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FLASH GENE

Symbol

PON1

contributors: npt/mct - updated : 29-11-2017

HGNC name	paraoxonase 1
HGNC id	9204

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000446 9 - 1769 NP_000437 - 355 - 1999 10052953

EXPRESSION

Type

widely

constitutive of

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver       highly Endocrine pancreas       highly Nervous brain       moderately Respiratory lung       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic         Epithelial secretory glandular endocrine   Epithelial secretory glandular exocrine

cell lineage
cell lines
fluid/secretion	serum, plasma

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

mono polymer

heteromer , oligo

HOMOLOGY

interspecies	homolog to rattus Pon1 (80.56 pc)
	homolog to murine Pon1 (81.97 pc)

Homologene

FAMILY

paraoxonase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	extracellular
text	secreted by the liver and transported in the blood complexed to HDL

basic FUNCTION	hydrolyzing the toxic metabolites of a variety of organophosphorous insecticides
	may mediate an enzymatic protection of low density lipoproteins against oxidative modification
	leading to anti-atherogenic effects by specifically binding to macrophage binding sites
	having antioxidative and atheroprotective role
	high-density lipoprotein (HDL)-bound enzyme that exerts antiatherogenic properties by protecting low-density lipoprotein (LDL)-cholesterol from oxidative modification

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

detoxification

PATHWAY

metabolism

signaling

a component

MPO, PON1, and high-density lipoprotein bind to one another, forming a ternary complex, wherein PON1 partially inhibits MPO activity, while MPO inactivates PON1

INTERACTION

DNA

RNA

small molecule

protein

cell & other

binding to macrophage

REGULATION

repressed by

bile acids through the actions of NR1H4 and FGF19

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   in atherosclerosis constitutional     --low   in patients with calcific aortic valve stenosis (AS) and its activity was inversely correlated with the severity of AS

Susceptibility

to coronary heart disease but not myocardial infarction atherosclerosis pesticide poisoning exsudative age-related macular degeneration to abdominal aortic aneurysm (Giusti 2008) Alzheimer disease (AD) to sporadic amyotrophic lateral sclerosis to attaining longevity to strocke

Variant & Polymorphism SNP , other	Arg192 allele increased survival at extreme advanced age
	polymorphism 192Q/R, 55M/L,and promoter variant 107C/T increases protection against coronary artery disease
	-161[C/T] SNP in creasing the risk of Alzheimer
	Q192R polymorphism increasing the risk of sporadic amyotrophic lateral sclerosis and associated with stroke and myocardial infarction
	variants at codon 192 impact on the probability of attaining longevity
	Q192R polymorphism could be an important risk factor for stroke
	rs854563 associated with coronary atherosclerosis
	multiple variants in PON influence serum paraoxonase activity, and low serum paraoxonase activity is a risk factor for AD

Candidate gene
Marker
Therapy target	for future cardio protection therapy via the macrophage PON1 binding sites

ANIMAL & CELL MODELS