PON1_HUMAN
ID PON1_HUMAN Reviewed; 355 AA.
AC P27169; B2RA40; Q16052; Q6B0J6; Q9UCB1;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 3.
DT 03-AUG-2022, entry version 219.
DE RecName: Full=Serum paraoxonase/arylesterase 1 {ECO:0000303|PubMed:7916578};
DE Short=PON 1 {ECO:0000303|PubMed:15772423};
DE EC=3.1.1.2 {ECO:0000269|PubMed:15098021, ECO:0000269|PubMed:15772423, ECO:0000269|PubMed:1673382, ECO:0000269|PubMed:1718413, ECO:0000269|PubMed:8393742};
DE EC=3.1.1.81 {ECO:0000269|PubMed:15098021, ECO:0000269|PubMed:15772423};
DE EC=3.1.8.1 {ECO:0000269|PubMed:15098021, ECO:0000269|PubMed:15772423, ECO:0000269|PubMed:1673382, ECO:0000269|PubMed:1718413, ECO:0000269|PubMed:8393742};
DE AltName: Full=Aromatic esterase 1;
DE Short=A-esterase 1;
DE AltName: Full=K-45;
DE AltName: Full=Serum aryldialkylphosphatase 1;
GN Name=PON1; Synonyms=PON;
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 [MRNA], AND VARIANTS MET-55 AND ARG-192.
RC TISSUE=Liver;
RX PubMed=1657140; DOI=10.1021/bi00106a010;
RA Hassett C., Richter R.J., Humbert R., Chapline C., Crabb J.W.,
RA Omiecinski C.J., Furlong C.E.;
RT "Characterization of cDNA clones encoding rabbit and human serum
RT paraoxonase: the mature protein retains its signal sequence.";
RL Biochemistry 30:10141-10149(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], POLYMORPHISM, AND VARIANTS MET-55 AND
RP ARG-192.
RX PubMed=7916578;
RA Adkins S., Gan K.N., Mody M., La Du B.N.;
RT "Molecular basis for the polymorphic forms of human serum
RT paraoxonase/arylesterase: glutamine or arginine at position 191, for the
RT respective A or B allozymes.";
RL Am. J. Hum. Genet. 52:598-608(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, AND VARIANTS MET-55 AND
RP ARG-192.
RC TISSUE=Liver;
RX PubMed=8393742; DOI=10.1016/0009-2797(93)90022-q;
RA La Du B.N., Adkins S., Kuo C.L., Lipsig D.;
RT "Studies on human serum paraoxonase/arylesterase.";
RL Chem. Biol. Interact. 87:25-34(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANTS MET-55 AND ARG-192, AND
RP CHARACTERIZATION.
RC TISSUE=Liver;
RX PubMed=8393745; DOI=10.1016/0009-2797(93)90023-r;
RA Furlong C.E., Costa L.G., Hassett C., Richter R.J., Sundstrom J.A.,
RA Adler D.A., Disteche C.M., Omiecinski C.J., Chapline C., Crabb J.W.;
RT "Human and rabbit paraoxonases: purification, cloning, sequencing, mapping
RT and role of polymorphism in organophosphate detoxification.";
RL Chem. Biol. Interact. 87:35-48(1993).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT MET-55.
RC TISSUE=Lymphoblast;
RX PubMed=8812495; DOI=10.1006/geno.1996.0401;
RA Clendenning J.B., Humbert R., Green E.D., Wood C., Traver D., Furlong C.E.;
RT "Structural organization of the human PON1 gene.";
RL Genomics 35:586-589(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=9261565; DOI=10.1038/cr.1997.9;
RA Wang K.K., Wan D.F., Qiu X.K., Lu P.X., Gu J.R.;
RT "Differential expression of a cDNA clone in human liver versus hepatic
RT cancer -- highly homologous to aryl-dialkyl-phosphatase.";
RL Cell Res. 7:79-90(1997).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-55.
RC TISSUE=Liver;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-192.
