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 27-MAR-2024, entry version 178.
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_011134.3.
DR AlphaFoldDB; P52430; -.
DR SMR; P52430; -.
DR IntAct; P52430; 1.
DR STRING; 10090.ENSMUSP00000002663; -.
DR GlyCosmos; P52430; 3 sites, No reported glycans.
DR GlyGen; P52430; 3 sites.
DR iPTMnet; P52430; -.
DR PhosphoSitePlus; P52430; -.
DR SwissPalm; P52430; -.
DR CPTAC; non-CPTAC-3380; -.
DR jPOST; P52430; -.
DR MaxQB; P52430; -.
DR PaxDb; 10090-ENSMUSP00000002663; -.
DR PeptideAtlas; P52430; -.
DR ProteomicsDB; 289787; -.
DR Pumba; P52430; -.
DR Antibodypedia; 883; 713 antibodies from 39 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; NAMYLLV; -.
DR OrthoDB; 2874974at2759; -.
DR PhylomeDB; P52430; -.
DR TreeFam; TF322436; -.
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 ChiTaRS; Pon1; mouse.
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 Genevisible; P52430; MM.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0034364; C:high-density lipoprotein particle; ISO:MGI.
DR GO; GO:0034366; C:spherical high-density lipoprotein particle; ISO:MGI.
DR GO; GO:0102007; F:acyl-L-homoserine-lactone lactonohydrolase activity; IEA:UniProtKB-EC.
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:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0019439; P:aromatic compound catabolic process; ISO:MGI.
DR GO; GO:0008015; P:blood circulation; TAS:MGI.
DR GO; GO:0046395; P:carboxylic acid catabolic process; ISO:MGI.
DR GO; GO:0008203; P:cholesterol metabolic process; IMP:MGI.
DR GO; GO:0046434; P:organophosphate catabolic process; ISO:MGI.
DR GO; GO:0046470; P:phosphatidylcholine metabolic process; ISO:MGI.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; ISO:MGI.
DR GO; GO:1902617; P:response to fluoride; ISO:MGI.
DR GO; GO:0009636; P:response to toxic substance; IMP:MGI.
DR Gene3D; 2.120.10.30; TolB, C-terminal domain; 1.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR002640; Arylesterase.
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
//
