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Protein

Serum paraoxonase/arylesterase 1

Gene

PON1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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.

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: Reactome
  • 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
  • lipoxygenase pathway Source: Reactome
  • 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 fatty acid Source: Ensembl
  • response to fluoride Source: Ensembl
  • response to nutrient levels Source: Ensembl
  • response to toxic substance Source: GO_Central

Keywordsi

Molecular functionHydrolase
LigandCalcium, Metal-binding

Enzyme and pathway databases

BRENDAi3.1.1.2 2681
3.1.1.25 2681
3.1.8.1 2681
ReactomeiR-HSA-2142688 Synthesis of 5-eicosatetraenoic acids
SABIO-RKiP27169
SIGNORiP27169

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

EuPathDBiHostDB:ENSG00000005421.8
HGNCiHGNC:9204 PON1
MIMi168820 gene+phenotype
neXtProtiNX_P27169

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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...) asparagine1 Publication1
Glycosylationi253N-linked (GlcNAc...) asparagine3 Publications1
Glycosylationi270N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi324N-linked (GlcNAc...) asparagine2 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
ProteomicsDBi54376

2D gel databases

SWISS-2DPAGEiP27169

PTM databases

GlyConnecti726
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

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
OMAiNCNLVKG
OrthoDBiEOG091G0AV9
PhylomeDBiP27169
TreeFamiTF322436

Family and domain databases

Gene3Di2.120.10.30, 1 hit
InterProiView protein in InterPro
IPR011042 6-blade_b-propeller_TolB-like
IPR002640 Arylesterase
IPR008363 Paraoxonase1
PANTHERiPTHR11799:SF16 PTHR11799:SF16, 1 hit
PfamiView protein in Pfam
PF01731 Arylesterase, 1 hit
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.2 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00604355L → M6 PublicationsCorresponds to variant dbSNP:rs854560EnsemblClinVar.1
Natural variantiVAR_015882102I → V Polymorphism; may be associated with an increased risk for prostate cancer; associated with decreased activity. 1 PublicationCorresponds to variant dbSNP:rs72552787Ensembl.1
Natural variantiVAR_055342160R → G. Corresponds to variant dbSNP:rs13306698Ensembl.1
Natural variantiVAR_006044192Q → R in allozyme B; functional polymorphism; increased arylesterase activity. 7 PublicationsCorresponds to variant dbSNP:rs662EnsemblClinVar.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

Similar proteinsi

Entry informationi

Entry nameiPON1_HUMAN
AccessioniPrimary (citable) accession number: P27169
Secondary accession number(s): B2RA40
, Q16052, Q6B0J6, Q9UCB1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: October 5, 2010
Last modified: June 20, 2018
This is version 197 of the entry and version 3 of the sequence. See 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

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

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