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PR01979

Identifier
IGFBPFAMILY3  [View Relations]  [View Alignment]  
Accession
PR01979
No. of Motifs
4
Creation Date
11-JUN-2009
Title
Insulin-like growth factor-binding protein 3 signature
Database References
PRINTS; PR01976 IGFBPFAMILY
INTERPRO; IPR012211
MIM; 146732
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. WEINZIMER, S., GIBSON, T., COLLETT-SOLBERG, P., KHARE, A., LIU, B. AND
COHEN, P.
Transferrin is an insulin-like growth factor-binding protein-3 binding 
protein.
J.CLIN.ENDOCRINOL.METAB. 86 1806-1813 (2001).
 
8. JAQUES, G., NOLL, K., WEGMANN, B., WITTEN, S., KOGAN, E., RADULESCU, R.
AND HAVEMANN, K.
Nuclear localization of insulin-like growth factor binding protein 3 in a 
lung cancer cell line. 
ENDOCRINOLOGY 138 1767-1770 (1997).

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].
 
IGFBP3 is the major IGF-binding protein in serum and is expressed in many 
tissues. The protein possesses IGF-independent growth-inhibitory and 
-potentiating effects, which are mediated through specific IGFBP3 binding 
proteins/receptors [7]. In common with IGFBP5, IGFBP3 possesses a nuclear
translocation signal, and can accumulate in the nucleus, where it may exert
its growth-modulating effects [8].
 
IGFBPFAMILY3 is a 4-element fingerprint that provides a signature for
insulin-like growth factor-binding protein 3. 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 IGFBP3 but distinguish it from other 
family members - motif 1 resides within the IGFBP domain; motifs 2 and 3
lie between the IGFBP and Tg1 domains; and motif 4 resides within the Tg1 
domain. Two iterations on SPTR57_40f were required to reach convergence, at
which point a true set comprising 17 sequences was identified. Five 
partial matches were also found (B3KRZ1_HUMAN, B3KWK7_HUMAN, B3KVY6_HUMAN,
B3KTS0_HUMAN and Q8BP94_MOUSE), all of which are human and mouse translated
cDNA sequences and IGFBP3 isoforms that fail to match motif 1.
Summary Information
  17 codes involving  4 elements
5 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
417171717
30555
20000
1234
True Positives
A6N8N6_CHICK  A6XNC9_HUMAN  A6XND0_HUMAN  A6XND1_HUMAN  
B3KTQ0_HUMAN B3KVF9_HUMAN B4DN53_HUMAN B4DP07_HUMAN
IBP3_BOVIN IBP3_HUMAN IBP3_MOUSE IBP3_PIG
IBP3_RAT Q66I28_DANRE Q6PE62_MOUSE Q6ZSD0_HUMAN
Q90YJ6_DANRE
True Positive Partials
Codes involving 3 elements
B3KRZ1_HUMAN B3KTS0_HUMAN B3KVY6_HUMAN B3KWK7_HUMAN
Q8BP94_MOUSE
Sequence Titles
A6N8N6_CHICK Insulin-like growth factor-binding protein 3 - Gallus gallus (Chicken). 
A6XNC9_HUMAN Insulin-like growth factor binding protein 3 isoform b - Homo sapiens (Human).
A6XND0_HUMAN Insulin-like growth factor binding protein 3 - Homo sapiens (Human).
A6XND1_HUMAN Insulin-like growth factor binding protein 3 isoform b - Homo sapiens (Human).
B3KTQ0_HUMAN cDNA FLJ38581 fis, clone HCHON2008672, highly similar to Insulin-like growth factor-binding protein 3 - Homo sapiens (Human).
B3KVF9_HUMAN cDNA FLJ16507 fis, clone HCHON2000364, highly similar to Insulin-like growth factor-binding protein 3 - Homo sapiens (Human).
B4DN53_HUMAN cDNA FLJ52568, highly similar to Insulin-like growth factor-binding protein 3 - Homo sapiens (Human).
B4DP07_HUMAN cDNA FLJ53634, highly similar to Insulin-like growth factor-binding protein 3 - Homo sapiens (Human).
IBP3_BOVIN Insulin-like growth factor-binding protein 3 - Bos taurus (Bovine).
IBP3_HUMAN Insulin-like growth factor-binding protein 3 - Homo sapiens (Human).
IBP3_MOUSE Insulin-like growth factor-binding protein 3 - Mus musculus (Mouse).
IBP3_PIG Insulin-like growth factor-binding protein 3 - Sus scrofa (Pig).
IBP3_RAT Insulin-like growth factor-binding protein 3 - Rattus norvegicus (Rat).
Q66I28_DANRE Insulin-like growth factor binding protein 3 - Danio rerio (Zebrafish) (Brachydanio rerio).
Q6PE62_MOUSE Igfbp3 protein - Mus musculus (Mouse).
Q6ZSD0_HUMAN cDNA FLJ45630 fis, clone CHONS2001287, moderately similar to INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN 3 - Homo sapiens (Human).
Q90YJ6_DANRE Insulin-like growth factor binding protein 3 - Danio rerio (Zebrafish) (Brachydanio rerio).

