Reviewed, UniProtKB/Swiss-Prot P27169 (PON1_HUMAN)

Names and origin

Protein names

Recommended name:
    Serum paraoxonase/arylesterase 1
      Short name=PON 1
    EC=3.1.1.2
    EC=3.1.8.1
Alternative name(s):
    Serum aryldialkylphosphatase 1
    A-esterase 1
    Aromatic esterase 1
    K-45

Gene names

Name:	PON1
Synonyms:	PON

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	355 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	Hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. Capable of hydrolyzing a broad spectrum of organophosphate substrates and a number of aromatic carboxylic acid esters. May mediate an enzymatic protection of low density lipoproteins against oxidative modification and the consequent series of events leading to atheroma formation.
Catalytic activity	A phenyl acetate + H(2)O = a phenol + acetate. An aryl dialkyl phosphate + H(2)O = dialkyl phosphate + an aryl alcohol.
Subunit structure	Heterooligomer with phosphate-binding protein (HPBP). Interacts with CLU.
Subcellular location	Secreted › extracellular space.
Tissue specificity	Plasma, associated with HDL (at protein level). Expressed in liver, but not in heart, brain, placenta, lung, skeletal muscle, kidney or pancreas.
Post-translational modification	Glycosylated. The signal sequence is not cleaved. Present in two forms, form B contains a disulfide bond, form A does not.
Polymorphism	The allelic form of the enzyme with Gln-192 (allozyme A) hydrolyzes paraoxon with a low turnover number and the one with Arg-192 (allozyme B) with a high turnover number.
Miscellaneous	The preferential association of PON1 with HDL is mediated in part by its signal peptide, by binding phospholipids directly, rather than binding apo AI. The retained signal peptide may allow transfer of the protein between phospholipid surfaces.
Sequence similarities	Belongs to the paraoxonase family.

Ontologies

Keywords
Cellular component	HDL Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Hydrolase
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	response to external stimulus Ref.1 Non-traceable author statement. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay. Source: HPA cytoskeleton Inferred from direct assay. Source: HPA extracellular region Non-traceable author statement. Source: UniProtKB
Molecular function	aryldialkylphosphatase activity Inferred from electronic annotation. Source: EC arylesterase activity Ref.16 Non-traceable author statement. Source: UniProtKB lipid transporter activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – ?

Not cleaved

Initiator methionine

1

1

Removed

Chain

2 – 355

354

Serum paraoxonase/arylesterase 1

PRO_0000223281

Amino acid modifications

Modified residue

76

1

Phosphoserine By similarity

Glycosylation

227

1

N-linked (GlcNAc...)

Glycosylation

253

1

N-linked (GlcNAc...)

Glycosylation

270

1

N-linked (GlcNAc...) Potential

Glycosylation

324

1

N-linked (GlcNAc...)

Disulfide bond

42 ↔ 353

In form B

Natural variations

Natural variant

55

1

M → L: dbSNP rs854560.

VAR_006043

Natural variant

102

1

I → V Polymorphism associated with decreased activity that seems to be associated with an increased risk for prostate cancer.

VAR_015882

Natural variant

192

1

Q → R Polymorphism important for activity. dbSNP rs662.

VAR_006044

Experimental info

Mutagenesis

20 – 21

2

HQ → AA: The signal peptide is cleaved; not associated with HDL

Mutagenesis

284

1

C → A or S: No loss of activity

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

355

Helix Strand Turn

Details...

