LCAT_MOUSE
ID LCAT_MOUSE Reviewed; 438 AA.
AC P16301; Q8K139;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Phosphatidylcholine-sterol acyltransferase;
DE EC=2.3.1.43 {ECO:0000269|PubMed:15654758, ECO:0000269|PubMed:19065001, ECO:0000269|PubMed:8820107};
DE AltName: Full=1-alkyl-2-acetylglycerophosphocholine esterase;
DE EC=3.1.1.47 {ECO:0000269|PubMed:10393212};
DE AltName: Full=Lecithin-cholesterol acyltransferase;
DE AltName: Full=Phospholipid-cholesterol acyltransferase;
DE AltName: Full=Platelet-activating factor acetylhydrolase {ECO:0000303|PubMed:10393212};
DE Short=PAF acetylhydrolase;
DE Flags: Precursor;
GN Name=Lcat;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=2600083; DOI=10.1016/s0021-9258(20)88222-2;
RA Warden C.H., Langner C.A., Gordon J.I., Taylor B.A., McLean J.W.,
RA Lusis A.J.;
RT "Tissue-specific expression, developmental regulation, and chromosomal
RT mapping of the lecithin: cholesterol acyltransferase gene. Evidence for
RT expression in brain and testes as well as liver.";
RL J. Biol. Chem. 264:21573-21581(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-14.
RA Meroni G., Malgaretti N., Magnaghi P., Taramelli R.;
RT "Promoter and 5' flanking sequences of the mouse LCAT gene.";
RL Submitted (MAY-1992) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP CATALYTIC ACTIVITY, FUNCTION, SUBSTRATE SPECIFICITY, SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RX PubMed=8820107;
RA Subbaiah P.V., Liu M.;
RT "Comparative studies on the substrate specificity of lecithin:cholesterol
RT acyltransferase towards the molecular species of phosphatidylcholine in the
RT plasma of 14 vertebrates.";
RL J. Lipid Res. 37:113-122(1996).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=10393212;
RA Forte T.M., Oda M.N., Knoff L., Frei B., Suh J., Harmony J.A., Stuart W.D.,
RA Rubin E.M., Ng D.S.;
RT "Targeted disruption of the murine lecithin:cholesterol acyltransferase
RT gene is associated with reductions in plasma paraoxonase and platelet-
RT activating factor acetylhydrolase activities but not in apolipoprotein J
RT concentration.";
RL J. Lipid Res. 40:1276-1283(1999).
RN [8]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=11809774; DOI=10.1074/jbc.m112320200;
RA Ng D.S., Maguire G.F., Wylie J., Ravandi A., Xuan W., Ahmed Z.,
RA Eskandarian M., Kuksis A., Connelly P.W.;
RT "Oxidative stress is markedly elevated in lecithin:cholesterol
RT acyltransferase-deficient mice and is paradoxically reversed in the
RT apolipoprotein E knockout background in association with a reduction in
RT atherosclerosis.";
RL J. Biol. Chem. 277:11715-11720(2002).
RN [9]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=11893779;
RA Furbee J.W. Jr., Francone O., Parks J.S.;
RT "In vivo contribution of LCAT to apolipoprotein B lipoprotein cholesteryl
RT esters in LDL receptor and apolipoprotein E knockout mice.";
RL J. Lipid Res. 43:428-437(2002).
RN [10]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=15654758; DOI=10.1021/bi0481489;
RA Zhao Y., Thorngate F.E., Weisgraber K.H., Williams D.L., Parks J.S.;
RT "Apolipoprotein E is the major physiological activator of lecithin-
RT cholesterol acyltransferase (LCAT) on apolipoprotein B lipoproteins.";
RL Biochemistry 44:1013-1025(2005).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-397 AND ASN-408.
RC STRAIN=C57BL/6J; TISSUE=Plasma;
RX PubMed=16944957; DOI=10.1021/pr060186m;
RA Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.;
RT "Proteome-wide characterization of N-glycosylation events by diagonal
RT chromatography.";
RL J. Proteome Res. 5:2438-2447(2006).
