ID   PON1_MOUSE              Reviewed;         355 AA.
AC   P52430; Q91X30;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   02-SEP-2026, entry version 188.
DE   RecName: Full=Serum paraoxonase/arylesterase 1;
DE            Short=PON 1;
DE            EC=3.1.1.2 {ECO:0000269|PubMed:15963993};
DE            EC=3.1.1.81 {ECO:0000269|PubMed:15963993};
DE            EC=3.1.8.1 {ECO:0000269|PubMed:15963993};
DE   AltName: Full=Aromatic esterase 1;
DE            Short=A-esterase 1;
DE   AltName: Full=Serum aryldialkylphosphatase 1;
GN   Name=Pon1; Synonyms=Pon;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=BALB/cJ; TISSUE=Liver;
RX   PubMed=7638166; DOI=10.1073/pnas.92.16.7187;
RA   Sorenson R.C., Primo-Parmo S.L., Kuo C.-L., Adkins S., Lockridge O.,
RA   La Du B.N.;
RT   "Reconsideration of the catalytic center and mechanism of mammalian
RT   paraoxonase/arylesterase.";
RL   Proc. Natl. Acad. Sci. U.S.A. 92:7187-7191(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=C57BL/6 X CBA; TISSUE=Liver;
RX   PubMed=8601628; DOI=10.1172/jci118589;
RA   Shih D.M., Gu L., Hama S., Xia Y.R., Navab M., Fogelman A.M., Lusis A.J.;
RT   "Genetic-dietary regulation of serum paraoxonase expression and its role in
RT   atherogenesis in a mouse model.";
RL   J. Clin. Invest. 97:1630-1639(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=BALB/cJ;
RX   PubMed=9170151; DOI=10.1097/00008571-199704000-00007;
RA   Li W.F., Matthews C., Disteche C.M., Costa L.G., Furlong C.E.;
RT   "Paraoxonase (PON1) gene in mice: sequencing, chromosomal localization and
RT   developmental expression.";
RL   Pharmacogenetics 7:137-144(1997).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Liver;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   CATALYTIC ACTIVITY.
RX   PubMed=15963993; DOI=10.1016/j.febslet.2005.05.060;
RA   Yang F., Wang L.H., Wang J., Dong Y.H., Hu J.Y., Zhang L.H.;
RT   "Quorum quenching enzyme activity is widely conserved in the sera of
RT   mammalian species.";
RL   FEBS Lett. 579:3713-3717(2005).
RN   [6]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-253.
RC   STRAIN=C57BL/6J; TISSUE=Plasma;
RX   PubMed=17330941; DOI=10.1021/pr0604559;
RA   Bernhard O.K., Kapp E.A., Simpson R.J.;
RT   "Enhanced analysis of the mouse plasma proteome using cysteine-containing
RT   tryptic glycopeptides.";
RL   J. Proteome Res. 6:987-995(2007).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brown adipose tissue, Liver, Lung, and Spleen;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Hydrolyzes the toxic metabolites of a variety of
CC       organophosphorus insecticides. Capable of hydrolyzing a broad spectrum
CC       of organophosphate substrates and lactones, and a number of aromatic
CC       carboxylic acid esters. Mediates an enzymatic protection of low density
CC       lipoproteins against oxidative modification.
CC       {ECO:0000250|UniProtKB:P27169}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a phenyl acetate + H2O = a phenol + acetate + H(+);
CC         Xref=Rhea:RHEA:17309, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:30089, ChEBI:CHEBI:33853, ChEBI:CHEBI:140310; EC=3.1.1.2;
CC         Evidence={ECO:0000269|PubMed:15963993};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=An aryl dialkyl phosphate + H2O = dialkyl phosphate + an aryl
CC         alcohol.; EC=3.1.8.1; Evidence={ECO:0000269|PubMed:15963993};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=an N-acyl-L-homoserine lactone + H2O = an N-acyl-L-homoserine
CC         + H(+); Xref=Rhea:RHEA:22576, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:55474, ChEBI:CHEBI:58921; EC=3.1.1.81;
CC         Evidence={ECO:0000269|PubMed:15963993};
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC       Note=Binds 2 calcium ions per subunit. {ECO:0000250};
CC   -!- SUBUNIT: Homodimer. Interacts with CLU. {ECO:0000250|UniProtKB:P27169}.
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space.
CC   -!- TISSUE SPECIFICITY: Plasma, liver, kidney, heart, brain, small
CC       intestine and lung. In the plasma, associated with HDL.
CC   -!- PTM: The signal sequence is not cleaved.
CC       {ECO:0000250|UniProtKB:P27169}.
CC   -!- MISCELLANEOUS: The preferential association of PON1 with HDL is
CC       mediated in part by its signal peptide, by binding phospholipids
CC       directly, rather than binding apo AI. The retained signal peptide may
CC       allow transfer of the protein between phospholipid surfaces.
CC       {ECO:0000250|UniProtKB:P27169}.
CC   -!- SIMILARITY: Belongs to the paraoxonase family. {ECO:0000305}.
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DR   EMBL; L40488; AAA99445.1; -; Genomic_DNA.
DR   EMBL; U32684; AAC52496.1; -; mRNA.
DR   EMBL; U72636; AAB17394.1; -; mRNA.
DR   EMBL; BC012706; AAH12706.1; -; mRNA.
DR   CCDS; CCDS19898.1; -.
DR   PIR; T10082; T10082.
DR   RefSeq; NP_035264.2; NM_011134.4.
DR   AlphaFoldDB; P52430; -.
DR   SMR; P52430; -.
DR   FunCoup; P52430; 6.
DR   IntAct; P52430; 1.
DR   STRING; 10090.ENSMUSP00000002663; -.
DR   GlyCosmos; P52430; 3 sites, No reported glycans.
DR   GlyGen; P52430; 4 sites, 2 N-linked glycans (2 sites), 1 O-linked glycan (1 site).
DR   iPTMnet; P52430; -.
DR   PhosphoSitePlus; P52430; -.
DR   SwissPalm; P52430; -.
DR   CPTAC; non-CPTAC-3380; -.
DR   jPOST; P52430; -.
DR   PaxDb; 10090-ENSMUSP00000002663; -.
DR   PeptideAtlas; P52430; -.
DR   ProteomicsDB; 289787; -.
DR   Pumba; P52430; -.
DR   Antibodypedia; 883; 666 antibodies from 41 providers.
DR   DNASU; 18979; -.
DR   Ensembl; ENSMUST00000002663.12; ENSMUSP00000002663.6; ENSMUSG00000002588.14.
DR   GeneID; 18979; -.
DR   KEGG; mmu:18979; -.
DR   UCSC; uc009awd.2; mouse.
DR   AGR; MGI:103295; -.
DR   CTD; 5444; -.
DR   MGI; MGI:103295; Pon1.
DR   VEuPathDB; HostDB:ENSMUSG00000002588; -.
DR   eggNOG; ENOG502S3B5; Eukaryota.
DR   GeneTree; ENSGT00390000008932; -.
DR   HOGENOM; CLU_049839_0_1_1; -.
DR   InParanoid; P52430; -.
DR   OMA; YFADPYF; -.
DR   OrthoDB; 423498at2759; -.
DR   PhylomeDB; P52430; -.
DR   BRENDA; 3.1.1.2; 3474.
DR   BRENDA; 3.1.1.25; 3474.
DR   BRENDA; 3.1.8.1; 3474.
DR   Reactome; R-MMU-2142688; Synthesis of 5-eicosatetraenoic acids.
DR   Reactome; R-MMU-9754706; Atorvastatin ADME.
DR   BioGRID-ORCS; 18979; 0 hits in 79 CRISPR screens.
DR   PRO; PR:P52430; -.
DR   Proteomes; UP000000589; Chromosome 6.
DR   RNAct; P52430; protein.
DR   Bgee; ENSMUSG00000002588; Expressed in pigmented layer of retina and 84 other cell types or tissues.
DR   ExpressionAtlas; P52430; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; ISO:GO_Central.
DR   GO; GO:0034364; C:high-density lipoprotein particle; ISO:GO_Central.
DR   GO; GO:0034366; C:spherical high-density lipoprotein particle; ISO:GO_Central.
DR   GO; GO:0102007; F:acyl-L-homoserine-lactone lactonohydrolase activity; ISO:GO_Central.
