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PR01785

Identifier
PARAOXONASE  [View Relations]  [View Alignment]  
Accession
PR01785
No. of Motifs
8
Creation Date
03-SEP-2002
Title
Paraoxonase family signature
Database References
PRINTS; PR01786 PARAOXONASE1; PR01787 PARAOXONASE2
PFAM; PF01731 Arylesterase
INTERPRO; IPR002640
Literature References
1. PRIMO-PARMO, S.L., SORENSON, R.C., TEIBER, J. AND LA DU, B.N.
The human serum paraoxonase/arylesterase gene (PON1) is one member of a
multigene family.
GENOMICS 33 498-507 (1996).
 
2. ALDRIDGE, W.N.
Serum esterases: II. An enzyme hydrolyzing diethyl p-nitrophenyl phosphate
BIOCHEM.J. 53 117-124 (1953).
 
3. LA DU, B.N.
Human serum paraoxonase/arylesterase.
IN PHARMACOGENETICS OF DRUG METABOLISM, KALOW, W., ED., PERGAMON PRESS,
NEW YORK, 1992, PP.51-91.
 
4. BREALEY, C.J., WALKER, C.H. AND BALDWIN, B.C.
A-esterase activities in relation to the differential toxicity of
pirimiphosmethyl to birds and mammals.
PESTICIDES SCI. 11 546-554 (1980).
 
5. SCOTT, D.L., WHITE, S.P., OTWINOWSKI, Z., YUAN, W., GELB, M.H. 
AND SIGLER, P.B.
Interfacial catalysis: the mechanism of phospholipase A2.
SCIENCE 250 1541-1546 (2000).
 
6. REDDY, S.T., WADLEIGH, D.J., GRIJALVA, V., NG, C., HAMA, S.,
GANGOPADHYAY, A., SHIH, D.M., LUSIS, A.J., NAVAB, M. AND FOGELMAN, A.M.
Human paraoxonase-3 is an HDL-associated enzyme with biological activity
similar to paraoxonase-1 protein but is not regulated by oxidized lipids.
ARTERIOSCLER.THROMB.VASC.BIOL. 21 542-547 (2001).
 
7. NG, C.J., WADLEIGH, D.J., GANGOPADHYAY, A., HAMA, S., GRIJALVA, V.R.,
NAVAB, M., FOGELMAN, A.M. AND REDDY, S.T.
Paraoxonase-2 is a ubiquitously expressed protein with antioxidant
properties and is capable of preventing cell-mediated oxidative modification
of low density lipoprotein.
J.BIOL.CHEM. 276 44444-44449 (2001).

Documentation
The serum paraoxonases/arylesterases are enzymes that catalyse the hydrolysis
of the toxic metabolites of a variety of organophosphorus insecticides. The
enzymes hydrolyse a broad spectrum of organophosphate substrates, including 
paraoxon and a number of aromatic carboxylic acid esters (e.g., phenly
acetate), and hence confer resistance to organophosphate toxicity [1]. 
 
Mammals have 3 distinct paraoxonase types, termed PON1-3 [1]. In mice and
humans, the PON genes are found on the same chromosome in close proximity. 
PON activity has been found in variety of tissues, with highest levels in 
liver and serum [2] - the source of serum PON is thought to be the liver 
[3]. Unlike mammals, fish and avian species lack paraoxonase activity [4]. 
The absence of this activity in chicken and turkey indicates that PON2 does 
not hydrolyse paraoxon [1]. 
 
Human and rabbit PONs appear to have two distinct Ca2+ binding sites, one
required for stability and one required for catalytic activity. The Ca2+
dependency of PONs suggests a mechanism of hydrolysis where Ca2+ acts as the
electrophilic catalyst, like that proposed for phospholipase A2 [5]. The
paraoxonase enzymes, PON1 and PON3, are high density lipoprotein (HDL)-
associated proteins capable of preventing oxidative modification of low
density lipoproteins (LPL) [6]. Although PON2 has oxidative properties, the
enzyme does not associate with HDL [7].
 
