| IED ID | IndEnz0005000519 |
| Enzyme Type ID | lipase000519 |
| Protein Name |
Phosphatidylcholine-sterol acyltransferase EC 2.3.1.43 1-alkyl-2-acetylglycerophosphocholine esterase EC 3.1.1.47 Lecithin-cholesterol acyltransferase Phospholipid-cholesterol acyltransferase Platelet-activating factor acetylhydrolase PAF acetylhydrolase |
| Gene Name | LCAT |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MGPPGSPWQWVTLLLGLLLPPAAPFWLLNVLFPPHTTPKAELSNHTRPVILVPGCLGNQLEAKLDKPDVVNWMCYRKTEDFFTIWLDLNMFLPLGVDCWIDNTRVVYNRSSGLVSNAPGVQIRVPGFGKTYSVEYLDSSKLAGYLHTLVQNLVNNGYVRDETVRAAPYDWRLEPGQQEEYYRKLAGLVEEMHAAYGKPVFLIGHSLGCLHLLYFLLRQPQAWKDRFIDGFISLGAPWGGSIKPMLVLASGDNQGIPIMSSIKLKEEQRITTTSPWMFPSRMAWPEDHVFISTPSFNYTGRDFQRFFADLHFEEGWYMWLQSRDLLAGLPAPGVEVYCLYGVGLPTPRTYIYDHGFPYTDPVGVLYEDGDDTVATRSTELCGLWQGRQPQPVHLLPLHGIQHLNMVFSNLTLEHINAILLGAYRQGPPASPTASPEPPPPE |
| Enzyme Length | 440 |
| Uniprot Accession Number | P04180 |
| Absorption | |
| Active Site | ACT_SITE 205; /note=Nucleophile; /evidence=ECO:0000305|PubMed:26195816; ACT_SITE 369; /note=Charge relay system; /evidence=ECO:0000305|PubMed:26195816; ACT_SITE 401; /note=Charge relay system; /evidence=ECO:0000305|PubMed:26195816 |
| Activity Regulation | ACTIVITY REGULATION: APOA1 is the most potent activator in plasma (PubMed:19065001, PubMed:8016111). Also activated by APOE, APOC1 and APOA4 (PubMed:19065001, PubMed:8016111). Inhibited by haptoglobin and 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) (PubMed:8016111, PubMed:24620755). {ECO:0000269|PubMed:19065001, ECO:0000269|PubMed:24620755, ECO:0000269|PubMed:8016111}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + a sterol = a 1-acyl-sn-glycero-3-phosphocholine + a sterol ester; Xref=Rhea:RHEA:21204, ChEBI:CHEBI:15889, ChEBI:CHEBI:35915, ChEBI:CHEBI:57643, ChEBI:CHEBI:58168; EC=2.3.1.43; Evidence={ECO:0000255|PROSITE-ProRule:PRU10037, ECO:0000269|PubMed:10222237, ECO:0000269|PubMed:10329423, ECO:0000269|PubMed:14636062, ECO:0000269|PubMed:19065001, ECO:0000269|PubMed:25727495, ECO:0000269|PubMed:26195816, ECO:0000269|PubMed:3458198, ECO:0000269|PubMed:8820107}; CATALYTIC ACTIVITY: Reaction=a 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-O-alkyl-sn-glycero-3-phosphocholine + acetate + H(+); Xref=Rhea:RHEA:17777, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:30909, ChEBI:CHEBI:36707; EC=3.1.1.47; Evidence={ECO:0000269|PubMed:8016111};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17778; Evidence={ECO:0000305|PubMed:8016111}; CATALYTIC ACTIVITY: Reaction=(24S)-hydroxycholesterol + 1-hexadecanoyl-2-acyl-sn-glycero-3-phosphocholine = (24S)-24-hydroxycholesterol ester + 1-hexadecanoyl-sn-glycero-3-phosphocholine; Xref=Rhea:RHEA:43216, ChEBI:CHEBI:34310, ChEBI:CHEBI:72998, ChEBI:CHEBI:77369, ChEBI:CHEBI:82869; Evidence={ECO:0000269|PubMed:24620755};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43217; Evidence={ECO:0000305|PubMed:24620755}; CATALYTIC ACTIVITY: Reaction=(24S)-hydroxycholesterol + 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine = (24S)-hydroxycholesterol 3-linoleoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine; Xref=Rhea:RHEA:43224, ChEBI:CHEBI:34310, ChEBI:CHEBI:72998, ChEBI:CHEBI:73002, ChEBI:CHEBI:82875; Evidence={ECO:0000269|PubMed:24620755};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43225; Evidence={ECO:0000305|PubMed:24620755}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + cholesterol = 1-hexadecanoyl-sn-glycero-3-phosphocholine + cholesteryl (5Z,8Z,11Z,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:53448, ChEBI:CHEBI:16113, ChEBI:CHEBI:72998, ChEBI:CHEBI:73003, ChEBI:CHEBI:82751; Evidence={ECO:0000269|PubMed:14636062};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53449; Evidence={ECO:0000305|PubMed:14636062}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + cholesterol = 1-hexadecanoyl-sn-glycero-3-phosphocholine + cholesteryl (9Z-octadecenoate); Xref=Rhea:RHEA:53456, ChEBI:CHEBI:16113, ChEBI:CHEBI:46898, ChEBI:CHEBI:72998, ChEBI:CHEBI:73001; Evidence={ECO:0000269|PubMed:14636062};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53457; Evidence={ECO:0000305|PubMed:14636062}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(8Z,11Z,14Z-eicosatrienoyl)-sn-glycero-3-phosphocholine + cholesterol = 1-hexadecanoyl-sn-glycero-3-phosphocholine + cholesteryl (8Z,11Z,14Z)-eicosatrienoate; Xref=Rhea:RHEA:53464, ChEBI:CHEBI:16113, ChEBI:CHEBI:72998, ChEBI:CHEBI:84346, ChEBI:CHEBI:86121; Evidence={ECO:0000269|PubMed:14636062};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53465; Evidence={ECO:0000305|PubMed:14636062}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(5Z,8Z,11Z-eicosatrienoyl)-sn-glycero-3-phosphocholine + cholesterol = 1-hexadecanoyl-sn-glycero-3-phosphocholine + cholesteryl (5Z,8Z,11Z)-eicosatrienoate; Xref=Rhea:RHEA:53460, ChEBI:CHEBI:16113, ChEBI:CHEBI:72998, ChEBI:CHEBI:86119, ChEBI:CHEBI:88752; Evidence={ECO:0000269|PubMed:14636062};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53461; Evidence={ECO:0000305|PubMed:14636062}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-sn-glycero-3-phosphocholine + cholesterol = (5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-cholesterol + 1-hexadecanoyl-sn-glycero-3-phosphocholine; Xref=Rhea:RHEA:53468, ChEBI:CHEBI:16113, ChEBI:CHEBI:72998, ChEBI:CHEBI:84969, ChEBI:CHEBI:86137; Evidence={ECO:0000269|PubMed:14636062};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53469; Evidence={ECO:0000305|PubMed:14636062}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine + cholesterol = 1-hexadecanoyl-sn-glycero-3-phosphocholine + cholesteryl (9Z,12Z)-octadecadienoate; Xref=Rhea:RHEA:53472, ChEBI:CHEBI:16113, ChEBI:CHEBI:41509, ChEBI:CHEBI:72998, ChEBI:CHEBI:73002; Evidence={ECO:0000269|PubMed:14636062};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53473; Evidence={ECO:0000305|PubMed:14636062}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(6Z,9Z,12Z-octadecatrienoyl)-sn-glycero-3-phosphocholine + cholesterol = (6Z,9Z,12Z-octadecatrienoyl)-cholesterol + 1-hexadecanoyl-sn-glycero-3-phosphocholine; Xref=Rhea:RHEA:53476, ChEBI:CHEBI:16113, ChEBI:CHEBI:72998, ChEBI:CHEBI:84786, ChEBI:CHEBI:88756; Evidence={ECO:0000269|PubMed:14636062};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53477; Evidence={ECO:0000305|PubMed:14636062}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(11Z,14Z,17Z-eicosatrienoyl)-sn-glycero-3-phosphocholine + cholesterol = (11Z,14Z,17Z-eicosatrienoyl)-cholesterol + 