ID LCAT_HUMAN Reviewed; 440 AA. AC P04180; Q53XQ3; DT 20-MAR-1987, integrated into UniProtKB/Swiss-Prot. DT 20-MAR-1987, sequence version 1. DT 24-JAN-2024, entry version 224. DE RecName: Full=Phosphatidylcholine-sterol acyltransferase; DE EC=2.3.1.43 {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}; DE AltName: Full=1-alkyl-2-acetylglycerophosphocholine esterase; DE EC=3.1.1.47 {ECO:0000269|PubMed:8016111}; DE AltName: Full=Lecithin-cholesterol acyltransferase; DE AltName: Full=Phospholipid-cholesterol acyltransferase; DE AltName: Full=Platelet-activating factor acetylhydrolase {ECO:0000303|PubMed:8016111}; DE Short=PAF acetylhydrolase; DE Flags: Precursor; GN Name=LCAT; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY. RX PubMed=3797244; DOI=10.1093/nar/14.23.9397; RA McLean J., Wion K., Drayna D., Fielding C., Lawn R.; RT "Human lecithin-cholesterol acyltransferase gene: complete gene sequence RT and sites of expression."; RL Nucleic Acids Res. 14:9397-9406(1986). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 25-39; 172-182; 269-280 AND RP 387-406, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=3458198; DOI=10.1073/pnas.83.8.2335; RA McLean J., Fielding C., Drayna D., Dieplinger H., Baer B., Kohr W., RA Henzel W., Lawn R.; RT "Cloning and expression of human lecithin-cholesterol acyltransferase RT cDNA."; RL Proc. Natl. Acad. Sci. U.S.A. 83:2335-2339(1986). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Nickerson D.A., Smith J.D., Fullerton S.M., Clark A.G., Stengard J.H., RA Salomaa V., Boerwinkle E., Sing C.F., Weiss K.M.; RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 17-440. RX PubMed=2823898; DOI=10.1016/0167-4781(87)90066-2; RA Tata F., Chaves M.E., Markham A.F., Scrace G.D., Waterfield M.D., RA McIntyre N., Williamson R., Humphries S.E.; RT "The isolation and characterisation of cDNA and genomic clones for human RT lecithin: cholesterol acyltransferase."; RL Biochim. Biophys. Acta 910:142-148(1987). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 13-440. RX PubMed=2823801; DOI=10.1016/0006-291x(87)91090-4; RA Rogne S., Skretting G., Larsen F., Myklebost O., Mevag B., Carlson L.A., RA Holmquist L., Gjone E., Prydz H.; RT "The isolation and characterisation of a cDNA clone for human RT lecithin:cholesterol acyl transferase and its use to analyse the genes in RT patients with LCAT deficiency and fish eye disease."; RL Biochem. Biophys. Res. Commun. 148:161-169(1987). RN [10] RP PARTIAL PROTEIN SEQUENCE, AND DISULFIDE BONDS. RX PubMed=2880847; DOI=10.1016/s0021-9258(18)61472-3; RA Yang C., Manoogian D., Pao Q., Lee F., Knapp R.D., Gotto A.M. Jr., RA Pownall H.J.; RT "Lecithin:cholesterol acyltransferase. Functional regions and a structural RT model of the enzyme."; RL J. Biol. Chem. 262:3086-3091(1987). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ACTIVITY REGULATION, RP AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=8016111; DOI=10.1073/pnas.91.13.6035; RA Liu M., Subbaiah P.V.; RT "Hydrolysis and transesterification of platelet-activating factor by RT lecithin-cholesterol acyltransferase."; RL Proc. Natl. Acad. Sci. U.S.A. 91:6035-6039(1994). RN [12] RP GLYCOSYLATION AT ASN-44; ASN-108; ASN-296; ASN-408; THR-431 AND SER-433, RP STRUCTURE OF CARBOHYDRATES, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=7613477; DOI=10.1002/pro.5560040419; RA Schindler P.A., Settineri C.A., Collet X., Fielding C.J., Burlingame A.L.; RT "Site-specific detection and structural characterization of the RT glycosylation of human plasma proteins lecithin:cholesterol acyltransferase RT and apolipoprotein D using HPLC/electrospray mass spectrometry and RT sequential glycosidase digestion."; RL Protein Sci. 4:791-803(1995). RN [13] 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 [14] RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY. RX PubMed=10222237; DOI=10.1006/bbrc.1999.0601; RA Collet X., Francone O., Besnard F., Fielding C.J.; RT "Secretion of lecithin:cholesterol acyltransferase by brain neuroglial cell RT lines."; RL Biochem. Biophys. Res. Commun. 258:73-76(1999). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=10329423; DOI=10.1006/bbrc.1999.0690; RA Kosek A.B., Durbin D., Jonas A.; RT "Binding affinity and reactivity of lecithin cholesterol acyltransferase RT with native lipoproteins."; RL Biochem. Biophys. Res. Commun. 258:548-551(1999). RN [16] RP FUNCTION IN HIGH-DENSITY LIPOPROTEIN PARTICLE REMODELING. RX PubMed=10722751; DOI=10.1074/jbc.275.12.9019; RA Clay M.A., Pyle D.H., Rye K.A., Barter P.J.; RT "Formation of spherical, reconstituted high density lipoproteins containing RT both apolipoproteins A-I and A-II is mediated by lecithin:cholesterol RT acyltransferase."; RL J. Biol. Chem. 275:9019-9025(2000). RN [17] RP FUNCTION. RX PubMed=12354767; DOI=10.1074/jbc.m206812200; RA Aoki J., Taira A., Takanezawa Y., Kishi Y., Hama K., Kishimoto T., RA Mizuno K., Saku K., Taguchi R., Arai H.; RT "Serum lysophosphatidic acid is produced through diverse phospholipase RT pathways."; RL J. Biol. Chem. 277:48737-48744(2002). RN [18] RP SUBSTRATE SPECIFICITY, MUTAGENESIS OF GLU-173, FUNCTION, AND CATALYTIC RP ACTIVITY. RX PubMed=14636062; DOI=10.1021/bi035460u; RA Zhao Y., Wang J., Gebre A.K., Chisholm J.W., Parks J.S.; RT "Negative charge at amino acid 149 is the molecular determinant for RT substrate specificity of lecithin: cholesterol acyltransferase for RT phosphatidylcholine containing 20-carbon sn-2 fatty acyl chains."; RL Biochemistry 42:13941-13949(2003). RN [19] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-44 AND ASN-296. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., RA Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [20] RP ASSOCIATION WITH OBESITY. RX PubMed=17950106; DOI=10.1016/j.metabol.2007.06.022; RA Bajnok L., Seres I., Varga Z., Jeges S., Peti A., Karanyi Z., Juhasz A., RA Csongradi E., Mezosi E., Nagy E.V., Paragh G.; RT "Relationship of endogenous hyperleptinemia to serum paraoxonase 1, RT cholesteryl ester transfer protein, and lecithin cholesterol RT acyltransferase in obese individuals."; RL Metabolism 56:1542-1549(2007). RN [21] RP ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND FUNCTION. 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 [22] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=24620755; DOI=10.1111/jnc.12713; RA La Marca V., Spagnuolo M.S., Cigliano L., Marasco D., Abrescia P.; RT "The enzyme lecithin-cholesterol acyltransferase esterifies cerebrosterol RT and limits the toxic effect of this oxysterol on SH-SY5Y cells."; RL J. Neurochem. 130:97-108(2014). RN [23] RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 25-440, DISULFIDE BONDS, RP FUNCTION, CATALYTIC ACTIVITY, AND GLYCOSYLATION AT ASN-108; ASN-296 AND RP ASN-408. RX PubMed=26195816; DOI=10.1194/jlr.m059873; RA Piper D.E., Romanow W.G., Gunawardane R.N., Fordstrom P., Masterman S., RA Pan O., Thibault S.T., Zhang R., Meininger D., Schwarz M., Wang Z., RA King C., Zhou M., Walker N.P.; RT "The high resolution crystal structure of human LCAT."; RL J. Lipid Res. 56:1711-1719(2015). RN [24] RP X-RAY CRYSTALLOGRAPHY (8.69 ANGSTROMS) OF 45-421, CATALYTIC ACTIVITY, RP DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-108; ASN-296 AND ASN-408. RX PubMed=25727495; DOI=10.1038/ncomms7250; RA Glukhova A., Hinkovska-Galcheva V., Kelly R., Abe A., Shayman J.A., RA Tesmer J.J.; RT "Structure and function of lysosomal phospholipase A2 and RT lecithin:cholesterol acyltransferase."; RL Nat. Commun. 6:6250-6250(2015). RN [25] RP VARIANT FED LEU-34. RX PubMed=1571050; DOI=10.1016/0006-291x(92)91772-i; RA Skretting G., Prydz H.; RT "An amino acid exchange in exon I of the human lecithin: cholesterol RT acyltransferase (LCAT) gene is associated with fish eye disease."; RL Biochem. Biophys. Res. Commun. 182:583-587(1992). RN [26] RP VARIANTS FED ILE-147 AND MET-371. RX PubMed=1737840; DOI=10.1172/jci115612; RA Klein H.-G., Lohse P., Pritchard P.H., Bojanovski D., Schmidt H., RA Brewer H.B. Jr.; RT "Two different allelic mutations in the lecithin-cholesterol RT acyltransferase gene associated with the fish eye syndrome. Lecithin- RT cholesterol acyltransferase (Thr123-->Ile) and lecithin-cholesterol RT acyltransferase (Thr347-->Met)."; RL J. Clin. Invest. 89:499-506(1992). RN [27] RP VARIANT LCATD TRP-171. RX PubMed=2370048; DOI=10.1007/bf00193195; RA Taramelli R., Pontoglio M., Candiani G., Ottolenghi S., Dieplinger H., RA Catapano A., Albers J., Vergani C., McLean J.; RT "Lecithin cholesterol acyl transferase deficiency: molecular analysis of a RT mutated allele."; RL Hum. Genet. 85:195-199(1990). RN [28] RP VARIANTS LCATD LYS-252 AND ILE-317. RX PubMed=1681161; DOI=10.1016/0140-6736(91)90665-c; RA Gotoda T., Yamada N., Murase T., Sakuma M., Murayama N., Shimano H., RA Kozaki K., Albers J.J., Yazaki Y., Akanuma Y.; RT "Differential phenotypic expression by three mutant alleles in familial RT lecithin:cholesterol acyltransferase deficiency."; RL Lancet 338:778-781(1991). RN [29] RP VARIANT FED LYS-276. RX PubMed=1516702; DOI=10.1016/0014-5793(92)80795-i; RA Skretting G., Blomhoff J.P., Solheim J., Prydz H.; RT "The genetic defect of the original Norwegian lecithin:cholesterol RT acyltransferase deficiency families."; RL FEBS Lett. 309:307-310(1992). RN [30] RP VARIANT LCATD ILE-317. RX PubMed=1859405; DOI=10.1016/0006-291x(91)90129-u; RA Maeda E., Naka Y., Matozaki T., Sakuma M., Akanuma Y., Yoshino G., RA Kasuga M.; RT "Lecithin-cholesterol acyltransferase (LCAT) deficiency with a missense RT mutation in exon 6 of the LCAT gene."; RL Biochem. Biophys. Res. Commun. 178:460-466(1991). RN [31] RP VARIANTS LCATD THR-117; TRP-159; PRO-233 AND MET-345, AND VARIANT CYS-182. RX PubMed=8432868; DOI=10.1172/jci116248; RA Funke H., von Eckardstein A., Pritchard P.H., Hornby A.E., Wiebusch H., RA Motti C., Hayden M.R., Dachet C., Jacotot B., Gerdes U., Faergeman O., RA Albers J.J., Colleoni N., Catapano A., Frohlich J., Assmann G.; RT "Genetic and phenotypic heterogeneity in familial lecithin: cholesterol RT acyltransferase (LCAT) deficiency. Six newly identified defective alleles RT further contribute to the structural heterogeneity in this disease."; RL J. Clin. Invest. 91:677-683(1993). RN [32] RP VARIANT LCATD THR-117, AND VARIANT CYS-182. RX PubMed=8318557; DOI=10.1016/0925-4439(93)90039-4; RA Hill J.S., O K., Wang X., Pritchard P.H.; RT "Lecithin:cholesterol acyltransferase deficiency: identification of a RT causative gene mutation and a co-inherited protein polymorphism."; RL Biochim. Biophys. Acta 1181:321-323(1993). RN [33] RP VARIANT LCATD HIS-164, AND CHARACTERIZATION OF VARIANT LCATD HIS-164. RX PubMed=7607641; DOI=10.1007/bf00214196; RA Steyrer E., Haubenwallner S., Hoerl G., Giessauf W., Kostner G.M., RA Zechner R.; RT "A single G to A nucleotide transition in exon IV of the lecithin: RT cholesterol acyltransferase (LCAT) gene results in an Arg140 to His RT substitution and causes LCAT-deficiency."; RL Hum. Genet. 96:105-109(1995). RN [34] RP VARIANTS LCATD ARG-57 AND LEU-LEU-PRO-PRO-ALA-ALA-PRO-PHE-TRP-LEU-17 INS. RX PubMed=7711728; DOI=10.1093/hmg/4.1.143; RA Wiebusch H., Cullen P., Owen J.S., Collins D., Sharp P.S., Funke H., RA Assmann G.; RT "Deficiency of lecithin:cholesterol acyltransferase due to compound RT heterozygosity of two novel mutations (Gly33Arg and 30 bp ins) in the LCAT RT gene."; RL Hum. Mol. Genet. 4:143-145(1995). RN [35] RP VARIANTS FED GLN-34 AND GLN-159. RX PubMed=8620346; DOI=10.1161/01.atv.16.2.294; RA Kuivenhoven J.A., Stalenhoef A.F., Hill J.S., Demacker P.N., Errami A., RA Kastelein J.J., Pritchard P.H.; RT "Two novel molecular defects in the LCAT gene are associated with fish eye RT disease."; RL Arterioscler. Thromb. Vasc. Biol. 16:294-303(1996). RN [36] RP VARIANT LCATD SER-54. RX PubMed=8807342; RX DOI=10.1002/(sici)1098-1004(1996)8:1<79::aid-humu13>3.0.co;2-o; RA Owen J.S., Wiebusch H., Cullen P., Watts G.F., Lima V.L.M., Funke H., RA Assmann G.; RT "Complete deficiency of plasma lecithin-cholesterol acyltransferase (LCAT) RT activity due to a novel homozygous mutation (Gly-30-Ser) in the LCAT RT gene."; RL Hum. Mutat. 8:79-82(1996). RN [37] RP VARIANT LCATD ILE-29. RX PubMed=9007616; DOI=10.1007/bf02602958; RA Okubo M., Aoyama Y., Shio H., Albers J.J., Murase T.; RT "A novel missense mutation (Asn5-->Ile) in lecithin: cholesterol RT acyltransferase (LCAT) gene in a Japanese patient with LCAT deficiency."; RL Int. J. Clin. Lab. Res. 26:250-254(1996). RN [38] RP VARIANT FED CYS-123. RX PubMed=9261271; DOI=10.1161/01.atv.17.7.1382; RA Blanco-Vaca F., Qu S.J., Fiol C., Fan H.Z., Pao Q., Marzal-Casacuberta A., RA Albers J.J., Hurtado I., Gracia V., Pinto X., Marti T., Pownall H.J.; RT "Molecular basis of fish-eye disease in a patient from Spain. RT Characterization of a novel mutation in the LCAT gene and lipid analysis of RT the cornea."; RL Arterioscler. Thromb. Vasc. Biol. 17:1382-1391(1997). RN [39] RP VARIANTS LCATD MET-37 AND SER-331. RX PubMed=9741700; RA Argyropoulos G., Jenkins A., Klein R.L., Lyons T., Wagenhorst B., RA St Armand J., Marcovina S.M., Albers J.J., Pritchard P.H., Garvey W.T.; RT "Transmission of two novel mutations in a pedigree with familial RT lecithin:cholesterol acyltransferase deficiency: structure-function RT relationships and studies in a compound heterozygous proband."; RL J. Lipid Res. 39:1870-1876(1998). RN [40] RP VARIANT LCATD ALA-298. RX PubMed=11423760; DOI=10.1159/000046001; RA Sessa A., Battini G., Meroni M., Daidone G., Carnera I., Brambilla P.L., RA Vigano G., Giordano F., Pallotti F., Torri Tarelli L., Calabresi L., RA Rolleri M., Bertolini S.; RT "Hypocomplementemic type II membranoproliferative glomerulonephritis in a RT male patient with familial lecithin-cholesterol acyltransferase deficiency RT due to two different allelic mutations."; RL Nephron 88:268-272(2001). RN [41] RP VARIANTS LCATD MET-345 AND VAL-406, AND VARIANT THR-232. RX PubMed=12957688; DOI=10.1016/s0021-9150(03)00241-7; RA Nanjee M.N., Stocks J., Cooke C.J., Molhuizen H.O., Marcovina S., Crook D., RA Kastelein J.P., Miller N.E.; RT "A novel LCAT mutation (Phe382-->Val) in a kindred with familial LCAT RT deficiency and defective apolipoprotein B-100."; RL Atherosclerosis 170:105-113(2003). RN [42] RP VARIANT THR-232. RX PubMed=12966036; DOI=10.1093/hmg/ddg314; RA Morabia A., Cayanis E., Costanza M.C., Ross B.M., Flaherty M.S., RA Alvin G.B., Das K., Gilliam T.C.; RT "Association of extreme blood lipid profile phenotypic variation with 11 RT reverse cholesterol transport genes and 10 non-genetic cardiovascular RT disease risk factors."; RL Hum. Mol. Genet. 12:2733-2743(2003). RN [43] RP VARIANTS FED GLU-70 AND ALA-298, VARIANTS LCATD CYS-164; TRP-171; ASN-205; RP ASN-242; HIS-268; ILE-298 AND MET-333, AND VARIANTS PRO-115; THR-165 AND RP ARG-396. RX PubMed=15994445; DOI=10.1161/01.atv.0000175751.30616.13; RA Calabresi L., Pisciotta L., Costantin A., Frigerio I., Eberini I., RA Alessandrini P., Arca M., Bon G.B., Boscutti G., Busnach G., Frasca G., RA Gesualdo L., Gigante M., Lupattelli G., Montali A., Pizzolitto S., RA Rabbone I., Rolleri M., Ruotolo G., Sampietro T., Sessa A., Vaudo G., RA Cantafora A., Veglia F., Calandra S., Bertolini S., Franceschini G.; RT "The molecular basis of lecithin:cholesterol acyltransferase deficiency RT syndromes: a comprehensive study of molecular and biochemical findings in RT 13 unrelated Italian families."; RL Arterioscler. Thromb. Vasc. Biol. 25:1972-1978(2005). RN [44] RP VARIANT LCATD MET-333. RX PubMed=16051254; DOI=10.1016/j.atherosclerosis.2005.06.022; RA Idzior-Walus B., Sieradzki J., Kostner G., Malecki M.T., Klupa T., RA Wesolowska T., Rostworowski W., Hartwich J., Walus M., Kiec A.D., RA Naruszewicz M.; RT "Familial lecithin-cholesterol acyltransferase deficiency: biochemical RT characteristics and molecular analysis of a new LCAT mutation in a Polish RT family."; RL Atherosclerosis 185:413-420(2006). RN [45] RP VARIANT ARG-95, VARIANT LCATD HIS-164, AND CHARACTERIZATION OF VARIANT RP ARG-95. RX PubMed=16216249; DOI=10.1016/j.atherosclerosis.2005.08.038; RA Hoerl G., Kroisel P.M., Wagner E., Tiran B., Petek E., Steyrer E.; RT "Compound heterozygosity (G71R/R140H) in the lecithin:cholesterol RT acyltransferase (LCAT) gene results in an intermediate phenotype between RT LCAT-deficiency and fish-eye disease."; RL Atherosclerosis 187:101-109(2006). RN [46] RP VARIANTS THR-232 AND ARG-396. RX PubMed=16874701; RA Gigante M., Ranieri E., Cerullo G., Calabresi L., Iolascon A., Assmann G., RA Morrone L., Pisciotta L., Schena F.P., Gesualdo L.; RT "LCAT deficiency: molecular and phenotypic characterization of an Italian RT family."; RL J. Nephrol. 19:375-381(2006). RN [47] RP VARIANTS 134-GLU-TYR-135 DELINS ASP-ASN; PHE-246; CYS-268 AND CYS-322, RP VARIANTS FED SER-99; PHE-338 AND CYS-347, CHARACTERIZATION OF VARIANTS RP 134-GLU-TYR-135 DELINS ASP-ASN; PHE-246; CYS-268 AND CYS-322, AND RP CHARACTERIZATION OF VARIANTS FED SER-99; PHE-338 CYS-347 AND CYS-347. RX PubMed=21901787; DOI=10.1002/humu.21578; RA Holleboom A.G., Kuivenhoven J.A., Peelman F., Schimmel A.W., Peter J., RA Defesche J.C., Kastelein J.J., Hovingh G.K., Stroes E.S., Motazacker M.M.; RT "High prevalence of mutations in LCAT in patients with low HDL cholesterol RT levels in The Netherlands: identification and characterization of eight RT novel mutations."; RL Hum. Mutat. 32:1290-1298(2011). 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:10329423, CC PubMed:19065001, PubMed:26195816). The cholesterol ester is then CC transported back to the liver. Has a preference for plasma 16:0-18:2 or CC 18:O-18:2 phosphatidylcholines (PubMed:8820107). Also produced in the CC brain by primary astrocytes, and esterifies free cholesterol on nascent CC APOE-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 CC (PubMed:10722751). 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:8016111). Also CC catalyzes the transfer of the acetate group from PAF to 1-hexadecanoyl- CC sn-glycero-3-phosphocholine forming lyso-PAF (PubMed:8016111). CC Catalyzes the esterification of (24S)-hydroxycholesterol (24(S)OH-C), CC also known as cerebrosterol to produce 24(S)OH-C monoesters CC (PubMed:24620755). {ECO:0000269|PubMed:10329423, CC ECO:0000269|PubMed:10722751, ECO:0000269|PubMed:12354767, CC ECO:0000269|PubMed:14636062, ECO:0000269|PubMed:19065001, CC ECO:0000269|PubMed:24620755, ECO:0000269|PubMed:26195816, CC ECO:0000269|PubMed:8016111, 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:10222237, ECO:0000269|PubMed:10329423, CC ECO:0000269|PubMed:14636062, ECO:0000269|PubMed:19065001, CC ECO:0000269|PubMed:25727495, ECO:0000269|PubMed:26195816, CC ECO:0000269|PubMed:3458198, 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:8016111}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17778; CC Evidence={ECO:0000305|PubMed:8016111}; 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:0000269|PubMed:24620755}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43217; CC Evidence={ECO:0000305|PubMed:24620755}; 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:0000269|PubMed:24620755}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43225; CC Evidence={ECO:0000305|PubMed:24620755}; 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:0000269|PubMed:14636062}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53449; CC Evidence={ECO:0000305|PubMed:14636062}; 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:0000269|PubMed:14636062}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53457; CC Evidence={ECO:0000305|PubMed:14636062}; 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:0000269|PubMed:14636062}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53465; CC Evidence={ECO:0000305|PubMed:14636062}; 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:0000269|PubMed:14636062}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53461; CC Evidence={ECO:0000305|PubMed:14636062}; 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:0000269|PubMed:14636062}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53469; CC Evidence={ECO:0000305|PubMed:14636062}; 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:0000269|PubMed:14636062}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53473; CC Evidence={ECO:0000305|PubMed:14636062}; 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:0000269|PubMed:14636062}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53477; CC Evidence={ECO:0000305|PubMed:14636062}; 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:0000269|PubMed:14636062}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53517; CC Evidence={ECO:0000305|PubMed:14636062}; 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:0000269|PubMed:14636062}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53521; CC Evidence={ECO:0000305|PubMed:14636062}; 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:0000269|PubMed:14636062}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40812; CC Evidence={ECO:0000305|PubMed:14636062}; 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:0000269|PubMed:14636062}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40428; CC Evidence={ECO:0000305|PubMed:14636062}; 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:0000269|PubMed:8016111}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53637; CC Evidence={ECO:0000305|PubMed:8016111}; CC -!- ACTIVITY REGULATION: APOA1 is the most potent activator in plasma CC (PubMed:19065001, PubMed:8016111). Also activated by APOE, APOC1 and CC APOA4 (PubMed:19065001, PubMed:8016111). Inhibited by haptoglobin and CC 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) (PubMed:8016111, CC PubMed:24620755). {ECO:0000269|PubMed:19065001, CC ECO:0000269|PubMed:24620755, ECO:0000269|PubMed:8016111}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.97 mM for LDL {ECO:0000269|PubMed:10329423}; CC KM=0.4 mM for HDL(2) {ECO:0000269|PubMed:10329423}; CC KM=0.1 mM for HDL(3) {ECO:0000269|PubMed:10329423}; CC KM=12.8 uM for 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine CC {ECO:0000269|PubMed:8016111}; CC KM=125.5 uM for (24S)-hydroxycholesterol (in the presence of APOA1) CC {ECO:0000269|PubMed:24620755}; CC KM=417.3 uM for (24S)-hydroxycholesterol (in the presence of APOE) CC {ECO:0000269|PubMed:24620755}; CC Vmax=8.3 mmol/min/mg enzyme with LDL as substrate CC {ECO:0000269|PubMed:10329423}; CC Vmax=0.58 mmol/min/mg enzyme with HDL(2) as substrate CC {ECO:0000269|PubMed:10329423}; CC Vmax=2 mmol/min/mg enzyme with HDL(3) as substrate CC {ECO:0000269|PubMed:10329423}; CC Vmax=0.2 umol/h/mg enzyme with CC 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine as substrate CC {ECO:0000269|PubMed:8016111}; CC Vmax=12 umol/h/mg enzyme with cholesterol as substrate CC {ECO:0000269|PubMed:8016111}; CC Note=Affinity for LDL is 2.3 to 4-fold lower than for HDL. Relative CC reactivities are 16% for HDL(3), 1.3% for HDL(2) and 6.5% for LDL.; CC -!- INTERACTION: CC P04180; P02647: APOA1; NbExp=2; IntAct=EBI-9104464, EBI-701692; CC P04180; O76024: WFS1; NbExp=3; IntAct=EBI-9104464, EBI-720609; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10222237, CC ECO:0000269|PubMed:19065001, ECO:0000269|PubMed:3458198, CC ECO:0000269|PubMed:8016111, ECO:0000269|PubMed:8820107}. Note=Secreted CC into blood plasma (PubMed:3458198, PubMed:8820107, PubMed:10222237). CC Produced in astrocytes and secreted into cerebral spinal fluid (CSF) CC (PubMed:10222237). {ECO:0000269|PubMed:10222237, CC ECO:0000269|PubMed:3458198, ECO:0000269|PubMed:8820107}. CC -!- TISSUE SPECIFICITY: Detected in blood plasma (PubMed:3458198, CC PubMed:8820107, PubMed:10222237). Detected in cerebral spinal fluid (at CC protein level) (PubMed:10222237). Detected in liver (PubMed:3797244, CC PubMed:3458198). Expressed mainly in brain, liver and testes. CC {ECO:0000269|PubMed:10222237, ECO:0000269|PubMed:3458198, CC ECO:0000269|PubMed:3797244, ECO:0000269|PubMed:8820107}. CC -!- PTM: O- and N-glycosylated. O-glycosylation on Thr-431 and Ser-433 CC consists of sialylated galactose beta 1-->3N-acetylgalactosamine CC structures. N-glycosylated sites contain sialylated triantennary and/or CC biantennary complex structures. {ECO:0000269|PubMed:16335952, CC ECO:0000269|PubMed:7613477}. CC -!- DISEASE: Lecithin-cholesterol acyltransferase deficiency (LCATD) CC [MIM:245900]: A disorder of lipoprotein metabolism characterized by CC inadequate esterification of plasmatic cholesterol. Two clinical forms CC are recognized: complete LCAT deficiency and fish-eye disease. LCATD is CC generally referred to the complete form which is associated with CC absence of both alpha and beta LCAT activities resulting in CC esterification anomalies involving both HDL (alpha-LCAT activity) and CC LDL (beta-LCAT activity). It causes a typical triad of diffuse corneal CC opacities, target cell hemolytic anemia, and proteinuria with renal CC failure. {ECO:0000269|PubMed:11423760, ECO:0000269|PubMed:12957688, CC ECO:0000269|PubMed:15994445, ECO:0000269|PubMed:16051254, CC ECO:0000269|PubMed:16216249, ECO:0000269|PubMed:1681161, CC ECO:0000269|PubMed:1859405, ECO:0000269|PubMed:2370048, CC ECO:0000269|PubMed:7607641, ECO:0000269|PubMed:7711728, CC ECO:0000269|PubMed:8318557, ECO:0000269|PubMed:8432868, CC ECO:0000269|PubMed:8807342, ECO:0000269|PubMed:9007616, CC ECO:0000269|PubMed:9741700}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Fish-eye disease (FED) [MIM:136120]: A disorder of lipoprotein CC metabolism due to partial lecithin-cholesterol acyltransferase CC deficiency that affects only alpha-LCAT activity. FED is characterized CC by low plasma HDL and corneal opacities due to accumulation of CC cholesterol deposits in the cornea ('fish-eye'). CC {ECO:0000269|PubMed:1516702, ECO:0000269|PubMed:1571050, CC ECO:0000269|PubMed:15994445, ECO:0000269|PubMed:1737840, CC ECO:0000269|PubMed:21901787, ECO:0000269|PubMed:8620346, CC ECO:0000269|PubMed:9261271}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Levels of LCAT activity correlates inversely with leptin CC levels as well as with obesity for a wide range of BMI values. CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Lipase family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Lecithin-cholesterol acyltransferase CC entry; CC URL="https://en.wikipedia.org/wiki/Lecithin-cholesterol_acyltransferase"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X04981; CAA28651.1; -; Genomic_DNA. DR EMBL; M12625; AAA59498.1; -; mRNA. DR EMBL; AY422210; AAR03499.1; -; Genomic_DNA. DR EMBL; BT009748; AAP88750.1; -; mRNA. DR EMBL; AC040162; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471092; EAW83190.1; -; Genomic_DNA. DR EMBL; BC014781; AAH14781.1; -; mRNA. DR EMBL; M26268; AAA59499.1; -; mRNA. DR EMBL; X06537; CAB56610.1; -; mRNA. DR EMBL; M17959; AAA59500.1; -; Genomic_DNA. DR CCDS; CCDS10854.1; -. DR PIR; A00571; XXHUN. DR RefSeq; NP_000220.1; NM_000229.1. DR PDB; 4X96; X-ray; 8.69 A; A/B/C/D=45-421. DR PDB; 4XWG; X-ray; 