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Protein

Serum paraoxonase/arylesterase 1

Gene

PON1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

A phenyl acetate + H2O = a phenol + acetate.5 Publications
An aryl dialkyl phosphate + H2O = dialkyl phosphate + an aryl alcohol.5 Publications
An N-acyl-L-homoserine lactone + H2O = an N-acyl-L-homoserine.2 Publications

Cofactori

Ca2+Note: Binds 2 calcium ions per subunit.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi53Calcium 1; catalytic1
Metal bindingi54Calcium 21
Active sitei115Proton acceptorCurated1
Metal bindingi117Calcium 2; via carbonyl oxygen1
Metal bindingi168Calcium 1; catalytic1
Metal bindingi169Calcium 21
Metal bindingi224Calcium 1; catalytic1
Metal bindingi269Calcium 1; catalytic1
Metal bindingi270Calcium 1; catalytic1

GO - Molecular functioni

  • acyl-L-homoserine-lactone lactonohydrolase activity Source: UniProtKB-EC
  • aryldialkylphosphatase activity Source: UniProtKB
  • arylesterase activity Source: UniProtKB
  • calcium ion binding Source: UniProtKB
  • phospholipid binding Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL

GO - Biological processi

  • aromatic compound catabolic process Source: BHF-UCL
  • carboxylic acid catabolic process Source: BHF-UCL
  • cholesterol metabolic process Source: Ensembl
  • organophosphate catabolic process Source: BHF-UCL
  • phosphatidylcholine metabolic process Source: BHF-UCL
  • positive regulation of binding Source: BHF-UCL
  • positive regulation of cholesterol efflux Source: BHF-UCL
  • positive regulation of transporter activity Source: BHF-UCL
  • response to external stimulus Source: UniProtKB
  • response to fatty acid Source: Ensembl
  • response to fluoride Source: Ensembl
  • response to nutrient levels Source: Ensembl
  • response to toxic substance Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:HS00141-MONOMER.
BRENDAi3.1.1.2. 2681.
3.1.1.25. 2681.
3.1.8.1. 2681.
ReactomeiR-HSA-2142688. Synthesis of 5-eicosatetraenoic acids.
SABIO-RKP27169.

Protein family/group databases

TCDBi1.A.6.2.6. the epithelial na(+) channel (enac) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Serum paraoxonase/arylesterase 11 Publication (EC:3.1.1.25 Publications, EC:3.1.1.812 Publications, EC:3.1.8.15 Publications)
Short name:
PON 11 Publication
Alternative name(s):
Aromatic esterase 1
Short name:
A-esterase 1
K-45
Serum aryldialkylphosphatase 1
Gene namesi
Name:PON1
Synonyms:PON
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:9204. PON1.

Subcellular locationi

GO - Cellular componenti

  • blood microparticle Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: UniProtKB
  • extracellular space Source: BHF-UCL
  • high-density lipoprotein particle Source: BHF-UCL
  • intracellular membrane-bounded organelle Source: Ensembl
  • spherical high-density lipoprotein particle Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

HDL, Secreted

Pathology & Biotechi

Involvement in diseasei

Microvascular complications of diabetes 5 (MVCD5)
Disease susceptibility is associated with variations affecting the gene represented in this entry. Homozygosity for the Leu-55 allele is strongly associated with the development of retinal disease in diabetic patients.
Disease descriptionPathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis.
See also OMIM:612633

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi20 – 21HQ → AA: The signal peptide is cleaved; not associated with HDL. 1 Publication2
Mutagenesisi115H → Q: Reduces activity 10000-fold. 1 Publication1
Mutagenesisi134H → Q: Substantially reduced activity. 1 Publication1
Mutagenesisi284C → A or S: No loss of activity. 1 Publication1

Organism-specific databases

DisGeNETi5444.
MalaCardsiPON1.
MIMi168820. gene+phenotype.
612633. phenotype.
OpenTargetsiENSG00000005421.
Orphaneti803. Amyotrophic lateral sclerosis.
PharmGKBiPA33529.

Chemistry databases

ChEMBLiCHEMBL3167.
DrugBankiDB01327. Cefazolin.

Polymorphism and mutation databases

BioMutaiPON1.
DMDMi308153572.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved3 Publications
ChainiPRO_00002232812 – 355Serum paraoxonase/arylesterase 1Add BLAST354
Signal peptidei2 – ?Not cleaved

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi42 ↔ 353In form B2 Publications
Glycosylationi227N-linked (GlcNAc...)1 Publication1
Glycosylationi253N-linked (GlcNAc...)3 Publications1
Glycosylationi270N-linked (GlcNAc...)Sequence analysis1
Glycosylationi324N-linked (GlcNAc...)2 Publications1

Post-translational modificationi

Glycosylated.3 Publications
The signal sequence is not cleaved.
Present in two forms, form B contains a disulfide bond, form A does not.

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP27169.
PaxDbiP27169.
PeptideAtlasiP27169.
PRIDEiP27169.

2D gel databases

SWISS-2DPAGEP27169.

PTM databases

iPTMnetiP27169.
PhosphoSitePlusiP27169.

Expressioni

Tissue specificityi

Plasma, associated with HDL (at protein level). Expressed in liver, but not in heart, brain, placenta, lung, skeletal muscle, kidney or pancreas.2 Publications

Gene expression databases

BgeeiENSG00000005421.
CleanExiHS_PON1.
ExpressionAtlasiP27169. baseline and differential.
GenevisibleiP27169. HS.

Organism-specific databases

HPAiHPA001610.

Interactioni

Subunit structurei

Homodimer. Heterooligomer with phosphate-binding protein (HPBP). Interacts with CLU.4 Publications

GO - Molecular functioni

  • protein homodimerization activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi111440. 7 interactors.
STRINGi9606.ENSP00000222381.

Chemistry databases

BindingDBiP27169.

Structurei

Secondary structure

1355
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi19 – 27Combined sources9
Turni28 – 31Combined sources4
Beta strandi54 – 57Combined sources4
Beta strandi61 – 67Combined sources7
Beta strandi84 – 89Combined sources6
Beta strandi92 – 94Combined sources3
Beta strandi97 – 99Combined sources3
Beta strandi101 – 103Combined sources3
Beta strandi105 – 107Combined sources3
Helixi109 – 111Combined sources3
Beta strandi114 – 121Combined sources8
Beta strandi127 – 133Combined sources7
Beta strandi140 – 147Combined sources8
Turni148 – 151Combined sources4
Beta strandi152 – 159Combined sources8
Beta strandi165 – 174Combined sources10
Beta strandi177 – 183Combined sources7
Helixi189 – 197Combined sources9
Beta strandi203 – 208Combined sources6
Beta strandi213 – 228Combined sources16
Beta strandi232 – 239Combined sources8
Turni240 – 243Combined sources4
Beta strandi244 – 250Combined sources7
Beta strandi256 – 263Combined sources8
Beta strandi265 – 273Combined sources9
Turni275 – 277Combined sources3
Beta strandi280 – 286Combined sources7
Helixi288 – 292Combined sources5
Beta strandi302 – 308Combined sources7
Beta strandi312 – 314Combined sources3
Beta strandi316 – 323Combined sources8
Beta strandi325 – 328Combined sources4
Beta strandi330 – 337Combined sources8
Beta strandi340 – 348Combined sources9
Beta strandi350 – 353Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1V04X-ray2.20A1-353[»]
1XHRmodel-A40-355[»]
ProteinModelPortaliP27169.
SMRiP27169.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP27169.

Family & Domainsi

Sequence similaritiesi

Belongs to the paraoxonase family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IHDV. Eukaryota.
ENOG4111QK7. LUCA.
GeneTreeiENSGT00390000008932.
HOGENOMiHOG000252960.
HOVERGENiHBG003604.
InParanoidiP27169.
KOiK01045.
OMAiFFYDSEN.
OrthoDBiEOG091G0AV9.
PhylomeDBiP27169.
TreeFamiTF322436.