1-hexadecanoyl-sn-glycero-3-phosphocholine; Xref=Rhea:RHEA:53516, ChEBI:CHEBI:16113, ChEBI:CHEBI:72998, ChEBI:CHEBI:137411, ChEBI:CHEBI:137412; Evidence={ECO:0000269|PubMed:14636062};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53517; Evidence={ECO:0000305|PubMed:14636062}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-phosphocholine + cholesterol = (9Z,12Z,15Z-octadecatrienoyl)-cholesterol + 1-hexadecanoyl-sn-glycero-3-phosphocholine; Xref=Rhea:RHEA:53520, ChEBI:CHEBI:16113, ChEBI:CHEBI:72998, ChEBI:CHEBI:84341, ChEBI:CHEBI:84789; Evidence={ECO:0000269|PubMed:14636062};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53521; Evidence={ECO:0000305|PubMed:14636062}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine + H2O = (9Z,12Z)-octadecadienoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:40811, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30245, ChEBI:CHEBI:72998, ChEBI:CHEBI:73002; Evidence={ECO:0000269|PubMed:14636062};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40812; Evidence={ECO:0000305|PubMed:14636062}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:40427, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32395, ChEBI:CHEBI:72998, ChEBI:CHEBI:73003; Evidence={ECO:0000269|PubMed:14636062};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40428; Evidence={ECO:0000305|PubMed:14636062}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-sn-glycero-3-phosphocholine + a 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine = 1-hexadecanoyl-2-acetyl-sn-glycero-3-phosphocholine + 1-O-alkyl-sn-glycero-3-phosphocholine; Xref=Rhea:RHEA:53636, ChEBI:CHEBI:30909, ChEBI:CHEBI:36707, ChEBI:CHEBI:72998, ChEBI:CHEBI:75219; Evidence={ECO:0000269|PubMed:8016111};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53637; Evidence={ECO:0000305|PubMed:8016111}; |
| DNA Binding | |
| EC Number | 2.3.1.43; 3.1.1.47 |
| Enzyme Function | 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) (PubMed:10329423, PubMed:19065001, PubMed:26195816). 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 (PubMed:8820107). 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 (PubMed:10722751). Catalyzes the hydrolysis of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor or PAF) to 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) (PubMed:8016111). Also catalyzes the transfer of the acetate group from PAF to 1-hexadecanoyl-sn-glycero-3-phosphocholine forming lyso-PAF (PubMed:8016111). Catalyzes the esterification of (24S)-hydroxycholesterol (24(S)OH-C), also known as cerebrosterol to produce 24(S)OH-C monoesters (PubMed:24620755). {ECO:0000269|PubMed:10329423, ECO:0000269|PubMed:10722751, ECO:0000269|PubMed:12354767, ECO:0000269|PubMed:14636062, ECO:0000269|PubMed:19065001, ECO:0000269|PubMed:24620755, ECO:0000269|PubMed:26195816, ECO:0000269|PubMed:8016111, ECO:0000269|PubMed:8820107}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Beta strand (19); Chain (1); Disulfide bond (2); Glycosylation (6); Helix (17); Mutagenesis (5); Natural variant (44); Sequence conflict (2); Signal peptide (1); Site (1); Turn (11) |
| Keywords | 3D-structure;Acyltransferase;Cholesterol metabolism;Corneal dystrophy;Direct protein sequencing;Disease variant;Disulfide bond;Glycoprotein;Hydrolase;Lipid metabolism;Reference proteome;Secreted;Signal;Steroid metabolism;Sterol metabolism;Transferase |
