ID PON1_HUMAN Reviewed; 355 AA. AC P27169; B2RA40; Q16052; Q6B0J6; Q9UCB1; DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 07-JUL-2009, entry version 116. DE RecName: Full=Serum paraoxonase/arylesterase 1; DE Short=PON 1; DE EC=3.1.1.2; DE EC=3.1.8.1; DE AltName: Full=Serum aryldialkylphosphatase 1; DE AltName: Full=A-esterase 1; DE AltName: Full=Aromatic esterase 1; DE AltName: Full=K-45; GN Name=PON1; Synonyms=PON; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS LEU-55 AND ARG-192. RC TISSUE=Liver; RX MEDLINE=92031445; 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], AND VARIANT ARG-192. RX MEDLINE=93190991; 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 RT the respective A or B allozymes."; RL Am. J. Hum. Genet. 52:598-608(1993). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, AND VARIANT ARG-192. RC TISSUE=Liver; RX MEDLINE=93345086; 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 LEU-55 AND ARG-192, AND RP CHARACTERIZATION. RC TISSUE=Liver; RX MEDLINE=93345100; 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, RT mapping and role of polymorphism in organophosphate detoxification."; RL Chem. Biol. Interact. 87:35-48(1993). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-55. RC TISSUE=Lymphoblast; RX MEDLINE=97001162; PubMed=8812495; DOI=10.1006/geno.1996.0401; RA Clendenning J.B., Humbert R., Green E.D., Wood C., Traver D., RA Furlong C.E.; RT "Structural organization of the human PON1 gene."; RL Genomics 35:586-589(1996). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LEU-55. RC TISSUE=Liver; RX PubMed=9261565; 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]. 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 VARIANTS LEU-55 AND 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], AND VARIANT LEU-55. RX MEDLINE=22737999; 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., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA 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., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., 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], AND VARIANT LEU-55. RX MEDLINE=22616434; 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., RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., RA 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., RA Mural R.J., 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], AND VARIANT LEU-55. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-55. 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [13] RP PROTEIN SEQUENCE OF 2-21, AND TISSUE SPECIFICITY. RX MEDLINE=93170324; PubMed=8382160; RX 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 RT subspecies defined by a lipoprotein-associated protein, K-45. Identity RT of K-45 with 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 RP WITH 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., RA Jordan-Starck T.C., 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 MEDLINE=92031444; 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 MEDLINE=91209153; PubMed=1673382; RA Gan K.N., Smolen A., Eckerson H.W., La Du B.N.; RT "Purification of human serum paraoxonase/arylesterase. Evidence for RT one esterase catalyzing both activities."; RL Drug Metab. Dispos. 19:100-106(1991). RN [17] RP MUTAGENESIS OF CYS-284. RX MEDLINE=95365333; 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 RP PEPTIDE. RX PubMed=10479665; RA Sorenson R.C., Bisgaier C.L., Aviram M., Hsu C., Billecke S., RA La Du B.N.; RT "Human serum paraoxonase/arylesterase's retained hydrophobic N- RT terminal leader sequence associates with HDLs by binding RT phospholipids: apolipoprotein A-I stabilizes activity."; RL Arterioscler. Thromb. Vasc. Biol. 19:2214-2225(1999). RN [19] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-253, AND MASS RP SPECTROMETRY. 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 GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-227; ASN-253 AND ASN-324, RP AND MASS SPECTROMETRY. 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., RA Moore R.J., 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 [21] 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., RA Rochu D., Chabriere E.; RT "Serendipitous discovery and X-ray structure of a human phosphate RT binding apolipoprotein."; RL Structure 14:601-609(2006). RN [22] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-253 AND ASN-324, AND MASS RP SPECTROMETRY. 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 RT multiple enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [23] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS). RX PubMed=15098021; DOI=10.1038/nsmb767; RA Harel M., Aharoni A., Gaidukov L., Brumshtein B., Khersonsky O., RA Meged R., Dvir H., Ravelli R.B., McCarthy A., Toker L., Silman I., RA Sussman J.L., Tawfik D.S.; RT "Structure and evolution of the serum paraoxonase family of RT detoxifying and anti-atherosclerotic enzymes."; RL Nat. Struct. Mol. Biol. 11:412-419(2004). RN [24] RP VARIANT ARG-192. RX MEDLINE=93258411; 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 [25] RP VARIANT LEU-55, AND ASSOCIATION WITH DIABETIC RETINOPATHY RP SUSCEPTIBILITY. RX PubMed=9661650; DOI=10.1210/jc.83.7.2589; 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 [26] RP VARIANT VAL-102. RX MEDLINE=22669158; PubMed=12783936; DOI=10.1093/jnci/95.11.812; RA Marchesani M., Hakkarainen A., Tuomainen T.P., Kaikkonen J., RA Pukkala E., Uimari P., Seppala E., Matikainen M., Kallioniemi O.-P., RA Schleutker J., Lehtimaki T., Salonen J.T.; RT "New paraoxonase 1 polymorphism I102V and the risk of prostate cancer RT in Finnish men."; RL J. Natl. Cancer Inst. 95:812-818(2003). RN [27] 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., RA Heath S., Shannon W.D., Nagarajan R., Walter M.J., Link D.C., RA Graubert T.A., 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 CC spectrum of organophosphate substrates and a number of aromatic CC carboxylic acid esters. May mediate an enzymatic protection of low CC density lipoproteins against oxidative modification and the CC consequent series of events leading to atheroma formation. CC -!- CATALYTIC ACTIVITY: A phenyl acetate + H(2)O = a phenol + acetate. CC -!- CATALYTIC ACTIVITY: An aryl dialkyl phosphate + H(2)O = dialkyl CC phosphate + an aryl alcohol. CC -!- SUBUNIT: Heterooligomer with phosphate-binding protein (HPBP). CC Interacts with CLU. CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space. CC -!- TISSUE SPECIFICITY: Plasma, associated with HDL (at protein CC level). Expressed in liver, but not in heart, brain, placenta, CC lung, skeletal muscle, kidney or pancreas. CC -!- PTM: Glycosylated. CC -!- PTM: The signal sequence is not cleaved. CC -!- PTM: Present in two forms, form B contains a disulfide bond, form CC A does not. CC -!- POLYMORPHISM: The allelic form of the enzyme with Gln-192 CC (allozyme A) hydrolyzes paraoxon with a low turnover number and CC the one with Arg-192 (allozyme B) with a high turnover number. CC -!- DISEASE: Genetic variation in PON1 is associated with CC susceptibility to diabetic retinopathy [MIM:612633]; also called CC microvascular complications of diabetes type 5 (MVCD5). Diabetic CC retinopathy is a major cause of blindness in diabetic patients. CC Retinal disease results from adverse effects on the blood vessels CC which supply the retina. 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 CC may allow transfer of the protein between phospholipid surfaces. CC -!- SIMILARITY: Belongs to the paraoxonase family. CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/pon1/"; CC -!- WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and CC polymorphism database; CC URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=PON1"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- 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; -; Unassigned_DNA. 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 IPI; IPI00218732; -. DR PIR; A45451; A45451. DR RefSeq; NP_000437.3; -. DR UniGene; Hs.370995; -. DR PDB; 1V04; X-ray; 2.20 A; A=1-355. DR PDB; 1XHR; Model; -; A=40-355. DR PDBsum; 1V04; -. DR PDBsum; 1XHR; -. DR SMR; P27169; 16-355. DR SWISS-2DPAGE; P27169; -. DR PeptideAtlas; P27169; -. DR PRIDE; P27169; -. DR Ensembl; ENSG00000005421; Homo sapiens. DR GeneID; 5444; -. DR GeneCards; GC07M094764; -. DR H-InvDB; HIX0033662; -. DR HGNC; HGNC:9204; PON1. DR HPA; HPA001610; -. DR MIM; 168820; gene+phenotype. DR MIM; 612633; phenotype. DR PharmGKB; PA33529; -. DR HOGENOM; P27169; -. DR HOVERGEN; P27169; -. DR BRENDA; 3.1.1.2; 247. DR BRENDA; 3.1.8.1; 247. DR DrugBank; DB01076; Atorvastatin. DR DrugBank; DB01327; Cefazolin. DR NextBio; 21069; -. DR ArrayExpress; P27169; -. DR Bgee; P27169; -. DR CleanEx; HS_PON1; -. DR GermOnline; ENSG00000005421; Homo sapiens. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005856; C:cytoskeleton; IDA:HPA. DR GO; GO:0034366; C:spherical high-density lipoprotein particle; IDA:UniProtKB. DR GO; GO:0004063; F:aryldialkylphosphatase activity; IDA:UniProtKB. DR GO; GO:0004064; F:arylesterase activity; NAS:UniProtKB. DR GO; GO:0005543; F:phospholipid binding; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0019439; P:aromatic compound catabolic process; IDA:UniProtKB. DR GO; GO:0046395; P:carboxylic acid catabolic process; IDA:UniProtKB. DR GO; GO:0046434; P:organophosphate catabolic process; IDA:UniProtKB. DR GO; GO:0046470; P:phosphatidylcholine metabolic process; IDA:UniProtKB. DR GO; GO:0051099; P:positive regulation of binding; IDA:UniProtKB. DR GO; GO:0010875; P:positive regulation of cholesterol efflux; IDA:UniProtKB. DR GO; GO:0032411; P:positive regulation of transporter activity; IDA:UniProtKB. DR GO; GO:0009605; P:response to external stimulus; NAS:UniProtKB. DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like. DR InterPro; IPR002640; Arylesterase. DR InterPro; IPR008363; Paraoxonase1. DR Gene3D; G3DSA:2.120.10.30; 6-blade_b-propeller_TolB-like; 1. DR Pfam; PF01731; Arylesterase; 1. DR PRINTS; PR01785; PARAOXONASE. DR PRINTS; PR01786; PARAOXONASE1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Direct protein sequencing; KW Disulfide bond; Glycoprotein; HDL; Hydrolase; Phosphoprotein; KW Polymorphism; Secreted; Signal. FT INIT_MET 1 1 Removed. FT CHAIN 2 355 Serum paraoxonase/arylesterase 1. FT /FTId=PRO_0000223281. FT SIGNAL 2 ? Not cleaved. FT MOD_RES 76 76 Phosphoserine (By similarity). FT CARBOHYD 227 227 N-linked (GlcNAc...). FT CARBOHYD 253 253 N-linked (GlcNAc...). FT CARBOHYD 270 270 N-linked (GlcNAc...) (Potential). FT CARBOHYD 324 324 N-linked (GlcNAc...). FT DISULFID 42 353 In form B. FT VARIANT 55 55 M -> L (associated with susceptibility to FT diabetic retinopathy; dbSNP:rs854560). FT /FTId=VAR_006043. FT VARIANT 102 102 I -> V (polymorphism associated with FT decreased activity that seems to be FT associated with an increased risk for FT prostate cancer). FT /FTId=VAR_015882. FT VARIANT 160 160 R -> G (in dbSNP:rs13306698). FT /FTId=VAR_055342. FT VARIANT 192 192 Q -> R (polymorphism important for FT activity; dbSNP:rs662). FT /FTId=VAR_006044. FT MUTAGEN 20 21 HQ->AA: The signal peptide is cleaved; FT not associated with HDL. FT MUTAGEN 284 284 C->A,S: No loss of activity. FT HELIX 18 26 FT TURN 27 30 FT STRAND 53 56 FT STRAND 60 66 FT STRAND 83 88 FT STRAND 91 93 FT STRAND 96 98 FT STRAND 100 102 FT STRAND 104 106 FT HELIX 108 110 FT STRAND 113 120 FT STRAND 126 132 FT STRAND 139 146 FT TURN 147 150 FT STRAND 151 158 FT STRAND 164 173 FT STRAND 176 182 FT HELIX 188 196 FT STRAND 202 207 FT STRAND 212 227 FT STRAND 231 238 FT TURN 239 242 FT STRAND 243 249 FT STRAND 255 262 FT STRAND 264 272 FT TURN 274 276 FT STRAND 279 285 FT HELIX 287 291 FT STRAND 301 307 FT STRAND 311 313 FT STRAND 315 322 FT STRAND 324 327 FT STRAND 329 336 FT STRAND 339 347 FT STRAND 349 353 SQ SEQUENCE 355 AA; 39749 MW; 9A2F4E3DE036536A CRC64; MAKLIALTLL GMGLALFRNH QSSYQTRLNA LREVQPVELP NCNLVKGIET GSEDMEILPN 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 //