LCAT_RABIT
ID LCAT_RABIT Reviewed; 440 AA.
AC P53761;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 25-MAY-2022, entry version 95.
DE RecName: Full=Phosphatidylcholine-sterol acyltransferase;
DE EC=2.3.1.43 {ECO:0000269|PubMed:8820107};
DE AltName: Full=1-alkyl-2-acetylglycerophosphocholine esterase;
DE EC=3.1.1.47 {ECO:0000250|UniProtKB:P04180};
DE AltName: Full=Lecithin-cholesterol acyltransferase;
DE AltName: Full=Phospholipid-cholesterol acyltransferase;
DE AltName: Full=Platelet-activating factor acetylhydrolase {ECO:0000250|UniProtKB:P04180};
DE Short=PAF acetylhydrolase;
DE Flags: Precursor;
GN Name=LCAT;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=New Zealand;
RX PubMed=8827532;
RA Murata Y., Maeda E., Yoshino G., Kasuga M.;
RT "Cloning of rabbit LCAT cDNA: increase in LCAT mRNA abundance in the liver
RT of cholesterol-fed rabbits.";
RL J. Lipid Res. 37:1616-1622(1996).
RN [2]
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).
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). The cholesterol ester is
CC then transported back to the liver. Also produced in the brain by
CC primary astrocytes, and esterifies free cholesterol on nascent APOE-
CC containing lipoproteins secreted from glia and influences cerebral
CC spinal fluid (CSF) APOE- and APOA1 levels. Together with APOE and the
CC cholesterol transporter ABCA1, plays a key role in the maturation of
CC glial-derived, nascent lipoproteins. Required for remodeling high-
CC density lipoprotein particles into their spherical forms (By
CC similarity). Has a preference for plasma 16:0-18:2 or 18:O-18:2
CC phosphatidylcholines (PubMed:8820107). Catalyzes the hydrolysis of 1-O-
CC alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor
CC or PAF) to 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) (By
CC similarity). Also catalyzes the transfer of the acetate group from PAF
CC to 1-hexadecanoyl-sn-glycero-3-phosphocholine forming lyso-PAF (By
CC similarity). Catalyzes the esterification of (24S)-hydroxycholesterol
CC (24(S)OH-C), also known as cerebrosterol to produce 24(S)OH-C
CC monoesters (By similarity). {ECO:0000250|UniProtKB:P04180,
CC 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: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:0000250|UniProtKB:P04180};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17778;
CC Evidence={ECO:0000250|UniProtKB:P04180};
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 -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8820107}.
CC Note=Secreted into blood plasma (PubMed:8820107). Produced in
CC astrocytes and secreted into cerebral spinal fluid (CSF) (By
CC similarity). {ECO:0000250|UniProtKB:P04180,
CC ECO:0000269|PubMed:8820107}.
CC -!- TISSUE SPECIFICITY: Detected in blood plasma (at protein level)
CC (PubMed:8820107). Highly expressed in liver.
CC {ECO:0000269|PubMed:8820107, ECO:0000269|PubMed:8827532}.
CC -!- INDUCTION: Levels increase up to 3-fold on a 6-week cholesterol-
CC enriched diet. {ECO:0000269|PubMed:8827532}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Lipase family.
CC {ECO:0000305}.
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DR EMBL; D13668; BAA02839.1; -; mRNA.
DR RefSeq; NP_001075659.1; NM_001082190.1.
DR AlphaFoldDB; P53761; -.
DR SMR; P53761; -.
DR STRING; 9986.ENSOCUP00000018119; -.
DR ESTHER; rabit-lcat; PC-sterol_acyltransferase.
DR PRIDE; P53761; -.
DR GeneID; 100008978; -.
DR KEGG; ocu:100008978; -.
DR CTD; 3931; -.
DR eggNOG; KOG2369; Eukaryota.
DR InParanoid; P53761; -.
DR OrthoDB; 828056at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0003847; F:1-alkyl-2-acetylglycerophosphocholine esterase activity; ISS:UniProtKB.
DR GO; GO:0004607; F:phosphatidylcholine-sterol O-acyltransferase activity; ISS:UniProtKB.
DR GO; GO:0047179; F:platelet-activating factor acetyltransferase activity; ISS:UniProtKB.
DR GO; GO:0034435; P:cholesterol esterification; ISS:UniProtKB.
DR GO; GO:0008203; P:cholesterol metabolic process; ISS:UniProtKB.
DR GO; GO:0046470; P:phosphatidylcholine metabolic process; ISS:UniProtKB.
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..440
FT /note="Phosphatidylcholine-sterol acyltransferase"
FT /id="PRO_0000017805"
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 408
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 74..98
FT /evidence="ECO:0000250|UniProtKB:P04180"
FT DISULFID 337..380
FT /evidence="ECO:0000250|UniProtKB:P04180"
SQ SEQUENCE 440 AA; 49560 MW; 1958C5B43BD534AD CRC64;
MGPPGSPWQW VLLLLGLLLP PAAPFWLLNV LFPPHTTPKA ELSNHTRPVI LVPGCLGNQL
EAKLDKPSVV NWMCYRKTED FFTIWLDLNM FLPLGVDCWI DNTRVVYNRS SGRVVISPGV
QIRVPGFGKT YSVEYLDNNK LAGYMHTLVQ NLVNNGYVRD ETVRAAPYDW RLEPSQQEEY
YGKLAGLVEE MHAAYGKPVF LIGHSLGCLH LLYFLLRQPQ SWKDRFIDGF ISLGAPWGGS
IKPMLVLASG DNQGIPLMSS IKLREEQRIT TTSPWMFPSQ GVWPEDHVFI STPSFNYTGR
DFKRFFEDLH FEEGWYMWLQ SRDLLAGLPA PGVEVYCLYG IGLPTPHTYI YDHGFPYTDP
VGVLYEDGDD TVATSSTDLC GLWRGRQPQP VHLLPLHETE HLNMVFSNQT LEHINAILLG
AYRSGTPASP TASPGSPPPE
