref.27
Corresponds to variant rs28940886 [ dbSNP | Ensembl ].
VAR_004255
Natural variant1231R → C in FED. Ref.33
VAR_039026
Natural variant134 – 1352EY → DN in a patient with low HDL-cholesterol levels; results in reduced activity.
VAR_066863
Natural variant1471T → I in FED. Ref.21
VAR_004256
Natural variant1591R → Q in FED. Ref.30
VAR_039027
Natural variant1591R → W in LCATD. Ref.26
Corresponds to variant rs28940887 [ dbSNP | Ensembl ].
VAR_004257
Natural variant1641R → C in LCATD. Ref.38
VAR_039028
Natural variant1641R → 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 variant1651A → T. Ref.38
VAR_039029
Natural variant1711R → W in LCATD. Ref.22 Ref.38
VAR_004259
Natural variant1801Y → N in LCATD.
VAR_004260
Natural variant1821R → C. Ref.26 Ref.27
VAR_004261
Natural variant2051S → N in LCATD. Ref.38
VAR_039030
Natural variant2321S → T. Ref.36 Ref.37 Ref.41
Corresponds to variant rs4986970 [ dbSNP | Ensembl ].
VAR_017030
Natural variant2331L → P in LCATD. Ref.26
Corresponds to variant rs28942087 [ dbSNP | Ensembl ].
VAR_004262
Natural variant2421K → N in LCATD. Ref.38
VAR_039031
Natural variant2461V → F in a patient with low HDL-cholesterol levels; the mutant is hardly secreted and is catalytically inactive. Ref.42
VAR_066864
Natural variant2521N → K in LCATD. Ref.23
VAR_004263
Natural variant2681R → C in a patient with low HDL-cholesterol levels; the mutant is hardly secreted and is catalytically inactive. Ref.42
VAR_066865
Natural variant2681R → H in LCATD. Ref.38
VAR_039032
Natural variant2761M → K in FED. Ref.24
VAR_004264
Natural variant2981T → A in FED and LCATD. Ref.35 Ref.38
VAR_039033
Natural variant2981T → I in LCATD. Ref.38
VAR_039034
Natural variant3171M → I in LCATD; partially defective enzyme. Ref.23 Ref.25
VAR_004265
Natural variant3221R → C in a patient with low HDL-cholesterol levels; reduced protein secretion. Ref.42
VAR_066866
Natural variant3311P → S in LCATD. Ref.34
VAR_039035
Natural variant3331V → M in LCATD. Ref.38 Ref.39
VAR_039036
Natural variant3381L → F in FED; results in reduced protein secretion and activity. Ref.42
VAR_066867
Natural variant3451T → M in LCATD. Ref.26 Ref.36
Corresponds to variant rs28940888 [ dbSNP | Ensembl ].
VAR_004266
Natural variant3471R → C in FED; results in reduced activity. Ref.42
VAR_066868
Natural variant3711T → M in FED. Ref.21
VAR_004267
Natural variant3961L → R in a patient with LCATD. Ref.38 Ref.41
VAR_039037
Natural variant4061F → V in LCATD. Ref.36
VAR_039038

Experimental info

Mutagenesis1731E → A: Increased activity towards PAPC. Increased PAPC/POPC activity ratio. Ref.16
Mutagenesis1731E → D: Little change in enzyme specific activity nor in PAPC/POPC activity ratio. Ref.16
Mutagenesis1731E → K: Decreased enzyme specific activity. Increased PAPC/POPC activity ratio. Ref.16
Mutagenesis1731E → L: Increased activity towards PAPC. Increased PAPC/POPC activity ratio. Ref.16
Mutagenesis1731E → Q: Decreased enzyme specific activity. Increased PAPC/POPC activity ratio. Ref.16
Sequence conflict2571I → H in CAB56610. Ref.8
Sequence conflict2571I → H in AAA59499. Ref.8

Sequences

Sequence LengthMass (Da)Tools
P04180 [UniParc].

Last modified March 20, 1987. Version 1.
Checksum: B315EF118AA7A378

FASTA44049,578
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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, IDENTIFICATION BY 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.
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. expand/collapse author list , 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.
PIRXXHUN. A00571.
RefSeqNP_000220.1. NM_000229.1.
UniGeneHs.387239.

3D structure databases

ProteinModelPortalP04180.
SMRP04180. Positions 159-241, 358-418.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110123. 5 interactions.
DIPDIP-29620N.
IntActP04180. 1 interaction.
STRING9606.ENSP00000264005.

Chemistry

ChEMBLCHEMBL5942.

PTM databases

PhosphoSiteP04180.
UniCarbKBP04180.

Polymorphism databases

DMDM125993.

Proteomic databases

PaxDbP04180.
PeptideAtlasP04180.
PRIDEP04180.

Protocols and materials databases

DNASU3931.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264005; ENSP00000264005; ENSG00000213398.
GeneID3931.
KEGGhsa:3931.
UCSCuc002euy.1. human.

Organism-specific databases

CTD3931.
GeneCardsGC16M067973.
H-InvDBHIX0134431.
HGNCHGNC:6522. LCAT.
HPAHPA044767.
MIM136120. phenotype.
245900. phenotype.
606967. gene.
neXtProtNX_P04180.
Orphanet79293. Familial LCAT deficiency.
79292. Fish-eye disease.
PharmGKBPA226.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG322613.
HOGENOMHOG000238654.
HOVERGENHBG017055.
InParanoidP04180.
KOK00650.
OMADWRLEPS.
PhylomeDBP04180.
TreeFamTF313258.

Enzyme and pathway databases

BRENDA2.3.1.43. 2681.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressP04180.
BgeeP04180.
CleanExHS_LCAT.
GenevestigatorP04180.

Family and domain databases

InterProIPR003386. LACT/PDAT_acylTrfase.
[Graphical view]
PfamPF02450. LCAT. 1 hit.
[Graphical view]
PROSITEPS00120. LIPASE_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiLecithin%E2%80%94cholesterol_acyltransferase.
GenomeRNAi3931.
NextBio15437.
PROP04180.
SOURCESearch...

Entry information

Entry nameLCAT_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 153 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM