PON1

Protein identityUniProt · HPA

UniProt accession

P27169

Gene

PON1

Ensembl

ENSG00000005421

Chromosome

7

Canonical length

355 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted secreted proteins, Transporters

Secretome location

Secreted to blood

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a member of the paraoxonase family of enzymes and exhibits lactonase and ester hydrolase activity. Following synthesis in the kidney and liver, the enzyme is secreted into the circulation, where it binds to high density lipoprotein (HDL) particles and hydrolyzes thiolactones and xenobiotics, including paraoxon, a metabolite of the insecticide parathion. Polymorphisms in this gene may be associated with coronary artery disease and diabetic retinopathy. The gene is found in a cluster of three related paraoxonase genes on chromosome 7. [provided by RefSeq, Aug 2017]

Canonical amino-acid sequenceUniProt

355 residues, UniProt reviewed canonical sequence.

>P27169|PON1
     1  MAKLIALTLL GMGLALFRNH QSSYQTRLNA LREVQPVELP NCNLVKGIET GSEDLEILPN
    61  GLAFISSGLK YPGIKSFNPN SPGKILLMDL NEEDPTVLEL GITGSKFDVS SFNPHGISTF
   121  TDEDNAMYLL VVNHPDAKST VELFKFQEEE KSLLHLKTIR HKLLPNLNDI VAVGPEHFYG
   181  TNDHYFLDPY LQSWEMYLGL AWSYVVYYSP SEVRVVAEGF DFANGINISP DGKYVYIAEL
   241  LAHKIHVYEK HANWTLTPLK SLDFNTLVDN ISVDPETGDL WVGCHPNGMK IFFYDSENPP
   301  ASEVLRIQNI LTEEPKVTQV YAENGTVLQG STVASVYKGK LLIGTVFHKA LYCEL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PON1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.24

Highest tissue expression

498 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PON1.

Disease | AllUniProt

Conditions PON1 is implicated in, by any mechanism.

• Microvascular complications of diabetes 5 (MVCD5) MIM:612633

ReferencesPubMed · IEDB

Publications for PON1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.29

gnomAD pLI

0

gnomAD missense Z

0.72

DepMap mean gene effect

-0.09

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• carboxylic acid catabolic process
• cholesterol metabolic process
• lactone catabolic process
• phosphatidylcholine metabolic process
• positive regulation of cholesterol efflux
• response to toxic substance
• organophosphate catabolic process

Molecular functions

• acyl-L-homoserine-lactone lactonohydrolase activity
• aryldialkylphosphatase activity
• arylesterase activity
• calcium ion binding
• phospholipid binding
• protein homodimerization activity

Cellular components

• blood microparticle
• endoplasmic reticulum membrane
• extracellular exosome
• extracellular region
• extracellular space
• high-density lipoprotein particle
• spherical high-density lipoprotein particle

Protein domainsUniProt · Pfam · InterPro

• Arylesterase
• Six-bladed beta-propeller, TolB-like
• Serum paraoxonase/arylesterase
• Arylesterase
• Paraoxonase1

KeywordsUniProt

• Calcium
• Disulfide bond
• Glycoprotein
• HDL
• Hydrolase
• Metal-binding
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of PON1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CLU