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Gene Review

IGFBP5  -  insulin-like growth factor binding protein 5

Homo sapiens

Synonyms: IBP-5, IBP5, IGF-binding protein 5, IGFBP-5, Insulin-like growth factor-binding protein 5
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Disease relevance of IGFBP5


High impact information on IGFBP5


Chemical compound and disease context of IGFBP5


Biological context of IGFBP5

  • Forty-nine sibships (2-4 affected siblings per sibship) with RA were genotyped with microsatellite markers covering an 11.2 cM interval in the IGFBP5/IDDM13 region [11].
  • Furthermore, the addition of exogenous IGFBP-5 alone increased apoptosis [12].
  • Because IGFBP-5 contains a nuclear localization sequence that mediates transport of IGFBP-5 into the nucleus, we propose that IGFBP-5 interacts with nuclear proteins to affect transcription of genes involved in bone formation [3].
  • Insulin-like growth factor-binding protein 5 (IGFBP-5) is a secreted protein that binds to insulin-like growth factors (IGFs) and modulates IGF actions on cell proliferation, differentiation, survival, and motility [13].
  • Using a series of deletion mutants, the transactivation domain of IGFBP-5 was mapped to its N-terminal region [14].

Anatomical context of IGFBP5

  • Furthermore, when IGFBP-5 was present in cell culture substrata, it potentiated the growth stimulatory effects of IGF-I on fibroblasts [15].
  • The role of FHL2 as an intracellular mediator of the effects of IGFBP-5 and other osteoregulatory agents in osteoblasts will need to be verified in future studies [3].
  • The present study determined whether IGFBP-5 exerts direct effects on growth in human intestinal smooth muscle cells and identified the intracellular signaling pathways involved [16].
  • IGFBP-5 is also found in the nuclei of cultured cells and has transactivation activity [14].
  • Increased collagen deposition, denser dermal connective tissue, and increased collagen bundle thickness were observed in IGFBP-5-overexpressing mice [17].

Associations of IGFBP5 with chemical compounds


Physical interactions of IGFBP5


Enzymatic interactions of IGFBP5

  • We showed that PAPP-A2 specifically cleaved IGFBP-5 at one site, between Ser-143 and Lys-144 [26].

Regulatory relationships of IGFBP5


Other interactions of IGFBP5

  • The next two linkages are Cys7-Cys9 and Cys8-Cys10, which are analogous to those previously determined for IGFBP-3 and IGFBP-5 [32].
  • IGFBP-4 and IGFBP-5 mRNA were expressed additionally in low abundance in the chorionic mesoderm [33].
  • Moderate expression of the IGFBP-4 and IGFBP-5 genes was seen in all cell types, including stromal cells, but no IGFBP-6 mRNA was detected [34].
  • Histologic parameters of bone formation showed significant positive correlations with serum levels of IGF-I, IGF-II, and IGFBP-5 [35].
  • To examine the functional significance of IGFs binding to VN, cell migration in MCF7 cells was measured and found to be enhanced when VN was prebound to IGF-I in the presence of IGFBP-5 [36].

Analytical, diagnostic and therapeutic context of IGFBP5


  1. Free insulin-like growth factor (IGF)-I and IGF binding proteins 2, 5, and 6 in spinal motor neurons in amyotrophic lateral sclerosis. Wilczak, N., de Vos, R.A., De Keyser, J. Lancet (2003) [Pubmed]
  2. Overexpression of IGFBP5, but not IGFBP3, correlates with the histologic grade of human diffuse glioma: a tissue microarray and immunohistochemical study. Wang, H., Wang, H., Zhang, W., Fuller, G.N. Technol. Cancer Res. Treat. (2006) [Pubmed]
  3. Insulin-like growth factor-binding protein 5 (IGFBP-5) interacts with a four and a half LIM protein 2 (FHL2). Amaar, Y.G., Thompson, G.R., Linkhart, T.A., Chen, S.T., Baylink, D.J., Mohan, S. J. Biol. Chem. (2002) [Pubmed]
  4. Evidence that IGF-binding protein-5 functions as a growth factor. Miyakoshi, N., Richman, C., Kasukawa, Y., Linkhart, T.A., Baylink, D.J., Mohan, S. J. Clin. Invest. (2001) [Pubmed]
  5. Protease-resistant form of insulin-like growth factor-binding protein 5 is an inhibitor of insulin-like growth factor-I actions on porcine smooth muscle cells in culture. Imai, Y., Busby, W.H., Smith, C.E., Clarke, J.B., Garmong, A.J., Horwitz, G.D., Rees, C., Clemmons, D.R. J. Clin. Invest. (1997) [Pubmed]
  6. Antiproliferative action of vitamin D-related compounds and insulin-like growth factor-binding protein 5 accumulation. Rozen, F., Yang, X.F., Huynh, H., Pollak, M. J. Natl. Cancer Inst. (1997) [Pubmed]
  7. Castration-induced up-regulation of insulin-like growth factor binding protein-5 potentiates insulin-like growth factor-I activity and accelerates progression to androgen independence in prostate cancer models. Miyake, H., Pollak, M., Gleave, M.E. Cancer Res. (2000) [Pubmed]
  8. C/EBP alpha and beta mimic retinoic acid activation of IGFBP-5 in neuroblastoma cells by a mechanism independent from binding to their site. Cesi, V., Giuffrida, M.L., Vitali, R., Tanno, B., Mancini, C., Calabretta, B., Raschellà, G. Exp. Cell Res. (2005) [Pubmed]
  9. Progesterone stimulation of human insulin-like growth factor-binding protein-5 gene transcription in human osteoblasts is mediated by a CACCC sequence in the proximal promoter. Boonyaratanakornkit, V., Strong, D.D., Mohan, S., Baylink, D.J., Beck, C.A., Linkhart, T.A. J. Biol. Chem. (1999) [Pubmed]
  10. Signalling pathways involved in the direct effects of IGFBP-5 on breast epithelial cell attachment and survival. McCaig, C., Perks, C.M., Holly, J.M. J. Cell. Biochem. (2002) [Pubmed]
  11. The IDDM13 region containing the insulin-like growth factor binding protein-5 (IGFBP5) gene on chromosome 2q33-q36 and the genetic susceptibility to rheumatoid arthritis. Slager, S.L., Carleu, L., Chung, W.K., Jackson, T., Winchester, R.J., Hodge, S.E., Gulko, P.S. Genes Immun. (2002) [Pubmed]
  12. Paradoxical actions of endogenous and exogenous insulin-like growth factor-binding protein-5 revealed by RNA interference analysis. Yin, P., Xu, Q., Duan, C. J. Biol. Chem. (2004) [Pubmed]
  13. Fibronectin binds insulin-like growth factor-binding protein 5 and abolishes Its ligand-dependent action on cell migration. Xu, Q., Yan, B., Li, S., Duan, C. J. Biol. Chem. (2004) [Pubmed]
  14. Several acidic amino acids in the N-domain of insulin-like growth factor-binding protein-5 are important for its transactivation activity. Zhao, Y., Yin, P., Bach, L.A., Duan, C. J. Biol. Chem. (2006) [Pubmed]
  15. Extracellular matrix contains insulin-like growth factor binding protein-5: potentiation of the effects of IGF-I. Jones, J.I., Gockerman, A., Busby, W.H., Camacho-Hubner, C., Clemmons, D.R. J. Cell Biol. (1993) [Pubmed]
  16. Insulin-like growth factor-binding protein-5 (IGFBP-5) stimulates growth and IGF-I secretion in human intestinal smooth muscle by Ras-dependent activation of p38 MAP kinase and Erk1/2 pathways. Kuemmerle, J.F., Zhou, H. J. Biol. Chem. (2002) [Pubmed]
  17. Insulin-like growth factor binding protein 5 induces skin fibrosis: A novel murine model for dermal fibrosis. Yasuoka, H., Jukic, D.M., Zhou, Z., Choi, A.M., Feghali-Bostwick, C.A. Arthritis Rheum. (2006) [Pubmed]
  18. Anatomy of the human ovarian insulin-like growth factor system. Zhou, J., Bondy, C. Biol. Reprod. (1993) [Pubmed]
  19. Diabetic microangiopathy: IGFBP control endothelial cell growth by a common mechanism in spite of their species specificity and tissue peculiarity. Giannini, S., Cresci, B., Manuelli, C., Pala, L., Rotella, C.M. J. Endocrinol. Invest. (2006) [Pubmed]
  20. Insulin-like growth factor-binding protein 5 complexes with the acid-labile subunit. Role of the carboxyl-terminal domain. Twigg, S.M., Kiefer, M.C., Zapf, J., Baxter, R.C. J. Biol. Chem. (1998) [Pubmed]
  21. The in vivo phosphorylation and glycosylation of human insulin-like growth factor-binding protein-5. Graham, M.E., Kilby, D.M., Firth, S.M., Robinson, P.J., Baxter, R.C. Mol. Cell Proteomics (2007) [Pubmed]
  22. ADAM-12 (meltrin alpha) is involved in chondrocyte proliferation via cleavage of insulin-like growth factor binding protein 5 in osteoarthritic cartilage. Okada, A., Mochizuki, S., Yatabe, T., Kimura, T., Shiomi, T., Fujita, Y., Matsumoto, H., Sehara-Fujisawa, A., Iwamoto, Y., Okada, Y. Arthritis Rheum. (2008) [Pubmed]
  23. Vitronectin binding to IGF binding protein-5 (IGFBP-5) alters IGFBP-5 modulation of IGF-I actions. Nam, T., Moralez, A., Clemmons, D. Endocrinology (2002) [Pubmed]
  24. Insulin-like growth factor binding protein-5 binds to plasminogen activator inhibitor-I. Nam, T.J., Busby, W., Clemmons, D.R. Endocrinology (1997) [Pubmed]
  25. Insulin-like growth factor binding protein-5 (IGFBP-5) interacts with thrombospondin-1 to induce negative regulatory effects on IGF-I actions. Moralez, A.M., Maile, L.A., Clarke, J., Busby, W.H., Clemmons, D.R. J. Cell. Physiol. (2005) [Pubmed]
  26. Pregnancy-associated plasma protein-A2 (PAPP-A2), a novel insulin-like growth factor-binding protein-5 proteinase. Overgaard, M.T., Boldt, H.B., Laursen, L.S., Sottrup-Jensen, L., Conover, C.A., Oxvig, C. J. Biol. Chem. (2001) [Pubmed]
  27. Ras-association domain family 1 protein, RASSF1C, is an IGFBP-5 binding partner and a potential regulator of osteoblast cell proliferation. Amaar, Y.G., Baylink, D.J., Mohan, S. J. Bone Miner. Res. (2005) [Pubmed]
  28. Selection of the dominant follicle and insulin-like growth factor (IGF)-binding proteins: evidence that pregnancy-associated plasma protein A contributes to proteolysis of IGF-binding protein 5 in bovine follicular fluid. Rivera, G.M., Fortune, J.E. Endocrinology (2003) [Pubmed]
  29. Insulin-like growth factor axis abnormalities in prostatic stromal cells from patients with benign prostatic hyperplasia. Cohen, P., Peehl, D.M., Baker, B., Liu, F., Hintz, R.L., Rosenfeld, R.G. J. Clin. Endocrinol. Metab. (1994) [Pubmed]
  30. IGFBP-3 and IGFBP-5 production by human intestinal muscle: reciprocal regulation by endogenous TGF-beta1. Bushman, T.L., Kuemmerle, J.F. Am. J. Physiol. (1998) [Pubmed]
  31. The effect of extracellular matrix proteins on porcine smooth muscle cell insulin-like growth factor (IGF) binding protein-5 synthesis and responsiveness to IGF-I. Zheng, B., Duan, C., Clemmons, D.R. J. Biol. Chem. (1998) [Pubmed]
  32. The N-terminal disulfide linkages of human insulin-like growth factor-binding protein-6 (hIGFBP-6) and hIGFBP-1 are different as determined by mass spectrometry. Neumann, G.M., Bach, L.A. J. Biol. Chem. (1999) [Pubmed]
  33. The expression of insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) genes in the human placenta and membranes: evidence for IGF-IGFBP interactions at the feto-maternal interface. Han, V.K., Bassett, N., Walton, J., Challis, J.R. J. Clin. Endocrinol. Metab. (1996) [Pubmed]
  34. Expression of the genes encoding the insulin-like growth factors (IGF-I and II), the IGF and insulin receptors, and IGF-binding proteins-1-6 and the localization of their gene products in normal and polycystic ovary syndrome ovaries. el-Roeiy, A., Chen, X., Roberts, V.J., Shimasakai, S., Ling, N., LeRoith, D., Roberts, C.T., Yen, S.S. J. Clin. Endocrinol. Metab. (1994) [Pubmed]
  35. Insulin-like growth factor system components in hyperparathyroidism and renal osteodystrophy. Jehle, P.M., Ostertag, A., Schulten, K., Schulz, W., Jehle, D.R., Stracke, S., Fiedler, R., Deuber, H.J., Keller, F., Boehm, B.O., Baylink, D.J., Mohan, S. Kidney Int. (2000) [Pubmed]
  36. Structural and functional evidence for the interaction of insulin-like growth factors (IGFs) and IGF binding proteins with vitronectin. Kricker, J.A., Towne, C.L., Firth, S.M., Herington, A.C., Upton, Z. Endocrinology (2003) [Pubmed]
  37. Identification of insulin-like growth factor-binding protein-3 (IGFBP-3) fragments and IGFBP-5 proteolytic activity in human seminal plasma: a comparison of normal and vasectomized patients. Lee, K.O., Oh, Y., Giudice, L.C., Cohen, P., Peehl, D.M., Rosenfeld, R.G. J. Clin. Endocrinol. Metab. (1994) [Pubmed]
  38. Insulin-like growth factor binding protein-5 expression by human trabecular meshwork. Wirtz, M.K., Xu, H., Rust, K., Alexander, J.P., Acott, T.S. Invest. Ophthalmol. Vis. Sci. (1998) [Pubmed]
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