Within a given species, PON1, PON2 and PON3 share ~60% amino acid sequence 
identity, whereas between mammalian species particular PONs (1,2 or 3) share
79-90% identity at the amino acid level. Human PON1 and PON3 share numerous 
conserved phosphorylation and N-glycosylation sites; however, it is not 
known whether the PON proteins are modified at these sites, or whether 
modification at these sites is required for activity in vivo [6].
 
PARAOXONASE is an 8-element fingerprint that provides a signature for the
paraoxonase family. The fingerprint was derived from an initial alignment of
7 sequences: the motifs were drawn from conserved regions spanning the full 
alignment length. Two iterations on SPTR40_20f were required to reach 
convergence, at which point a true set containing 15 sequences was 
identified. Two partial matches were also found, both truncated murine PON-
like proteins that matched two or three motifs.
Summary Information
  15 codes involving  8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
1 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
81515151515151515
700000000
600000000
500000000
400000000
311100000
200000011
12345678
True Positives
PON1_HUMAN    PON1_MOUSE    PON1_RABIT    PON1_RAT      
PON2_CANFA PON2_CHICK PON2_HUMAN PON2_MELGA
PON2_MOUSE PON3_HUMAN PON3_MOUSE Q91X30
Q9BGN0 Q9BGN1 Q9BGN2
True Positive Partials
Codes involving 3 elements
Q8VDG8
Codes involving 2 elements
Q99JS7
Sequence Titles
PON1_HUMAN  Serum paraoxonase/arylesterase 1 (EC 3.1.1.2) (EC 3.1.8.1) (PON 1) (Serum aryldiakylphosphatase 1) (A-esterase 1) (Aromatic esterase 1) (K-45) - Homo sapiens (Human). 
PON1_MOUSE Serum paraoxonase/arylesterase 1 (EC 3.1.1.2) (EC 3.1.8.1) (PON 1) (Serum aryldiakylphosphatase 1) (A-esterase 1) (Aromatic esterase 1) - Mus musculus (Mouse).
PON1_RABIT Serum paraoxonase/arylesterase 1 (EC 3.1.1.2) (EC 3.1.8.1) (PON 1) (Serum aryldiakylphosphatase 1) (A-esterase 1) (Aromatic esterase 1) - Oryctolagus cuniculus (Rabbit).
PON1_RAT Serum paraoxonase/arylesterase 1 (EC 3.1.1.2) (EC 3.1.8.1) (PON 1) (Serum aryldiakylphosphatase 1) (A-esterase 1) (Aromatic esterase 1) - Rattus norvegicus (Rat).
PON2_CANFA Serum paraoxonase/arylesterase 2 (EC 3.1.1.2) (EC 3.1.8.1) (PON 2) (Serum aryldiakylphosphatase 2) (A-esterase 2) (Aromatic esterase 2) - Canis familiaris (Dog).
PON2_CHICK Serum paraoxonase/arylesterase 2 (EC 3.1.1.2) (EC 3.1.8.1) (PON 2) (Serum aryldiakylphosphatase 2) (A-esterase 2) (Aromatic esterase 2) - Gallus gallus (Chicken).
PON2_HUMAN Serum paraoxonase/arylesterase 2 (EC 3.1.1.2) (EC 3.1.8.1) (PON 2) (Serum aryldialkylphosphatase 2) (A-esterase 2) (Aromatic esterase 2) - Homo sapiens (Human).
PON2_MELGA Serum paraoxonase/arylesterase 2 (EC 3.1.1.2) (EC 3.1.8.1) (PON 2) (Serum aryldiakylphosphatase 2) (A-esterase 2) (Aromatic esterase 2) - Meleagris gallopavo (Common turkey).
PON2_MOUSE Serum paraoxonase/arylesterase 2 (EC 3.1.1.2) (EC 3.1.8.1) (PON 2) (Serum aryldiakylphosphatase 2) (A-esterase 2) (Aromatic esterase 2) - Mus musculus (Mouse).
PON3_HUMAN Serum paraoxonase/arylesterase 3 (EC 3.1.1.2) (EC 3.1.8.1) (PON 3) (Serum aryldiakylphosphatase 3) (A-esterase 3) (Aromatic esterase 3) - Homo sapiens (Human).
PON3_MOUSE Serum paraoxonase/arylesterase 3 (EC 3.1.1.2) (EC 3.1.8.1) (PON 3) (Serum aryldiakylphosphatase 3) (A-esterase 3) (Aromatic esterase 3) - Mus musculus (Mouse).
Q91X30 PARAOXONASE 1 - Mus musculus (Mouse).
Q9BGN0 PARAOXONASE 3 - Oryctolagus cuniculus (Rabbit).
Q9BGN1 PARAOXONASE 1A - Oryctolagus cuniculus (Rabbit).
Q9BGN2 PARAOXONASE 1B - Oryctolagus cuniculus (Rabbit).

