SPRINT Home UMBER Home Contents Standard Search Advanced Search Relation Search

==SPRINT==> PRINTS View



  selected as


PR01786

Identifier
PARAOXONASE1  [View Relations]  [View Alignment]  
Accession
PR01786
No. of Motifs
3
Creation Date
06-SEP-2002
Title
Paraoxonase 1 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. BILLECKE, S., DRAGANOV, D., COUNSELL, R., STETSON, P., WATSON, C., HSU,
C. AND LA DU, B.N.
Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and
cyclic carbonate esters.
DRUG METAB.DISPOS. 28 1335-1342 (2000).
 
9. HUMBERT, R., ADLER, D.A., DISTECHE, C.M., HASSETT, C., OMIECINSKI, C.J. 
AND FURLONG, C.E.
The molecular basis of the human serum paraoxonase activity polymorphism.
NAT.GENET. 3 73-76 (1993).
 
10. HEGELE, R.A., BRUNT, J.H. AND CONNELLY, P.W.
A polymorphism of the paraoxonase gene associated with variation in plasma
lipoproteins in a genetic isolate.
ARTERIOSCLER.THROMB.VASC.BIOL. 15 89-95 (1995).

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].
 
Rabbit and human serum PON1 also hydrolyse a variety of lactones and cyclic
carbonate esters, including naturally occurring lactones and pharmacological
agents [8]. Humans have 2 common PON1 allozymes, determined by the presence
of either arginine or glutamine at position 191. The A-type allozyme
(glutamine at position 191) causes low paraoxonase activity [9]; this
polymorphism is associated with variations in cholesterol and lipoprotein
levels [10].
 
PARAOXONASE1 is a 3-element fingerprint that provides a signature for the
paraoxonase 1 enzymes. The fingerprint was derived from an initial alignment
of 4 sequences: the motifs were drawn from conserved regions spanning the
N-terminal portion of the alignment, focusing on those sections that
characterise the type 1 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 7 sequences was identified.
Summary Information
7 codes involving  3 elements
0 codes involving 2 elements
Composite Feature Index
3777
2000
123
True Positives
PON1_HUMAN    PON1_MOUSE    PON1_RABIT    PON1_RAT      
Q91X30 Q9BGN1 Q9BGN2
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).
Q91X30 PARAOXONASE 1 - Mus musculus (Mouse).
Q9BGN1 PARAOXONASE 1A - Oryctolagus cuniculus (Rabbit).
Q9BGN2 PARAOXONASE 1B - Oryctolagus cuniculus (Rabbit).
Scan History
SPTR40_20f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
FDGQKSSFQTRFN Q9BGN2 17 17 -
YKNHRSSYQTRLN Q91X30 17 17 -
YKNHRSSYQTRLN PON1_RAT 16 16 -
FRNHQSSYQTRLN PON1_HUMAN 16 16 -

Motif 2 width=14
Element Seqn Id St Int Rpt
PVVLELSITGSTFD Q9BGN2 95 65 -
PAVSELEIIGNTLD Q91X30 95 65 -
PAVSELAIMGNTLD PON1_RAT 94 65 -
PTVLELGITGSKFD PON1_HUMAN 94 65 -

Motif 3 width=11
Element Seqn Id St Int Rpt
DEDNIVYLMVV Q9BGN2 122 13 -
DEDNTVYLLVV Q91X30 122 13 -
DEDNTVYLLVV PON1_RAT 121 13 -
DEDNAMYLLVV PON1_HUMAN 121 13 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
FDGQKSSFQTRFN PON1_RABIT 16 16 -
FDGQKSSFQTRFN Q9BGN1 17 17 -
FDGQKSSFQTRFN Q9BGN2 17 17 -
YKNHRSSYQTRLN PON1_MOUSE 16 16 -
YKNHRSSYQTRLN Q91X30 17 17 -
YKNHRSSYQTRLN PON1_RAT 16 16 -
FRNHQSSYQTRLN PON1_HUMAN 16 16 -

Motif 2 width=14
Element Seqn Id St Int Rpt
PVVLELSITGSTFD PON1_RABIT 94 65 -
PVVLELGITGSTFD Q9BGN1 95 65 -
PVVLELSITGSTFD Q9BGN2 95 65 -
PAVSELEIIGNTLD PON1_MOUSE 94 65 -
PAVSELEIIGNTLD Q91X30 95 65 -
PAVSELAIMGNTLD PON1_RAT 94 65 -
PTVLELGITGSKFD PON1_HUMAN 94 65 -

Motif 3 width=11
Element Seqn Id St Int Rpt
DEDNIVYLMVV PON1_RABIT 121 13 -
DEDNIVYLMVV Q9BGN1 122 13 -
DEDNIVYLMVV Q9BGN2 122 13 -
DEDNTVYLLVV PON1_MOUSE 121 13 -
DEDNTVYLLVV Q91X30 122 13 -
DEDNTVYLLVV PON1_RAT 121 13 -
DEDNAMYLLVV PON1_HUMAN 121 13 -