Helix

18 – 26

9

Turn

27 – 30

4

Beta strand

53 – 56

4

Beta strand

60 – 66

7

Beta strand

83 – 88

6

Beta strand

91 – 93

3

Beta strand

96 – 98

3

Beta strand

100 – 102

3

Beta strand

104 – 106

3

Helix

108 – 110

3

Beta strand

113 – 120

8

Beta strand

126 – 132

7

Beta strand

139 – 146

8

Turn

147 – 150

4

Beta strand

151 – 158

8

Beta strand

164 – 173

10

Beta strand

176 – 182

7

Helix

188 – 196

9

Beta strand

202 – 207

6

Beta strand

212 – 227

16

Beta strand

231 – 238

8

Turn

239 – 242

4

Beta strand

243 – 249

7

Beta strand

255 – 262

8

Beta strand

264 – 272

9

Turn

274 – 276

3

Beta strand

279 – 285

7

Helix

287 – 291

5

Beta strand

301 – 307

7

Beta strand

311 – 313

3

Beta strand

315 – 322

8

Beta strand

324 – 327

4

Beta strand

329 – 336

8

Beta strand

339 – 347

9

Beta strand

349 – 353

5

Sequences

	Sequence		Length	Mass (Da)
	P27169-1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 9A2F4E3DE036536A	FASTA	355	39,749
	10 20 30 40 50 60 MAKLIALTLL GMGLALFRNH QSSYQTRLNA LREVQPVELP NCNLVKGIET GSEDMEILPN 70 80 90 100 110 120 GLAFISSGLK YPGIKSFNPN SPGKILLMDL NEEDPTVLEL GITGSKFDVS SFNPHGISTF 130 140 150 160 170 180 TDEDNAMYLL VVNHPDAKST VELFKFQEEE KSLLHLKTIR HKLLPNLNDI VAVGPEHFYG 190 200 210 220 230 240 TNDHYFLDPY LQSWEMYLGL AWSYVVYYSP SEVRVVAEGF DFANGINISP DGKYVYIAEL 250 260 270 280 290 300 LAHKIHVYEK HANWTLTPLK SLDFNTLVDN ISVDPETGDL WVGCHPNGMK IFFYDSENPP 310 320 330 340 350 ASEVLRIQNI LTEEPKVTQV YAENGTVLQG STVASVYKGK LLIGTVFHKA LYCEL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of cDNA clones encoding rabbit and human serum paraoxonase: the mature protein retains its signal sequence." Hassett C., Richter R.J., Humbert R., Chapline C., Crabb J.W., Omiecinski C.J., Furlong C.E. Biochemistry 30:10141-10149(1991) [PubMed: 1657140] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-55 AND ARG-192. Tissue: Liver.
[2]	"Molecular basis for the polymorphic forms of human serum paraoxonase/arylesterase: glutamine or arginine at position 191, for the respective A or B allozymes." Adkins S., Gan K.N., Mody M., La Du B.N. Am. J. Hum. Genet. 52:598-608(1993) [PubMed: 7916578] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-192.
[3]	"Studies on human serum paraoxonase/arylesterase." La Du B.N., Adkins S., Kuo C.L., Lipsig D. Chem. Biol. Interact. 87:25-34(1993) [PubMed: 8393742] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, VARIANT ARG-192. Tissue: Liver.
[4]	"Human and rabbit paraoxonases: purification, cloning, sequencing, mapping and role of polymorphism in organophosphate detoxification." Furlong C.E., Costa L.G., Hassett C., Richter R.J., Sundstrom J.A., Adler D.A., Disteche C.M., Omiecinski C.J., Chapline C., Crabb J.W. Chem. Biol. Interact. 87:35-48(1993) [PubMed: 8393745] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-55 AND ARG-192, CHARACTERIZATION. Tissue: Liver.
[5]	"Structural organization of the human PON1 gene." Clendenning J.B., Humbert R., Green E.D., Wood C., Traver D., Furlong C.E. Genomics 35:586-589(1996) [PubMed: 8812495] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LEU-55. Tissue: Lymphoblast.
[6]	"Differential expression of a cDNA clone in human liver versus hepatic cancer -- highly homologous to aryl-dialkyl-phosphatase." Wang K.K., Wan D.F., Qiu X.K., Lu P.X., Gu J.R. Cell Res. 7:79-90(1997) [PubMed: 9261565] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT LEU-55. Tissue: Liver.
[7]	"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. , 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
[8]	SeattleSNPs program for genomic applications Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-55 AND ARG-192.
[9]	"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: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT LEU-55.
[10]	"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. , Christ