Q8VDG8 SIMILAR TO PARAOXONASE 2 - Mus musculus (Mouse).

Q99JS7 SIMILAR TO PARAOXONASE 3 - Mus musculus (Mouse).
Scan History
SPTR40_20f 2  250  NSINGLE    
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
GIDNGSEDLEILPNG Q9BGN2 47 47 -
GIETGSEDMEILPNG PON1_HUMAN 46 46 -
GIEAGAEDLEILPNG PON1_RAT 46 46 -
GIEAGSEDIDILPNG PON2_MELGA 47 47 -
GIEAGADDIDILPNG PON2_CANFA 47 47 -
GLENGSEDIDILPSG Q9BGN0 47 47 -
GLENGSEDIDILPSG PON3_MOUSE 47 47 -

Motif 2 width=14
Element Seqn Id St Int Rpt
KYPGIMSFDPDKPG Q9BGN2 70 8 -
KYPGIKSFNPNSPG PON1_HUMAN 69 8 -
KYPGIKSFDPSKPG PON1_RAT 69 8 -
KYPGLKSLAPDKPG PON2_MELGA 70 8 -
KCPGLHSFSPDKPG PON2_CANFA 70 8 -
KYPGMPNFAPDEPG Q9BGN0 70 8 -
KYPGMPAFAPDKPG PON3_MOUSE 70 8 -

Motif 3 width=14
Element Seqn Id St Int Rpt
NHPDSKSTVELFKF Q9BGN2 133 49 -
NHPDAKSTVELFKF PON1_HUMAN 132 49 -
SHPDSSSTVEVFKF PON1_RAT 132 49 -
NHPHQKSTVELFKF PON2_MELGA 132 48 -
NHPEFKNTVEIFKF PON2_CANFA 132 48 -
NHPHMKSTVEIFKF Q9BGN0 132 48 -
NHPNMDSTVEIFKF PON3_MOUSE 132 48 -

Motif 4 width=13
Element Seqn Id St Int Rpt
GPEHFYATNDHYF Q9BGN2 174 27 -
GPEHFYGTNDHYF PON1_HUMAN 173 27 -
GPESFYATNDHYF PON1_RAT 173 27 -
GPDSFYATNDHYF PON2_MELGA 173 27 -
GPAHFYATNDHYF PON2_CANFA 173 27 -
GPEQFYATRDHYF Q9BGN0 173 27 -
GPEQFYATRDHYF PON3_MOUSE 173 27 -

Motif 5 width=14
Element Seqn Id St Int Rpt
YYSPNDVRVVAEGF Q9BGN2 207 20 -
YYSPSEVRVVAEGF PON1_HUMAN 206 20 -
YYSPDKVRVVADGF PON1_RAT 206 20 -
YYSPKEVKEVAAGF PON2_MELGA 206 20 -
YYSPDEVKVVAEGF PON2_CANFA 206 20 -
FYSPKEVKVVAKGF Q9BGN0 206 20 -
FYSPKEVKVVAQGF PON3_MOUSE 206 20 -