RG SeattleSNPs variation discovery resource;
RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [11]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
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 [13]
RP PROTEIN SEQUENCE OF 2-21, AND TISSUE SPECIFICITY.
RX PubMed=8382160; DOI=10.1111/j.1432-1033.1993.tb17620.x;
RA Blatter M.-C., James R.W., Messmer S., Barja F., Pometta D.;
RT "Identification of a distinct human high-density lipoprotein subspecies
RT defined by a lipoprotein-associated protein, K-45. Identity of K-45 with
RT paraoxonase.";
RL Eur. J. Biochem. 211:871-879(1993).
RN [14]
RP PROTEIN SEQUENCE OF 2-21; 234-244; 291-305 AND 350-355, INTERACTION WITH
RP CLU, TISSUE SPECIFICITY, AND DISULFIDE BOND.
RC TISSUE=Plasma;
RX PubMed=8292612; DOI=10.1021/bi00169a026;
RA Kelso G.J., Stuart W.D., Richter R.J., Furlong C.E., Jordan-Starck T.C.,
RA Harmony J.A.K.;
RT "Apolipoprotein J is associated with paraoxonase in human plasma.";
RL Biochemistry 33:832-839(1994).
RN [15]
RP PROTEIN SEQUENCE OF 2-11, AND CATALYTIC ACTIVITY.
RX PubMed=1718413; DOI=10.1021/bi00106a009;
RA Furlong C.E., Richter R.J., Chapline C., Crabb J.W.;
RT "Purification of rabbit and human serum paraoxonase.";
RL Biochemistry 30:10133-10140(1991).
RN [16]
RP CATALYTIC ACTIVITY.
RX PubMed=1673382;
RA Gan K.N., Smolen A., Eckerson H.W., La Du B.N.;
RT "Purification of human serum paraoxonase/arylesterase. Evidence for one
RT esterase catalyzing both activities.";
RL Drug Metab. Dispos. 19:100-106(1991).
RN [17]
RP MUTAGENESIS OF CYS-284.
RX PubMed=7638166; DOI=10.1073/pnas.92.16.7187;
RA Sorenson R.C., Primo-Parmo S.L., Kuo C.-L., Adkins S., Lockridge O.,
RA La Du B.N.;
RT "Reconsideration of the catalytic center and mechanism of mammalian
RT paraoxonase/arylesterase.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:7187-7191(1995).
RN [18]
RP MUTAGENESIS OF 20-HIS-GLN-21, AND FUNCTION OF THE UNCLEAVED SIGNAL PEPTIDE.
RX PubMed=10479665; DOI=10.1161/01.atv.19.9.2214;
RA Sorenson R.C., Bisgaier C.L., Aviram M., Hsu C., Billecke S., La Du B.N.;
RT "Human serum paraoxonase/arylesterase's retained hydrophobic N-terminal
RT leader sequence associates with HDLs by binding phospholipids:
RT apolipoprotein A-I stabilizes activity.";
RL Arterioscler. Thromb. Vasc. Biol. 19:2214-2225(1999).
RN [19]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-253.
RC TISSUE=Plasma;
RX PubMed=14760718; DOI=10.1002/pmic.200300556;
RA Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.;
RT "Screening for N-glycosylated proteins by liquid chromatography mass
RT spectrometry.";
RL Proteomics 4:454-465(2004).
RN [20]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=15772423; DOI=10.1194/jlr.m400511-jlr200;
RA Draganov D.I., Teiber J.F., Speelman A., Osawa Y., Sunahara R., La Du B.N.;
RT "Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping
RT and distinct substrate specificities.";
RL J. Lipid Res. 46:1239-1247(2005).
RN [21]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-253 AND ASN-324.
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 [22]
RP INTERACTION WITH HPBP.
