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PR01787

Identifier
PARAOXONASE2  [View Relations]  [View Alignment]  
Accession
PR01787
No. of Motifs
3
Creation Date
09-SEP-2002
Title
Paraoxonase 2 signature
Database References
PRINTS; PR01785 PARAOXONASE
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).
 
8. BORIGHT, A.P, CONNELLY, P.W., BRUNT, J.H., SCHERER, S.W., 
TSUI, L.C. AND HEGELE, R.A.
Genetic variation in paraoxonase-1 and paraoxonase-2 is associated with
variation in plasma lipoproteins in Alberta Hutterites.
ATHEROSCLEROSIS 139 131-136 (1998).
 
9. MACKNESS, B., DURRINGTON, P.N., ABUASHIA, B., BOULTON, A.J. AND
MACKNESS, M.I.
Low paraoxonase activity in type II diabetes mellitus complicated by
retinopathy.
CLIN.SCI. (LONDON) 98 355-363 (2000).
 
10. BUSCH, C.P., RAMDATH, D.D., RAMSEWAK, S. AND HEGELE, R A.
Association of PON2 variation with birth weight in Trinidadian neonates of
South Asian ancestry.
PHARMACOGENETICS 9 351-356 (1999).
 
11. SANGHERA, D.K., ASTON, C.E., SAHA, N. AND KAMBOH, M.I.
DNA polymorphisms in two paraoxonase genes (PON1 and PON2) are associated
with the risk of coronary heart disease.
AM.J.HUM.GENET. 62 36-44 (1998).

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].
 
The PON2 enzyme is able to lower the intracellular oxidative stress of a
cell and prevent cell-mediated oxidation of LDL [7]. Polymorphisms in human
PON2 are associated with numerous pathophysiological indicators, including
variations in plasma lipoprotein [8], glucose levels in fasting type II
diabetics [9], neonatal birth weight [10], and the risk of coronary heart
disease [11]. Although genetic associations between PON2 and these 
conditions have been shown, the exact function of PON2 in humans is unknown.
 
PARAOXONASE2 is a 3-element fingerprint that provides a signature for the
paraoxonase 2 enzymes. The fingerprint was derived from an initial alignment
of 4 sequences: the motifs were drawn from conserved regions spanning the 
full alignment length, focusing on those sections that characterise the type 
2 enzymes but distinguish them from the rest of the paraoxonase family. Two 
iterations on SPTR40_20f were required to reach convergence, at which point 
a true set comprising 5 sequences was identified.
Summary Information
5 codes involving  3 elements
0 codes involving 2 elements
Composite Feature Index
3555
2000
123
True Positives
PON2_CANFA    PON2_CHICK    PON2_HUMAN    PON2_MELGA    
PON2_MOUSE
Sequence Titles
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).
Scan History
SPTR40_20f 2  45   NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
ERLLALRNRLKAS PON2_HUMAN 19 19 -
ERLLALRNRLKAS PON2_CANFA 19 19 -
ERLLAFRNRLNAT PON2_MELGA 19 19 -
ERFLALSSRLKGS PON2_MOUSE 19 19 -

Motif 2 width=13
Element Seqn Id St Int Rpt
SDPFLKYLETYLN PON2_HUMAN 186 154 -
SDPFLKYLETYLN PON2_CANFA 186 154 -
YDFILMFLEMYLG PON2_MELGA 186 154 -
SDPFLKYLETYLN PON2_MOUSE 186 154 -

Motif 3 width=13
Element Seqn Id St Int Rpt
QKLFVYDPNNPPS PON2_HUMAN 288 89 -
QKLFIYDPNNPPS PON2_CANFA 288 89 -
MKLFYNDPDNPPA PON2_MELGA 288 89 -
QRLFVYHPNHPPT PON2_MOUSE 288 89 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
ERLLALRNRLKAS PON2_HUMAN 19 19 -
ERLLALRNRLKAS PON2_CANFA 19 19 -
ERLLAFRNRLNAT PON2_CHICK 19 19 -
ERLLAFRNRLNAT PON2_MELGA 19 19 -
ERFLALSSRLKGS PON2_MOUSE 19 19 -

Motif 2 width=13
Element Seqn Id St Int Rpt
SDPFLKYLETYLN PON2_HUMAN 186 154 -
SDPFLKYLETYLN PON2_CANFA 186 154 -
YDFILMFLEMYLG PON2_CHICK 186 154 -
YDFILMFLEMYLG PON2_MELGA 186 154 -
SDPFLKYLETYLN PON2_MOUSE 186 154 -

Motif 3 width=13
Element Seqn Id St Int Rpt
QKLFVYDPNNPPS PON2_HUMAN 288 89 -
QKLFIYDPNNPPS PON2_CANFA 288 89 -
MKLFYDDPDNPPA PON2_CHICK 288 89 -
MKLFYNDPDNPPA PON2_MELGA 288 89 -
QRLFVYHPNHPPT PON2_MOUSE 288 89 -