Motif 6 width=19
Element Seqn Id St Int Rpt
KYVYIAELLAHKIHVYEKH Q9BGN2 233 12 -
KYVYIAELLAHKIHVYEKH PON1_HUMAN 232 12 -
KYVYIAELLAHKIHVYEKH PON1_RAT 232 12 -
KYIYIADIFDHNVHVMEKH PON2_MELGA 232 12 -
KYIYVADILAHEIHVLEKH PON2_CANFA 232 12 -
KYVYVADATAKNVHVMEKH Q9BGN0 232 12 -
KFVYVADVTAKNIHIMEKH PON3_MOUSE 232 12 -

Motif 7 width=22
Element Seqn Id St Int Rpt
DNISVDPVTGDLWVGCHPNGMR Q9BGN2 269 17 -
DNISVDPETGDLWVGCHPNGMK PON1_HUMAN 268 17 -
DNISVDPVTGDLWVGCHPNGMR PON1_RAT 268 17 -
DNLSVDPDTGDIWTGCHPNGMK PON2_MELGA 268 17 -
DNLSIDPSSGDILVGCHPNGQK PON2_CANFA 268 17 -
DNLSVDPATGDILAGCHPNGMK Q9BGN0 268 17 -
DNLTVAPATGDILAGCHPNPMK PON3_MOUSE 268 17 -

Motif 8 width=17
Element Seqn Id St Int Rpt
YKGKMLVGTVFHKALYC Q9BGN2 337 46 -
YKGKLLIGTVFHKALYC PON1_HUMAN 336 46 -
YKGKLLIGTVFHRALCC PON1_RAT 336 46 -
YNRKLLIGTVYHRALYC PON2_MELGA 336 46 -
YDRKLLIGTLYHRALYC PON2_CANFA 336 46 -
YQGKILIGTIFHKTLYC Q9BGN0 336 46 -
YHKRMLIGTIFHKALYC PON3_MOUSE 336 46 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
GIDNGSEDLEILPNG PON1_RABIT 46 46 -
GIDNGSEDLEILPNG Q9BGN2 47 47 -
GIETGAEDLEILPNG PON1_MOUSE 46 46 -
GIDNGSEDLEILPNG Q9BGN1 47 47 -
GIETGAEDLEILPNE Q91X30 47 47 -
GIETGSEDMEILPNG PON1_HUMAN 46 46 -
GIETGSEDIDILPNG PON2_CHICK 47 47 -
GIEAGAEDLEILPNG PON1_RAT 46 46 -
GIEAGSEDIDILPNG PON2_HUMAN 47 47 -
GIEAGSEDIDILPNG PON2_MELGA 47 47 -
GIEAGADDIDILPNG PON2_CANFA 47 47 -
GIETGAEDIDILPNG PON2_MOUSE 47 47 -
GLENGSEDIDILPSG Q9BGN0 47 47 -
ELESGSEDIDILPSG PON3_HUMAN 47 47 -
GLENGSEDIDILPSG PON3_MOUSE 47 47 -

Motif 2 width=14
Element Seqn Id St Int Rpt
KYPGIMSFDPDKPG PON1_RABIT 69 8 -
KYPGIMSFDPDKPG Q9BGN2 70 8 -
KYPGIKSFDPSKPG PON1_MOUSE 69 8 -
KYPGIMSFDPDKSG Q9BGN1 70 8 -
KYPGIKSFDPSKPG Q91X30 70 8 -
KYPGIKSFNPNSPG PON1_HUMAN 69 8 -
KYPGLKSFAPDKPG PON2_CHICK 70 8 -
KYPGIKSFDPSKPG PON1_RAT 69 8 -
KFPGLHSFAPDKPG PON2_HUMAN 70 8 -
KYPGLKSLAPDKPG PON2_MELGA 70 8 -
KCPGLHSFSPDKPG PON2_CANFA 70 8 -
KFPGLHSFAPDKPG PON2_MOUSE 70 8 -
KYPGMPNFAPDEPG Q9BGN0 70 8 -
KYPGMPNFAPDEPG PON3_HUMAN 70 8 -
KYPGMPAFAPDKPG PON3_MOUSE 70 8 -

