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Q15166 (PON3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serum paraoxonase/lactonase 3

EC=3.1.1.2
EC=3.1.1.81
EC=3.1.8.1
Gene names
Name:PON3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length354 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Has low activity towards the organophosphate paraxon and aromatic carboxylic acid esters. Rapidly hydrolyzes lactones such as statin prodrugs (e.g. lovastatin). Hydrolyzes aromatic lactones and 5- or 6-member ring lactones with aliphatic substituents but not simple lactones or those with polar substituents. Ref.9

Catalytic activity

A phenyl acetate + H2O = a phenol + acetate. Ref.9

An aryl dialkyl phosphate + H2O = dialkyl phosphate + an aryl alcohol. Ref.9

An N-acyl-L-homoserine lactone + H2O = an N-acyl-L-homoserine. Ref.9

Cofactor

Binds 2 calcium ions per subunit By similarity.

Subunit structure

Homodimer. Ref.9

Subcellular location

Secretedextracellular space By similarity.

Post-translational modification

The signal sequence is not cleaved By similarity.

Sequence similarities

Belongs to the paraoxonase family.

Ontologies

Keywords
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DomainSignal
   LigandCalcium
Metal-binding
   Molecular functionHydrolase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaromatic compound catabolic process

Inferred from direct assay Ref.9. Source: BHF-UCL

carboxylic acid catabolic process

Inferred from direct assay Ref.9. Source: BHF-UCL

coumarin catabolic process

Inferred from electronic annotation. Source: Ensembl

phenylacetate catabolic process

Inferred from electronic annotation. Source: Ensembl

response to external stimulus

Non-traceable author statement Ref.8. Source: UniProtKB

   Cellular_componentextracellular space

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular vesicular exosome

Inferred from direct assay PubMed 19199708. Source: UniProt

intracellular membrane-bounded organelle

Inferred from electronic annotation. Source: Ensembl

   Molecular_function3,4-dihydrocoumarin hydrolase activity

Inferred from electronic annotation. Source: Ensembl

aryldialkylphosphatase activity

Inferred from electronic annotation. Source: UniProtKB-EC

arylesterase activity

Non-traceable author statement Ref.8. Source: UniProtKB

dihydrocoumarin hydrolase activity

Inferred from electronic annotation. Source: Ensembl

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein homodimerization activity

Inferred from direct assay Ref.9. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 354353Serum paraoxonase/lactonase 3
PRO_0000223290
Signal peptide2 – ?Not cleaved Potential

Sites

Active site1141Proton acceptor By similarity
Metal binding531Calcium 1; catalytic By similarity
Metal binding541Calcium 2 By similarity
Metal binding1161Calcium 2; via carbonyl oxygen By similarity
Metal binding1671Calcium 1; catalytic By similarity
Metal binding1681Calcium 2 By similarity
Metal binding2231Calcium 1; catalytic By similarity
Metal binding2681Calcium 1; catalytic By similarity
Metal binding2691Calcium 1; catalytic By similarity

Amino acid modifications

Modified residue1651Phosphoserine Ref.11
Glycosylation291N-linked (GlcNAc...) Potential
Glycosylation2691N-linked (GlcNAc...) Potential
Glycosylation3231N-linked (GlcNAc...) Ref.10
Disulfide bond42 ↔ 352 By similarity

Natural variations

Natural variant1461E → K. Ref.3
Corresponds to variant rs17878827 [ dbSNP | Ensembl ].
VAR_021082
Natural variant1791A → D. Ref.3
Corresponds to variant rs17883013 [ dbSNP | Ensembl ].
VAR_021083

Experimental info

Sequence conflict181G → E in AAC41996. Ref.8
Sequence conflict321R → Q in AAC41996. Ref.8
Sequence conflict501S → N in AAH70374. Ref.7
Sequence conflict58 – 592LP → FL in AAK07629. Ref.1
Sequence conflict631A → S in AAC41996. Ref.8
Sequence conflict681G → E in AAC41996. Ref.8

Sequences

Sequence LengthMass (Da)Tools
Q15166 [UniParc].

Last modified July 19, 2004. Version 3.
Checksum: 1B861B35E8533921

FASTA35439,607
        10         20         30         40         50         60 
MGKLVALVLL GVGLSLVGEM FLAFRERVNA SREVEPVEPE NCHLIEELES GSEDIDILPS 

        70         80         90        100        110        120 
GLAFISSGLK YPGMPNFAPD EPGKIFLMDL NEQNPRAQAL EISGGFDKEL FNPHGISIFI 

       130        140        150        160        170        180 
DKDNTVYLYV VNHPHMKSTV EIFKFEEQQR SLVYLKTIKH ELLKSVNDIV VLGPEQFYAT 

       190        200        210        220        230        240 
RDHYFTNSLL SFFEMILDLR WTYVLFYSPR EVKVVAKGFC SANGITVSAD QKYVYVADVA 

       250        260        270        280        290        300 
AKNIHIMEKH DNWDLTQLKV IQLGTLVDNL TVDPATGDIL AGCHPNPMKL LNYNPEDPPG 

       310        320        330        340        350 
SEVLRIQNVL SEKPRVSTVY ANNGSVLQGT SVASVYHGKI LIGTVFHKTL YCEL 

« Hide

References

« Hide 'large scale' references
[1]"Human paraoxanase-3 is an HDL-associated enzyme."
Reddy S.T., Wadleigh D.J., Grijalva V., Ng C., Hama S., Gangopadhyay A., Khorsan R., Shih D., Lusis A.J., Navab M., Fogelman A.M.
Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Hepatoma.
[2]"Human PON3 has lactonase activity."
Draganov D.I., Watson C.E.
Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[3]SeattleSNPs variation discovery resource
Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LYS-146 AND ASP-179.
[4]"Human chromosome 7: DNA sequence and biology."
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. expand/collapse author list , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Liver.
[8]"The human serum paraoxonase/arylesterase gene (PON1) is one member of a multigene family."
Primo-Parmo S.L., Sorenson R.C., Teiber J., La Du B.N.
Genomics 33:498-507(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 14-354.
Tissue: Liver.
[9]"Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities."
Draganov D.I., Teiber J.F., Speelman A., Osawa Y., Sunahara R., La Du B.N.
J. Lipid Res. 46:1239-1247(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBUNIT.
[10]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-323.
Tissue: Plasma.
[11]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF320003 mRNA. Translation: AAK07629.1.
AF329433 mRNA. Translation: AAO15365.1.
AY805220 Genomic DNA. Translation: AAV50000.1.
AC004022 Genomic DNA. No translation available.
AC005021 Genomic DNA. No translation available.
CH236949 Genomic DNA. Translation: EAL24132.1.
CH471091 Genomic DNA. Translation: EAW76768.1.
BC070374 mRNA. Translation: AAH70374.1.
L48516 mRNA. Translation: AAC41996.1.
CCDSCCDS5639.1.
RefSeqNP_000931.1. NM_000940.2.
UniGeneHs.440967.

3D structure databases

ProteinModelPortalQ15166.
SMRQ15166. Positions 23-354.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ15166. 1 interaction.
STRING9606.ENSP00000265627.

PTM databases

PhosphoSiteQ15166.

Polymorphism databases

DMDM50403778.

Proteomic databases

MaxQBQ15166.
PaxDbQ15166.
PeptideAtlasQ15166.
PRIDEQ15166.

Protocols and materials databases

DNASU5446.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265627; ENSP00000265627; ENSG00000105852.
GeneID5446.
KEGGhsa:5446.
UCSCuc003unt.3. human.

Organism-specific databases

CTD5446.
GeneCardsGC07M094989.
HGNCHGNC:9206. PON3.
HPACAB025250.
HPA014848.
MIM602720. gene.
neXtProtNX_Q15166.
Orphanet803. Amyotrophic lateral sclerosis.
PharmGKBPA33531.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG68009.
HOVERGENHBG003604.
InParanoidQ15166.
KOK01045.
OMAHVLFYSP.
PhylomeDBQ15166.
TreeFamTF322436.

Gene expression databases

ArrayExpressQ15166.
BgeeQ15166.
CleanExHS_PON3.
GenevestigatorQ15166.

Family and domain databases

Gene3D2.120.10.30. 1 hit.
InterProIPR011042. 6-blade_b-propeller_TolB-like.
IPR002640. Arylesterase.
IPR008364. Paraoxonase2.
[Graphical view]
PfamPF01731. Arylesterase. 1 hit.
[Graphical view]
PRINTSPR01785. PARAOXONASE.
PR01787. PARAOXONASE2.
ProtoNetSearch...

Other

GeneWikiPON3.
GenomeRNAi5446.
NextBio21079.
PROQ15166.
SOURCESearch...

Entry information

Entry namePON3_HUMAN
AccessionPrimary (citable) accession number: Q15166
Secondary accession number(s): A4D1H8 expand/collapse secondary AC list , O75855, O76060, Q6IRU9, Q8IX97, Q9BZH9
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 19, 2004
Last modified: July 9, 2014
This is version 118 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM