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PR01977

Identifier
IGFBPFAMILY1  [View Relations]  [View Alignment]  
Accession
PR01977
No. of Motifs
5
Creation Date
11-JUN-2009
Title
Insulin-like growth factor-binding protein 1 signature
Database References
PRINTS; PR01976 IGFBPFAMILY
PDB; 1ZT3; 1ZT5; 2DSQ
SCOP; 1ZT3; 1ZT5; 2DSQ
CATH; 1ZT3; 1ZT5; 2DSQ
MIM; 146730
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. FANT, M., SALAFIA, C., BAXTER, R., SCHWANDER, J., VOGEL, C., PEZZULLO, J. 
AND MOYA, F.
Circulating levels of IGFs and IGF binding proteins in human cord serum: 
relationships to intrauterine growth.
REGUL.PEPT. 48 29-39 (1993).
 
8. LEU, J., CRISSEY, M. AND TAUB, R.
Massive hepatic apoptosis associated with TGF-beta1 activation after Fas 
ligand treatment of IGF binding protein-1-deficient mice.
J.CLIN.INVEST. 111 129-139 (2003).

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].
 
IGFBP1 (also known as amniotic fluid binding protein (AFBP) and placental 
protein-12) is involved in the regulation of foetal growth: there is a 
strong inverse correlation between circulating IGFBP1 levels and foetal 
size [7]. It also functions as a survival factor and pro-regeneration
factor in the liver [8].
 
IGFBPFAMILY1 is a 5-element fingerprint that provides a signature for
insulin-like growth factor-binding protein 1. The fingerprint was derived 
from an initial alignment of 7 sequences: the motifs were drawn from 
conserved regions spanning virtually the full alignment length, focusing on
those sections that characterise IGFBP1 but distinguish it from other 
family members - motifs 1 and 2 reside within the IGFBP domain; motif 3 
lies immediately prior to the Tg1 domain; and motifs 4 and 5 reside within
the Tg1 domain. Two iterations on SPTR57_40f were required to reach
convergence, at which point a true set comprising 18 sequences was 
identified. Two partial matches were also found, Q5XHD1_XENLA and 
A4K8J2_DANRE, which are frog and fish sequences that fail to match motifs 
4 and 5, and motifs 3 and 5, respectively.
Summary Information
  18 codes involving  5 elements
0 codes involving 4 elements
2 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
51818181818
400000
322110
200000
12345
True Positives
A4D2F4_HUMAN  B9VQ08_SHEEP  IBP1_BOVIN    IBP1_HUMAN    
IBP1_MOUSE IBP1_PIG IBP1_RAT IBP1_SPETR
Q3HWG3_ONCMY Q499C6_XENTR Q5GBG2_ONCTS Q5SVY8_MOUSE
Q6PAX6_XENLA Q6PEY6_HUMAN Q6PN72_CHICK Q8JHX6_DANRE
Q90YJ7_DANRE Q91WV8_MOUSE
True Positive Partials
Codes involving 3 elements
A4K8J2_DANRE Q5XHD1_XENLA
Sequence Titles
A4D2F4_HUMAN Insulin-like growth factor binding protein 1 (Insulin-like growth factor binding protein 1, isoform CRA_a) - Homo sapiens (Human). 
B9VQ08_SHEEP Insulin-like growth factor-binding protein-1 - Ovis aries (Sheep).
IBP1_BOVIN Insulin-like growth factor-binding protein 1 - Bos taurus (Bovine).
IBP1_HUMAN Insulin-like growth factor-binding protein 1 - Homo sapiens (Human).
IBP1_MOUSE Insulin-like growth factor-binding protein 1 - Mus musculus (Mouse).
IBP1_PIG Insulin-like growth factor-binding protein 1 - Sus scrofa (Pig).
IBP1_RAT Insulin-like growth factor-binding protein 1 - Rattus norvegicus (Rat).
IBP1_SPETR Insulin-like growth factor-binding protein 1 - Spermophilus tridecemlineatus (Thirteen-lined ground squirrel).
Q3HWG3_ONCMY Insulin-like growth factor binding protein 1 - Oncorhynchus mykiss (Rainbow trout) (Salmo gairdneri).
Q499C6_XENTR Insulin-like growth factor binding protein 1 - Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
Q5GBG2_ONCTS Insulin-like growth factor binding protein-1 - Oncorhynchus tschawytscha (Chinook salmon) (King salmon).
Q5SVY8_MOUSE Insulin-like growth factor binding protein 1 - Mus musculus (Mouse).
Q6PAX6_XENLA MGC68538 protein - Xenopus laevis (African clawed frog).
Q6PEY6_HUMAN Insulin-like growth factor binding protein 1 - Homo sapiens (Human).
Q6PN72_CHICK Insulin-like growth factor binding protein 1 - Gallus gallus (Chicken).
Q8JHX6_DANRE Insulin-like growth factor binding protein 1 - Danio rerio (Zebrafish) (Brachydanio rerio).
Q90YJ7_DANRE Insulin-like growth factor binding protein 1 - Danio rerio (Zebrafish) (Brachydanio rerio).
Q91WV8_MOUSE Insulin-like growth factor binding protein 1 - Mus musculus (Mouse).

A4K8J2_DANRE Insulin-like growth factor binding protein-1b - Danio rerio (Zebrafish) (Brachydanio rerio).
Q5XHD1_XENLA LOC495033 protein - Xenopus laevis (African clawed frog).
Scan History
SPTR57_40f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
CPPVPASCPELT IBP1_BOVIN 43 43 -
CPPVPSSCPELS IBP1_SPETR 43 43 -
CPPVPSDCPELA Q6PAX6_XENLA 41 41 -
CPPVEPGCPETA Q6PN72_CHICK 45 45 -
CPAVDAGCEEVL Q90YJ7_DANRE 47 47 -
CPSVPNDCPELA Q499C6_XENTR 41 41 -
CPAISPDCKQVL Q3HWG3_ONCMY 47 47 -

Motif 2 width=11
Element Seqn Id St Int Rpt
CRALPGEPRPL IBP1_BOVIN 86 31 -
CRALPGEPRPL IBP1_SPETR 86 31 -
CHPKAGETRPL Q6PAX6_XENLA 84 31 -
CHVPSGETRPL Q6PN72_CHICK 88 31 -
CLPKPGEARPL Q90YJ7_DANRE 90 31 -
CHPKAGESRPL Q499C6_XENTR 84 31 -
CSPRAGDPRPL Q3HWG3_ONCMY 90 31 -

Motif 3 width=13
Element Seqn Id St Int Rpt
RALEISDVKKWKE IBP1_BOVIN 166 69 -
RAREMADIKKWKQ IBP1_SPETR 175 78 -
KARKMLERRKWKE Q6PAX6_XENLA 169 74 -
KAKRISEHKKWKE Q6PN72_CHICK 170 71 -
KAKVNAIRKKLVE Q90YJ7_DANRE 165 64 -
KARKLLERRKWKE Q499C6_XENTR 167 72 -
KAKVNTIRKKLEE Q3HWG3_ONCMY 150 49 -

Motif 4 width=14
Element Seqn Id St Int Rpt
QQKAGDKLYKFYLP IBP1_BOVIN 195 16 -
QQKAGEEIYKFYLP IBP1_SPETR 204 16 -
QQRPGEDVFKFHIP Q6PAX6_XENLA 201 19 -
QQRSGGDIYKFYLP Q6PN72_CHICK 201 18 -
QQKLGDKLTRFYLP Q90YJ7_DANRE 196 18 -
QQRPGEDVFKFHIP Q499C6_XENTR 199 19 -
QQELGEKFTNFYLP Q3HWG3_ONCMY 181 18 -

Motif 5 width=12
Element Seqn Id St Int Rpt
GKRILGSVAVRG IBP1_BOVIN 240 31 -
GRRIPGSLEIRG IBP1_SPETR 249 31 -
GKKIPGSPENRG Q6PAX6_XENLA 246 31 -
GIKIPGSPEVKG Q6PN72_CHICK 246 31 -
GKKIPGSSDLPA Q90YJ7_DANRE 241 31 -
GKRIPGSPENRG Q499C6_XENTR 244 31 -
GKKILGSNYLPG Q3HWG3_ONCMY 226 31 -
Final Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
CPPVPASCPEIS IBP1_RAT 43 43 -
CPPVPASCPEIS IBP1_MOUSE 43 43 -
CPPVPASCPEIS Q91WV8_MOUSE 43 43 -
CPPVPASCPEIS Q5SVY8_MOUSE 43 43 -
CPPVPASCPELT B9VQ08_SHEEP 43 43 -
CPPVPASCPEAT IBP1_PIG 43 43 -
CPPVPASCPELT IBP1_BOVIN 43 43 -
CPPVPSSCPELS IBP1_SPETR 43 43 -
CPPVSASCSEVT A4D2F4_HUMAN 41 41 -
CPPVSASCSEVT Q6PEY6_HUMAN 41 41 -
CPPVSASCSEVT IBP1_HUMAN 41 41 -
CPPVPSDCPELA Q6PAX6_XENLA 41 41 -
CPPVEPGCPETA Q6PN72_CHICK 45 45 -
CPAVDAGCEEVL Q8JHX6_DANRE 47 47 -
CPAVDAGCEEVL Q90YJ7_DANRE 47 47 -
CPSVPNDCPELA Q499C6_XENTR 41 41 -
CPAISPDCKQVL Q5GBG2_ONCTS 47 47 -
CPAISPDCKQVL Q3HWG3_ONCMY 47 47 -

Motif 2 width=11
Element Seqn Id St Int Rpt
CRALPGEPRPL IBP1_RAT 86 31 -
CRALPGEPRPL IBP1_MOUSE 86 31 -
CRALPGEPRPL Q91WV8_MOUSE 86 31 -
CRALPGEPRPL Q5SVY8_MOUSE 86 31 -
CRALPGEPRPL B9VQ08_SHEEP 86 31 -
CRALPGEPRPL IBP1_PIG 85 30 -
CRALPGEPRPL IBP1_BOVIN 86 31 -
CRALPGEPRPL IBP1_SPETR 86 31 -
CRALPGEQQPL A4D2F4_HUMAN 84 31 -
CRALPGEQQPL Q6PEY6_HUMAN 84 31 -
CRALPGEQQPL IBP1_HUMAN 84 31 -
CHPKAGETRPL Q6PAX6_XENLA 84 31 -
CHVPSGETRPL Q6PN72_CHICK 88 31 -
CLPKPGEARPL Q8JHX6_DANRE 90 31 -
CLPKPGEARPL Q90YJ7_DANRE 90 31 -
CHPKAGESRPL Q499C6_XENTR 84 31 -
CSPRAGDPRPL Q5GBG2_ONCTS 90 31 -
CSPRAGDPRPL Q3HWG3_ONCMY 90 31 -

Motif 3 width=13
Element Seqn Id St Int Rpt
RAREITDLKKWKE IBP1_RAT 175 78 -
RAREIADLKKWKE IBP1_MOUSE 175 78 -
RAREIADLKKWKE Q91WV8_MOUSE 175 78 -
RAREIADLKKWKE Q5SVY8_MOUSE 175 78 -
KALEISDVKKWKE B9VQ08_SHEEP 166 69 -
KALEATDIKKWKE IBP1_PIG 165 69 -
RALEISDVKKWKE IBP1_BOVIN 166 69 -
RAREMADIKKWKQ IBP1_SPETR 175 78 -
KALHVTNIKKWKE A4D2F4_HUMAN 162 67 -
KALHVTNIKKWKE Q6PEY6_HUMAN 162 67 -
KALHVTNIKKWKE IBP1_HUMAN 162 67 -
KARKMLERRKWKE Q6PAX6_XENLA 169 74 -
KAKRISEHKKWKE Q6PN72_CHICK 170 71 -
KAKVNAIRKKLVE Q8JHX6_DANRE 165 64 -
KAKVNAIRKKLVE Q90YJ7_DANRE 165 64 -
KARKLLERRKWKE Q499C6_XENTR 167 72 -
KAKVNTIRKKLVE Q5GBG2_ONCTS 150 49 -
KAKVNTIRKKLEE Q3HWG3_ONCMY 150 49 -

Motif 4 width=14
Element Seqn Id St Int Rpt
QQKAGDEIYKFYLP IBP1_RAT 204 16 -
QQKAGDEIYKFYLP IBP1_MOUSE 204 16 -
QQKAGDEIYKFYLP Q91WV8_MOUSE 204 16 -
QQKAGDEIYKFYLP Q5SVY8_MOUSE 204 16 -
QQKAGDKLYKFYLP B9VQ08_SHEEP 195 16 -
QQKAGDRLYKFYLP IBP1_PIG 194 16 -
QQKAGDKLYKFYLP IBP1_BOVIN 195 16 -
QQKAGEEIYKFYLP IBP1_SPETR 204 16 -
QETSGEEISKFYLP A4D2F4_HUMAN 191 16 -
QETSGEEISKFYLP Q6PEY6_HUMAN 191 16 -
QETSGEEISKFYLP IBP1_HUMAN 191 16 -
QQRPGEDVFKFHIP Q6PAX6_XENLA 201 19 -
QQRSGGDIYKFYLP Q6PN72_CHICK 201 18 -
QQKLGDKLTRFYLP Q8JHX6_DANRE 196 18 -
QQKLGDKLTRFYLP Q90YJ7_DANRE 196 18 -
QQRPGEDVFKFHIP Q499C6_XENTR 199 19 -
QQELGEKFTNFYLP Q5GBG2_ONCTS 181 18 -
QQELGEKFTNFYLP Q3HWG3_ONCMY 181 18 -

Motif 5 width=12
Element Seqn Id St Int Rpt
GKKIPGSLETRG IBP1_RAT 249 31 -
GKKIPGSLETRG IBP1_MOUSE 249 31 -
GKKIPGSLETRG Q91WV8_MOUSE 249 31 -
GKKIPGSLETRG Q5SVY8_MOUSE 249 31 -
GKRILGSVAIRG B9VQ08_SHEEP 240 31 -
GKKILGSTAVRG IBP1_PIG 239 31 -
GKRILGSVAVRG IBP1_BOVIN 240 31 -
GRRIPGSLEIRG IBP1_SPETR 249 31 -
GKRIPGSPEIRG A4D2F4_HUMAN 236 31 -
GKRIPGSPEIRG Q6PEY6_HUMAN 236 31 -
GKRIPGSPEIRG IBP1_HUMAN 236 31 -
GKKIPGSPENRG Q6PAX6_XENLA 246 31 -
GIKIPGSPEVKG Q6PN72_CHICK 246 31 -
GKKIPGSSDLPA Q8JHX6_DANRE 241 31 -
GKKIPGSSDLPA Q90YJ7_DANRE 241 31 -
GKRIPGSPENRG Q499C6_XENTR 244 31 -
GKKILGSNYLPG Q5GBG2_ONCTS 226 31 -
GKKILGSNYLPG Q3HWG3_ONCMY 226 31 -