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PR01980

Identifier
IGFBPFAMILY4  [View Relations]  [View Alignment]  
Accession
PR01980
No. of Motifs
3
Creation Date
11-JUN-2009
Title
Insulin-like growth factor-binding protein 4 signature
Database References
PRINTS; PR01976 IGFBPFAMILY
PDB; 1WQJ; 2DSP; 2DSQ; 2DSR
SCOP; 1WQJ; 2DSP; 2DSQ; 2DSR
CATH; 1WQJ; 2DSP; 2DSQ; 2DSR
MIM; 146733
Literature References
1. STEWART, C. AND ROTWEIN, P.
Growth, differentiation and survival: multiple physiological functions for
insulin-like growth factors.
PHYSIOL.REV. 76 1005-1026 (1996).
 
2. HWA, V., OH, Y. AND ROSENFELD, R.
The Insulin-Like Growth Factor-Binding Protein (IGFBP) Superfamily.
ENDOCR.REV. 20 761-787 (1999).
 
3. OH, Y., MULLER. H., PHAM, H. AND ROSENFELD, R.
Demonstration of receptors for insulin-like growth factor binding
protein-3 on Hs578T human breast cancer cells.
J.BIOL.CHEM. 268 26045-26048 (1993).
 
4. ANDRESS, D.
Heparin modulates the binding of insulin-like growth factor (IGF) binding 
protein-5 to a membrane protein in osteoblastic cells.
J.BIOL.CHEM. 270 28289-28296 (1995).
 
5. MOHAN, S., NAKAO, Y., HONDA, Y., LANDALE, E., LESSER, U., DONY, C., 
LANG, K. AND BAYLINK, D. 
Studies on the mechanisms by which insulin-like growth factor (IGF) binding
protein-4 (IGFBP-4) and IGFBP-5 modulate IGF actions in bone cells. 
J.BIOL.CHEM.270 20424-20431 (1995).
 
6. RAJAH, R., VALENTINIS, B. AND COHEN, P.
Insulin-like growth factor (IGF)-binding protein-3 induces apoptosis and 
mediates the effects of transforming growth factor-beta1 on programmed cell
death through a p53- and IGF-independent mechanism.
J.BIOL.CHEM. 272 12181-12188 (1997).
 
7. ZHU, W., SHIOJIMA, I., ITO, Y., LI, Z., IKEDA, H., YOSHIDA, M.,
NAITO, A., NISHI, J., UENO, H., UMEZAWA, A., MINAMINO, T., NAGAI, T.,
KIKUCHI, A., ASASHIMA, M. AND KOMURO, I.
IGFBP-4 is an inhibitor of canonical Wnt signalling required for 
cardiogenesis.
NATURE 454 345-349 (2008).

Documentation
Insulin-like growth factors (IGFs)-I and -II are small secreted peptides 
that stimulate the survival, and promote the proliferation and 
differentiation, of many cell types [1]. In biological fluids, these growth
factors are usually bound to IGF binding proteins (IGFBPs), which regulate
their availability and activity by prolonging their half-life and 
modulating their receptor interactions.
 
To date, six IGFBP family members have been identified (termed IGFBP1-6)
[2]. They share a conserved gene (intron-exon) organisation and high IGF
binding affinity. Structurally, the proteins also share a common domain 
architecture, possessing a conserved N-terminal IGFBP domain, a highly 
variable mid-section, and a thyroglobulin type-1 (Tg1) domain in their 
C-terminal regions.
 
In addition to their role in the regulation of IGF activity, there is 
evidence for the direct association of IGFBPs with a variety of 
extracellular and cell surface molecules [3,4], with consequent effects 
upon important biological processes. These include modulation of bone cell
proliferation [5], and growth arrest of breast and prostate cancer cells 
[3,6].
 
IGFBP4 is abundant in serum, and is expressed in many different tissues. The
protein functions as a cardiogenic growth factor in mice - an effect that
is IGF-independent, and mediated by inhibition on the canonical Wnt
signalling pathway [7]. 
 
IGFBPFAMILY4 is a 3-element fingerprint that provides a signature for
insulin-like growth factor-binding protein 4. The fingerprint was derived
from an initial alignment of 4 sequences: the motifs were drawn from
conserved regions spanning virtually the full alignment length, focusing on
those sections that characterise IGFBP4 but distinguish it from other 
family members - motif 1 resides within the IGFBP domain; motif 2 lies 
between the IGFBP and Tg1 domains; and motif 3 resides within the Tg1 
domain. Two iterations on SPTR57_40f were required to reach convergence, at
which point a true set comprising 12 sequences was identified. A single
partial match was also found, B4E351_HUMAN, a translated human cDNA 
sequence that fails to match motif 1.
Summary Information
  12 codes involving  3 elements
1 codes involving 2 elements
Composite Feature Index
3121212
2011
123
True Positives
B2CZF1_CAPHI  B5AZT5_SHEEP  B5LNQ9_SALSA  B6RNJ3_FUGRU  
IBP4_BOVIN IBP4_HUMAN IBP4_MOUSE IBP4_PIG
IBP4_RAT IBP4_SHEEP Q801D7_CHICK Q8BSM9_MOUSE
True Positive Partials
Codes involving 2 elements
B4E351_HUMAN
Sequence Titles
B2CZF1_CAPHI IBP4 - Capra hircus (Goat).                   
B5AZT5_SHEEP Insulin-like growth factor binding protein-4 - Ovis aries (Sheep).
B5LNQ9_SALSA Insulin-like growth factor binding protein 4 - Salmo salar (Atlantic salmon).
B6RNJ3_FUGRU Insulin-like growth factor binding protein 4 - Fugu rubripes (Japanese pufferfish) (Takifugu rubripes).
IBP4_BOVIN Insulin-like growth factor-binding protein 4 - Bos taurus (Bovine).
IBP4_HUMAN Insulin-like growth factor-binding protein 4 - Homo sapiens (Human).
IBP4_MOUSE Insulin-like growth factor-binding protein 4 - Mus musculus (Mouse).
IBP4_PIG Insulin-like growth factor-binding protein 4 - Sus scrofa (Pig).
IBP4_RAT Insulin-like growth factor-binding protein 4 - Rattus norvegicus (Rat).
IBP4_SHEEP Insulin-like growth factor-binding protein 4 - Ovis aries (Sheep).
Q801D7_CHICK Insulin-like growth factor-binding protein-4 - Gallus gallus (Chicken).
Q8BSM9_MOUSE Putative uncharacterized protein - Mus musculus (Mouse).