RN [12]
RP DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, ACTIVITY REGULATION, FUNCTION,
RP CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=19065001; DOI=10.1194/jlr.m800584-jlr200;
RA Hirsch-Reinshagen V., Donkin J., Stukas S., Chan J., Wilkinson A., Fan J.,
RA Parks J.S., Kuivenhoven J.A., Lutjohann D., Pritchard H., Wellington C.L.;
RT "LCAT synthesized by primary astrocytes esterifies cholesterol on glia-
RT derived lipoproteins.";
RL J. Lipid Res. 50:885-893(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Liver, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Central enzyme in the extracellular metabolism of plasma
CC lipoproteins. Synthesized mainly in the liver and secreted into plasma
CC where it converts cholesterol and phosphatidylcholines (lecithins) to
CC cholesteryl esters and lysophosphatidylcholines on the surface of high
CC and low density lipoproteins (HDLs and LDLs) (PubMed:19065001). The
CC cholesterol ester is then transported back to the liver. Also produced
CC in the brain by primary astrocytes, and esterifies free cholesterol on
CC nascent APOE-containing lipoproteins secreted from glia and influences
CC cerebral spinal fluid (CSF) APOE- and APOA1 levels (PubMed:19065001).
CC Together with APOE and the cholesterol transporter ABCA1, plays a key
CC role in the maturation of glial-derived, nascent lipoproteins
CC (PubMed:19065001). Required for remodeling high-density lipoprotein
CC particles into their spherical forms (PubMed:19065001). Has a
CC preference for plasma 16:0-18:2 or 18:O-18:2 phosphatidylcholines
CC (PubMed:8820107). Catalyzes the hydrolysis of 1-O-alkyl-2-acetyl-sn-
CC glycero-3-phosphocholine (platelet-activating factor or PAF) to 1-O-
CC alkyl-sn-glycero-3-phosphocholine (lyso-PAF) (PubMed:10393212). Also
CC catalyzes the transfer of the acetate group from PAF to 1-hexadecanoyl-
CC sn-glycero-3-phosphocholine forming lyso-PAF (By similarity). Catalyzes
CC the esterification of (24S)-hydroxycholesterol (24(S)OH-C), also known
CC as cerebrosterol to produce 24(S)OH-C monoesters (By similarity).
CC {ECO:0000250|UniProtKB:P04180, ECO:0000269|PubMed:11809774,
CC ECO:0000269|PubMed:11893779, ECO:0000269|PubMed:15654758,
CC ECO:0000269|PubMed:19065001, ECO:0000269|PubMed:8820107}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + a sterol = a 1-
CC acyl-sn-glycero-3-phosphocholine + a sterol ester;
CC Xref=Rhea:RHEA:21204, ChEBI:CHEBI:15889, ChEBI:CHEBI:35915,
CC ChEBI:CHEBI:57643, ChEBI:CHEBI:58168; EC=2.3.1.43;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10037,
CC ECO:0000269|PubMed:15654758, ECO:0000269|PubMed:19065001,
CC ECO:0000269|PubMed:8820107};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-O-
CC alkyl-sn-glycero-3-phosphocholine + acetate + H(+);
CC Xref=Rhea:RHEA:17777, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30089, ChEBI:CHEBI:30909, ChEBI:CHEBI:36707; EC=3.1.1.47;
CC Evidence={ECO:0000269|PubMed:10393212};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17778;
CC Evidence={ECO:0000305|PubMed:10393212};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(24S)-hydroxycholesterol + 1-hexadecanoyl-2-acyl-sn-glycero-3-
CC phosphocholine = (24S)-24-hydroxycholesterol ester + 1-hexadecanoyl-
CC sn-glycero-3-phosphocholine; Xref=Rhea:RHEA:43216, ChEBI:CHEBI:34310,
CC ChEBI:CHEBI:72998, ChEBI:CHEBI:77369, ChEBI:CHEBI:82869;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43217;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(24S)-hydroxycholesterol + 1-hexadecanoyl-2-(9Z,12Z-
CC octadecadienoyl)-sn-glycero-3-phosphocholine = (24S)-
CC hydroxycholesterol 3-linoleoate + 1-hexadecanoyl-sn-glycero-3-
CC phosphocholine; Xref=Rhea:RHEA:43224, ChEBI:CHEBI:34310,
CC ChEBI:CHEBI:72998, ChEBI:CHEBI:73002, ChEBI:CHEBI:82875;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43225;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC 3-phosphocholine + cholesterol = 1-hexadecanoyl-sn-glycero-3-
CC phosphocholine + cholesteryl (5Z,8Z,11Z,14Z)-eicosatetraenoate;
CC Xref=Rhea:RHEA:53448, ChEBI:CHEBI:16113, ChEBI:CHEBI:72998,
CC ChEBI:CHEBI:73003, ChEBI:CHEBI:82751;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53449;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine
CC + cholesterol = 1-hexadecanoyl-sn-glycero-3-phosphocholine +
CC cholesteryl (9Z-octadecenoate); Xref=Rhea:RHEA:53456,
CC ChEBI:CHEBI:16113, ChEBI:CHEBI:46898, ChEBI:CHEBI:72998,
CC ChEBI:CHEBI:73001; Evidence={ECO:0000250|UniProtKB:P04180};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53457;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(8Z,11Z,14Z-eicosatrienoyl)-sn-glycero-3-
CC phosphocholine + cholesterol = 1-hexadecanoyl-sn-glycero-3-
CC phosphocholine + cholesteryl (8Z,11Z,14Z)-eicosatrienoate;
CC Xref=Rhea:RHEA:53464, ChEBI:CHEBI:16113, ChEBI:CHEBI:72998,
CC ChEBI:CHEBI:84346, ChEBI:CHEBI:86121;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53465;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(5Z,8Z,11Z-eicosatrienoyl)-sn-glycero-3-
CC phosphocholine + cholesterol = 1-hexadecanoyl-sn-glycero-3-
CC phosphocholine + cholesteryl (5Z,8Z,11Z)-eicosatrienoate;
CC Xref=Rhea:RHEA:53460, ChEBI:CHEBI:16113, ChEBI:CHEBI:72998,
CC ChEBI:CHEBI:86119, ChEBI:CHEBI:88752;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53461;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-sn-
CC glycero-3-phosphocholine + cholesterol = (5Z,8Z,11Z,14Z,17Z-
CC eicosapentaenoyl)-cholesterol + 1-hexadecanoyl-sn-glycero-3-
CC phosphocholine; Xref=Rhea:RHEA:53468, ChEBI:CHEBI:16113,
CC ChEBI:CHEBI:72998, ChEBI:CHEBI:84969, ChEBI:CHEBI:86137;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53469;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-
CC phosphocholine + cholesterol = 1-hexadecanoyl-sn-glycero-3-
CC phosphocholine + cholesteryl (9Z,12Z)-octadecadienoate;
CC Xref=Rhea:RHEA:53472, ChEBI:CHEBI:16113, ChEBI:CHEBI:41509,
CC ChEBI:CHEBI:72998, ChEBI:CHEBI:73002;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53473;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(6Z,9Z,12Z-octadecatrienoyl)-sn-glycero-3-
CC phosphocholine + cholesterol = (6Z,9Z,12Z-octadecatrienoyl)-
CC cholesterol + 1-hexadecanoyl-sn-glycero-3-phosphocholine;
CC Xref=Rhea:RHEA:53476, ChEBI:CHEBI:16113, ChEBI:CHEBI:72998,
CC ChEBI:CHEBI:84786, ChEBI:CHEBI:88756;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53477;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(11Z,14Z,17Z-eicosatrienoyl)-sn-glycero-3-
CC phosphocholine + cholesterol = (11Z,14Z,17Z-eicosatrienoyl)-
CC cholesterol + 1-hexadecanoyl-sn-glycero-3-phosphocholine;
CC Xref=Rhea:RHEA:53516, ChEBI:CHEBI:16113, ChEBI:CHEBI:72998,
CC ChEBI:CHEBI:137411, ChEBI:CHEBI:137412;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53517;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-
CC phosphocholine + cholesterol = (9Z,12Z,15Z-octadecatrienoyl)-
CC cholesterol + 1-hexadecanoyl-sn-glycero-3-phosphocholine;
CC Xref=Rhea:RHEA:53520, ChEBI:CHEBI:16113, ChEBI:CHEBI:72998,
CC ChEBI:CHEBI:84341, ChEBI:CHEBI:84789;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53521;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-
CC phosphocholine + H2O = (9Z,12Z)-octadecadienoate + 1-hexadecanoyl-sn-
CC glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:40811,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30245,
CC ChEBI:CHEBI:72998, ChEBI:CHEBI:73002;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40812;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC 3-phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-
CC hexadecanoyl-sn-glycero-3-phosphocholine + H(+);
CC Xref=Rhea:RHEA:40427, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:72998, ChEBI:CHEBI:73003;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40428;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-sn-glycero-3-phosphocholine + a 1-O-alkyl-2-
CC acetyl-sn-glycero-3-phosphocholine = 1-hexadecanoyl-2-acetyl-sn-
CC glycero-3-phosphocholine + 1-O-alkyl-sn-glycero-3-phosphocholine;
CC Xref=Rhea:RHEA:53636, ChEBI:CHEBI:30909, ChEBI:CHEBI:36707,
CC ChEBI:CHEBI:72998, ChEBI:CHEBI:75219;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53637;
CC Evidence={ECO:0000250|UniProtKB:P04180};
CC -!- ACTIVITY REGULATION: APOA1 is the most potent activator in plasma. Also
CC activated by APOE, APOC1 and APOA4. {ECO:0000269|PubMed:15654758,
CC ECO:0000269|PubMed:19065001}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:19065001,
CC ECO:0000269|PubMed:8820107}. Note=Secreted into blood plasma
CC (PubMed:8820107). Produced in astrocytes and secreted into cerebral
CC spinal fluid (CSF) (By similarity). {ECO:0000250|UniProtKB:P04180,
CC ECO:0000269|PubMed:8820107}.
