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MGP001802

UniProt Annotations

Entry Information

Gene Name	lecithin-cholesterol acyltransferase
Protein Entry	LCAT_HUMAN
UniProt ID	P04180
Species	Human

Comments

Comment type	Description
Biophysicochemical Properties	Kinetic parameters: KM=0.97 mM for LDL {ECO:0000269\|PubMed:10329423}; KM=0.4 mM for HDL(2) {ECO:0000269\|PubMed:10329423}; KM=0.10 mM for HDL(3) {ECO:0000269\|PubMed:10329423}; Vmax=8.3 mmol/min/mg enzyme with LDL as substrate {ECO:0000269\|PubMed:10329423}; Vmax=0.58 mmol/min/mg enzyme with HDL(2) as substrate {ECO:0000269\|PubMed:10329423}; Vmax=2.0 mmol/min/mg enzyme with HDL(3) as substrate {ECO:0000269\|PubMed:10329423}; Note=Affinity for LDL is 2.3 to 4-fold lower than for HDL. Relative reactivities are 16% for HDL(3), 1.3% for HDL(2) and 6.5% for LDL.;
Catalytic Activity	Phosphatidylcholine + a sterol = 1- acylglycerophosphocholine + a sterol ester. {ECO:0000255\|PROSITE- ProRule:PRU10037}.
Disease	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'). {ECO:0000269\|PubMed:1516702, ECO:0000269\|PubMed:1571050, ECO:0000269\|PubMed:15994445, ECO:0000269\|PubMed:1737840, ECO:0000269\|PubMed:21901787, ECO:0000269\|PubMed:8620346, ECO:0000269\|PubMed:9261271}. Note=The disease is caused by mutations affecting the gene represented in this entry.
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. {ECO:0000269\|PubMed:11423760, ECO:0000269\|PubMed:12957688, ECO:0000269\|PubMed:15994445, ECO:0000269\|PubMed:16051254, ECO:0000269\|PubMed:16216249, ECO:0000269\|PubMed:1681161, ECO:0000269\|PubMed:1859405, ECO:0000269\|PubMed:2370048, ECO:0000269\|PubMed:7607641, ECO:0000269\|PubMed:7711728, ECO:0000269\|PubMed:8318557, ECO:0000269\|PubMed:8432868, ECO:0000269\|PubMed:8807342, ECO:0000269\|PubMed:9007616, ECO:0000269\|PubMed:9741700}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Enzyme Regulation	APOA1 is the most potent activator in plasma. Also activated by APOE, APOC1 and APOA4. {ECO:0000269\|PubMed:19065001}.
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. {ECO:0000269\|PubMed:10722751}.
Miscellaneous	Levels of LCAT activity correlates inversely with leptin levels as well as with obesity for a wide range of BMI values.
Ptm	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. {ECO:0000269\|PubMed:16335952, ECO:0000269\|PubMed:7613477}.
Similarity	Belongs to the AB hydrolase superfamily. Lipase family. {ECO:0000305}.
Subcellular Location	Secreted {ECO:0000269\|PubMed:19065001}. Note=Secreted into blood plasma. Produced in astrocytes and secreted into cerebral spinal fluid (CSF).
Tissue Specificity	Expressed mainly in brain, liver and testes. Secreted into plasma and cerebral spinal fluid. Expressed in Hep- G2 cell line. {ECO:0000269\|PubMed:10222237, ECO:0000269\|PubMed:3797244}.
Web Resource	Name=Wikipedia; Note=Lecithin-cholesterol acyltransferase entry; URL="http://en.wikipedia.org/wiki/Lecithin-cholesterol_acyltransferase";