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Q15165 (PON2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 129. 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·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serum paraoxonase/arylesterase 2

Short name=PON 2
EC=3.1.1.2
EC=3.1.1.81
Alternative name(s):
Aromatic esterase 2
Short name=A-esterase 2
Serum aryldialkylphosphatase 2
Gene names
Name:PON2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length354 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Capable of hydrolyzing lactones and a number of aromatic carboxylic acid esters. Has antioxidant activity. Is not associated with high density lipoprotein. Prevents LDL lipid peroxidation, reverses the oxidation of mildly oxidized LDL, and inhibits the ability of MM-LDL to induce monocyte chemotaxis. Ref.9 Ref.10

Catalytic activity

A phenyl acetate + H2O = a phenol + acetate. Ref.10

An N-acyl-L-homoserine lactone + H2O = an N-acyl-L-homoserine. Ref.10

Cofactor

Binds 2 calcium ions per subunit By similarity.

Subunit structure

Homotrimer. Ref.10

Subcellular location

Membrane; Peripheral membrane protein Ref.9.

Tissue specificity

Widely expressed with highest expression in liver, lung, placenta, testis and heart. Ref.9

Post-translational modification

The signal sequence is not cleaved By similarity.

Sequence similarities

Belongs to the paraoxonase family.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 2 (identifier: Q15165-2)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 1 (identifier: Q15165-1)

The sequence of this isoform differs from the canonical sequence as follows:
     1-16: MGRLVAVGLLGIALAL → MGAWVGCGLAGDRAGF
Isoform 3 (identifier: Q15165-3)

The sequence of this isoform differs from the canonical sequence as follows:
     123-134: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 354354Serum paraoxonase/arylesterase 2
PRO_0000223287
Signal peptide1 – ?Not cleaved By similarity

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

Glycosylation2541N-linked (GlcNAc...) Ref.11
Glycosylation2691N-linked (GlcNAc...) Potential
Glycosylation3231N-linked (GlcNAc...) Potential
Disulfide bond42 ↔ 352 By similarity

Natural variations

Alternative sequence1 – 1616MGRLV…IALAL → MGAWVGCGLAGDRAGF in isoform 1.
VSP_004533
Alternative sequence123 – 13412Missing in isoform 3.
VSP_040715
Natural variant1481A → G Associated with elevated mean fasting plasma glucose level. Ref.2 Ref.5 Ref.13
Corresponds to variant rs12026 [ dbSNP | Ensembl ].
VAR_006045
Natural variant1721V → L. Ref.5
Corresponds to variant rs17876152 [ dbSNP | Ensembl ].
VAR_020786
Natural variant3111C → S Associated with increased risk of coronary heart disease; CHD. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.7 Ref.14
Corresponds to variant rs7493 [ dbSNP | Ensembl ].
VAR_006046

Experimental info

Sequence conflict49 – 502EA → VW in AAC27945. Ref.2
Sequence conflict531E → D in BAG37646. Ref.4
Sequence conflict631A → V in BAG58797. Ref.4
Sequence conflict1941E → G in AAC41995. Ref.1
Sequence conflict2821G → V in AAC27944. Ref.2
Sequence conflict2821G → V in BAD89420. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 [UniParc].

Last modified March 8, 2011. Version 3.
Checksum: 05CEDC84D5E7EC2A

FASTA35439,397
        10         20         30         40         50         60 
MGRLVAVGLL GIALALLGER LLALRNRLKA SREVESVDLP HCHLIKGIEA GSEDIDILPN 

        70         80         90        100        110        120 
GLAFFSVGLK FPGLHSFAPD KPGGILMMDL KEEKPRAREL RISRGFDLAS FNPHGISTFI 

       130        140        150        160        170        180 
DNDDTVYLFV VNHPEFKNTV EIFKFEEAEN SLLHLKTVKH ELLPSVNDIT AVGPAHFYAT 

       190        200        210        220        230        240 
NDHYFSDPFL KYLETYLNLH WANVVYYSPN EVKVVAEGFD SANGINISPD DKYIYVADIL 

       250        260        270        280        290        300 
AHEIHVLEKH TNMNLTQLKV LELDTLVDNL SIDPSSGDIW VGCHPNGQKL FVYDPNNPPS 

       310        320        330        340        350 
SEVLRIQNIL CEKPTVTTVY ANNGSVLQGS SVASVYDGKL LIGTLYHRAL YCEL 

« Hide

Isoform 1 [UniParc].

Checksum: AAA1980D3850889D
Show »

FASTA35439,398
Isoform 3 [UniParc].

Checksum: 71F47B3E08154500
Show »

FASTA34237,996

References

« Hide 'large scale' references
[1]"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] (ISOFORM 1), VARIANT SER-311.
Tissue: Liver.
[2]"Human PON2 gene at 7q21.3: cloning, multiple mRNA forms, and missense polymorphisms in the coding sequence."
Mochizuki H., Scherer S.W., Xi T., Nickle D.C., Majer M., Huizenga J.J., Tsui L.-C., Prochazka M.
Gene 213:149-157(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 50-67, ALTERNATIVE SPLICING, VARIANTS GLY-148 AND SER-311.
[3]"Paraoxonase mRNA,nirs splice variant1."
Sameshima E., Tabata Y., Hayashi A., Iida K., Mitsuyama M., Kanai S., Furuya T., Saito T.
Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), VARIANT SER-311.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), VARIANT SER-311.
Tissue: Subthalamic nucleus and Testis.
[5]SeattleSNPs variation discovery resource
Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLY-148; LEU-172 AND SER-311.
[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]"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], VARIANT SER-311.
[8]"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] (ISOFORM 2).
Tissue: Skin.
[9]"Paraoxonase-2 is a ubiquitously expressed protein with antioxidant properties and is capable of preventing cell-mediated oxidative modification of low density lipoprotein."
Ng C.J., Wadleigh D.J., Gangopadhyay A., Hama S., Grijalva V.R., Navab M., Fogelman A.M., Reddy S.T.
J. Biol. Chem. 276:44444-44449(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[10]"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.
[11]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-254.
Tissue: Liver.
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Paraoxonase-2 gene (PON2) G148 variant associated with elevated fasting plasma glucose in noninsulin-dependent diabetes mellitus."
Hegele R.A., Connelly P.W., Scherer S.W., Hanley A.J.G., Harris S.B., Tsui L.-C., Zinman B.
J. Clin. Endocrinol. Metab. 82:3373-3377(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLY-148.
[14]"DNA polymorphisms in two paraoxonase genes (PON1 and PON2) are associated with the risk of coronary heart disease."
Sanghera D.K., Aston C.E., Saha N., Kamboh M.I.
Am. J. Hum. Genet. 62:36-44(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SER-311.
+Additional computationally mapped references.

Web resources

SeattleSNPs
SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L48513 mRNA. Translation: AAC41995.1.
AF001601 mRNA. Translation: AAC27944.1.
AF001602 mRNA. Translation: AAC27945.1.
AF001603 Genomic DNA. Translation: AAC27946.1.
AB102891 mRNA. Translation: BAD89420.1.
AK291103 mRNA. Translation: BAF83792.1.
AK296029 mRNA. Translation: BAG58797.1.
AK315209 mRNA. Translation: BAG37646.1.
AY210982 Genomic DNA. Translation: AAO18083.1.
AC005021 Genomic DNA. Translation: AAC62431.1.
CH236949 Genomic DNA. Translation: EAL24131.1.
BC040010 mRNA. Translation: AAH40010.1.
CCDSCCDS47644.1. [Q15165-3]
CCDS5640.1. [Q15165-2]
RefSeqNP_000296.2. NM_000305.2.
UniGeneHs.744912.

3D structure databases

ProteinModelPortalQ15165.
SMRQ15165. Positions 23-354.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111441. 13 interactions.
IntActQ15165. 3 interactions.
STRING9606.ENSP00000222572.

PTM databases

PhosphoSiteQ15165.

Polymorphism databases

DMDM325511384.

Proteomic databases

MaxQBQ15165.
PaxDbQ15165.
PRIDEQ15165.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000222572; ENSP00000222572; ENSG00000105854.
ENST00000446142; ENSP00000405211; ENSG00000105854.
GeneID5445.
KEGGhsa:5445.

Organism-specific databases

CTD5445.
GeneCardsGC07M095034.
HGNCHGNC:9205. PON2.
HPACAB025430.
HPA029193.
MIM602447. gene.
neXtProtNX_Q15165.
Orphanet803. Amyotrophic lateral sclerosis.
PharmGKBPA33530.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG68009.
HOVERGENHBG003604.
KOK01045.
PhylomeDBQ15165.
TreeFamTF322436.

Gene expression databases

ArrayExpressQ15165.
BgeeQ15165.
CleanExHS_PON2.
GenevestigatorQ15165.

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

GeneWikiPON2.
GenomeRNAi5445.
NextBio21073.
PROQ15165.
SOURCESearch...

Entry information

Entry namePON2_HUMAN
AccessionPrimary (citable) accession number: Q15165
Secondary accession number(s): A4D1H7 expand/collapse secondary AC list , B2RCP9, B4DJD5, O15114, O15115, O75856, Q5FBX7, Q86YL0
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: March 8, 2011
Last modified: July 9, 2014
This is version 129 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