RX PubMed=16531243; DOI=10.1016/j.str.2005.12.012;
RA Morales R., Berna A., Carpentier P., Contreras-Martel C., Renault F.,
RA Nicodeme M., Chesne-Seck M.-L., Bernier F., Dupuy J., Schaeffer C.,
RA Diemer H., van Dorsselaer A., Fontecilla-Camps J.C., Masson P., Rochu D.,
RA Chabriere E.;
RT "Serendipitous discovery and X-ray structure of a human phosphate binding
RT apolipoprotein.";
RL Structure 14:601-609(2006).
RN [23]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-253 AND ASN-324.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH CALCIUM IONS,
RP MUTAGENESIS OF HIS-115 AND HIS-134, CATALYTIC ACTIVITY, AND DISULFIDE BOND.
RX PubMed=15098021; DOI=10.1038/nsmb767;
RA Harel M., Aharoni A., Gaidukov L., Brumshtein B., Khersonsky O., Meged R.,
RA Dvir H., Ravelli R.B.G., McCarthy A., Toker L., Silman I., Sussman J.L.,
RA Tawfik D.S.;
RT "Structure and evolution of the serum paraoxonase family of detoxifying and
RT anti-atherosclerotic enzymes.";
RL Nat. Struct. Mol. Biol. 11:412-419(2004).
RN [26]
RP POLYMORPHISM, VARIANT ARG-192, AND CHARACTERIZATION OF VARIANT ARG-192.
RX PubMed=8098250; DOI=10.1038/ng0193-73;
RA Humbert R., Adler D.A., Disteche C.M., Hassett C., Omiecinski C.J.,
RA Furlong C.E.;
RT "The molecular basis of the human serum paraoxonase activity
RT polymorphism.";
RL Nat. Genet. 3:73-76(1993).
RN [27]
RP ASSOCIATION WITH DIABETIC RETINOPATHY SUSCEPTIBILITY.
RX PubMed=9661650; DOI=10.1210/jcem.83.7.5096;
RA Kao Y.-L., Donaghue K., Chan A., Knight J., Silink M.;
RT "A variant of paraoxonase (PON1) gene is associated with diabetic
RT retinopathy in IDDM.";
RL J. Clin. Endocrinol. Metab. 83:2589-2592(1998).
RN [28]
RP VARIANT VAL-102.
RX PubMed=12783936; DOI=10.1093/jnci/95.11.812;
RA Marchesani M., Hakkarainen A., Tuomainen T.P., Kaikkonen J., Pukkala E.,
RA Uimari P., Seppala E., Matikainen M., Kallioniemi O.-P., Schleutker J.,
RA Lehtimaki T., Salonen J.T.;
RT "New paraoxonase 1 polymorphism I102V and the risk of prostate cancer in
RT Finnish men.";
RL J. Natl. Cancer Inst. 95:812-818(2003).
RN [29]
RP VARIANT [LARGE SCALE ANALYSIS] ARG-192.
RX PubMed=18987736; DOI=10.1038/nature07485;
RA Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K.,
RA Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L.,
RA Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A.,
RA Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V.,
RA Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R.,
RA Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E.,
RA Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S.,
RA Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A.,
RA DiPersio J.F., Wilson R.K.;
RT "DNA sequencing of a cytogenetically normal acute myeloid leukaemia
RT genome.";
RL Nature 456:66-72(2008).
