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PR01254

Identifier
PGNDSYNTHASE  [View Relations]  [View Alignment]  
Accession
PR01254
No. of Motifs
6
Creation Date
22-DEC-1999
Title
Prostaglandin D synthase signature
Database References
PRINTS; PR00179 LIPOCALIN
PROSITE; PS00213 LIPOCALIN
BLOCKS; BL00213
PFAM; PF00061 lipocalin
INTERPRO; IPR002972
Literature References
1. PERVAIS, S. AND BREW, K. 
Homology of beta-lactoglobulin, serum retinol-binding protein and 
protein HC.
SCIENCE 228 335-337 (1985).
 
2. FLOWER, D.R.
The Lipocalin protein family: structure and function.
BIOCHEM.J. 318 1-14 (1996).
 
3. FLOWER, D.R., NORTH, A.C.T. AND ATTWOOD, T.K.
Structural and sequence relationships in the lipocalins and related
proteins.
PROTEIN SCI. 2 753-761 (1993). 
 
4. FLOWER, D.R.
Multiple molecular recognition properties of the lipocalin protein family.
J.MOL.REC. 8 185-195 (1995).
 
5. URADE, Y., NAGATA, A., SUZUKI, Y., FUJII, Y. AND HAYAISHI, O.
Primary structure of rat brain prostaglandin D synthetase deduced from 
cDNA sequence. 
J.BIOL.CHEM. 284 1041-1045 (1989).
 
6. NAGATA, A., SUZUKI, Y., IGARASHI, M., EGUCHI, N., TOH, H., URADE, Y. AND 
HAYAISHI, O. 
Human brain prostaglandin D synthase has been evolutionarily differentiated 
from lipophilic-ligand carrier proteins. 
PROC.NATL.ACAD.SCI.U.S.A. 88 4020-4024 (1991).
 
7. ACHEN, M.G., HARMS, P.J., THOMAS, T., RICHARDSON, S.J., WETTENHALL, R.E.H.
AND SCHREIBER, G. 
Protein synthesis at the blood-brain barrier. The major protein secreted by 
amphibian choroid plexus is a lipocalin. 
J.BIOL.CHEM. 267 23170-23174 (1992).
 
8. LEPPERDINGER, G., STROBL, B., JILEK, A., WEBER, A., THALHAMER, J., 
FLOCKNER, H. AND MOLLAY, C.
The lipocalin Xlcpl1 expressed in the neural plate of Xenopus laevis embryos
is a secreted retinaldehyde binding protein.
PROTEIN SCI. 5 1250-1260 (1996).

Documentation
The lipocalins are a diverse, interesting, yet poorly understood family of 
proteins composed, in the main, of extracellular ligand-binding proteins
displaying high specificity for small hydrophobic molecules [1,2]. Functions
of these proteins include transport of nutrients, control of cell regula-
tion, pheromone transport, cryptic colouration and the enzymatic synthesis
of prostaglandins.
   
The crystal structures of several lipocalins have been solved and show a 
novel 8-stranded anti-parallel beta-barrel fold well conserved within the
family. Sequence similarity within the family is at a much lower level and
would seem to be restricted to conserved disulphides and 3 motifs, which
form a juxtaposed cluster that may act as a common cell surface receptor
site [2]. By contrast, at the more variable end of the fold are found an 
internal ligand binding site and a putative surface for the formation of 
macromolecular complexes [4]. The anti-parallel beta-barrel fold is also
exploited by the fatty acid-binding proteins (which function similarly by
binding small hydrophobic molecules), by avidin and the closely related
metalloprotease inhibitors, and by triabin. Similarity at the sequence 
level, however, is less obvious, being confined to a single short 
N-terminal motif.
 
The lipocalin family can be subdivided into kernal and outlier sets. The
kernal lipocalins form the largest self-consistent group (see LIPOCALIN
signature). The outlier lipocalins form several smaller distinct subgroups: 
the OBPs, the von Ebner's gland proteins, alpha-1-acid glycoproteins, 
tick histamine binding proteins and the nitrophorins.
 