B4E351_HUMAN cDNA FLJ52130, highly similar to Insulin-like growth factor-binding protein 4 - Homo sapiens (Human).
Scan History
SPTR57_40f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
PPRGVEKPLHTLVH IBP4_BOVIN 82 82 -
PPRGVEKPLRTLMH IBP4_RAT 82 82 -
PPRGVERPLHSLMH B6RNJ3_FUGRU 91 91 -
PPRNVERPLHSLMH B5LNQ9_SALSA 92 92 -

Motif 2 width=15
Element Seqn Id St Int Rpt
CSAHDRKCLQKHLAK IBP4_BOVIN 131 35 -
CSAHDHRCLQKHMAK IBP4_RAT 131 35 -
CSPQDKRCIQKTLAR B6RNJ3_FUGRU 139 34 -
CSPQDKRCIQKTLAR B5LNQ9_SALSA 140 34 -

Motif 3 width=16
Element Seqn Id St Int Rpt
VDRKTGVKLPGGLEPK IBP4_BOVIN 229 83 -
VDRKTGVKLPGGLEPK IBP4_RAT 225 79 -
VDQKTGMRLPGPLELR B6RNJ3_FUGRU 231 77 -
VDQKTGMRLPGPLELR B5LNQ9_SALSA 232 77 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
PPRGVEKPLHTLVH B2CZF1_CAPHI 82 82 -
PPRGVEKPLHTLVH IBP4_SHEEP 61 61 -
PPRGVEKPLHTLVH IBP4_BOVIN 82 82 -
PPRGVEKPLHTLVH B5AZT5_SHEEP 82 82 -
PPRGVEKPLHTLMH IBP4_HUMAN 82 82 -
PPRGVEKPLHTLMH IBP4_PIG 83 83 -
PPRGVEKPLRTLMH IBP4_MOUSE 82 82 -
PPRGVEKPLRTLMH IBP4_RAT 82 82 -
PPRGVEKPLRTLMH Q8BSM9_MOUSE 82 82 -
PPRGVPRPLHTLMH Q801D7_CHICK 87 87 -
PPRGVERPLHSLMH B6RNJ3_FUGRU 91 91 -
PPRNVERPLHSLMH B5LNQ9_SALSA 92 92 -

Motif 2 width=15
Element Seqn Id St Int Rpt
CSAHDRKCLQKHLAK B2CZF1_CAPHI 131 35 -
CSAHDRKCLQKHLAK IBP4_SHEEP 110 35 -
CSAHDRKCLQKHLAK IBP4_BOVIN 131 35 -
CSAHDRKCLQKHLAK B5AZT5_SHEEP 131 35 -
CSAHDRRCLQKHFAK IBP4_HUMAN 131 35 -
CSPQDRRCLQKHLAK IBP4_PIG 132 35 -
CSAHDHRCLQKHMAK IBP4_MOUSE 131 35 -
CSAHDHRCLQKHMAK IBP4_RAT 131 35 -
CSAHDHRCLQKHMAK Q8BSM9_MOUSE 131 35 -
CSIHDRKCLQKQQAK Q801D7_CHICK 136 35 -
CSPQDKRCIQKTLAR B6RNJ3_FUGRU 139 34 -
CSPQDKRCIQKTLAR B5LNQ9_SALSA 140 34 -

Motif 3 width=16
Element Seqn Id St Int Rpt
VDRKTGVKLPGGLEPK B2CZF1_CAPHI 229 83 -
VDRKTGVKLPGGLEPK IBP4_SHEEP 208 83 -
VDRKTGVKLPGGLEPK IBP4_BOVIN 229 83 -
VDRKTGVKLPGGLEPK B5AZT5_SHEEP 229 83 -
VDRKTGVKLPGGLEPK IBP4_HUMAN 229 83 -
VDRKTGVKLPGGLEPK IBP4_PIG 230 83 -
VDRKTGVKLPGGLEPK IBP4_MOUSE 225 79 -
VDRKTGVKLPGGLEPK IBP4_RAT 225 79 -
VDRKTGVELPGGLEPK Q8BSM9_MOUSE 225 79 -
VDRKTGVKLPGFLELK Q801D7_CHICK 233 82 -
VDQKTGMRLPGPLELR B6RNJ3_FUGRU 231 77 -
VDQKTGMRLPGPLELR B5LNQ9_SALSA 232 77 -