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PR01982

Identifier
IGFBPFAMILY6  [View Relations]  [View Alignment]  
Accession
PR01982
No. of Motifs
4
Creation Date
04-SEP-2009
Title
Insulin-like growth factor-binding protein 6 signature
Database References
PRINTS; PR01976 IGFBPFAMILY
PDB; 1RMJ
SCOP; 1RMJ
CATH; 1RMJ
MIM; 146735
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.
 
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. SUEOKA, N., LEE, H., WIEHLE, S., CRISTIANO, R., FANG, B., JI, L.,
ROTH, J., HONG, W., COHEN, P. and KURIE, J.
Insulin-like growth factor binding protein-6 activates programmed cell
death in non-small cell lung cancer cells.
ONCOGENE 19 4432-4436 (2000).

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].
 
IGFBP6 is a potent inducer of programmed cell death in lung cancer cells 
[7]. The protein may therefore represent a potential target as a cancer 
therapeutic.
 
IGFBPFAMILY6 is a 4-element fingerprint that provides a signature for
insulin-like growth factor-binding protein 6. The fingerprint was derived 
from an initial alignment of 7 sequences: the motifs were drawn from
conserved regions in the N- and C-terminal thirds of the alignment, 
focusing on those sections that characterise IGFBP6 but distinguish it from
other family members - motif 1 resides within the IGFBP domain, and motifs
2 and 3 lie within the Tg1 domain. Two iterations on SPTR57_40f were 
required to reach convergence, at which point a true set comprising 11
sequences was identified. 
Summary Information
11 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
411111111
30000
20000
1234
True Positives
A6ZIC9_PIG    A9NJ32_PIG    B5AN56_SHEEP  B5X2D8_SALSA  
IBP6_BOVIN IBP6_HUMAN IBP6_MOUSE IBP6_RAT
Q3HWG4_ONCMY Q4TAM5_TETNG Q91X24_MOUSE
Sequence Titles
A6ZIC9_PIG  Insulin-like growth factor binding protein 6 - Sus scrofa (Pig). 
A9NJ32_PIG Insulin-like growth factor binding protein-6 - Sus scrofa (Pig).
B5AN56_SHEEP Insulin-like growth factor-binding protein-6 - Ovis aries (Sheep).
B5X2D8_SALSA Insulin-like growth factor-binding protein 6 - Salmo salar (Atlantic salmon).
IBP6_BOVIN Insulin-like growth factor-binding protein 6 - Bos taurus (Bovine).
IBP6_HUMAN Insulin-like growth factor-binding protein 6 - Homo sapiens (Human).
IBP6_MOUSE Insulin-like growth factor-binding protein 6 - Mus musculus (Mouse).
IBP6_RAT Insulin-like growth factor-binding protein 6 - Rattus norvegicus (Rat).
Q3HWG4_ONCMY Insulin-like growth factor binding protein 6 - Oncorhynchus mykiss (Rainbow trout) (Salmo gairdneri).
Q4TAM5_TETNG Chromosome undetermined SCAF7283, whole genome shotgun sequence - Tetraodon nigroviridis (Green puffer).
Q91X24_MOUSE Igfbp6 protein - Mus musculus (Mouse).
Scan History
SPTR57_40f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
QPRENEETPL IBP6_MOUSE 86 86 -
QPPEKEDLPL IBP6_BOVIN 83 83 -
QPAGDDEAPL A9NJ32_PIG 83 83 -
HPPKDDEAPL IBP6_HUMAN 85 85 -
VPLPQEHSPL B5X2D8_SALSA 76 76 -
VPLPQEHSPL Q3HWG4_ONCMY 76 76 -
VPPPRDHSPL Q4TAM5_TETNG 78 78 -

Motif 2 width=13
Element Seqn Id St Int Rpt
LDSVLQQLQTEVF IBP6_MOUSE 164 68 -
LDSVLQQLQTEVF IBP6_BOVIN 163 70 -
LDSVLQQLQTEVF A9NJ32_PIG 165 72 -
LDSVLQQLQTEVY IBP6_HUMAN 167 72 -
LNSVLRGVELTIF B5X2D8_SALSA 129 43 -
LNSVLRGVELTIF Q3HWG4_ONCMY 129 43 -
LNSVLRGLELTII Q4TAM5_TETNG 131 43 -