Glutathione-independent prostaglandin D (PGD2) synthase (EC 5.3.99.2) is the
main factor involved in synthesis of PGD2 in the brain, accounting for over
90% of activity in the rat; it is responsible for catalysing the conversion
of PGH2 into PGD2 in the presence of various thiol compounds [5,6]. PGD2 is
a major prostaglandin in mammalian brains, functioning in the central 
nervous system as both a neuromodulator and a trophic factor. The enzymic
activity of PGD synthase makes it unique among the lipocalins. It is 
localised in the choroid plexus, meninges and oligodendrocytes, but is also 
a major component of cerebrospinal fiuid. Immunocytochemistry indicates that
the protein is associated with the rough endoplasmic reticulum and the outer
nuclear membranes of rat oligodendrocytes, and seems to be a peripheral 
membrane protein easily dissociated by detergents.
 
A near homologue of PGD2 synthase has been identified in cane-toad (Bufo 
marinus) choroid plexus, where it is the most abundant protein secreted into
the cerebrospinal fluid [7]. It is also found in other areas of the brain,
albeit at much lower levels, and is expressed throughout amphibian 
metamorphosis. The choroid plexus helps form the barrier between blood and 
cerebrospinal fluid, and it has been suggested that this lipocalin may help 
transport lipophilic molecules across the blood/brain barrier.
 
The PGD2 syhnthase homologue cpl-1 is expressed in the early neural plate of
Xenopus laevis embryos and the adult choroid plexus [8]. In AtT20 cells, 
cpl-1 is secreted via the constitutive secretory pathway. The protein was 
found to bind retinal at nanomolar concentration, retinoic acid at
micromolar concentration, but shows no retinol binding. It also binds 
thyroxine. Cpl1 is thought to bind retinaldehyde during its transport
through secretory pathway compartments. It has been suggested that the
protein is an integral member of the retinoid signalling pathway and plays
a key role in early embryo pattern formation.
 