CC -!- FUNCTION: Hydrolyzes the toxic metabolites of a variety of
CC organophosphorus insecticides. Capable of hydrolyzing a broad spectrum
CC of organophosphate substrates and lactones, and a number of aromatic
CC carboxylic acid esters. Mediates an enzymatic protection of low density
CC lipoproteins against oxidative modification and the consequent series
CC of events leading to atheroma formation. {ECO:0000269|PubMed:10479665,
CC ECO:0000269|PubMed:15772423}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a phenyl acetate + H2O = a phenol + acetate + H(+);
CC Xref=Rhea:RHEA:17309, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30089, ChEBI:CHEBI:33853, ChEBI:CHEBI:140310; EC=3.1.1.2;
CC Evidence={ECO:0000269|PubMed:15098021, ECO:0000269|PubMed:15772423,
CC ECO:0000269|PubMed:1673382, ECO:0000269|PubMed:1718413,
CC ECO:0000269|PubMed:8393742};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=An aryl dialkyl phosphate + H2O = dialkyl phosphate + an aryl
CC alcohol.; EC=3.1.8.1; Evidence={ECO:0000269|PubMed:15098021,
CC ECO:0000269|PubMed:15772423, ECO:0000269|PubMed:1673382,
CC ECO:0000269|PubMed:1718413, ECO:0000269|PubMed:8393742};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-acyl-L-homoserine lactone + H2O = an N-acyl-L-homoserine
CC + H(+); Xref=Rhea:RHEA:22576, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:55474, ChEBI:CHEBI:58921; EC=3.1.1.81;
CC Evidence={ECO:0000269|PubMed:15098021, ECO:0000269|PubMed:15772423};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Note=Binds 2 calcium ions per subunit.;
CC -!- SUBUNIT: Homodimer. Heterooligomer with phosphate-binding protein
CC (HPBP). Interacts with CLU. {ECO:0000269|PubMed:15098021,
CC ECO:0000269|PubMed:15772423, ECO:0000269|PubMed:16531243,
CC ECO:0000269|PubMed:8292612}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space.
CC -!- TISSUE SPECIFICITY: Plasma, associated with HDL (at protein level).
CC Expressed in liver, but not in heart, brain, placenta, lung, skeletal
CC muscle, kidney or pancreas. {ECO:0000269|PubMed:8292612,
CC ECO:0000269|PubMed:8382160}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:14760718,
CC ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218}.
CC -!- PTM: The signal sequence is not cleaved.
CC -!- PTM: Present in two forms, form B contains a disulfide bond, form A
CC does not.
CC -!- POLYMORPHISM: The allelic form of the enzyme with Gln-192 (allozyme A)
CC hydrolyzes paraoxon with a low turnover number and the one with Arg-192
CC (allozyme B) with a high turnover number. {ECO:0000269|PubMed:7916578,
CC ECO:0000269|PubMed:8098250}.
CC -!- DISEASE: Microvascular complications of diabetes 5 (MVCD5)
CC [MIM:612633]: Pathological conditions that develop in numerous tissues
CC and organs as a consequence of diabetes mellitus. They include diabetic
CC retinopathy, diabetic nephropathy leading to end-stage renal disease,
CC and diabetic neuropathy. Diabetic retinopathy remains the major cause
CC of new-onset blindness among diabetic adults. It is characterized by
CC vascular permeability and increased tissue ischemia and angiogenesis.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry. Homozygosity for the Leu-55 allele is
CC strongly associated with the development of retinal disease in diabetic
CC patients.
CC -!- MISCELLANEOUS: The preferential association of PON1 with HDL is
CC mediated in part by its signal peptide, by binding phospholipids
CC directly, rather than binding apo AI. The retained signal peptide may
CC allow transfer of the protein between phospholipid surfaces.
CC -!- SIMILARITY: Belongs to the paraoxonase family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/pon1/";
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DR EMBL; M63012; AAB59538.1; -; mRNA.
DR EMBL; M63013; AAA60142.1; -; mRNA.
DR EMBL; M63014; AAA60143.1; -; mRNA.
DR EMBL; S56555; AAB25717.1; -; Genomic_DNA.
DR EMBL; S56546; AAB25717.1; JOINED; Genomic_DNA.
DR EMBL; S56548; AAB25717.1; JOINED; Genomic_DNA.
DR EMBL; S64696; AAB27899.1; -; mRNA.
DR EMBL; S64615; AAB27714.2; -; mRNA.
DR EMBL; U55885; AAB41835.1; -; Genomic_DNA.
DR EMBL; U55877; AAB41835.1; JOINED; Genomic_DNA.
DR EMBL; U55878; AAB41835.1; JOINED; Genomic_DNA.
DR EMBL; U55879; AAB41835.1; JOINED; Genomic_DNA.
DR EMBL; U55880; AAB41835.1; JOINED; Genomic_DNA.
DR EMBL; U55881; AAB41835.1; JOINED; Genomic_DNA.
DR EMBL; U55882; AAB41835.1; JOINED; Genomic_DNA.
DR EMBL; U55883; AAB41835.1; JOINED; Genomic_DNA.
DR EMBL; D84371; BAA12327.1; -; mRNA.
DR EMBL; U53784; AAA97957.1; -; mRNA.
DR EMBL; Z70723; CAA94728.1; -; mRNA.
DR EMBL; AK314027; BAG36737.1; -; mRNA.
DR EMBL; AF539592; AAM97935.1; -; Genomic_DNA.
DR EMBL; AC004022; AAC35293.1; -; Genomic_DNA.
DR EMBL; CH236949; EAL24133.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76771.1; -; Genomic_DNA.
DR EMBL; BC074719; AAH74719.1; -; mRNA.
DR CCDS; CCDS5638.1; -.
DR PIR; A45451; A45451.
DR RefSeq; NP_000437.3; NM_000446.5.
DR PDB; 1V04; X-ray; 2.20 A; A=1-353.
DR PDBsum; 1V04; -.
DR AlphaFoldDB; P27169; -.
DR SMR; P27169; -.
DR BioGRID; 111440; 18.
DR IntAct; P27169; 7.
DR STRING; 9606.ENSP00000222381; -.
DR BindingDB; P27169; -.
DR ChEMBL; CHEMBL3167; -.
DR DrugBank; DB01327; Cefazolin.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB01395; Drospirenone.
DR DrugBank; DB14598; Edetate calcium disodium anhydrous.
DR DrugBank; DB14600; Edetate disodium anhydrous.
DR DrugBank; DB14596; Loteprednol etabonate.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR TCDB; 1.A.6.2.6; the epithelial na(+) channel (enac) family.
DR GlyConnect; 726; 20 N-Linked glycans (3 sites).
DR GlyGen; P27169; 4 sites, 30 N-linked glycans (3 sites).
DR iPTMnet; P27169; -.
DR PhosphoSitePlus; P27169; -.
DR BioMuta; PON1; -.
DR DMDM; 308153572; -.
DR SWISS-2DPAGE; P27169; -.
DR CPTAC; CPTAC-2233; -.
DR CPTAC; non-CPTAC-2695; -.
DR jPOST; P27169; -.
DR MassIVE; P27169; -.
DR MaxQB; P27169; -.
DR PaxDb; P27169; -.
DR PeptideAtlas; P27169; -.
DR PRIDE; P27169; -.
DR ProteomicsDB; 54376; -.
DR Antibodypedia; 883; 644 antibodies from 39 providers.
DR DNASU; 5444; -.
DR Ensembl; ENST00000222381.8; ENSP00000222381.3; ENSG00000005421.9.
DR GeneID; 5444; -.
DR KEGG; hsa:5444; -.
DR MANE-Select; ENST00000222381.8; ENSP00000222381.3; NM_000446.7; NP_000437.3.
DR UCSC; uc003uns.4; human.
DR CTD; 5444; -.
DR DisGeNET; 5444; -.
DR GeneCards; PON1; -.
DR HGNC; HGNC:9204; PON1.
DR HPA; ENSG00000005421; Tissue enriched (liver).
DR MalaCards; PON1; -.
DR MIM; 168820; gene+phenotype.
DR MIM; 612633; phenotype.
DR neXtProt; NX_P27169; -.
DR OpenTargets; ENSG00000005421; -.
DR Orphanet; 803; Amyotrophic lateral sclerosis.
DR PharmGKB; PA33529; -.
DR VEuPathDB; HostDB:ENSG00000005421; -.
DR eggNOG; ENOG502S3B5; Eukaryota.
DR GeneTree; ENSGT00390000008932; -.
DR HOGENOM; CLU_049839_0_1_1; -.
DR InParanoid; P27169; -.
DR OMA; NAMYLLV; -.
DR OrthoDB; 888266at2759; -.
DR PhylomeDB; P27169; -.
DR TreeFam; TF322436; -.
DR BRENDA; 3.1.1.2; 2681.
DR BRENDA; 3.1.1.25; 2681.
DR BRENDA; 3.1.1.81; 2681.
DR BRENDA; 3.1.8.1; 2681.
DR BRENDA; 3.1.8.2; 2681.
DR PathwayCommons; P27169; -.
DR Reactome; R-HSA-2142688; Synthesis of 5-eicosatetraenoic acids.
DR Reactome; R-HSA-9754706; Atorvastatin ADME.
DR SABIO-RK; P27169; -.
DR SignaLink; P27169; -.
DR SIGNOR; P27169; -.
DR BioGRID-ORCS; 5444; 13 hits in 1065 CRISPR screens.
DR ChiTaRS; PON1; human.
DR EvolutionaryTrace; P27169; -.
DR GeneWiki; PON1; -.
DR GenomeRNAi; 5444; -.
DR Pharos; P27169; Tbio.
DR PRO; PR:P27169; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P27169; protein.
DR Bgee; ENSG00000005421; Expressed in right lobe of liver and 101 other tissues.
DR ExpressionAtlas; P27169; baseline and differential.
DR Genevisible; P27169; HS.
DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
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:BHF-UCL.
DR GO; GO:0034364; C:high-density lipoprotein particle; IDA:BHF-UCL.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IEA:Ensembl.
DR GO; GO:0034366; C:spherical high-density lipoprotein particle; IDA:BHF-UCL.
DR GO; GO:0102007; F:acyl-L-homoserine-lactone lactonohydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0004063; F:aryldialkylphosphatase activity; IDA:UniProtKB.
DR GO; GO:0004064; F:arylesterase activity; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; IDA:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
DR GO; GO:0019439; P:aromatic compound catabolic process; IDA:BHF-UCL.
DR GO; GO:0046395; P:carboxylic acid catabolic process; IDA:BHF-UCL.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:Ensembl.
DR GO; GO:0046434; P:organophosphate catabolic process; IDA:BHF-UCL.
DR GO; GO:0046470; P:phosphatidylcholine metabolic process; IDA:BHF-UCL.
DR GO; GO:0051099; P:positive regulation of binding; IDA:BHF-UCL.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; IDA:BHF-UCL.
DR GO; GO:0032411; P:positive regulation of transporter activity; IDA:BHF-UCL.
DR GO; GO:0070542; P:response to fatty acid; IEA:Ensembl.
DR GO; GO:1902617; P:response to fluoride; IEA:Ensembl.
DR GO; GO:0031667; P:response to nutrient levels; IEA:Ensembl.
DR GO; GO:0009636; P:response to toxic substance; IBA:GO_Central.
DR Gene3D; 2.120.10.30; -; 1.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR002640; Arylesterase.
DR InterPro; IPR008363; Paraoxonase1.
DR PANTHER; PTHR11799:SF16; PTHR11799:SF16; 1.
DR Pfam; PF01731; Arylesterase; 1.
DR PRINTS; PR01785; PARAOXONASE.
DR PRINTS; PR01786; PARAOXONASE1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; HDL; Hydrolase; Metal-binding; Reference proteome; Secreted;
KW Signal.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:1718413,
FT ECO:0000269|PubMed:8292612, ECO:0000269|PubMed:8382160"
FT CHAIN 2..355
FT /note="Serum paraoxonase/arylesterase 1"
FT /id="PRO_0000223281"
FT SIGNAL 2..?
