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Identification
HMDB Protein ID HMDBP00091
Secondary Accession Numbers
  • 5323
Name Serum paraoxonase/arylesterase 1
Synonyms
  1. A-esterase 1
  2. Aromatic esterase 1
  3. K-45
  4. PON 1
  5. Serum aryldialkylphosphatase 1
Gene Name PON1
Protein Type Enzyme
Biological Properties
General Function Involved in arylesterase activity
Specific Function Hydrolyzes 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.
Pathways
  • Clopidogrel Action Pathway
  • Clopidogrel Metabolism Pathway
Reactions
A phenyl acetate + Water → a phenol + Acetic acid details
An aryl dialkyl phosphate + Water → dialkyl phosphate + an aryl alcohol details
An N-acyl-L-homoserine lactone + Water → an N-acyl-L-homoserine details
Parathion + Water → Diethylthiophosphate + 4-Nitrophenol details
Paraoxon + Water → Diethylphosphate + 4-Nitrophenol details
4-Hydroxyphenyl acetate + Water → Hydroquinone + Acetic acid details
GO Classification
Biological Process
aromatic compound catabolic process
phosphatidylcholine metabolic process
carboxylic acid catabolic process
organophosphate catabolic process
positive regulation of binding
positive regulation of cholesterol efflux
response to external stimulus
response to toxin
positive regulation of transporter activity
Cellular Component
spherical high-density lipoprotein particle
Component
extracellular region
Function
hydrolase activity, acting on ester bonds
catalytic activity
hydrolase activity
carboxylesterase activity
arylesterase activity
Molecular Function
phospholipid binding
protein homodimerization activity
calcium ion binding
aryldialkylphosphatase activity
arylesterase activity
Cellular Location
  1. Secreted
  2. extracellular space
Gene Properties
Chromosome Location 7
Locus 7q21.3
SNPs PON1
Gene Sequence
>1068 bp
ATGGCGAAGCTGATTGCGCTCACCCTCTTGGGGATGGGACTGGCACTCTTCAGGAACCAC
CAGTCTTCTTACCAAACACGACTTAATGCTCTCCGAGAGGTACAACCCGTAGAACTTCCT
AACTGTAATTTAGTTAAAGGAATCGAAACTGGCTCTGAAGACTTGGAGATACTGCCTAAT
GGACTGGCTTTCATTAGCTCTGGATTAAAGTATCCTGGAATAAAGAGCTTCAACCCCAAC
AGTCCTGGAAAAATACTTCTGATGGACCTGAATGAAGAAGATCCAACAGTGTTGGAATTG
GGGATCACTGGAAGTAAATTTGATGTATCTTCATTTAACCCTCATGGGATTAGCACATTC
ACAGATGAAGATAATGCCATGTACCTCCTGGTGGTGAACCATCCAGATGCCAAGTCCACA
GTGGAGTTGTTTAAATTTCAAGAAGAAGAAAAATCGCTTTTGCATCTAAAAACCATCAGA
CATAAACTTCTGCCTAATTTGAATGATATTGTTGCTGTGGGACCTGAGCACTTTTATGGC
ACAAATGATCACTATTTTCTTGACCCCTACTTACAATCCTGGGAGATGTATTTGGGTTTA
GCGTGGTCGTATGTTGTCTACTATAGTCCAAGTGAAGTTCGAGTGGTGGCAGAAGGATTT
GATTTTGCTAATGGAATCAACATTTCACCCGATGGCAAGTATGTCTATATAGCTGAGTTG
CTGGCTCATAAGATTCATGTGTATGAAAAGCATGCTAATTGGACTTTAACTCCATTGAAG
TCCCTTGACTTTAATACCCTCGTGGATAACATATCTGTGGATCCTGAGACAGGAGACCTT
TGGGTTGGATGCCATCCCAATGGCATGAAAATCTTCTTCTATGACTCAGAGAATCCTCCT
GCATCAGAGGTGCTTCGAATCCAGAACATTCTAACAGAAGAACCTAAAGTGACACAGGTT
TATGCAGAAAATGGCACAGTGTTGCAAGGCAGTACAGTTGCCTCTGTGTACAAAGGGAAA
CTGCTGATTGGCACAGTGTTTCACAAAGCTCTTTACTGTGAGCTCTAA
Protein Properties
Number of Residues 355
Molecular Weight 39730.99
Theoretical pI 5.225
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Serum paraoxonase/arylesterase 1
MAKLIALTLLGMGLALFRNHQSSYQTRLNALREVQPVELPNCNLVKGIETGSEDLEILPN
GLAFISSGLKYPGIKSFNPNSPGKILLMDLNEEDPTVLELGITGSKFDVSSFNPHGISTF
TDEDNAMYLLVVNHPDAKSTVELFKFQEEEKSLLHLKTIRHKLLPNLNDIVAVGPEHFYG
TNDHYFLDPYLQSWEMYLGLAWSYVVYYSPSEVRVVAEGFDFANGINISPDGKYVYIAEL
LAHKIHVYEKHANWTLTPLKSLDFNTLVDNISVDPETGDLWVGCHPNGMKIFFYDSENPP
ASEVLRIQNILTEEPKVTQVYAENGTVLQGSTVASVYKGKLLIGTVFHKALYCEL
GenBank ID Protein 2795823
UniProtKB/Swiss-Prot ID P27169
UniProtKB/Swiss-Prot Entry Name PON1_HUMAN
PDB IDs
GenBank Gene ID AC004022
GeneCard ID PON1
GenAtlas ID PON1
HGNC ID HGNC:9204
References
General References
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  5. 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. [PubMed:16335952 ]
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  7. 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. [PubMed:15772423 ]
  8. 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. [PubMed:1657140 ]
  9. 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. [PubMed:7916578 ]
  10. 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. [PubMed:8393742 ]
  11. 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. [PubMed:8393745 ]
  12. 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. [PubMed:8812495 ]
  13. 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. [PubMed:9261565 ]
  14. 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. [PubMed:8382160 ]
  15. 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. [PubMed:8292612 ]
  16. Furlong CE, Richter RJ, Chapline C, Crabb JW: Purification of rabbit and human serum paraoxonase. Biochemistry. 1991 Oct 22;30(42):10133-40. [PubMed:1718413 ]
  17. 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. [PubMed:1673382 ]
  18. 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. [PubMed:7638166 ]
  19. 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. [PubMed:10479665 ]
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  22. 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. [PubMed:15098021 ]
  23. 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. [PubMed:8098250 ]
  24. 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. [PubMed:9661650 ]
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