PGNDSYNTHASE is a 6-element fingerprint that provides a signature for the 
prostagladin D synthases. The fingerprint was derived from an initial
alignment of 4 sequences: the motifs were drawn from conserved regions
spanning virtually the full alignment length - motif 1 covers the N-terminal
310 helix and strand A, which includes the region encoded by PROSITE pattern
LIPOCALIN (PS00213) and corresponds to motif 1 of the LIPOCALIN fingerprint;
motif 2 encodes the end of the large loop L1 and the second beta-strand; 
motif 3 spans strands 2 and 3; motif 4, which spans the C-terminus of
strand 6 and strand 7, corresponds to the second LIPOCALIN motif; motif 5,
which spans strand 8 and the N-terminus of the main C-terminal alpha helix, is similar 
corresponds to the third LIPOCALIN motif; and motif 6 spans the end of the
C-terminal helix and also includes the short beta-strand 9. Two iterations
on SPRT37_10f were required to reach convergence, at which point a true set
comprising 12 sequences was identified.
Summary Information
12 codes involving  6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
6121212121212
5000000
4000000
3000000
2000000
123456
True Positives
LIPO_BUFMA    O35091        O97921        PGHD_BOVIN    
PGHD_FELCA PGHD_HUMAN PGHD_MOUSE PGHD_PIG
PGHD_RAT PGHD_URSAR Q91721 Q92136
Sequence Titles
LIPO_BUFMA  LIPOCALIN PRECURSOR - BUFO MARINUS (GIANT TOAD) (CANE TOAD). 
O35091 PROSTAGLANDIN D SYNTHETASE - MUS MUSCULUS (MOUSE).
O97921 PROSTAGLANDIN D2 SYNTHASE (EC 5.3.99.2) - EQUUS CABALLUS (HORSE).
PGHD_BOVIN PROSTAGLANDIN-H2 D-ISOMERASE PRECURSOR (EC 5.3.99.2) (PROSTAGLANDIN-D SYNTHASE) (GLUTATHIONE-INDEPENDENT PGD SYNTHETASE) (PROSTAGLANDIN D2 SYNTHASE) (PGD2 SYNTHASE) (PGDS2) - BOS TAURUS (BOVINE).
PGHD_FELCA PROSTAGLANDIN-H2 D-ISOMERASE PRECURSOR (EC 5.3.99.2) (PROSTAGLANDIN-D SYNTHASE) (GLUTATHIONE-INDEPENDENT PGD SYNTHETASE) (PROSTAGLANDIN D2 SYNTHASE) (PGD2 SYNTHASE) (PGDS2) - FELIS SILVESTRIS CATUS (CAT).
PGHD_HUMAN PROSTAGLANDIN-H2 D-ISOMERASE PRECURSOR (EC 5.3.99.2) (PROSTAGLANDIN-D SYNTHASE) (GLUTATHIONE-INDEPENDENT PGD SYNTHETASE) (PROSTAGLANDIN D2 SYNTHASE) (PGD2 SYNTHASE) (PGDS2) (BETA-TRACE PROTEIN) - HOMO SAPIENS (HUMAN).
PGHD_MOUSE PROSTAGLANDIN-H2 D-ISOMERASE PRECURSOR (EC 5.3.99.2) (PROSTAGLANDIN-D SYNTHASE) (GLUTATHIONE-INDEPENDENT PGD SYNTHETASE) (PROSTAGLANDIN D2 SYNTHASE) (PGD2 SYNTHASE) (PGDS2) - MUS MUSCULUS (MOUSE).
PGHD_PIG PROSTAGLANDIN-H2 D-ISOMERASE PRECURSOR (EC 5.3.99.2) (PROSTAGLANDIN-D SYNTHASE) (GLUTATHIONE-INDEPENDENT PGD SYNTHETASE) (PROSTAGLANDIN D2 SYNTHASE) (PGD2 SYNTHASE) (PGDS2) - SUS SCROFA (PIG).
PGHD_RAT PROSTAGLANDIN-H2 D-ISOMERASE PRECURSOR (EC 5.3.99.2) (PROSTAGLANDIN-D SYNTHASE) (GLUTATHIONE-INDEPENDENT PGD SYNTHETASE) (PROSTAGLANDIN D2 SYNTHASE) (PGD2 SYNTHASE) (PGDS2) - RATTUS NORVEGICUS (RAT).
PGHD_URSAR PROSTAGLANDIN-H2 D-ISOMERASE PRECURSOR (EC 5.3.99.2) (PROSTAGLANDIN-D SYNTHASE) (GLUTATHIONE-INDEPENDENT PGD SYNTHETASE) (PROSTAGLANDIN D2 SYNTHASE) (PGD2 SYNTHASE) (PGDS2) - URSUS ARCTOS (BROWN BEAR) (GRIZZLY BEAR).
Q91721 CPL-1 - XENOPUS LAEVIS (AFRICAN CLAWED FROG).
Q92136 PROSTAGLANDIN D SYNTHASE (EC 5.3.99.2) - XENOPUS LAEVIS (AFRICAN CLAWED FROG).
Scan History
SPTR37_10f 2  12   NSINGLE    
Initial Motifs
Motif 1  width=24
Element Seqn Id St Int Rpt
QPNFQEDKFLGRWFTSGLASNSSW PGHD_PIG 29 29 -
QPNFQQDKFLGRWFSAGLASNSSW PGHD_HUMAN 31 31 -
QPNFQQDKFLGRWYSAGLASNSSW PGHD_RAT 31 31 -
QPDFQKEKVLGKWYGIGLASNSNW Q92136 26 26 -

Motif 2 width=11
Element Seqn Id St Int Rpt
EKKAALSMCKS PGHD_HUMAN 57 2 -
EKKKVLSMCKS PGHD_PIG 55 2 -
EKKELLFMCQT PGHD_RAT 57 2 -
DRKSHMKMCTT Q92136 52 2 -

Motif 3 width=19
Element Seqn Id St Int Rpt
DGNVEVTATYPKMDRCETK Q92136 69 6 -
DGGLNLTSTFLRKNQCETR PGHD_HUMAN 74 6 -
DGGFNLTSTFLRKDQCVTR PGHD_PIG 72 6 -
EGGLNLTSTFLRKNQCETK PGHD_RAT 74 6 -

Motif 4 width=24
Element Seqn Id St Int Rpt
SPRYGSEHDMRVVETNYDEYILMY Q92136 104 16 -
SPHWGSTYSVSVVETDYDQYALLY PGHD_HUMAN 109 16 -
SPHGGSNLEVSVVETDYKNYALLH PGHD_PIG 107 16 -
SPHWGSFHSLSVVETDYDEYAFLF PGHD_RAT 109 16 -

Motif 5 width=15
Element Seqn Id St Int Rpt
MATLYSRTQTPRAEL PGHD_HUMAN 145 12 -
MATLYSRSQAPGAAV PGHD_PIG 143 12 -
MATLYSRAQLLKEEL PGHD_RAT 145 12 -
IVSLFGRDKDLRPEL Q92136 139 11 -

Motif 6 width=19
Element Seqn Id St Int Rpt
KFTAFCKAQGFTEDTIVFL PGHD_HUMAN 162 2 -
KFTAFAKARGFTEDGIVFL PGHD_PIG 160 2 -
KFITFSKDQGLTEEDIVFL PGHD_RAT 162 2 -
KFQNFAKSQGLADDNIIIL Q92136 156 2 -
Final Motifs
Motif 1  width=24
Element Seqn Id St Int Rpt
QPNFQQDKFLGRWFSAGLASNSSW PGHD_HUMAN 31 31 -
QPNFQQDKFLGRWFTSGLASNSSW O97921 31 31 -
QPNFQQDKFLGRWYSAGLASNSSW PGHD_MOUSE 31 31 -
QPNFQQDKFLGRWFTSGLASNSSW PGHD_URSAR 31 31 -
QPNFQQDKFLGRWFTSGLASNSSW PGHD_FELCA 31 31 -
QPNFEEDKFLGRWFTSGLASNSSW PGHD_BOVIN 31 31 -
QPNFQEDKFLGRWFTSGLASNSSW PGHD_PIG 29 29 -
QPNFQQDKFLGRWYSAGLASNSSW PGHD_RAT 31 31 -
SPTFNKTSSWGAGTARVLASNSSW O35091 51 51 -
QPDFQEDKILGKWYGIGLASNSNW LIPO_BUFMA 25 25 -
QPDFQKEKVLGKWYGIGLASNSNW Q91721 26 26 -
QPDFQKEKVLGKWYGIGLASNSNW Q92136 26 26 -

Motif 2 width=11
Element Seqn Id St Int Rpt
EKKKVLSMCVS PGHD_URSAR 57 2 -
EKKAALSMCKS PGHD_HUMAN 57 2 -
EKKKVLSMCTS O97921 57 2 -
EKKAVLYMCKT PGHD_MOUSE 57 2 -
EKKNALSMCIS PGHD_FELCA 57 2 -
EKKKVLSMCKS PGHD_BOVIN 57 2 -
EKKKVLSMCKS PGHD_PIG 55 2 -
EKKELLFMCQT PGHD_RAT 57 2 -
EKKAVLYMCKT O35091 77 2 -
SKKQQLKMCTT LIPO_BUFMA 51 2 -
DRKSHMKMCTT Q91721 52 2 -
DRKSHMKMCTT Q92136 52 2 -