Motif 3 width=14
Element Seqn Id St Int Rpt
NHPDSKSTVELFKF PON1_RABIT 132 49 -
NHPDSKSTVELFKF Q9BGN2 133 49 -
NHPDSSSTVEVFKF PON1_MOUSE 132 49 -
NHPDSKSTVELFKF Q9BGN1 133 49 -
NHPDSSSTVEVFKF Q91X30 133 49 -
NHPDAKSTVELFKF PON1_HUMAN 132 49 -
NHPHQKSTVELFKF PON2_CHICK 132 48 -
SHPDSSSTVEVFKF PON1_RAT 132 49 -
NHPEFKNTVEIFKF PON2_HUMAN 132 48 -
NHPHQKSTVELFKF PON2_MELGA 132 48 -
NHPEFKNTVEIFKF PON2_CANFA 132 48 -
NHPQFSNTVEIFKF PON2_MOUSE 132 48 -
NHPHMKSTVEIFKF Q9BGN0 132 48 -
NHPHMKSTVEIFKF PON3_HUMAN 132 48 -
NHPNMDSTVEIFKF PON3_MOUSE 132 48 -

Motif 4 width=13
Element Seqn Id St Int Rpt
GPEHFYATNDHYF PON1_RABIT 173 27 -
GPEHFYATNDHYF Q9BGN2 174 27 -
GPESFYATNDHYF PON1_MOUSE 173 27 -
GPEHFYATNDHYF Q9BGN1 174 27 -
GPESFYATNDHYF Q91X30 174 27 -
GPEHFYGTNDHYF PON1_HUMAN 173 27 -
GPDSFYATNDHYF PON2_CHICK 173 27 -
GPESFYATNDHYF PON1_RAT 173 27 -
GPAHFYATNDHYF PON2_HUMAN 173 27 -
GPDSFYATNDHYF PON2_MELGA 173 27 -
GPAHFYATNDHYF PON2_CANFA 173 27 -
GPAHFYATNDHYF PON2_MOUSE 173 27 -
GPEQFYATRDHYF Q9BGN0 173 27 -
GPEQFYATRDHYF PON3_HUMAN 173 27 -
GPEQFYATRDHYF PON3_MOUSE 173 27 -

Motif 5 width=14
Element Seqn Id St Int Rpt
YYSPNDVRVVAEGF PON1_RABIT 206 20 -
YYSPNDVRVVAEGF Q9BGN2 207 20 -
YYSPDKVQVVAEGF PON1_MOUSE 206 20 -
YYSPNDVRVVAEGF Q9BGN1 207 20 -
YYSPDKVQVVAEGF Q91X30 207 20 -
YYSPSEVRVVAEGF PON1_HUMAN 206 20 -
YYSPKEVKEVAAGF PON2_CHICK 206 20 -
YYSPDKVRVVADGF PON1_RAT 206 20 -
YYSPNEVKVVAEGF PON2_HUMAN 206 20 -
YYSPKEVKEVAAGF PON2_MELGA 206 20 -
YYSPDEVKVVAEGF PON2_CANFA 206 20 -
YYSPEEVKLVAEGF PON2_MOUSE 206 20 -
FYSPKEVKVVAKGF Q9BGN0 206 20 -
FYSPREVKVVAKGF PON3_HUMAN 206 20 -
FYSPKEVKVVAQGF PON3_MOUSE 206 20 -