| Interact With | P02647; O76024 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10222237, ECO:0000269|PubMed:19065001, ECO:0000269|PubMed:3458198, ECO:0000269|PubMed:8016111, ECO:0000269|PubMed:8820107}. Note=Secreted into blood plasma (PubMed:3458198, PubMed:8820107, PubMed:10222237). Produced in astrocytes and secreted into cerebral spinal fluid (CSF) (PubMed:10222237). {ECO:0000269|PubMed:10222237, ECO:0000269|PubMed:3458198, ECO:0000269|PubMed:8820107}. |
| Modified Residue | |
| Post Translational Modification | 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}. |
| Signal Peptide | SIGNAL 1..24; /evidence=ECO:0000269|PubMed:3458198 |
| Structure 3D | X-ray crystallography (6) |
| Cross Reference PDB | 4X96; 4XWG; 4XX1; 5BV7; 5TXF; 6MVD; |
| Mapped Pubmed ID | 11369005; 11882335; 11966470; 12032172; 12048121; 12051518; 12139471; 12174215; 12573451; 12673583; 15102891; 15110745; 15115696; 15297675; 15472210; 15544352; 1587806; 15936482; 16061733; 16115486; 16542392; 16543491; 16770077; 16780378; 16883530; 17113061; 17206937; 17216278; 17272829; 17357073; 17526537; 17711302; 17855807; 18178167; 18193043; 18397721; 18485513; 18676680; 18719109; 18782872; 18823627; 18922527; 18996102; 19060906; 19060910; 19170196; 19306528; 19336370; 19515369; 19625176; 19671930; 19687369; 19692168; 19800416; 19878569; 19913121; 19948975; 20031551; 20160193; 20167577; 20571754; 20628086; 20634891; 20679960; 20714348; 20855565; 20884842; 20890173; 20972250; 21315357; 21597230; 21600519; 21798542; 21822774; 21875686; 22090275; 22133847; 22189200; 22326749; 22418575; 23023370; 23132909; 23142243; 23152129; 24140107; 24383078; 24423117; 24789697; 24842300; 25110219; 25589508; 25894629; 25948084; 25964513; 26073399; 26117245; 26232163; 26644477; 29030428; 29208698; 29570220; 29758034; 29773713; 29947103; 30059844; 30479275; 30500525; 30518338; 31039173; 31103331; 31164121; 31779197; 32450892; 32561542; 32618730; 33173066; 33298249; 4335615; 4340992; 8820100; 9829992; |
| Motif | |
| Gene Encoded By | |
| Mass | 49,578 |
| Kinetics | 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}; KM=12.8 uM for 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine {ECO:0000269|PubMed:8016111}; KM=125.5 uM for (24S)-hydroxycholesterol (in the presence of APOA1) {ECO:0000269|PubMed:24620755}; KM=417.3 uM for (24S)-hydroxycholesterol (in the presence of APOE) {ECO:0000269|PubMed:24620755}; 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}; Vmax=0.2 umol/h/mg enzyme with 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine as substrate {ECO:0000269|PubMed:8016111}; Vmax=12 umol/h/mg enzyme with cholesterol as substrate {ECO:0000269|PubMed:8016111}; 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.; |
| Metal Binding | |
| Rhea ID | RHEA:21204; RHEA:17777; RHEA:17778; RHEA:43216; RHEA:43217; RHEA:43224; RHEA:43225; RHEA:53448; RHEA:53449; RHEA:53456; RHEA:53457; RHEA:53464; RHEA:53465; RHEA:53460; RHEA:53461; RHEA:53468; RHEA:53469; RHEA:53472; RHEA:53473; RHEA:53476; RHEA:53477; RHEA:53516; RHEA:53517; RHEA:53520; RHEA:53521; RHEA:40811; RHEA:40812; RHEA:40427; RHEA:40428; RHEA:53636; RHEA:53637 |
| Cross Reference Brenda | 2.3.1.43; |