CC -!- TISSUE SPECIFICITY: Detected in blood plasma (PubMed:8820107). Produced
CC and secreted by astrocytes (at protein level) (PubMed:19065001).
CC Abundantly expressed in liver, brain and testis with highest levels in
CC liver. In the brain, found in cerebellum, cerebral cortex, hippocampus
CC and brain stem. Located to neurons and neuroglia.
CC {ECO:0000269|PubMed:19065001, ECO:0000269|PubMed:2600083}.
CC -!- DEVELOPMENTAL STAGE: In the testis, expressed days 4,8, 14, and 35 of
CC postnatal life with highest levels at day 35. In the brain, expressed
CC in fetal stages and levels begin to rise after day 4 after birth and
CC continue to increase through suckling and weaning reaching a peak at
CC postnatal day 24. In the liver, expressed in fetal life from day 16-21
CC of gestation with a 3-fold increase in the four final days of
CC gestation. {ECO:0000269|PubMed:2600083}.
CC -!- DISRUPTION PHENOTYPE: Null mice exhibit a 7-fold increase in the
CC cholesteryl ester fatty acid CEFA ratio of APOB lipoprotein CEs. There
CC is also a 3.6 increase in vascular ring O(2) production and plasma
CC phospholipid (PL)-bound-F2-isoprostane levels. This effect is
CC paradoxically reversed in the APOE knockout background
CC (PubMed:11809774, PubMed:11893779). Mice show a significant reduction
CC in total cholesterol, HDL-cholesterol, apoA-I, serum paraoxonase and
CC PAF acetylhydrolase enzyme activities and show a modest (36%) but
CC significant increase in apoJ levels (PubMed:10393212).
CC {ECO:0000269|PubMed:10393212, ECO:0000269|PubMed:11809774,
CC ECO:0000269|PubMed:11893779}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Lipase family.
CC {ECO:0000305}.
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DR EMBL; J05154; AAA39419.1; -; mRNA.
DR EMBL; AK149476; BAE28903.1; -; mRNA.
DR EMBL; AC159265; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC028861; AAH28861.1; -; mRNA.
DR EMBL; X54095; CAA38029.1; -; Genomic_DNA.
DR CCDS; CCDS22622.1; -.
DR PIR; A34158; XXMSN.
DR RefSeq; NP_032516.2; NM_008490.2.
DR AlphaFoldDB; P16301; -.
DR SMR; P16301; -.
DR STRING; 10090.ENSMUSP00000038232; -.
DR SwissLipids; SLP:000001729; -.
DR ESTHER; mouse-lcat; PC-sterol_acyltransferase.
DR GlyConnect; 2582; 5 N-Linked glycans (2 sites).
DR GlyGen; P16301; 5 sites, 4 N-linked glycans (2 sites).
DR iPTMnet; P16301; -.
DR PhosphoSitePlus; P16301; -.
DR CPTAC; non-CPTAC-5612; -.
DR MaxQB; P16301; -.
DR PaxDb; P16301; -.
DR PeptideAtlas; P16301; -.
DR PRIDE; P16301; -.
DR ProteomicsDB; 263703; -.
DR Antibodypedia; 15960; 400 antibodies from 34 providers.
DR Ensembl; ENSMUST00000038896; ENSMUSP00000038232; ENSMUSG00000035237.
DR GeneID; 16816; -.
DR KEGG; mmu:16816; -.
DR UCSC; uc009neq.2; mouse.
DR CTD; 3931; -.
DR MGI; MGI:96755; Lcat.
DR VEuPathDB; HostDB:ENSMUSG00000035237; -.
DR eggNOG; KOG2369; Eukaryota.
DR GeneTree; ENSGT00940000160052; -.
DR HOGENOM; CLU_037070_1_0_1; -.
DR InParanoid; P16301; -.
DR OMA; WEDTKNL; -.
DR OrthoDB; 828056at2759; -.
DR PhylomeDB; P16301; -.
DR TreeFam; TF313258; -.
DR Reactome; R-MMU-8964058; HDL remodeling.
DR BioGRID-ORCS; 16816; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Lcat; mouse.
DR PRO; PR:P16301; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P16301; protein.