B3KRZ1_HUMAN cDNA FLJ35128 fis, clone PLACE6008768, moderately similar to Insulin-like growth factor-binding protein 3 - Homo sapiens (Human).
B3KTS0_HUMAN cDNA FLJ38655 fis, clone HHDPC2009208, highly similar to Insulin-like growth factor-binding protein 3 - Homo sapiens (Human).
B3KVY6_HUMAN cDNA FLJ41741 fis, clone HSYRA2003168, highly similar to Insulin-like growth factor-binding protein 3 - Homo sapiens (Human).
B3KWK7_HUMAN cDNA FLJ43234 fis, clone HCHON2002964, highly similar to Insulin-like growth factor-binding protein 3 - Homo sapiens (Human).
Q8BP94_MOUSE Putative uncharacterized protein - Mus musculus (Mouse).
Scan History
SPTR57_40f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
CQPPPGEPRP IBP3_PIG 96 96 -
CQPRPAEQYP IBP3_RAT 96 96 -
CQPRQEEARP A6N8N6_CHICK 85 85 -
CQHRPGESKP Q90YJ6_DANRE 83 83 -

Motif 2 width=12
Element Seqn Id St Int Rpt
KGHAKDSQRYKV IBP3_PIG 179 73 -
KGQARDSQRYKV IBP3_RAT 178 72 -
KEQAKNTQRYKV A6N8N6_CHICK 168 73 -
KEQVKKSQVHKV Q90YJ6_DANRE 178 85 -

Motif 3 width=11
Element Seqn Id St Int Rpt
TDTQNFSSESK IBP3_PIG 197 6 -
TDTQNFSSESK IBP3_RAT 196 6 -
TDTLNFSSESK A6N8N6_CHICK 186 6 -
QDIHNFSLESK Q90YJ6_DANRE 198 8 -

Motif 4 width=12
Element Seqn Id St Int Rpt
FLNMLSPRGIHI IBP3_PIG 228 20 -
FLNVLSPRGVHI IBP3_RAT 227 20 -
ILNVLSPRGFHI A6N8N6_CHICK 217 20 -
FTNVLNPRRFRI Q90YJ6_DANRE 229 20 -
Final Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
CQPSPDEARP A6XND0_HUMAN 73 73 -
CQPSPDEARP Q6ZSD0_HUMAN 108 108 -
CQPSPDEARP IBP3_HUMAN 94 94 -
CQPSPDEARP B4DP07_HUMAN 49 49 -
CQPSPDEARP B4DN53_HUMAN 79 79 -
CQPSPDEARP B3KVF9_HUMAN 71 71 -
CQPSPDEARP B3KTQ0_HUMAN 46 46 -
CQPSPDEARP A6XND1_HUMAN 66 66 -
CAPPPDEARP A6XNC9_HUMAN 51 51 -
CQPRPAEQYP IBP3_MOUSE 95 95 -
CQPRPAEQYP Q6PE62_MOUSE 96 96 -
CQPPPGEPRP IBP3_PIG 96 96 -
CQPRPAEQYP IBP3_RAT 96 96 -
CQPPPGDPRP IBP3_BOVIN 96 96 -
CQPRQEEARP A6N8N6_CHICK 85 85 -
CQHRPGESKP Q66I28_DANRE 83 83 -
CQHRPGESKP Q90YJ6_DANRE 83 83 -