Family and domain databases

Gene3Di2.120.10.30. 1 hit.
InterProiIPR011042. 6-blade_b-propeller_TolB-like.
IPR002640. Arylesterase.
IPR008363. Paraoxonase1.
[Graphical view]
PfamiPF01731. Arylesterase. 1 hit.
[Graphical view]
PRINTSiPR01785. PARAOXONASE.
PR01786. PARAOXONASE1.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P27169-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAKLIALTLL GMGLALFRNH QSSYQTRLNA LREVQPVELP NCNLVKGIET
60 70 80 90 100
GSEDLEILPN GLAFISSGLK YPGIKSFNPN SPGKILLMDL NEEDPTVLEL
110 120 130 140 150
GITGSKFDVS SFNPHGISTF TDEDNAMYLL VVNHPDAKST VELFKFQEEE
160 170 180 190 200
KSLLHLKTIR HKLLPNLNDI VAVGPEHFYG TNDHYFLDPY LQSWEMYLGL
210 220 230 240 250
AWSYVVYYSP SEVRVVAEGF DFANGINISP DGKYVYIAEL LAHKIHVYEK
260 270 280 290 300
HANWTLTPLK SLDFNTLVDN ISVDPETGDL WVGCHPNGMK IFFYDSENPP
310 320 330 340 350
ASEVLRIQNI LTEEPKVTQV YAENGTVLQG STVASVYKGK LLIGTVFHKA

LYCEL
Length:355
Mass (Da):39,731
Last modified:October 5, 2010 - v3
Checksum:i9B5895509166167E
GO

Polymorphismi

The allelic form of the enzyme with Gln-192 (allozyme A) hydrolyzes paraoxon with a low turnover number and the one with Arg-192 (allozyme B) with a high turnover number.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00604355L → M.6 PublicationsCorresponds to variant rs854560dbSNPEnsembl.1
Natural variantiVAR_015882102I → V Polymorphism; may be associated with an increased risk for prostate cancer; associated with decreased activity. 1 PublicationCorresponds to variant rs72552787dbSNPEnsembl.1
Natural variantiVAR_055342160R → G.Corresponds to variant rs13306698dbSNPEnsembl.1
Natural variantiVAR_006044192Q → R Polymorphism; important for activity. 7 PublicationsCorresponds to variant rs662dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M63012 mRNA. Translation: AAB59538.1.
M63013 mRNA. Translation: AAA60142.1.
M63014 mRNA. Translation: AAA60143.1.
S56555, S56546, S56548 Genomic DNA. Translation: AAB25717.1.
S64696 mRNA. Translation: AAB27899.1.
S64615 mRNA. Translation: AAB27714.2.
U55885
, U55877, U55878, U55879, U55880, U55881, U55882, U55883 Genomic DNA. Translation: AAB41835.1.
D84371 mRNA. Translation: BAA12327.1.
U53784 mRNA. Translation: AAA97957.1.
Z70723 mRNA. Translation: CAA94728.1.
AK314027 mRNA. Translation: BAG36737.1.
AF539592 Genomic DNA. Translation: AAM97935.1.
AC004022 Genomic DNA. Translation: AAC35293.1.
CH236949 Genomic DNA. Translation: EAL24133.1.
CH471091 Genomic DNA. Translation: EAW76771.1.
BC074719 mRNA. Translation: AAH74719.1.
CCDSiCCDS5638.1.
PIRiA45451.
RefSeqiNP_000437.3. NM_000446.5.
UniGeneiHs.370995.

Genome annotation databases

EnsembliENST00000222381; ENSP00000222381; ENSG00000005421.
GeneIDi5444.
KEGGihsa:5444.
UCSCiuc003uns.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs
SHMPD