DR Bgee; ENSMUSG00000035237; Expressed in left lobe of liver and 137 other tissues.
DR Genevisible; P16301; MM.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0034364; C:high-density lipoprotein particle; ISO:MGI.
DR GO; GO:0003847; F:1-alkyl-2-acetylglycerophosphocholine esterase activity; ISS:UniProtKB.
DR GO; GO:0034186; F:apolipoprotein A-I binding; ISO:MGI.
DR GO; GO:0004607; F:phosphatidylcholine-sterol O-acyltransferase activity; IDA:MGI.
DR GO; GO:0004623; F:phospholipase A2 activity; ISO:MGI.
DR GO; GO:0047179; F:platelet-activating factor acetyltransferase activity; IDA:UniProtKB.
DR GO; GO:0034435; P:cholesterol esterification; ISS:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; ISO:MGI.
DR GO; GO:0008203; P:cholesterol metabolic process; IDA:MGI.
DR GO; GO:0030301; P:cholesterol transport; ISO:MGI.
DR GO; GO:0034375; P:high-density lipoprotein particle remodeling; ISO:MGI.
DR GO; GO:0006629; P:lipid metabolic process; IBA:GO_Central.
DR GO; GO:0042158; P:lipoprotein biosynthetic process; IDA:MGI.
DR GO; GO:0042157; P:lipoprotein metabolic process; ISO:MGI.
DR GO; GO:0006656; P:phosphatidylcholine biosynthetic process; ISO:MGI.
DR GO; GO:0046470; P:phosphatidylcholine metabolic process; ISS:UniProtKB.
DR GO; GO:0006644; P:phospholipid metabolic process; ISO:MGI.
DR GO; GO:0090107; P:regulation of high-density lipoprotein particle assembly; IDA:UniProtKB.
DR GO; GO:0046688; P:response to copper ion; ISO:MGI.
DR GO; GO:0051384; P:response to glucocorticoid; ISO:MGI.
DR GO; GO:0043691; P:reverse cholesterol transport; ISO:MGI.
DR GO; GO:0034372; P:very-low-density lipoprotein particle remodeling; ISO:MGI.
DR Gene3D; 3.40.50.1820; -; 3.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR003386; LACT/PDAT_acylTrfase.
DR Pfam; PF02450; LCAT; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS00120; LIPASE_SER; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Cholesterol metabolism; Disulfide bond; Glycoprotein;
KW Hydrolase; Lipid metabolism; Reference proteome; Secreted; Signal;
KW Steroid metabolism; Sterol metabolism; Transferase.
FT SIGNAL 1..24
FT /evidence="ECO:0000250|UniProtKB:P04180"
FT CHAIN 25..438
FT /note="Phosphatidylcholine-sterol acyltransferase"
FT /id="PRO_0000017804"
FT ACT_SITE 205
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P04180"
FT ACT_SITE 369
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04180"
FT ACT_SITE 401
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04180"
FT SITE 173
FT /note="Determinant for substrate specificity"
FT /evidence="ECO:0000250|UniProtKB:P04180"
FT CARBOHYD 44
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 108
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 296
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 397
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16944957"
FT CARBOHYD 408
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16944957"
FT DISULFID 74..98
FT /evidence="ECO:0000250|UniProtKB:P04180"
FT DISULFID 337..380
FT /evidence="ECO:0000250|UniProtKB:P04180"
FT CONFLICT 411
FT /note="L -> M (in Ref. 1; AAA39419)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 438 AA; 49747 MW; 2FDD571853523136 CRC64;
MGLPGSPWQR VLLLLGLLLP PATPFWLLNV LFPPHTTPKA ELSNHTRPVI LVPGCLGNRL
EAKLDKPDVV NWMCYRKTED FFTIWLDFNL FLPLGVDCWI DNTRIVYNHS SGRVSNAPGV
QIRVPGFGKT ESVEYVDDNK LAGYLHTLVQ NLVNNGYVRD ETVRAAPYDW RLAPHQQDEY
YKKLAGLVEE MYAAYGKPVF LIGHSLGCLH VLHFLLRQPQ SWKDHFIDGF ISLGAPWGGS
IKAMRILASG DNQGIPILSN IKLKEEQRIT TTSPWMLPAP HVWPEDHVFI STPNFNYTVQ
DFERFFTDLH FEEGWHMFLQ SRDLLERLPA PGVEVYCLYG VGRPTPHTYI YDHNFPYKDP
VAALYEDGDD TVATRSTELC GQWQGRQSQP VHLLPMNETD HLNMVFSNKT LEHINAILLG
AYRTPKSPAA SPSPPPPE
