Serum paraoxonase/arylesterase 1

NameSerum paraoxonase/arylesterase 1
Synonyms
  • 3.1.1.2
  • A-esterase 1
  • Aromatic esterase 1
  • K-45
  • PON
  • PON 1
  • Serum aryldialkylphosphatase 1
Gene NamePON1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0020496|Serum paraoxonase/arylesterase 1
MAKLIALTLLGMGLALFRNHQSSYQTRLNALREVQPVELPNCNLVKGIETGSEDLEILPN
GLAFISSGLKYPGIKSFNPNSPGKILLMDLNEEDPTVLELGITGSKFDVSSFNPHGISTF
TDEDNAMYLLVVNHPDAKSTVELFKFQEEEKSLLHLKTIRHKLLPNLNDIVAVGPEHFYG
TNDHYFLDPYLQSWEMYLGLAWSYVVYYSPSEVRVVAEGFDFANGINISPDGKYVYIAEL
LAHKIHVYEKHANWTLTPLKSLDFNTLVDNISVDPETGDLWVGCHPNGMKIFFYDSENPP
ASEVLRIQNILTEEPKVTQVYAENGTVLQGSTVASVYKGKLLIGTVFHKALYCEL
Number of residues355
Molecular Weight39730.99
Theoretical pI4.89
GO Classification
Functions
  • calcium ion binding
  • aryldialkylphosphatase activity
  • phospholipid binding
  • arylesterase activity
  • protein homodimerization activity
Processes
  • response to toxic substance
  • positive regulation of cholesterol efflux
  • response to fatty acid
  • dephosphorylation
  • positive regulation of binding
  • aromatic compound catabolic process
  • phosphatidylcholine metabolic process
  • response to external stimulus
  • carboxylic acid catabolic process
  • organophosphate catabolic process
  • positive regulation of transporter activity
  • response to fluoride
  • response to nutrient levels
Components
  • extracellular region
  • high-density lipoprotein particle
  • spherical high-density lipoprotein particle
  • extracellular space
  • extracellular exosome
  • intracellular membrane-bounded organelle
  • blood microparticle
General FunctionProtein homodimerization activity
Specific FunctionHydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. Capable of hydrolyzing a broad spectrum of organophosphate substrates and lactones, and a number of aromatic carboxylic acid esters. Mediates an enzymatic protection of low density lipoproteins against oxidative modification and the consequent series of events leading to atheroma formation.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID190192
UniProtKB IDP27169
UniProtKB Entry NamePON1_HUMAN
Cellular LocationSecreted
Gene sequence
>lcl|BSEQ0020497|Serum paraoxonase/arylesterase 1 (PON1)
ATGGCGAAGCTGATTGCGCTCACCCTCTTGGGGATGGGACTGGCACTCTTCAGGAACCAC
CAGTCTTCTTACCAAACACGACTTAATGCTCTCCGAGAGGTACAACCCGTAGAACTTCCT
AACTGTAATTTAGTTAAAGGAATCGAAACTGGCTCTGAAGACTTGGAGATACTGCCTAAT
GGACTGGCTTTCATTAGCTCTGGATTAAAGTATCCTGGAATAAAGAGCTTCAACCCCAAC
AGTCCTGGAAAAATACTTCTGATGGACCTGAATGAAGAAGATCCAACAGTGTTGGAATTG
GGGATCACTGGAAGTAAATTTGATGTATCTTCATTTAACCCTCATGGGATTAGCACATTC
ACAGATGAAGATAATGCCATGTACCTCCTGGTGGTGAACCATCCAGATGCCAAGTCCACA
GTGGAGTTGTTTAAATTTCAAGAAGAAGAAAAATCGCTTTTGCATCTAAAAACCATCAGA
CATAAACTTCTGCCTAATTTGAATGATATTGTTGCTGTGGGACCTGAGCACTTTTATGGC
ACAAATGATCACTATTTTCTTGACCCCTACTTACAATCCTGGGAGATGTATTTGGGTTTA
GCGTGGTCGTATGTTGTCTACTATAGTCCAAGTGAAGTTCGAGTGGTGGCAGAAGGATTT
GATTTTGCTAATGGAATCAACATTTCACCCGATGGCAAGTATGTCTATATAGCTGAGTTG
CTGGCTCATAAGATTCATGTGTATGAAAAGCATGCTAATTGGACTTTAACTCCATTGAAG
TCCCTTGACTTTAATACCCTCGTGGATAACATATCTGTGGATCCTGAGACAGGAGACCTT
TGGGTTGGATGCCATCCCAATGGCATGAAAATCTTCTTCTATGACTCAGAGAATCCTCCT
GCATCAGAGGTGCTTCGAATCCAGAACATTCTAACAGAAGAACCTAAAGTGACACAGGTT
TATGCAGAAAATGGCACAGTGTTGCAAGGCAGTACAGTTGCCTCTGTGTACAAAGGGAAA
CTGCTGATTGGCACAGTGTTTCACAAAGCTCTTTACTGTGAGCTCTAA
GenBank Gene IDM63012
GeneCard IDNot Available
GenAtlas IDPON1
HGNC IDHGNC:9204
Chromosome Location7
Locus7q21.3
References
  1. Hassett C, Richter RJ, Humbert R, Chapline C, Crabb JW, Omiecinski CJ, Furlong CE: Characterization of cDNA clones encoding rabbit and human serum paraoxonase: the mature protein retains its signal sequence. Biochemistry. 1991 Oct 22;30(42):10141-9. 1657140
  2. Adkins S, Gan KN, Mody M, La Du BN: Molecular basis for the polymorphic forms of human serum paraoxonase/arylesterase: glutamine or arginine at position 191, for the respective A or B allozymes. Am J Hum Genet. 1993 Mar;52(3):598-608. 7916578
  3. La Du BN, Adkins S, Kuo CL, Lipsig D: Studies on human serum paraoxonase/arylesterase. Chem Biol Interact. 1993 Jun;87(1-3):25-34. 8393742
  4. Furlong CE, Costa LG, Hassett C, Richter RJ, Sundstrom JA, Adler DA, Disteche CM, Omiecinski CJ, Chapline C, Crabb JW, et al.: Human and rabbit paraoxonases: purification, cloning, sequencing, mapping and role of polymorphism in organophosphate detoxification. Chem Biol Interact. 1993 Jun;87(1-3):35-48. 8393745
  5. Clendenning JB, Humbert R, Green ED, Wood C, Traver D, Furlong CE: Structural organization of the human PON1 gene. Genomics. 1996 Aug 1;35(3):586-9. 8812495
  6. Wang KK, Wan DF, Qiu XK, Lu PX, Gu JR: Differential expression of a cDNA clone in human liver versus hepatic cancer--highly homologous to aryl-dialkyl-phosphatase. Cell Res. 1997 Jun;7(1):79-90. 9261565
  7. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  8. Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. 12853948
  9. Scherer SW, Cheung J, MacDonald JR, Osborne LR, Nakabayashi K, Herbrick JA, Carson AR, Parker-Katiraee L, Skaug J, Khaja R, Zhang J, Hudek AK, Li M, Haddad M, Duggan GE, Fernandez BA, Kanematsu E, Gentles S, Christopoulos CC, Choufani S, Kwasnicka D, Zheng XH, Lai Z, Nusskern D, Zhang Q, Gu Z, Lu F, Zeesman S, Nowaczyk MJ, Teshima I, Chitayat D, Shuman C, Weksberg R, Zackai EH, Grebe TA, Cox SR, Kirkpatrick SJ, Rahman N, Friedman JM, Heng HH, Pelicci PG, Lo-Coco F, Belloni E, Shaffer LG, Pober B, Morton CC, Gusella JF, Bruns GA, Korf BR, Quade BJ, Ligon AH, Ferguson H, Higgins AW, Leach NT, Herrick SR, Lemyre E, Farra CG, Kim HG, Summers AM, Gripp KW, Roberts W, Szatmari P, Winsor EJ, Grzeschik KH, Teebi A, Minassian BA, Kere J, Armengol L, Pujana MA, Estivill X, Wilson MD, Koop BF, Tosi S, Moore GE, Boright AP, Zlotorynski E, Kerem B, Kroisel PM, Petek E, Oscier DG, Mould SJ, Dohner H, Dohner K, Rommens JM, Vincent JB, Venter JC, Li PW, Mural RJ, Adams MD, Tsui LC: Human chromosome 7: DNA sequence and biology. Science. 2003 May 2;300(5620):767-72. Epub 2003 Apr 10. 12690205
  10. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  11. Blatter MC, James RW, Messmer S, Barja F, Pometta D: Identification of a distinct human high-density lipoprotein subspecies defined by a lipoprotein-associated protein, K-45. Identity of K-45 with paraoxonase. Eur J Biochem. 1993 Feb 1;211(3):871-9. 8382160
  12. Kelso GJ, Stuart WD, Richter RJ, Furlong CE, Jordan-Starck TC, Harmony JA: Apolipoprotein J is associated with paraoxonase in human plasma. Biochemistry. 1994 Jan 25;33(3):832-9. 8292612
  13. Furlong CE, Richter RJ, Chapline C, Crabb JW: Purification of rabbit and human serum paraoxonase. Biochemistry. 1991 Oct 22;30(42):10133-40. 1718413
  14. Gan KN, Smolen A, Eckerson HW, La Du BN: Purification of human serum paraoxonase/arylesterase. Evidence for one esterase catalyzing both activities. Drug Metab Dispos. 1991 Jan-Feb;19(1):100-6. 1673382
  15. Sorenson RC, Primo-Parmo SL, Kuo CL, Adkins S, Lockridge O, La Du BN: Reconsideration of the catalytic center and mechanism of mammalian paraoxonase/arylesterase. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7187-91. 7638166
  16. Sorenson RC, Bisgaier CL, Aviram M, Hsu C, Billecke S, La Du BN: Human serum Paraoxonase/Arylesterase's retained hydrophobic N-terminal leader sequence associates with HDLs by binding phospholipids : apolipoprotein A-I stabilizes activity. Arterioscler Thromb Vasc Biol. 1999 Sep;19(9):2214-25. 10479665
  17. Bunkenborg J, Pilch BJ, Podtelejnikov AV, Wisniewski JR: Screening for N-glycosylated proteins by liquid chromatography mass spectrometry. Proteomics. 2004 Feb;4(2):454-65. 14760718
  18. Draganov DI, Teiber JF, Speelman A, Osawa Y, Sunahara R, La Du BN: Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. J Lipid Res. 2005 Jun;46(6):1239-47. Epub 2005 Mar 16. 15772423
  19. Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, Smith RD: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res. 2005 Nov-Dec;4(6):2070-80. 16335952
  20. Morales R, Berna A, Carpentier P, Contreras-Martel C, Renault F, Nicodeme M, Chesne-Seck ML, Bernier F, Dupuy J, Schaeffer C, Diemer H, Van-Dorsselaer A, Fontecilla-Camps JC, Masson P, Rochu D, Chabriere E: Serendipitous discovery and X-ray structure of a human phosphate binding apolipoprotein. Structure. 2006 Mar;14(3):601-9. 16531243
  21. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. 19159218
  22. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  23. Harel M, Aharoni A, Gaidukov L, Brumshtein B, Khersonsky O, Meged R, Dvir H, Ravelli RB, McCarthy A, Toker L, Silman I, Sussman JL, Tawfik DS: Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes. Nat Struct Mol Biol. 2004 May;11(5):412-9. Epub 2004 Apr 18. 15098021
  24. Humbert R, Adler DA, Disteche CM, Hassett C, Omiecinski CJ, Furlong CE: The molecular basis of the human serum paraoxonase activity polymorphism. Nat Genet. 1993 Jan;3(1):73-6. 8098250
  25. Kao YL, Donaghue K, Chan A, Knight J, Silink M: A variant of paraoxonase (PON1) gene is associated with diabetic retinopathy in IDDM. J Clin Endocrinol Metab. 1998 Jul;83(7):2589-92. 9661650
  26. Marchesani M, Hakkarainen A, Tuomainen TP, Kaikkonen J, Pukkala E, Uimari P, Seppala E, Matikainen M, Kallioniemi OP, Schleutker J, Lehtimaki T, Salonen JT: New paraoxonase 1 polymorphism I102V and the risk of prostate cancer in Finnish men. J Natl Cancer Inst. 2003 Jun 4;95(11):812-8. 12783936
  27. Ley TJ, Mardis ER, Ding L, Fulton B, McLellan MD, Chen K, Dooling D, Dunford-Shore BH, McGrath S, Hickenbotham M, Cook L, Abbott R, Larson DE, Koboldt DC, Pohl C, Smith S, Hawkins A, Abbott S, Locke D, Hillier LW, Miner T, Fulton L, Magrini V, Wylie T, Glasscock J, Conyers J, Sander N, Shi X, Osborne JR, Minx P, Gordon D, Chinwalla A, Zhao Y, Ries RE, Payton JE, Westervelt P, Tomasson MH, Watson M, Baty J, Ivanovich J, Heath S, Shannon WD, Nagarajan R, Walter MJ, Link DC, Graubert TA, DiPersio JF, Wilson RK: DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature. 2008 Nov 6;456(7218):66-72. doi: 10.1038/nature07485. 18987736