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PR01275

Identifier
NGELATINASE  [View Relations]  [View Alignment]  
Accession
PR01275
No. of Motifs
7
Creation Date
07-JAN-2000
Title
Neutrophil gelatinase lipocalin signature
Database References
PRINTS; PR00179 LIPOCALIN
PDB; 1NGL; 1QQS
SCOP; 1NGL
CATH; 1NGL
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. HRABA-RENEVEY, S., TURLER, H., KRESS, M., SALOMON, C. AND WEIL, R. 
SV40-induced expression of mouse gene 24p3 involves a post-transcriptional
mechanism.
ONCOGENE 4 601-608 (1989).
 
6. MEHEUS, L.H., FRANSEN, L.M., RAYMACKERS, J.G., BLOCKX, H.A., 
VAN BEEUMEN, J.J., VAN BUN, S.M. AND VAN DE VOORDE, A.
Identification by microsequencing of lipopolysaccharide-induced proteins
secreted  by mouse macrophages. 
J.IMMUNOL. 151 1535-1547 (1993),
 
7. LIU, O. AND NILSEN-HAMILTON, M. 
Identification of a new acute phase protein. 
J.BIOL.CHEM. 270 22565-22570 (1995).
 
8. TREIBEL, S., BLASER, J., REINKE, H. AND TSCHESCHE, H. 
A 25kDa alpha 2-microglobulin-related protein is a component of the 125 kDa
form of human gelatinase.
FEBS LETT. 314 386-388 (1992).
 
9. KASIK, J.W. AND RICE, E.J. 
An increase in expression of the lipocalin 24p3 is found in mouse uterus 
coincident with birth.
AM.J.OBSTET.GYNECOL. 173 613-617 (1995).

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
metalloproteinase 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.
 
Murine neutrophil gelatinase-associated lipocalin precursor (NGAL) exhibits
a 7-10-fold increase in expression in cultured mouse kidney cells infected
by simian-virus 40 or other viruses [5]. NGAL has been identified as a 
major secretory product of lipopolysaccharide-stimulated cultured mouse 
macrophages, suggesting that the protein might function in defence against
infection [6]. Recently, NGAL has been shown to be identical to SIP24, a 
previously identified secretory product of quiescent mouse fibroblasts 
induced by serum, dexamethasone, basic fibroblast growth factor, and phorbol
ester [7]. Mouse plasma levels of NGAL rise as a result of increased 
expression levels in the liver, in response to intramuscular turpentine 
injection. Tumour necrosis factor can regulate NGAL expression in cultured 
liver cells. These findings indicate that NGAL is a positive acute phase
protein and may possess immunosuppressive or anti-inflammatory properties, 
possibly linked to its regulation of neutrophil gelatinase or other plasma
protein [8]. The uterus is also a major site of NGAL synthesis, especially
at parturition, when expression increases significantly, suggesting a
physiological role for the protein in uterine secretions [9].
 
NGELATINASE is a 7-element fingerprint that provides a signature for the 
neutrophil gelatinase associated lipocalin. The fingerprint was derived from
an initial alignment of 2 sequences: the motifs were drawn from conserved 
regions spanning virtually the full alignment length - motif 1 includes the
long, unstructured but functionally important N-terminal peptide; motif 2 
spans the first beta-strand of the lipocalin barrel, including the region
encoded by PROSITE pattern LIPOCALIN (PS00213) and corresponds to the 
LIPOCALIN fingerprint motif 1; motif 3 spans strands B and C, and the
intervening loop; likewise, motif 4 spans strands D and E and the loop
between them; motif 5 spans strands F and G, and corresponds to the second
LIPOCALIN motif; motif 6, which corresponds to strand H and the loop 
connecting it to the main C-terminal alpha helix, is similar to the third
motif of the LIPOCALIN fingerprint; and motif 7 spans the C-terminus of the
large C-terminal helix and the short beta-strand I. Two iterations on
SPRT37_10f were required to reach convergence, at which point a true set 
comprising 3 sequences was identified.
Summary Information
3 codes involving  7 elements
0 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
73333333
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
NGAL_HUMAN    NGAL_MOUSE    NGAL_RAT      
Sequence Titles
NGAL_HUMAN  NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN PRECURSOR (NGAL) (P25) (25 KD ALPHA-2-MICROGLOBULIN-RELATED SUBUNIT OF MMP-9) (LIPOCALIN-2) (ONCOGENE 24P3) - HOMO SAPIENS (HUMAN). 
NGAL_MOUSE NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN PRECURSOR (NGAL) (P25) (SV-40 INDUCED 24P3 PROTEIN) - MUS MUSCULUS (MOUSE).
NGAL_RAT NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN PRECURSOR (NGAL) (P25) (ALPHA-2-MICROGLOBULIN-RELATED PROTEIN) (ALPHA-2U GLOBULIN-RELATED PROTEIN) - RATTUS NORVEGICUS (RAT).
Scan History
SPTR37_10f 2  3    NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
QDSTQNLIPAPPL NGAL_RAT 21 21 -
QDSTSDLIPAPPL NGAL_HUMAN 21 21 -

Motif 2 width=11
Element Seqn Id St Int Rpt
FQGRWFVVGLA NGAL_RAT 47 13 -
FQGKWYVVGLA NGAL_HUMAN 47 13 -

Motif 3 width=20
Element Seqn Id St Int Rpt
MYSTIYELQEDNSYNVTSIL NGAL_RAT 71 13 -
MYATIYELKEDKSYNVTSVL NGAL_HUMAN 71 13 -

Motif 4 width=20
Element Seqn Id St Int Rpt
YWIRTFVPSSRPGQFTLGNI NGAL_RAT 98 7 -
YWIRTFVPGCQPGEFTLGNI NGAL_HUMAN 98 7 -

Motif 5 width=19
Element Seqn Id St Int Rpt
SYDVQVADTDYDQFAMVFF NGAL_RAT 125 7 -
SYLVRVVSTNYNQHAMVFF NGAL_HUMAN 125 7 -

Motif 6 width=19
Element Seqn Id St Int Rpt
YFKVTLYGRTKGLSDELKE NGAL_RAT 152 8 -
YFKITLYGRTKELTSELKE NGAL_HUMAN 152 8 -

Motif 7 width=17
Element Seqn Id St Int Rpt
FAKSLGLKDNNIVFSVP NGAL_RAT 175 4 -
FSKSLGLPENHIVFPVP NGAL_HUMAN 175 4 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
QDSTQNLIPAPPL NGAL_RAT 21 21 -
QDSTQNLIPAPSL NGAL_MOUSE 21 21 -
QDSTSDLIPAPPL NGAL_HUMAN 21 21 -

Motif 2 width=11
Element Seqn Id St Int Rpt
FQGRWFVVGLA NGAL_RAT 47 13 -
FRGRWYVVGLA NGAL_MOUSE 47 13 -
FQGKWYVVGLA NGAL_HUMAN 47 13 -

Motif 3 width=20
Element Seqn Id St Int Rpt
MYSTIYELQEDNSYNVTSIL NGAL_RAT 71 13 -
MYSTIYELQENNSYNVTSIL NGAL_MOUSE 71 13 -
MYATIYELKEDKSYNVTSVL NGAL_HUMAN 71 13 -

Motif 4 width=20
Element Seqn Id St Int Rpt
YWIRTFVPSSRPGQFTLGNI NGAL_RAT 98 7 -
YWIRTFVPSSRAGQFTLGNM NGAL_MOUSE 100 9 -
YWIRTFVPGCQPGEFTLGNI NGAL_HUMAN 98 7 -

Motif 5 width=19
Element Seqn Id St Int Rpt
SYDVQVADTDYDQFAMVFF NGAL_RAT 125 7 -
SYNVQVATTDYNQFAMVFF NGAL_MOUSE 127 7 -
SYLVRVVSTNYNQHAMVFF NGAL_HUMAN 125 7 -

Motif 6 width=19
Element Seqn Id St Int Rpt
YFKVTLYGRTKGLSDELKE NGAL_RAT 152 8 -
YFKITLYGRTKELSPELKE NGAL_MOUSE 154 8 -
YFKITLYGRTKELTSELKE NGAL_HUMAN 152 8 -

Motif 7 width=17
Element Seqn Id St Int Rpt
FAKSLGLKDNNIVFSVP NGAL_RAT 175 4 -
FAKSLGLKDDNIIFSVP NGAL_MOUSE 177 4 -
FSKSLGLPENHIVFPVP NGAL_HUMAN 175 4 -