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. (updated: April 1, 2015)
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
No sequence conservation computed yet.
Total structural coverage: 100%
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The reference OMIM entry for this protein is 168820
Paraoxonase 1; pon1
Pon
Paraoxonase, plasma
Arylesterase
Esterase a; esa pon1 enzyme activity, variation in, included
Organophosphate poisoning, susceptibility to, included
Coronary artery disease, susceptibility to, included
Coronary a
DESCRIPTION
The paraoxonase (PON) gene family includes 3 genes, PON1, PON2 (
602447), and PON3 (
602720), aligned next to each other on chromosome 7. PON1 (EC 3.1.1.2) hydrolyzes the toxic oxon metabolites of several organophosphorous insecticides, including parathion, diazinon, and chlorpyrifos, as well as nerve agents, such as sarin and soman. PON1 also hydrolyzes aromatic esters, preferably those of acetic acid. In addition, PON1 hydrolyzes a variety of aromatic and aliphatic lactones, and it also catalyzes the reverse reaction, lactonization, of gamma- and delta-hydroxycarboxylic acids. Human PON1 is synthesized in liver and secreted into blood, where it is associated exclusively with high density lipoproteins (HDLs) and may protect against development of atherosclerosis (Draganov et al., 2005).
CLONING
Hassett et al. (1991) isolated a full-length PON1 cDNA from a human liver cDNA library using rabbit Pon1 as a hybridization probe. The deduced PON1 protein contains 355 amino acids and is more than 85% similar to the rabbit protein. N-terminal sequences derived from purified rabbit and human PON1 proteins suggested that the PON1 signal sequence is retained, except for the initiator methionine. Characterization of the rabbit and human PON1 cDNAs confirmed that the signal sequences are not processed, except for the N-terminal methionine. Using SDS-PAGE, Draganov et al. (2005) found that PON1 appeared as a doublet of about 39 and 42 kD. However, using nondenaturing PAGE, they observed human serum PON1 and recombinant PON1 at apparent molecular masses of 91.9 and 95.6 kD, respectively, suggesting that PON1 forms dimers. Glycosidase treatment of human serum PON1 suggested that the secreted form of PON1 contains complex carbohydrates. Lu et al. (2006) stated that human PON1, PON2, and PON3 have 3 conserved cysteines. Cys41 and cys351 are predicted to form an intramolecular disulfide bond, and cys283 is predicted to be involved in antioxidant activity.
GENE STRUCTURE
Clendenning et al. (1996) characterized a 28-kb contig encompassing 300 bp of 5-prime sequence, the entire coding region, and 2 kb of 3-prime flanking sequence of the PON1 gene. The structural portion of the paraoxonase protein is encoded by 9 exons that form the primary transcript through the use of typical splice donor and acceptor sites. Sorenson et al. (1995) showed that the Pon1 gene in mice contains 9 exons spanning approximately 25 to 26 kb.
MAPPING
Eiberg and Mohr (1979) presented linkage data. No linkage with any of 19 markers was found by Mueller et al. (1983). Eiberg et al. (1985) showed that cystic fibrosis (
219700) and PON are linked on chromosome 7 (maximum lod 3.70 at theta = 0.07 in males and 0.00 in females)--the first step in the cloning of the CF gene in 1989. Tsui et al. (1985) confirmed the PON-CF linkage by finding linkage of PON to a DNA marker that is also linked to CF. Schmiegelow et al. (1986) found the PON and CF loci linked with lod score of 3.46 at recombination fraction 0.07 in males and 0.13 in females. By in situ hybridization, Humbert et al. (1993) demonstrated that the PON gene maps to chromosome 7q21-q22. Mochizuki et al. (1998) pointed out that the PON1, PON2, and PON3 genes are physically linked on chromosome 7q21.3. Sorenson et al. (1995) mapped the mouse Pon1 gene to the proximal end of chromosome 6 by interspecific backcross analysis. Li et al. (1997) likewise mapped the gene to mouse chromosome 6 ...
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Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for PON1
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 168820 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed