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Q15166

- PON3_HUMAN

UniProt

Q15166 - PON3_HUMAN

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Protein

Serum paraoxonase/lactonase 3

Gene

PON3

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

Functioni

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.1 Publication

Catalytic activityi

A phenyl acetate + H2O = a phenol + acetate.1 Publication
An aryl dialkyl phosphate + H2O = dialkyl phosphate + an aryl alcohol.1 Publication
An N-acyl-L-homoserine lactone + H2O = an N-acyl-L-homoserine.1 Publication

Cofactori

Ca2+By similarityNote: Binds 2 calcium ions per subunit.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi53 – 531Calcium 1; catalyticBy similarity
Metal bindingi54 – 541Calcium 2By similarity
Active sitei114 – 1141Proton acceptorBy similarity
Metal bindingi116 – 1161Calcium 2; via carbonyl oxygenBy similarity
Metal bindingi167 – 1671Calcium 1; catalyticBy similarity
Metal bindingi168 – 1681Calcium 2By similarity
Metal bindingi223 – 2231Calcium 1; catalyticBy similarity
Metal bindingi268 – 2681Calcium 1; catalyticBy similarity
Metal bindingi269 – 2691Calcium 1; catalyticBy similarity

GO - Molecular functioni

  1. 3,4-dihydrocoumarin hydrolase activity Source: Ensembl
  2. aryldialkylphosphatase activity Source: UniProtKB-EC
  3. arylesterase activity Source: UniProtKB
  4. dihydrocoumarin hydrolase activity Source: Ensembl
  5. metal ion binding Source: UniProtKB-KW
  6. protein homodimerization activity Source: BHF-UCL

GO - Biological processi

  1. aromatic compound catabolic process Source: BHF-UCL
  2. carboxylic acid catabolic process Source: BHF-UCL
  3. coumarin catabolic process Source: Ensembl
  4. phenylacetate catabolic process Source: Ensembl
  5. response to external stimulus Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Calcium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Serum paraoxonase/lactonase 3 (EC:3.1.1.2, EC:3.1.1.81, EC:3.1.8.1)
Gene namesi
Name:PON3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 7

Organism-specific databases

HGNCiHGNC:9206. PON3.

Subcellular locationi

Secretedextracellular space By similarity

GO - Cellular componenti

  1. extracellular space Source: Ensembl
  2. extracellular vesicular exosome Source: UniProt
  3. intracellular membrane-bounded organelle Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

Orphaneti803. Amyotrophic lateral sclerosis.
PharmGKBiPA33531.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 354353Serum paraoxonase/lactonase 3PRO_0000223290Add
BLAST
Signal peptidei2 – ?Not cleavedSequence Analysis

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi29 – 291N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi42 ↔ 352By similarity
Modified residuei165 – 1651Phosphoserine1 Publication
Glycosylationi269 – 2691N-linked (GlcNAc...)Sequence Analysis
Glycosylationi323 – 3231N-linked (GlcNAc...)1 Publication

Post-translational modificationi

The signal sequence is not cleaved.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ15166.
PaxDbiQ15166.
PeptideAtlasiQ15166.
PRIDEiQ15166.

PTM databases

PhosphoSiteiQ15166.

Expressioni

Gene expression databases

BgeeiQ15166.
CleanExiHS_PON3.
ExpressionAtlasiQ15166. baseline and differential.
GenevestigatoriQ15166.

Organism-specific databases

HPAiCAB025250.
HPA014848.

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

IntActiQ15166. 1 interaction.
STRINGi9606.ENSP00000265627.

Structurei

3D structure databases

ProteinModelPortaliQ15166.
SMRiQ15166. Positions 23-354.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the paraoxonase family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG68009.
GeneTreeiENSGT00390000008932.
HOVERGENiHBG003604.
InParanoidiQ15166.
KOiK01045.
OMAiHVLFYSP.
PhylomeDBiQ15166.
TreeFamiTF322436.

Family and domain databases

Gene3Di2.120.10.30. 1 hit.
InterProiIPR011042. 6-blade_b-propeller_TolB-like.
IPR002640. Arylesterase.
IPR008364. Paraoxonase2.
[Graphical view]
PfamiPF01731. Arylesterase. 1 hit.
[Graphical view]
PRINTSiPR01785. PARAOXONASE.
PR01787. PARAOXONASE2.

Sequencei

Sequence statusi: Complete.

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

Q15166-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MGKLVALVLL GVGLSLVGEM FLAFRERVNA SREVEPVEPE NCHLIEELES
60 70 80 90 100
GSEDIDILPS GLAFISSGLK YPGMPNFAPD EPGKIFLMDL NEQNPRAQAL
110 120 130 140 150
EISGGFDKEL FNPHGISIFI DKDNTVYLYV VNHPHMKSTV EIFKFEEQQR
160 170 180 190 200
SLVYLKTIKH ELLKSVNDIV VLGPEQFYAT RDHYFTNSLL SFFEMILDLR
210 220 230 240 250
WTYVLFYSPR EVKVVAKGFC SANGITVSAD QKYVYVADVA AKNIHIMEKH
260 270 280 290 300
DNWDLTQLKV IQLGTLVDNL TVDPATGDIL AGCHPNPMKL LNYNPEDPPG
310 320 330 340 350
SEVLRIQNVL SEKPRVSTVY ANNGSVLQGT SVASVYHGKI LIGTVFHKTL

YCEL
Length:354
Mass (Da):39,607
Last modified:July 19, 2004 - v3
Checksum:i1B861B35E8533921
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti18 – 181G → E in AAC41996. (PubMed:8661009)Curated
Sequence conflicti32 – 321R → Q in AAC41996. (PubMed:8661009)Curated
Sequence conflicti50 – 501S → N in AAH70374. (PubMed:15489334)Curated
Sequence conflicti58 – 592LP → FL in AAK07629. 1 PublicationCurated
Sequence conflicti63 – 631A → S in AAC41996. (PubMed:8661009)Curated
Sequence conflicti68 – 681G → E in AAC41996. (PubMed:8661009)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti146 – 1461E → K.1 Publication
Corresponds to variant rs17878827 [ dbSNP | Ensembl ].
VAR_021082
Natural varianti179 – 1791A → D.1 Publication
Corresponds to variant rs17883013 [ dbSNP | Ensembl ].
VAR_021083

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS5639.1.
RefSeqiNP_000931.1. NM_000940.2.
UniGeneiHs.440967.

Genome annotation databases

EnsembliENST00000265627; ENSP00000265627; ENSG00000105852.
GeneIDi5446.
KEGGihsa:5446.
UCSCiuc003unt.3. human.

Polymorphism databases

DMDMi50403778.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
CCDSi CCDS5639.1.
RefSeqi NP_000931.1. NM_000940.2.
UniGenei Hs.440967.

3D structure databases

ProteinModelPortali Q15166.
SMRi Q15166. Positions 23-354.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q15166. 1 interaction.
STRINGi 9606.ENSP00000265627.

Chemistry

DrugBanki DB00974. Edetic Acid.
DB00227. Lovastatin.

PTM databases

PhosphoSitei Q15166.

Polymorphism databases

DMDMi 50403778.

Proteomic databases

MaxQBi Q15166.
PaxDbi Q15166.
PeptideAtlasi Q15166.
PRIDEi Q15166.

Protocols and materials databases

DNASUi 5446.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000265627 ; ENSP00000265627 ; ENSG00000105852 .
GeneIDi 5446.
KEGGi hsa:5446.
UCSCi uc003unt.3. human.

Organism-specific databases

CTDi 5446.
GeneCardsi GC07M094989.
HGNCi HGNC:9206. PON3.
HPAi CAB025250.
HPA014848.
MIMi 602720. gene.
neXtProti NX_Q15166.
Orphaneti 803. Amyotrophic lateral sclerosis.
PharmGKBi PA33531.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG68009.
GeneTreei ENSGT00390000008932.
HOVERGENi HBG003604.
InParanoidi Q15166.
KOi K01045.
OMAi HVLFYSP.
PhylomeDBi Q15166.
TreeFami TF322436.

Miscellaneous databases

GeneWikii PON3.
GenomeRNAii 5446.
NextBioi 21079.
PROi Q15166.
SOURCEi Search...

Gene expression databases

Bgeei Q15166.
CleanExi HS_PON3.
ExpressionAtlasi Q15166. baseline and differential.
Genevestigatori Q15166.

Family and domain databases

Gene3Di 2.120.10.30. 1 hit.
InterProi IPR011042. 6-blade_b-propeller_TolB-like.
IPR002640. Arylesterase.
IPR008364. Paraoxonase2.
[Graphical view ]
Pfami PF01731. Arylesterase. 1 hit.
[Graphical view ]
PRINTSi PR01785. PARAOXONASE.
PR01787. PARAOXONASE2.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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.
    , 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.

Entry informationi

Entry nameiPON3_HUMAN
AccessioniPrimary (citable) accession number: Q15166
Secondary accession number(s): A4D1H8
, O75855, O76060, Q6IRU9, Q8IX97, Q9BZH9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 19, 2004
Last modified: November 26, 2014
This is version 121 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

Keywords - Technical termi

Complete proteome, 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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3