Q15166 (PON3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serum paraoxonase/lactonase 3
EC=3.1.1.2
EC=3.1.1.81
EC=3.1.8.1

Gene names

Name:

PON3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	354 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Secreted › extracellular space By similarity.
Post-translational modification	The signal sequence is not cleaved By similarity.
Sequence similarities	Belongs to the paraoxonase family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Calcium Metal-binding
Molecular function	Hydrolase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	aromatic 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: Compara phenylacetate catabolic process Inferred from electronic annotation. Source: Compara response to external stimulus Non-traceable author statement Ref.8. Source: UniProtKB
Cellular_component	extracellular region Non-traceable author statement. Source: UniProtKB extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell intracellular membrane-bounded organelle Inferred from electronic annotation. Source: Compara
Molecular_function	3,4-dihydrocoumarin hydrolase activity Inferred from electronic annotation. Source: Compara aryldialkylphosphatase activity Inferred from electronic annotation. Source: EC arylesterase activity Non-traceable author statement Ref.8. Source: UniProtKB dihydrocoumarin hydrolase activity Inferred from electronic annotation. Source: Compara 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 354	353	Serum paraoxonase/lactonase 3		PRO_0000223290
	Signal peptide	2 – ?		Not cleaved Potential
Sites
	Active site	114	1	Proton acceptor By similarity
	Metal binding	53	1	Calcium 1; catalytic By similarity
	Metal binding	54	1	Calcium 2 By similarity
	Metal binding	116	1	Calcium 2; via carbonyl oxygen By similarity
	Metal binding	167	1	Calcium 1; catalytic By similarity
	Metal binding	168	1	Calcium 2 By similarity
	Metal binding	223	1	Calcium 1; catalytic By similarity
	Metal binding	268	1	Calcium 1; catalytic By similarity
	Metal binding	269	1	Calcium 1; catalytic By similarity
Amino acid modifications
	Modified residue	165	1	Phosphoserine Ref.11
	Glycosylation	29	1	N-linked (GlcNAc...) Potential
	Glycosylation	269	1	N-linked (GlcNAc...) Potential
	Glycosylation	323	1	N-linked (GlcNAc...) Ref.10
	Disulfide bond	42 ↔ 352		By similarity
Natural variations
	Natural variant	146	1	E → K. Ref.3 Corresponds to variant rs17878827 [ dbSNP | Ensembl ].		VAR_021082
	Natural variant	179	1	A → D. Ref.3 Corresponds to variant rs17883013 [ dbSNP | Ensembl ].		VAR_021083
Experimental info
	Sequence conflict	18	1	G → E in AAC41996. Ref.8
	Sequence conflict	32	1	R → Q in AAC41996. Ref.8
	Sequence conflict	50	1	S → N in AAH70374. Ref.7
	Sequence conflict	58 – 59	2	LP → FL in AAK07629. Ref.1
	Sequence conflict	63	1	A → S in AAC41996. Ref.8
	Sequence conflict	68	1	G → E in AAC41996. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Q15166 [UniParc]. Last modified July 19, 2004. Version 3. Checksum: 1B861B35E8533921	FASTA	354	39,607
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

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.
IPI	IPI00299778.
RefSeq	NP_000931.1. NM_000940.2.
UniGene	Hs.440967.
3D structure databases
ProteinModelPortal	Q15166.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000265627.
PTM databases
PhosphoSite	Q15166.
Polymorphism databases
DMDM	50403778.
Proteomic databases
PaxDb	Q15166.
PeptideAtlas	Q15166.
PRIDE	Q15166.
Protocols and materials databases
DNASU	5446.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000265627; ENSP00000265627; ENSG00000105852.
GeneID	5446.
KEGG	hsa:5446.
UCSC	uc003unt.3. human.
Organism-specific databases
CTD	5446.
GeneCards	GC07M094989.
HGNC	HGNC:9206. PON3.
HPA	CAB025250. HPA014848.
MIM	602720. gene.
neXtProt	NX_Q15166.
Orphanet	803. Amyotrophic lateral sclerosis.
PharmGKB	PA33531.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG68009.
HOVERGEN	HBG003604.
InParanoid	Q15166.
KO	K01045.
OMA	QKYVYVA.
OrthoDB	EOG4XD3RN.
PhylomeDB	Q15166.
Gene expression databases
ArrayExpress	Q15166.
Bgee	Q15166.
CleanEx	HS_PON3.
Genevestigator	Q15166.
GermOnline	ENSG00000105852. Homo sapiens.
Family and domain databases
Gene3D	2.120.10.30. 1 hit.
InterPro	IPR011042. 6-blade_b-propeller_TolB-like. IPR002640. Arylesterase. IPR008364. Paraoxonase2. [Graphical view]
Pfam	PF01731. Arylesterase. 1 hit. [Graphical view]
PRINTS	PR01785. PARAOXONASE. PR01787. PARAOXONASE2.
ProtoNet	Search...
Other
GenomeRNAi	5446.
NextBio	21079.
SOURCE	Search...

Entry information

Entry name

PON3_HUMAN

Accession

Primary (citable) accession number: Q15166
Secondary accession number(s): A4D1H8 , O75855, O76060, Q6IRU9, Q8IX97, Q9BZH9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 19, 2004
Last modified:	May 1, 2013
This is version 109 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.