FT /note="Not cleaved"
FT ACT_SITE 115
FT /note="Proton acceptor"
FT /evidence="ECO:0000305"
FT BINDING 53
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT BINDING 54
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 117
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 168
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT BINDING 169
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 224
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT BINDING 269
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT BINDING 270
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT CARBOHYD 253
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14760718,
FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218"
FT CARBOHYD 270
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 324
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218"
FT DISULFID 42..353
FT /note="In form B"
FT /evidence="ECO:0000269|PubMed:15098021,
FT ECO:0000269|PubMed:8292612"
FT VARIANT 55
FT /note="L -> M (in dbSNP:rs854560)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:1657140, ECO:0000269|PubMed:7916578,
FT ECO:0000269|PubMed:8393742, ECO:0000269|PubMed:8393745,
FT ECO:0000269|PubMed:8812495"
FT /id="VAR_006043"
FT VARIANT 102
FT /note="I -> V (may be associated with an increased risk for
FT prostate cancer; associated with decreased activity;
FT dbSNP:rs72552787)"
FT /evidence="ECO:0000269|PubMed:12783936"
FT /id="VAR_015882"
FT VARIANT 160
FT /note="R -> G (in dbSNP:rs13306698)"
FT /id="VAR_055342"
FT VARIANT 192
FT /note="Q -> R (in allozyme B; increased arylesterase
FT activity; dbSNP:rs662)"
FT /evidence="ECO:0000269|PubMed:1657140,
FT ECO:0000269|PubMed:18987736, ECO:0000269|PubMed:7916578,
FT ECO:0000269|PubMed:8098250, ECO:0000269|PubMed:8393742,
FT ECO:0000269|PubMed:8393745, ECO:0000269|Ref.8"
FT /id="VAR_006044"
FT MUTAGEN 20..21
FT /note="HQ->AA: The signal peptide is cleaved; not
FT associated with HDL."
FT /evidence="ECO:0000269|PubMed:10479665"
FT MUTAGEN 115
FT /note="H->Q: Reduces activity 10000-fold."
FT /evidence="ECO:0000269|PubMed:15098021"
FT MUTAGEN 134
FT /note="H->Q: Substantially reduced activity."
FT /evidence="ECO:0000269|PubMed:15098021"
FT MUTAGEN 284
FT /note="C->A,S: No loss of activity."
FT /evidence="ECO:0000269|PubMed:7638166"
FT HELIX 19..27
FT /evidence="ECO:0007829|PDB:1V04"
FT TURN 28..31
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 54..57
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 61..67
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 84..89
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 97..99
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:1V04"
FT HELIX 109..111
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 114..121
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 127..133
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 140..147
FT /evidence="ECO:0007829|PDB:1V04"
FT TURN 148..151
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 152..159
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 165..174
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 177..183
FT /evidence="ECO:0007829|PDB:1V04"
FT HELIX 189..197
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 203..208
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 213..228
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 232..239
FT /evidence="ECO:0007829|PDB:1V04"
FT TURN 240..243
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 244..250
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 256..263
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 265..273
FT /evidence="ECO:0007829|PDB:1V04"
FT TURN 275..277
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 280..286
FT /evidence="ECO:0007829|PDB:1V04"
FT HELIX 288..292
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 302..308
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 312..314
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 316..323
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 325..328
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 330..337
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 340..348
FT /evidence="ECO:0007829|PDB:1V04"
FT STRAND 350..353
FT /evidence="ECO:0007829|PDB:1V04"
SQ SEQUENCE 355 AA; 39731 MW; 9B5895509166167E CRC64;
MAKLIALTLL GMGLALFRNH QSSYQTRLNA LREVQPVELP NCNLVKGIET GSEDLEILPN
GLAFISSGLK YPGIKSFNPN SPGKILLMDL NEEDPTVLEL GITGSKFDVS SFNPHGISTF
TDEDNAMYLL VVNHPDAKST VELFKFQEEE KSLLHLKTIR HKLLPNLNDI VAVGPEHFYG
TNDHYFLDPY LQSWEMYLGL AWSYVVYYSP SEVRVVAEGF DFANGINISP DGKYVYIAEL
LAHKIHVYEK HANWTLTPLK SLDFNTLVDN ISVDPETGDL WVGCHPNGMK IFFYDSENPP
ASEVLRIQNI LTEEPKVTQV YAENGTVLQG STVASVYKGK LLIGTVFHKA LYCEL