Motif 3 width=10
Element Seqn Id St Int Rpt
VDPMGQPLPV IBP6_MOUSE 213 36 -
VERMGQPLPG IBP6_BOVIN 211 35 -
VDRMGQPLAG A9NJ32_PIG 213 35 -
VDRMGKSLPG IBP6_HUMAN 215 35 -
VDELGTALSS B5X2D8_SALSA 177 35 -
VDELGTALSS Q3HWG4_ONCMY 177 35 -
VDELGSPVPS Q4TAM5_TETNG 179 35 -

Motif 4 width=10
Element Seqn Id St Int Rpt
GQGSTQCSAR IBP6_MOUSE 226 3 -
GDGSSLCPTG IBP6_BOVIN 225 4 -
GDGNAPCPSG A9NJ32_PIG 226 3 -
GNGSSSCPTG IBP6_HUMAN 228 3 -
EDGTLPCDGD B5X2D8_SALSA 190 3 -
EDGTLPCDGD Q3HWG4_ONCMY 190 3 -
DDGTLPCDGE Q4TAM5_TETNG 192 3 -
Final Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
QPPEKEDLPL B5AN56_SHEEP 82 82 -
QPRENEETPL IBP6_RAT 77 77 -
QPRENEEAPL Q91X24_MOUSE 86 86 -
QPRENEETPL IBP6_MOUSE 86 86 -
QPPEKEDLPL IBP6_BOVIN 83 83 -
QPAGDDEAPL A9NJ32_PIG 83 83 -
HPPKDDEAPL IBP6_HUMAN 85 85 -
QPPEEDQAPL A6ZIC9_PIG 83 83 -
VPLPQEHSPL B5X2D8_SALSA 76 76 -
VPLPQEHSPL Q3HWG4_ONCMY 76 76 -
VPPPRDHSPL Q4TAM5_TETNG 78 78 -

Motif 2 width=13
Element Seqn Id St Int Rpt
LDSVLQQLQTEVF B5AN56_SHEEP 162 70 -
LDSVLQQLQTEVF IBP6_RAT 152 65 -
LDSVLQQLQTEVF Q91X24_MOUSE 164 68 -
LDSVLQQLQTEVF IBP6_MOUSE 164 68 -
LDSVLQQLQTEVF IBP6_BOVIN 163 70 -
LDSVLQQLQTEVF A9NJ32_PIG 165 72 -
LDSVLQQLQTEVY IBP6_HUMAN 167 72 -
LDSVLQQLQTEVF A6ZIC9_PIG 163 70 -
LNSVLRGVELTIF B5X2D8_SALSA 129 43 -
LNSVLRGVELTIF Q3HWG4_ONCMY 129 43 -
LNSVLRGLELTII Q4TAM5_TETNG 131 43 -

Motif 3 width=10
Element Seqn Id St Int Rpt
VDRMGQPLPG B5AN56_SHEEP 210 35 -
VDPMGQPLPV IBP6_RAT 201 36 -
VDPMGQPLPV Q91X24_MOUSE 213 36 -
VDPMGQPLPV IBP6_MOUSE 213 36 -
VERMGQPLPG IBP6_BOVIN 211 35 -
VDRMGQPLAG A9NJ32_PIG 213 35 -
VDRMGKSLPG IBP6_HUMAN 215 35 -
VDRMGQPLAG A6ZIC9_PIG 211 35 -
VDELGTALSS B5X2D8_SALSA 177 35 -
VDELGTALSS Q3HWG4_ONCMY 177 35 -
VDELGSPVPS Q4TAM5_TETNG 179 35 -

Motif 4 width=10
Element Seqn Id St Int Rpt
GDGSSLCPTG B5AN56_SHEEP 224 4 -
GQGSSQCSAR IBP6_RAT 214 3 -
GQGSTQCSAR Q91X24_MOUSE 226 3 -
GQGSTQCSAR IBP6_MOUSE 226 3 -
GDGSSLCPTG IBP6_BOVIN 225 4 -
GDGNAPCPSG A9NJ32_PIG 226 3 -
GNGSSSCPTG IBP6_HUMAN 228 3 -
GDGNAPCPSG A6ZIC9_PIG 224 3 -
EDGTLPCDGD B5X2D8_SALSA 190 3 -
EDGTLPCDGD Q3HWG4_ONCMY 190 3 -
DDGTLPCDGE Q4TAM5_TETNG 192 3 -