Motif 3 width=19
Element Seqn Id St Int Rpt
DGNLEVTATYPKMDRCETK Q91721 69 6 -
DGGLNLTSTFLRKEQCETR PGHD_URSAR 74 6 -
DGGLNLTSTFLRKNQCETR PGHD_HUMAN 74 6 -
DGGFNLTSTFLRKDQCETR O97921 74 6 -
EGGLNLTSTFLRKNQCETK PGHD_MOUSE 74 6 -
EGGLNLTTTFLRKDQCETR PGHD_FELCA 74 6 -
DGGLNLTSTFLRKDQCETR PGHD_BOVIN 74 6 -
DGGFNLTSTFLRKDQCVTR PGHD_PIG 72 6 -
EGGLNLTSTFLRKNQCETK PGHD_RAT 74 6 -
EGGLNLTSTFLRKNQCETK O35091 94 6 -
DGNLDVVATFPKLDRCEKK LIPO_BUFMA 68 6 -
DGNVEVTATYPKMDRCETK Q92136 69 6 -

Motif 4 width=24
Element Seqn Id St Int Rpt
SPHSGSIHSVSVVEANYDEYALLF O35091 129 16 -
SPHWGSTHDVWVAMTDYDEYALLY PGHD_URSAR 109 16 -
SPHWGSTYSVSVVETDYDQYALLY PGHD_HUMAN 109 16 -
SPHWGMVHEVSVVETDYEEYALLY O97921 109 16 -
SPHSGSIHSVSVVEANYDEYALLF PGHD_MOUSE 109 16 -
SPHWGSTHDVWVVATDYEEYALLY PGHD_FELCA 109 16 -
SPHWSSTHEVSVAETDYETYALLY PGHD_BOVIN 109 16 -
SPHGGSNLEVSVVETDYKNYALLH PGHD_PIG 107 16 -
SPHWGSFHSLSVVETDYDEYAFLF PGHD_RAT 109 16 -
SPRYGSDHVIRVVESNYDEYTLMH LIPO_BUFMA 103 16 -
SPRYGSEHDMRVVETNYDEYILMY Q91721 104 16 -
SPRYGSEHDMRVVETNYDEYILMY Q92136 104 16 -

Motif 5 width=15
Element Seqn Id St Int Rpt
MATLYSRTQTPRAEI PGHD_URSAR 145 12 -
MATLYSRVQSPRPEV O97921 148 15 -
MATLYSRTQTLKDEL PGHD_MOUSE 145 12 -
MATLYSRTQTPRAEV PGHD_FELCA 145 12 -
MATLYSRSQNPRAEV PGHD_BOVIN 145 12 -
MATLYSRSQAPGAAV PGHD_PIG 143 12 -
MATLYSRAQLLKEEL PGHD_RAT 145 12 -
MATLYSRTQTLKDEL O35091 165 12 -
IVSLFGRRKTLSPEL LIPO_BUFMA 138 11 -
MATLYSRTQTPRAEL PGHD_HUMAN 145 12 -
IVSLFGRDKDLRPEL Q91721 139 11 -
IVSLFGRDKDLRPEL Q92136 139 11 -

Motif 6 width=19
Element Seqn Id St Int Rpt
KFQNFAKSQGLADDNIIIL Q91721 156 2 -
KFTTFAKTQGFTEDAIVFL PGHD_URSAR 162 2 -
KFTAFCKAQGFTEDTIVFL PGHD_HUMAN 162 2 -
KFSTFAKAQGFTEDAIVFL O97921 165 2 -
KFTTFSKAQGLTEEDIVFL PGHD_MOUSE 162 2 -
KFSTFAKTRGFTEDAIVFL PGHD_FELCA 162 2 -
HFTTFAKSLGFTEEGIVFL PGHD_BOVIN 162 2 -
KFTAFAKARGFTEDGIVFL PGHD_PIG 160 2 -
KFITFSKDQGLTEEDIVFL PGHD_RAT 162 2 -
KFTTFSKAQGLTEEDIVFL O35091 182 2 -
KFQQFAKEQGLTDDNILIL LIPO_BUFMA 155 2 -
KFQNFAKSQGLADDNIIIL Q92136 156 2 -