The Singapore human mutation and polymorphism database

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M63012 mRNA. Translation: AAB59538.1.
M63013 mRNA. Translation: AAA60142.1.
M63014 mRNA. Translation: AAA60143.1.
S56555, S56546, S56548 Genomic DNA. Translation: AAB25717.1.
S64696 mRNA. Translation: AAB27899.1.
S64615 mRNA. Translation: AAB27714.2.
U55885
, U55877, U55878, U55879, U55880, U55881, U55882, U55883 Genomic DNA. Translation: AAB41835.1.
D84371 mRNA. Translation: BAA12327.1.
U53784 mRNA. Translation: AAA97957.1.
Z70723 mRNA. Translation: CAA94728.1.
AK314027 mRNA. Translation: BAG36737.1.
AF539592 Genomic DNA. Translation: AAM97935.1.
AC004022 Genomic DNA. Translation: AAC35293.1.
CH236949 Genomic DNA. Translation: EAL24133.1.
CH471091 Genomic DNA. Translation: EAW76771.1.
BC074719 mRNA. Translation: AAH74719.1.
CCDSiCCDS5638.1.
PIRiA45451.
RefSeqiNP_000437.3. NM_000446.5.
UniGeneiHs.370995.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1V04X-ray2.20A1-353[»]
1XHRmodel-A40-355[»]
ProteinModelPortaliP27169.
SMRiP27169.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111440. 7 interactors.
STRINGi9606.ENSP00000222381.

Chemistry databases

BindingDBiP27169.
ChEMBLiCHEMBL3167.
DrugBankiDB01327. Cefazolin.

Protein family/group databases

TCDBi1.A.6.2.6. the epithelial na(+) channel (enac) family.

PTM databases

iPTMnetiP27169.
PhosphoSitePlusiP27169.

Polymorphism and mutation databases

BioMutaiPON1.
DMDMi308153572.

2D gel databases

SWISS-2DPAGEP27169.

Proteomic databases

MaxQBiP27169.
PaxDbiP27169.
PeptideAtlasiP27169.
PRIDEiP27169.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000222381; ENSP00000222381; ENSG00000005421.
GeneIDi5444.
KEGGihsa:5444.
UCSCiuc003uns.4. human.

Organism-specific databases

CTDi5444.
DisGeNETi5444.
GeneCardsiPON1.
H-InvDBHIX0033662.
HGNCiHGNC:9204. PON1.
HPAiHPA001610.
MalaCardsiPON1.
MIMi168820. gene+phenotype.
612633. phenotype.
neXtProtiNX_P27169.
OpenTargetsiENSG00000005421.
Orphaneti803. Amyotrophic lateral sclerosis.
PharmGKBiPA33529.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IHDV. Eukaryota.
ENOG4111QK7. LUCA.
GeneTreeiENSGT00390000008932.
HOGENOMiHOG000252960.
HOVERGENiHBG003604.
InParanoidiP27169.
KOiK01045.
OMAiFFYDSEN.
OrthoDBiEOG091G0AV9.
PhylomeDBiP27169.
TreeFamiTF322436.

Enzyme and pathway databases

BioCyciZFISH:HS00141-MONOMER.
BRENDAi3.1.1.2. 2681.
3.1.1.25. 2681.
3.1.8.1. 2681.
ReactomeiR-HSA-2142688. Synthesis of 5-eicosatetraenoic acids.
SABIO-RKP27169.

Miscellaneous databases

ChiTaRSiPON1. human.
EvolutionaryTraceiP27169.
GeneWikiiPON1.
GenomeRNAii5444.
PROiP27169.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000005421.
CleanExiHS_PON1.
ExpressionAtlasiP27169. baseline and differential.
GenevisibleiP27169. HS.

Family and domain databases

Gene3Di2.120.10.30. 1 hit.
InterProiIPR011042. 6-blade_b-propeller_TolB-like.
IPR002640. Arylesterase.
IPR008363. Paraoxonase1.
[Graphical view]
PfamiPF01731. Arylesterase. 1 hit.
[Graphical view]
PRINTSiPR01785. PARAOXONASE.
PR01786. PARAOXONASE1.
ProtoNetiSearch...

Entry informationi

Entry nameiPON1_HUMAN
AccessioniPrimary (citable) accession number: P27169
Secondary accession number(s): B2RA40
, Q16052, Q6B0J6, Q9UCB1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: October 5, 2010
Last modified: November 30, 2016
This is version 186 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

The preferential association of PON1 with HDL is mediated in part by its signal peptide, by binding phospholipids directly, rather than binding apo AI. The retained signal peptide may allow transfer of the protein between phospholipid surfaces.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.