DR   GO; GO:0004063; F:aryldialkylphosphatase activity; ISS:UniProtKB.
DR   GO; GO:0004064; F:arylesterase activity; IMP:MGI.
DR   GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR   GO; GO:0008035; F:high-density lipoprotein particle binding; TAS:MGI.
DR   GO; GO:0005543; F:phospholipid binding; ISO:GO_Central.
DR   GO; GO:0042803; F:protein homodimerization activity; ISO:GO_Central.
DR   GO; GO:0008015; P:blood circulation; TAS:MGI.
DR   GO; GO:0046395; P:carboxylic acid catabolic process; ISO:GO_Central.
DR   GO; GO:0008203; P:cholesterol metabolic process; IMP:MGI.
DR   GO; GO:1901335; P:lactone catabolic process; ISO:GO_Central.
DR   GO; GO:0046434; P:organophosphate catabolic process; ISO:GO_Central.
DR   GO; GO:0046470; P:phosphatidylcholine metabolic process; ISO:GO_Central.
DR   GO; GO:0010875; P:positive regulation of cholesterol efflux; ISO:GO_Central.
DR   GO; GO:1902617; P:response to fluoride; ISO:GO_Central.
DR   GO; GO:0009636; P:response to toxic substance; IMP:MGI.
DR   FunFam; 2.120.10.30:FF:000023; Serum paraoxonase/arylesterase 2; 1.
DR   Gene3D; 2.120.10.30; TolB, C-terminal domain; 1.
DR   InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR   InterPro; IPR002640; Arylesterase-like.
DR   InterPro; IPR008363; Paraoxonase1.
DR   PANTHER; PTHR11799; PARAOXONASE; 1.
DR   PANTHER; PTHR11799:SF16; SERUM PARAOXONASE_ARYLESTERASE 1; 1.
DR   Pfam; PF01731; Arylesterase; 1.
DR   PRINTS; PR01785; PARAOXONASE.
DR   PRINTS; PR01786; PARAOXONASE1.
DR   SUPFAM; SSF63829; Calcium-dependent phosphotriesterase; 1.
PE   1: Evidence at protein level;
KW   Calcium; Disulfide bond; Glycoprotein; HDL; Hydrolase; Metal-binding;
KW   Reference proteome; Secreted; Signal.
FT   CHAIN           1..355
FT                   /note="Serum paraoxonase/arylesterase 1"
FT                   /id="PRO_0000223282"
FT   SIGNAL          1..?
FT                   /note="Not cleaved"
FT   ACT_SITE        115
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P27169"
FT   BINDING         53
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:P27169"
FT   BINDING         54
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P27169"
FT   BINDING         117
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P27169"
FT   BINDING         168
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:P27169"
FT   BINDING         169
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P27169"
FT   BINDING         224
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:P27169"
FT   BINDING         269
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:P27169"
FT   BINDING         270
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:P27169"
FT   CARBOHYD        253
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:17330941"
FT   CARBOHYD        270
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        324
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        42..353
FT                   /evidence="ECO:0000250|UniProtKB:P27169"
FT   CONFLICT        61
FT                   /note="G -> E (in Ref. 4; AAH12706)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        186
FT                   /note="F -> L (in Ref. 2; AAC52496)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   355 AA;  39565 MW;  FFA0A71445BB80B4 CRC64;
     MAKLLALTLV GLVLALYKNH RSSYQTRLNA FREVTPVELP NCNLVKGIET GAEDLEILPN
     GLTFFSTGLK YPGIKSFDPS KPGKILLMDL NKKEPAVSEL EIIGNTLDIS SFNPHGISTF
     TDEDNTVYLL VVNHPDSSST VEVFKFQEEE RSLLHLKTIT HELLPSINDI AAIGPESFYA
     TNDHYFADPY LRSWEMYLGL SWSNVVYYSP DKVQVVAEGF DFANGIGISL DGKYVYIAEL
     LAHKIHVYEK HANWTLTPLK VLNFDTLVDN ISVDPVTGDL WVGCHPNGMR IFFYDAENPP
     GSEVLRIQNI LSEDPKITVV YAENGTVLQG TTVASVYKGK LLIGTVFHKA LYCDL
//