2.65 A; A=25-440. DR PDB; 4XX1; X-ray; 3.60 A; A/B/J=25-440. DR PDB; 5BV7; X-ray; 2.45 A; A=25-440. DR PDB; 5TXF; X-ray; 3.10 A; A/B/C/D=25-440. DR PDB; 6MVD; X-ray; 3.10 A; A/B=45-421. DR PDBsum; 4X96; -. DR PDBsum; 4XWG; -. DR PDBsum; 4XX1; -. DR PDBsum; 5BV7; -. DR PDBsum; 5TXF; -. DR PDBsum; 6MVD; -. DR AlphaFoldDB; P04180; -. DR SMR; P04180; -. DR BioGRID; 110123; 6. DR DIP; DIP-29620N; -. DR IntAct; P04180; 2. DR STRING; 9606.ENSP00000264005; -. DR BindingDB; P04180; -. DR ChEMBL; CHEMBL5942; -. DR SwissLipids; SLP:000000660; -. DR ESTHER; human-LCAT; PC-sterol_acyltransferase. DR GlyConnect; 495; 13 N-Linked glycans (2 sites). DR GlyCosmos; P04180; 6 sites, 18 glycans. DR GlyGen; P04180; 7 sites, 18 N-linked glycans (3 sites), 1 O-linked glycan (1 site). DR iPTMnet; P04180; -. DR PhosphoSitePlus; P04180; -. DR BioMuta; LCAT; -. DR DMDM; 125993; -. DR jPOST; P04180; -. DR MassIVE; P04180; -. DR MaxQB; P04180; -. DR PaxDb; 9606-ENSP00000264005; -. DR PeptideAtlas; P04180; -. DR ProteomicsDB; 51671; -. DR ABCD; P04180; 3 sequenced antibodies. DR Antibodypedia; 15960; 467 antibodies from 34 providers. DR DNASU; 3931; -. DR Ensembl; ENST00000264005.10; ENSP00000264005.5; ENSG00000213398.8. DR GeneID; 3931; -. DR KEGG; hsa:3931; -. DR MANE-Select; ENST00000264005.10; ENSP00000264005.5; NM_000229.2; NP_000220.1. DR UCSC; uc002euy.2; human. DR AGR; HGNC:6522; -. DR CTD; 3931; -. DR DisGeNET; 3931; -. DR GeneCards; LCAT; -. DR HGNC; HGNC:6522; LCAT. DR HPA; ENSG00000213398; Tissue enhanced (liver). DR MalaCards; LCAT; -. DR MIM; 136120; phenotype. DR MIM; 245900; phenotype. DR MIM; 606967; gene. DR neXtProt; NX_P04180; -. DR OpenTargets; ENSG00000213398; -. DR Orphanet; 79293; Familial LCAT deficiency. DR Orphanet; 79292; Fish-eye disease. DR PharmGKB; PA226; -. DR VEuPathDB; HostDB:ENSG00000213398; -. DR eggNOG; KOG2369; Eukaryota. DR GeneTree; ENSGT00940000160052; -. DR InParanoid; P04180; -. DR OMA; PWQWVPL; -. DR OrthoDB; 353098at2759; -. DR PhylomeDB; P04180; -. DR TreeFam; TF313258; -. DR BRENDA; 2.3.1.43; 2681. DR PathwayCommons; P04180; -. DR Reactome; R-HSA-8964058; HDL remodeling. DR SABIO-RK; P04180; -. DR SignaLink; P04180; -. DR SIGNOR; P04180; -. DR BioGRID-ORCS; 3931; 11 hits in 1156 CRISPR screens. DR ChiTaRS; LCAT; human. DR GeneWiki; Lecithin%E2%80%94cholesterol_acyltransferase; -. DR GenomeRNAi; 3931; -. DR Pharos; P04180; Tchem. DR PRO; PR:P04180; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; P04180; Protein. DR Bgee; ENSG00000213398; Expressed in right lobe of liver and 123 other cell types or tissues. DR ExpressionAtlas; P04180; baseline and differential. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0034364; C:high-density lipoprotein particle; IDA:BHF-UCL. DR GO; GO:0003847; F:1-alkyl-2-acetylglycerophosphocholine esterase activity; IDA:UniProtKB. DR GO; GO:0034186; F:apolipoprotein A-I binding; IPI:BHF-UCL. DR GO; GO:0004607; F:phosphatidylcholine-sterol O-acyltransferase activity; IDA:UniProtKB. DR GO; GO:0047179; F:platelet-activating factor acetyltransferase activity; IDA:UniProtKB. DR GO; GO:0004771; F:sterol esterase activity; IDA:ARUK-UCL. DR GO; GO:0042632; P:cholesterol homeostasis; IDA:BHF-UCL. DR GO; GO:0008203; P:cholesterol metabolic process; IDA:UniProtKB. DR GO; GO:0030301; P:cholesterol transport; IDA:MGI. DR GO; GO:0034375; P:high-density lipoprotein particle remodeling; IDA:UniProtKB. DR GO; GO:0006629; P:lipid metabolic process; IBA:GO_Central. DR GO; GO:0042158; P:lipoprotein biosynthetic process; IEA:Ensembl. DR GO; GO:0006656; P:phosphatidylcholine biosynthetic process; IDA:BHF-UCL. DR GO; GO:0046470; P:phosphatidylcholine metabolic process; IDA:UniProtKB. DR GO; GO:0006644; P:phospholipid metabolic process; IDA:BHF-UCL. DR GO; GO:0090107; P:regulation of high-density lipoprotein particle assembly; IEA:Ensembl. DR GO; GO:0043691; P:reverse cholesterol transport; IDA:BHF-UCL. DR GO; GO:0034372; P:very-low-density lipoprotein particle remodeling; IDA:BHF-UCL. DR Gene3D; 3.40.50.1820; alpha/beta hydrolase; 3. DR InterPro; IPR029058; AB_hydrolase. DR InterPro; IPR003386; LACT/PDAT_acylTrfase. DR PANTHER; PTHR11440; LECITHIN-CHOLESTEROL ACYLTRANSFERASE-RELATED; 1. DR PANTHER; PTHR11440:SF18; PHOSPHATIDYLCHOLINE-STEROL ACYLTRANSFERASE; 1. DR Pfam; PF02450; LCAT; 1. DR SUPFAM; SSF53474; alpha/beta-Hydrolases; 1. DR PROSITE; PS00120; LIPASE_SER; 1. DR Genevisible; P04180; HS. PE 1: Evidence at protein level; KW 3D-structure; Acyltransferase; Cholesterol metabolism; Corneal dystrophy; KW Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; KW Hydrolase; Lipid metabolism; Reference proteome; Secreted; Signal; KW Steroid metabolism; Sterol metabolism; Transferase. FT SIGNAL 1..24 FT /evidence="ECO:0000269|PubMed:3458198" FT CHAIN 25..440 FT /note="Phosphatidylcholine-sterol acyltransferase" FT /id="PRO_0000017802" FT ACT_SITE 205 FT /note="Nucleophile" FT /evidence="ECO:0000305|PubMed:26195816" FT ACT_SITE 369 FT /note="Charge relay system" FT /evidence="ECO:0000305|PubMed:26195816" FT ACT_SITE 401 FT /note="Charge relay system" FT /evidence="ECO:0000305|PubMed:26195816" FT SITE 173 FT /note="Determinant for substrate specificity" FT /evidence="ECO:0000305|PubMed:14636062" FT CARBOHYD 44 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:7613477" FT CARBOHYD 108 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:26195816, FT ECO:0000269|PubMed:7613477, ECO:0007744|PDB:4X96" FT