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PR01978

Identifier
IGFBPFAMILY2  [View Relations]  [View Alignment]  
Accession
PR01978
No. of Motifs
3
Creation Date
11-JUN-2009
Title
Insulin-like growth factor-binding protein 2 signature
Database References
PRINTS; PR01976 IGFBPFAMILY
INTERPRO; IPR012210
PDB; 2H7T
CATH; 2H7T
MIM; 146731
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. FROMMER K., REICHENMILLER, K., SCHUTT, B., HOEFLICH, A., RANKE, M., 
DODT, G. AND ELMLINGER, M.
IGF-independent effects of IGFBP-2 on the human breast cancer cell line 
Hs578T.
J.MOL.ENDOCRINOL. 37 13-23 (2006).
 
8. BUSUND, L., RICHARDSEN, E., BUSUND, R., UKKONEN, T., BJORNSEN, T., 
BUSCH, C. AND STALSBERG, H.
Significant expression of IGFBP2 in breast cancer compared with benign 
lesions. 
J.CLIN.PATHOL. 58 361-366 (2005).
 
9. FUKUSHIMA, T. AND KATAOKA, H.
Roles of insulin-like growth factor binding protein-2 (IGFBP-2) in 
glioblastoma.
ANTICANCER RES. 27 3685-3692 (2007).
 
10. ZUMKELLER, W. 
IGFs and IGFBPs: surrogate markers for diagnosis and surveillance of tumour
growth?
MOL.PATHOL. 54 285-288 (2001).

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].
 
IGFBP2 is involved in a variety of biological processes, including the 
regulation of cell adhesion, migration and proliferation [7]. The protein 
is overexpressed in a number of carcinomas [8,9], and increased IGFBP2 
concentrations have been described in serum and cyst fluids surrounding 
tumours of different histologies, such as lung tumours, prostate cancer and
brain tumours [10]. Consequently, IGFBP2 may represent a valuable marker 
for tumour diagnosis and surveillance.
 
IGFBPFAMILY2 is a 3-element fingerprint that provides a signature for
insulin-like growth factor-binding protein 2. The fingerprint was derived 
from an initial alignment of 9 sequences: the motifs were drawn from 
conserved regions in the N- and C-terminal thirds of the alignment,
focusing on those sections that characterise IGFBP2 but distinguish it from
other family members - motif 1 resides within the IGFBP domain; motif
2 lies partially within the Tg1 domain; and motif 3 resides wholly within 
the Tg1 domain. Two iterations on SPTR57_40f were required to reach 
convergence, at which point a true set comprising 16 sequences was 
identified. A single partial match was also found, Q9D057_MOUSE, a 
mouse sequence that fails to match motif 1.
Summary Information
  16 codes involving  3 elements
1 codes involving 2 elements
Composite Feature Index
3161616
2011
123
True Positives
A4IIA2_XENTR  A8E5I5_DANRE  B2CM69_DICLA  B3F211_DANRE  
IBP2_BOVIN IBP2_CHICK IBP2_DANRE IBP2_HUMAN
IBP2_MOUSE IBP2_PIG IBP2_RAT IBP2_SHEEP
Q3I344_ONCMY Q3I346_ONCMY Q5XHC5_XENLA Q8UVU5_SPAAU
True Positive Partials
Codes involving 2 elements
Q9D057_MOUSE
Sequence Titles
A4IIA2_XENTR Igfbp2 protein - Xenopus tropicalis (Western clawed frog) (Silurana tropicalis). 
A8E5I5_DANRE Insulin-like growth factor binding protein 2 - Danio rerio (Zebrafish) (Brachydanio rerio).
B2CM69_DICLA Insulin-like growth factor binding protein-2 - Dicentrarchus labrax (European sea bass).
B3F211_DANRE Insulin-like growth factor binding protein 2b - Danio rerio (Zebrafish) (Brachydanio rerio).
IBP2_BOVIN Insulin-like growth factor-binding protein 2 - Bos taurus (Bovine).
IBP2_CHICK Insulin-like growth factor-binding protein 2 - Gallus gallus (Chicken).
IBP2_DANRE Insulin-like growth factor-binding protein 2 - Danio rerio (Zebrafish) (Brachydanio rerio).
IBP2_HUMAN Insulin-like growth factor-binding protein 2 - Homo sapiens (Human).
IBP2_MOUSE Insulin-like growth factor-binding protein 2 - Mus musculus (Mouse).
IBP2_PIG Insulin-like growth factor-binding protein 2 - Sus scrofa (Pig).
IBP2_RAT Insulin-like growth factor-binding protein 2 - Rattus norvegicus (Rat).
IBP2_SHEEP Insulin-like growth factor-binding protein 2 - Ovis aries (Sheep).
Q3I344_ONCMY Insulin-like growth factor binding protein 2 - Oncorhynchus mykiss (Rainbow trout) (Salmo gairdneri).
Q3I346_ONCMY Insulin-like growth factor binding protein 3 - Oncorhynchus mykiss (Rainbow trout) (Salmo gairdneri).
Q5XHC5_XENLA LOC495038 protein - Xenopus laevis (African clawed frog).
Q8UVU5_SPAAU Insulin-like growth factor binding protein-2 - Sparus aurata (Gilthead sea bream).

Q9D057_MOUSE Putative uncharacterized protein - Mus musculus (Mouse).
Scan History
SPTR57_40f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
CSVCARLEGEAC IBP2_HUMAN 90 90 -
CSVCARLEGERC IBP2_BOVIN 79 79 -
CPVCARLEDEAC IBP2_CHICK 73 73 -
CPVCARLEGESC A4IIA2_XENTR 59 59 -
CPVCARQEGELC B2CM69_DICLA 58 58 -
CPVCARQVGELC Q8UVU5_SPAAU 58 58 -
CPVCARQEGELC Q3I344_ONCMY 61 61 -
CPVCARQKGELC B3F211_DANRE 52 52 -
CPVCARQEGEQC IBP2_DANRE 58 58 -

Motif 2 width=14
Element Seqn Id St Int Rpt
ISTMRLPDERGPLE IBP2_HUMAN 241 139 -
ISTMRLPDERGPLE IBP2_BOVIN 230 139 -
ISTMRLPDERGPLE IBP2_CHICK 223 138 -
ISGMHLPDDRGPLE A4IIA2_XENTR 198 127 -
ISKMTSEDNRGPLE B2CM69_DICLA 183 113 -
ISRMTSEDNRGPLE Q8UVU5_SPAAU 202 132 -
ISKMPFRDNRGPLE Q3I344_ONCMY 198 125 -
ISRMAFHDNKGPLE B3F211_DANRE 180 116 -
ISKITFKDNRTPLE IBP2_DANRE 191 121 -

Motif 3 width=10
Element Seqn Id St Int Rpt
DPECHLFYNE IBP2_HUMAN 306 51 -
DPECHLFYNE IBP2_BOVIN 295 51 -
DPECHLFYTA IBP2_CHICK 288 51 -
DPECHLYYTS A4IIA2_XENTR 263 51 -
DPNCNQFQEE B2CM69_DICLA 248 51 -
DPNCNQFQEE Q8UVU5_SPAAU 267 51 -
DPNCSQYLRG Q3I344_ONCMY 263 51 -
DPNCSQYYGG B3F211_DANRE 245 51 -
DPNCNQYLDG IBP2_DANRE 256 51 -
Final Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
CSVCARLEGEAC IBP2_HUMAN 90 90 -
CSVCARQEGEAC IBP2_MOUSE 71 71 -
CSVCARQEGEAC IBP2_RAT 71 71 -
CSVCARLEGERC IBP2_BOVIN 79 79 -
CSVCARLEGERC IBP2_SHEEP 79 79 -
CSVCARLEGERC IBP2_PIG 79 79 -
CPVCARLEGESC Q5XHC5_XENLA 59 59 -
CPVCARLEDEAC IBP2_CHICK 73 73 -
CPVCARLEGESC A4IIA2_XENTR 59 59 -
CPVCARQEGELC B2CM69_DICLA 58 58 -
CPVCARQVGELC Q8UVU5_SPAAU 58 58 -
CPVCARQEGELC Q3I344_ONCMY 61 61 -
CPVCARQKGELC B3F211_DANRE 52 52 -
CPVCARQEGEQC A8E5I5_DANRE 58 58 -
CPVCARQEGEQC IBP2_DANRE 58 58 -
CPVCARLEGEFC Q3I346_ONCMY 59 59 -

Motif 2 width=14
Element Seqn Id St Int Rpt
ISTMRLPDERGPLE IBP2_HUMAN 241 139 -
ISTMRLPDDRGPLE IBP2_MOUSE 218 135 -
ISTMRLPDDRGPLE IBP2_RAT 217 134 -
ISTMRLPDERGPLE IBP2_BOVIN 230 139 -
ISTMRLPDERGPLE IBP2_SHEEP 230 139 -
ISTMRLPDERGPLE IBP2_PIG 229 138 -
ISGMHLPDDRGPLE Q5XHC5_XENLA 194 123 -
ISTMRLPDERGPLE IBP2_CHICK 223 138 -
ISGMHLPDDRGPLE A4IIA2_XENTR 198 127 -
ISKMTSEDNRGPLE B2CM69_DICLA 183 113 -
ISRMTSEDNRGPLE Q8UVU5_SPAAU 202 132 -
ISKMPFRDNRGPLE Q3I344_ONCMY 198 125 -
ISRMAFHDNKGPLE B3F211_DANRE 180 116 -
ISKITFKDNRTPLE A8E5I5_DANRE 191 121 -
ISKITFKDNRTPLE IBP2_DANRE 191 121 -
ISKMSFHDNRGHVD Q3I346_ONCMY 191 120 -

Motif 3 width=10
Element Seqn Id St Int Rpt
DPECHLFYNE IBP2_HUMAN 306 51 -
DPECHLFYNE IBP2_MOUSE 283 51 -
DPECHLFYNE IBP2_RAT 282 51 -
DPECHLFYNE IBP2_BOVIN 295 51 -
DPECHLFYNE IBP2_SHEEP 295 51 -
DPECHLFYNE IBP2_PIG 294 51 -
DPECHLFYTN Q5XHC5_XENLA 259 51 -
DPECHLFYTA IBP2_CHICK 288 51 -
DPECHLYYTS A4IIA2_XENTR 263 51 -
DPNCNQFQEE B2CM69_DICLA 248 51 -
DPNCNQFQEE Q8UVU5_SPAAU 267 51 -
DPNCSQYLRG Q3I344_ONCMY 263 51 -
DPNCSQYYGG B3F211_DANRE 245 51 -
DPNCNQYLDG A8E5I5_DANRE 256 51 -
DPNCNQYLDG IBP2_DANRE 256 51 -
DPNCSQYVEE Q3I346_ONCMY 256 51 -