Motif 6 width=19
Element Seqn Id St Int Rpt
KYVYIAELLAHKIHVYEKH PON1_RABIT 232 12 -
KYVYIAELLAHKIHVYEKH Q9BGN2 233 12 -
KYVYIAELLAHKIHVYEKH PON1_MOUSE 232 12 -
KYVYIAELLAHKIHVYEKH Q9BGN1 233 12 -
KYVYIAELLAHKIHVYEKH Q91X30 233 12 -
KYVYIAELLAHKIHVYEKH PON1_HUMAN 232 12 -
KYIYIADILDHNVHVMEKH PON2_CHICK 232 12 -
KYVYIAELLAHKIHVYEKH PON1_RAT 232 12 -
KYIYVADILAHEIHVLEKH PON2_HUMAN 232 12 -
KYIYIADIFDHNVHVMEKH PON2_MELGA 232 12 -
KYIYVADILAHEIHVLEKH PON2_CANFA 232 12 -
KYVYVADILAHEIHVLEKQ PON2_MOUSE 232 12 -
KYVYVADATAKNVHVMEKH Q9BGN0 232 12 -
KYVYVADVAAKNIHIMEKH PON3_HUMAN 232 12 -
KFVYVADVTAKNIHIMEKH PON3_MOUSE 232 12 -

Motif 7 width=22
Element Seqn Id St Int Rpt
DNISVDPVTGDLWVGCHPNGMR PON1_RABIT 268 17 -
DNISVDPVTGDLWVGCHPNGMR Q9BGN2 269 17 -
DNISVDPVTGDLWVGCHPNGMR PON1_MOUSE 268 17 -
DNISVDPVTGDLWVGCHPNGMR Q9BGN1 269 17 -
DNISVDPVTGDLWVGCHPNGMR Q91X30 269 17 -
DNISVDPETGDLWVGCHPNGMK PON1_HUMAN 268 17 -
DNLSVDPDTGDIWTGCHPNGMK PON2_CHICK 268 17 -
DNISVDPVTGDLWVGCHPNGMR PON1_RAT 268 17 -
DNLSIDPSSGDIWVGCHPNGQK PON2_HUMAN 268 17 -
DNLSVDPDTGDIWTGCHPNGMK PON2_MELGA 268 17 -
DNLSIDPSSGDILVGCHPNGQK PON2_CANFA 268 17 -
DNLSIDPSSGDIWVGCHPNGQR PON2_MOUSE 268 17 -
DNLSVDPATGDILAGCHPNGMK Q9BGN0 268 17 -
DNLTVDPATGDILAGCHPNPMK PON3_HUMAN 268 17 -
DNLTVAPATGDILAGCHPNPMK PON3_MOUSE 268 17 -

Motif 8 width=17
Element Seqn Id St Int Rpt
YKGKMLVGTVFHKALYC PON1_RABIT 336 46 -
YKGKMLVGTVFHKALYC Q9BGN2 337 46 -
YKGKLLIGTVFHKALYC PON1_MOUSE 336 46 -
YKGKMLVGTVFHKALYC Q9BGN1 337 46 -
YKGKLLIGTVFHKALYC Q91X30 337 46 -
YKGKLLIGTVFHKALYC PON1_HUMAN 336 46 -
YDGKLLIGTVFHRALYC PON2_CHICK 336 46 -
YKGKLLIGTVFHRALCC PON1_RAT 336 46 -
YDGKLLIGTLYHRALYC PON2_HUMAN 336 46 -
YNRKLLIGTVYHRALYC PON2_MELGA 336 46 -
YDRKLLIGTLYHRALYC PON2_CANFA 336 46 -
YDRKLLVGTLYQKALYC PON2_MOUSE 336 46 -
YQGKILIGTIFHKTLYC Q9BGN0 336 46 -
YHGKILIGTVFXKTLYC PON3_HUMAN 336 46 -
YHKRMLIGTIFHKALYC PON3_MOUSE 336 46 -