CARBOHYD 296 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:26195816, ECO:0000269|PubMed:7613477, FT ECO:0007744|PDB:4X96" FT CARBOHYD 408 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:26195816, FT ECO:0000269|PubMed:7613477, ECO:0007744|PDB:4X96" FT CARBOHYD 431 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000269|PubMed:7613477" FT CARBOHYD 433 FT /note="O-linked (GalNAc...) serine" FT /evidence="ECO:0000269|PubMed:7613477" FT DISULFID 74..98 FT /evidence="ECO:0000269|PubMed:26195816, FT ECO:0000269|PubMed:2880847, ECO:0007744|PDB:4X96, FT ECO:0007744|PDB:4XWG, ECO:0007744|PDB:4XX1" FT DISULFID 337..380 FT /evidence="ECO:0000269|PubMed:26195816, FT ECO:0000269|PubMed:2880847, ECO:0007744|PDB:4X96, FT ECO:0007744|PDB:4XWG, ECO:0007744|PDB:4XX1" FT VARIANT 17 FT /note="L -> LLLPPAAPFWL (in LCATD)" FT /id="VAR_004251" FT VARIANT 29 FT /note="N -> I (in LCATD)" FT /evidence="ECO:0000269|PubMed:9007616" FT /id="VAR_039020" FT VARIANT 34 FT /note="P -> L (in FED; dbSNP:rs121908051)" FT /evidence="ECO:0000269|PubMed:1571050" FT /id="VAR_004252" FT VARIANT 34 FT /note="P -> Q (in FED)" FT /evidence="ECO:0000269|PubMed:8620346" FT /id="VAR_039021" FT VARIANT 37 FT /note="T -> M (in LCATD; dbSNP:rs971887742)" FT /evidence="ECO:0000269|PubMed:9741700" FT /id="VAR_039022" FT VARIANT 54 FT /note="G -> S (in LCATD; dbSNP:rs1461145750)" FT /evidence="ECO:0000269|PubMed:8807342" FT /id="VAR_004253" FT VARIANT 57 FT /note="G -> R (in LCATD)" FT /evidence="ECO:0000269|PubMed:7711728" FT /id="VAR_004254" FT VARIANT 70 FT /note="V -> E (in FED; dbSNP:rs748427834)" FT /evidence="ECO:0000269|PubMed:15994445" FT /id="VAR_039023" FT VARIANT 95 FT /note="G -> R (found in a patient with intermediate FT phenotype between LCATD and FED; reduction of activity)" FT /evidence="ECO:0000269|PubMed:16216249" FT /id="VAR_039024" FT VARIANT 99 FT /note="W -> S (in FED; loss of activity)" FT /evidence="ECO:0000269|PubMed:21901787" FT /id="VAR_066862" FT VARIANT 115 FT /note="S -> P (in dbSNP:rs1412883954)" FT /evidence="ECO:0000269|PubMed:15994445" FT /id="VAR_039025" FT VARIANT 117 FT /note="A -> T (in LCATD; dbSNP:rs28940886)" FT /evidence="ECO:0000269|PubMed:8318557, FT ECO:0000269|PubMed:8432868" FT /id="VAR_004255" FT VARIANT 123 FT /note="R -> C (in FED; dbSNP:rs140068549)" FT /evidence="ECO:0000269|PubMed:9261271" FT /id="VAR_039026" FT VARIANT 134..135 FT /note="EY -> DN (in a patient with low HDL-cholesterol FT levels; results in reduced activity)" FT /evidence="ECO:0000269|PubMed:21901787" FT /id="VAR_066863" FT VARIANT 147 FT /note="T -> I (in FED; dbSNP:rs121908050)" FT /evidence="ECO:0000269|PubMed:1737840" FT /id="VAR_004256" FT VARIANT 159 FT /note="R -> Q (in FED; dbSNP:rs768017317)" FT /evidence="ECO:0000269|PubMed:8620346" FT /id="VAR_039027" FT VARIANT 159 FT /note="R -> W (in LCATD; dbSNP:rs28940887)" FT /evidence="ECO:0000269|PubMed:8432868" FT /id="VAR_004257" FT VARIANT 164 FT /note="R -> C (in LCATD; dbSNP:rs1380009545)" FT /evidence="ECO:0000269|PubMed:15994445" FT /id="VAR_039028" FT VARIANT 164 FT /note="R -> H (in LCATD; also found in a patient with FT intermediate phenotype between LCATD and FED; loss of FT activity; dbSNP:rs769485083)" FT /evidence="ECO:0000269|PubMed:16216249, FT ECO:0000269|PubMed:7607641" FT /id="VAR_004258" FT VARIANT 165 FT /note="A -> T (in dbSNP:rs1369994093)" FT /evidence="ECO:0000269|PubMed:15994445" FT /id="VAR_039029" FT VARIANT 171 FT /note="R -> W (in LCATD)" FT /evidence="ECO:0000269|PubMed:15994445, FT ECO:0000269|PubMed:2370048" FT /id="VAR_004259" FT VARIANT 180 FT /note="Y -> N (in LCATD; dbSNP:rs749740660)" FT /id="VAR_004260" FT VARIANT 182 FT /note="R -> C (in dbSNP:rs387906300)" FT /evidence="ECO:0000269|PubMed:8318557, FT ECO:0000269|PubMed:8432868" FT /id="VAR_004261" FT VARIANT 205 FT /note="S -> N (in LCATD)" FT /evidence="ECO:0000269|PubMed:15994445" FT /id="VAR_039030" FT VARIANT 232 FT /note="S -> T (in dbSNP:rs4986970)" FT /evidence="ECO:0000269|PubMed:12957688, FT ECO:0000269|PubMed:12966036, ECO:0000269|PubMed:16874701" FT /id="VAR_017030" FT VARIANT 233 FT /note="L -> P (in LCATD; dbSNP:rs28942087)" FT /evidence="ECO:0000269|PubMed:8432868" FT /id="VAR_004262" FT VARIANT 242 FT /note="K -> N (in LCATD)" FT /evidence="ECO:0000269|PubMed:15994445" FT /id="VAR_039031" FT VARIANT 246 FT /note="V -> F (in a patient with low HDL-cholesterol FT levels; the mutant is hardly secreted and is catalytically FT inactive)" FT /evidence="ECO:0000269|PubMed:21901787" FT /id="VAR_066864" FT VARIANT 252 FT /note="N -> K (in LCATD; dbSNP:rs121908049)" FT /evidence="ECO:0000269|PubMed:1681161" FT /id="VAR_004263" FT VARIANT 268 FT /note="R -> C (in a patient with low HDL-cholesterol FT levels; the mutant is hardly secreted and is catalytically FT inactive; dbSNP:rs745320775)" FT /evidence="ECO:0000269|PubMed:21901787" FT /id="VAR_066865" FT VARIANT 268 FT /note="R -> H (in LCATD; dbSNP:rs780824776)" FT /evidence="ECO:0000269|PubMed:15994445" FT /id="VAR_039032" FT VARIANT 276 FT /note="M -> K (in FED; dbSNP:rs121908054)" FT /evidence="ECO:0000269|PubMed:1516702" FT /id="VAR_004264" FT VARIANT 298 FT /note="T -> A (in FED and LCATD)" FT /evidence="ECO:0000269|PubMed:11423760, FT ECO:0000269|PubMed:15994445" FT /id="VAR_039033" FT VARIANT 298 FT /note="T -> I (in LCATD)" FT /evidence="ECO:0000269|PubMed:15994445" FT /id="VAR_039034" FT VARIANT 317 FT /note="M -> I (in LCATD; partially defective enzyme; FT dbSNP:rs121908048)" FT /evidence="ECO:0000269|PubMed:1681161, FT ECO:0000269|PubMed:1859405" FT /id="VAR_004265" FT VARIANT 322 FT /note="R -> C (in a patient with low HDL-cholesterol FT levels; reduced protein secretion; dbSNP:rs1407191796)" FT /evidence="ECO:0000269|PubMed:21901787" FT /id="VAR_066866" FT VARIANT 331 FT /note="P -> S (in LCATD)" FT /evidence="ECO:0000269|PubMed:9741700" FT /id="VAR_039035" FT VARIANT 333 FT /note="V -> M (in LCATD; dbSNP:rs776035233)" FT /evidence="ECO:0000269|PubMed:15994445, FT ECO:0000269|PubMed:16051254" FT /id="VAR_039036" FT VARIANT 338 FT /note="L -> F (in FED; results in reduced protein secretion FT and activity; dbSNP:rs1330635214)" FT /evidence="ECO:0000269|PubMed:21901787" FT /id="VAR_066867" FT VARIANT 345 FT /note="T -> M (in LCATD; dbSNP:rs28940888)" FT /evidence="ECO:0000269|PubMed:12957688, FT ECO:0000269|PubMed:8432868" FT /id="VAR_004266" FT VARIANT 347 FT /note="R -> C (in FED; results in reduced activity; FT dbSNP:rs202017590)" FT /evidence="ECO:0000269|PubMed:21901787" FT /id="VAR_066868" FT VARIANT 371 FT /note="T -> M (in FED; dbSNP:rs121908053)" FT /evidence="ECO:0000269|PubMed:1737840" FT /id="VAR_004267" FT VARIANT 396 FT /note="L -> R (in a patient with LCATD)" FT /evidence="ECO:0000269|PubMed:15994445, FT ECO:0000269|PubMed:16874701" FT /id="VAR_039037" FT VARIANT 406 FT /note="F -> V (in LCATD)" FT /evidence="ECO:0000269|PubMed:12957688" FT /id="VAR_039038" FT MUTAGEN 173 FT /note="E->A: Increased activity towards PAPC. Increased FT PAPC/POPC activity ratio." FT /evidence="ECO:0000269|PubMed:14636062" FT MUTAGEN 173 FT /note="E->D: Little change in enzyme specific activity nor FT in PAPC/POPC activity ratio." FT /evidence="ECO:0000269|PubMed:14636062" FT MUTAGEN 173 FT /note="E->K: Decreased enzyme specific activity. Increased FT PAPC/POPC activity ratio." FT /evidence="ECO:0000269|PubMed:14636062" FT MUTAGEN 173 FT /note="E->L: Increased activity towards PAPC. Increased FT PAPC/POPC activity ratio." FT /evidence="ECO:0000269|PubMed:14636062" FT MUTAGEN 173 FT /note="E->Q: Decreased enzyme specific activity. Increased FT PAPC/POPC activity ratio." FT /evidence="ECO:0000269|PubMed:14636062" FT CONFLICT 257 FT /note="I -> H (in Ref. 8; CAB56610/AAA59499)" FT /evidence="ECO:0000305" FT STRAND 49..52 FT /evidence="ECO:0007829|PDB:5BV7" FT STRAND 60..63 FT /evidence="ECO:0007829|PDB:5BV7" FT STRAND 82..86 FT /evidence="ECO:0007829|PDB:5BV7" FT HELIX 88..91 FT /evidence="ECO:0007829|PDB:5BV7" FT HELIX 95..103 FT /evidence="ECO:0007829|PDB:5BV7" FT STRAND 105..107 FT /evidence="ECO:0007829|PDB:5BV7" FT TURN 109..111 FT /evidence="ECO:0007829|PDB:5BV7" FT STRAND 114..117 FT /evidence="ECO:0007829|PDB:5BV7" FT STRAND 121..123 FT /evidence="ECO:0007829|PDB:5BV7" FT TURN 125..128 FT /evidence="ECO:0007829|PDB:4XWG" FT HELIX 131..134 FT /evidence="ECO:0007829|PDB:5BV7" FT STRAND 135..137 FT /evidence="ECO:0007829|PDB:5BV7" FT STRAND 142..145 FT /evidence="ECO:0007829|PDB:5BV7" FT HELIX 146..153 FT /evidence="ECO:0007829|PDB:5BV7" FT TURN 154..156 FT /evidence="ECO:0007829|PDB:5BV7" FT TURN 160..162 FT /evidence="ECO:0007829|PDB:5BV7" FT STRAND 163..165 FT /evidence="ECO:0007829|PDB:5BV7" FT HELIX 174..176 FT /evidence="ECO:0007829|PDB:5BV7" FT HELIX 178..195 FT /evidence="ECO:0007829|PDB:5BV7" FT STRAND 199..204 FT /evidence="ECO:0007829|PDB:5BV7" FT HELIX 206..217 FT /evidence="ECO:0007829|PDB:5BV7" FT HELIX 220..226 FT /evidence="ECO:0007829|PDB:5BV7" FT STRAND 227..234 FT /evidence="ECO:0007829|PDB:5BV7" FT HELIX 242..248 FT /evidence="ECO:0007829|PDB:5BV7" FT TURN 250..252 FT /evidence="ECO:0007829|PDB:5BV7" FT TURN 255..257 FT /evidence="ECO:0007829|PDB:5BV7" FT STRAND 258..260 FT /evidence="ECO:0007829|PDB:5TXF" FT STRAND 270..272 FT /evidence="ECO:0007829|PDB:5BV7" FT HELIX 274..276 FT /evidence="ECO:0007829|PDB:5BV7" FT TURN 280..282 FT /evidence="ECO:0007829|PDB:5BV7" FT STRAND 288..291 FT /evidence="ECO:0007829|PDB:5BV7" FT STRAND 296..298 FT /evidence="ECO:0007829|PDB:5BV7" FT HELIX 299..301 FT /evidence="ECO:0007829|PDB:5TXF" FT HELIX 302..308 FT /evidence="ECO:0007829|PDB:5BV7" FT HELIX 312..321 FT /evidence="ECO:0007829|PDB:5BV7" FT TURN 322..327 FT /evidence="ECO:0007829|PDB:5BV7" FT STRAND 335..350 FT /evidence="ECO:0007829|PDB:5BV7" FT TURN 353..357 FT /evidence="ECO:0007829|PDB:5BV7" FT STRAND 361..373 FT /evidence="ECO:0007829|PDB:5BV7" FT HELIX 374..377 FT /evidence="ECO:0007829|PDB:5BV7" FT HELIX 378..383 FT /evidence="ECO:0007829|PDB:5BV7" FT STRAND 386..389 FT /evidence="ECO:0007829|PDB:5BV7" FT STRAND 391..397 FT /evidence="ECO:0007829|PDB:5BV7" FT HELIX 401..403 FT /evidence="ECO:0007829|PDB:5BV7" FT TURN 404..406 FT /evidence="ECO:0007829|PDB:5BV7" FT HELIX 408..419 FT /evidence="ECO:0007829|PDB:5BV7" FT TURN 420..422 FT /evidence="ECO:0007829|PDB:5BV7" SQ SEQUENCE 440 AA; 49578 MW; B315EF118AA7A378 CRC64; MGPPGSPWQW VTLLLGLLLP PAAPFWLLNV LFPPHTTPKA ELSNHTRPVI LVPGCLGNQL EAKLDKPDVV NWMCYRKTED FFTIWLDLNM FLPLGVDCWI DNTRVVYNRS SGLVSNAPGV QIRVPGFGKT YSVEYLDSSK LAGYLHTLVQ NLVNNGYVRD ETVRAAPYDW RLEPGQQEEY YRKLAGLVEE MHAAYGKPVF LIGHSLGCLH LLYFLLRQPQ AWKDRFIDGF ISLGAPWGGS IKPMLVLASG DNQGIPIMSS IKLKEEQRIT TTSPWMFPSR MAWPEDHVFI STPSFNYTGR DFQRFFADLH FEEGWYMWLQ SRDLLAGLPA PGVEVYCLYG VGLPTPRTYI YDHGFPYTDP VGVLYEDGDD TVATRSTELC GLWQGRQPQP VHLLPLHGIQ HLNMVFSNLT LEHINAILLG AYRQGPPASP TASPEPPPPE //