Motif 2 width=12
Element Seqn Id St Int Rpt
KGHAKDSQRYKV A6XND0_HUMAN 156 73 -
KGHAKDSQRYKV Q6ZSD0_HUMAN 163 45 -
KGHAKDSQRYKV IBP3_HUMAN 177 73 -
KGHAKDSQRYKV B4DP07_HUMAN 132 73 -
KGHAKDSQRYKV B4DN53_HUMAN 162 73 -
KGHAKDSQRYKV B3KVF9_HUMAN 154 73 -
KGHAKDSQRYKV B3KTQ0_HUMAN 129 73 -
KGHAKDSQRYKV A6XND1_HUMAN 149 73 -
KGHAKDSQRYKV A6XNC9_HUMAN 134 73 -
KGHARDSQRYKV IBP3_MOUSE 177 72 -
KGHARDSQRYKV Q6PE62_MOUSE 178 72 -
KGHAKDSQRYKV IBP3_PIG 179 73 -
KGQARDSQRYKV IBP3_RAT 178 72 -
KGHAKDSQRYKV IBP3_BOVIN 177 71 -
KEQAKNTQRYKV A6N8N6_CHICK 168 73 -
KEQVKKSQVHKV Q66I28_DANRE 178 85 -
KEQVKKSQVHKV Q90YJ6_DANRE 178 85 -

Motif 3 width=11
Element Seqn Id St Int Rpt
TDTQNFSSESK A6XND0_HUMAN 174 6 -
TDTQNFSSESK Q6ZSD0_HUMAN 181 6 -
TDTQNFSSESK IBP3_HUMAN 195 6 -
TDTQNFSSESK B4DP07_HUMAN 150 6 -
TDTQNFSSESK B4DN53_HUMAN 180 6 -
TDTQNFSSESK B3KVF9_HUMAN 172 6 -
TDTQNFSSESK B3KTQ0_HUMAN 147 6 -
TDTQNFSSESK A6XND1_HUMAN 167 6 -
TDTQNFSSESK A6XNC9_HUMAN 152 6 -
TDTQNFSSESK IBP3_MOUSE 195 6 -
TDTQNFSSESK Q6PE62_MOUSE 196 6 -
TDTQNFSSESK IBP3_PIG 197 6 -
TDTQNFSSESK IBP3_RAT 196 6 -
TDTQNFSSESK IBP3_BOVIN 195 6 -
TDTLNFSSESK A6N8N6_CHICK 186 6 -
QDIHNFSLESK Q66I28_DANRE 198 8 -
QDIHNFSLESK Q90YJ6_DANRE 198 8 -

Motif 4 width=12
Element Seqn Id St Int Rpt
FLNVLSPRGVHI A6XND0_HUMAN 205 20 -
FLNVLSPRGVHI Q6ZSD0_HUMAN 212 20 -
FLNVLSPRGVHI IBP3_HUMAN 226 20 -
FLNVLSPRGVHI B4DP07_HUMAN 181 20 -
FLNVLSPRGVHI B4DN53_HUMAN 211 20 -
FLNVLSPRGVHI B3KVF9_HUMAN 203 20 -
FLNVLSPRGVHI B3KTQ0_HUMAN 178 20 -
FLNVLSPRGVHI A6XND1_HUMAN 198 20 -
FLNVLSPRGVHI A6XNC9_HUMAN 183 20 -
FLNVLSPRGVHI IBP3_MOUSE 226 20 -
FLNVLSPRGVHI Q6PE62_MOUSE 227 20 -
FLNMLSPRGIHI IBP3_PIG 228 20 -
FLNVLSPRGVHI IBP3_RAT 227 20 -
FLNMLSPRGIHI IBP3_BOVIN 226 20 -
ILNVLSPRGFHI A6N8N6_CHICK 217 20 -
FTNVLNPRRFRI Q66I28_DANRE 229 20 -
FTNVLNPRRFRI Q90YJ6_DANRE 229 20 -