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Insulin-like growth factor binding protein 3
Symbols IGFBP3 ; BP-53; IBP3
External IDs OMIM146732 MGI96438 HomoloGene500 ChEMBL: 3997 GeneCards: IGFBP3 Gene
RNA expression pattern
PBB GE IGFBP3 212143 s at tn.png
PBB GE IGFBP3 210095 s at tn.png
More reference expression data
Species Human Mouse
Entrez 3486 16009
Ensembl ENSG00000146674 ENSMUSG00000020427
UniProt P17936 P47878
RefSeq (mRNA) NM_000598 NM_008343
RefSeq (protein) NP_000589 NP_032369
Location (UCSC) Chr 7:
45.95 – 45.96 Mb
Chr 11:
7.21 – 7.21 Mb
PubMed search [1] [2]

Insulin-like growth factor-binding protein 3, also known as IGFBP3, is a protein that, in humans, is encoded by the IGFBP3 gene.[1][2]


This gene is a member of the insulin-like growth factor-binding protein (IGFBP) family and encodes a protein with an IGFBP domain and a thyroglobulin type-I domain. The protein forms a ternary complex with insulin-like growth factor acid-labile subunit (IGFALS) and either insulin-like growth factor (IGF) I or II. In this form, it circulates in the plasma, prolonging the half-life of IGFs and altering their interaction with cell surface receptors. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.[2]

Clinical significance[edit]

IGFBP3 protein levels decrease during the progression of prostate cancer from benign to metastatic disease.[3] Although, production of the protein does not cease completely. IGFBP3 is still made (at a lower level) by prostate cancer cells and secreted into the surrounding environment. However, instead of the full length, functional protein, IGFBP3 is found to be cleaved.[4] This prevents IGFBP3 from binding and sequestering IGFs and the growth factors are free to bind the IGF-1R and promote cell survival.

See also[edit]


IGFBP3 has been shown to interact with:


  1. ^ Cubbage ML, Suwanichkul A, Powell DR (July 1990). "Insulin-like growth factor binding protein-3. Organization of the human chromosomal gene and demonstration of promoter activity". J. Biol. Chem. 265 (21): 12642–9. PMID 1695633. 
  2. ^ a b "Entrez Gene: IGFBP3 insulin-like growth factor binding protein 3". 
  3. ^ Miyake H, Pollak M, Gleave ME (June 2000). "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". Cancer Res. 60 (11): 3058–64. PMID 10850457.  For IGFBP-3 it refers to Figueroa, JA; De Raad, S; Tadlock, L; Speights, VO; Rinehart, JJ (1998). "Differential expression of insulin-like growth factor binding proteins in high versus low Gleason score prostate cancer". J. Urol. 159 (4): 1379–83. doi:10.1016/S0022-5347(01)63620-6. PMID 9507888. 
  4. ^ Birnbaum RS, Ware JL, Plymate SR (June 1994). "Insulin-like growth factor-binding protein-3 expression and secretion by cultures of human prostate epithelial cells and stromal fibroblasts". J. Endocrinol. 141 (3): 535–40. doi:10.1677/joe.0.1410535. PMID 7520932. 
  5. ^ Shi Z, Xu W, Loechel F, Wewer UM, Murphy LJ (2000). "ADAM 12, a disintegrin metalloprotease, interacts with insulin-like growth factor-binding protein-3". J. Biol. Chem. 275 (24): 18574–80. doi:10.1074/jbc.M002172200. PMID 10849447. 
  6. ^ Loechel F, Fox JW, Murphy G, Albrechtsen R, Wewer UM (2000). "ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3". Biochem. Biophys. Res. Commun. 278 (3): 511–5. doi:10.1006/bbrc.2000.3835. PMID 11095942. 
  7. ^ Mochizuki S, Shimoda M, Shiomi T, Fujii Y, Okada Y (2004). "ADAM28 is activated by MMP-7 (matrilysin-1) and cleaves insulin-like growth factor binding protein-3". Biochem. Biophys. Res. Commun. 315 (1): 79–84. doi:10.1016/j.bbrc.2004.01.022. PMID 15013428. 
  8. ^ a b Liu B, Weinzimer SA, Gibson TB, Mascarenhas D, Cohen P (2003). "Type Ialpha collagen is an IGFBP-3 binding protein". Growth Horm. IGF Res. 13 (2–3): 89–97. doi:10.1016/S1096-6374(03)00007-8. PMID 12735930. 
  9. ^ Martin JA, Miller BA, Scherb MB, Lembke LA, Buckwalter JA (2002). "Co-localization of insulin-like growth factor binding protein 3 and fibronectin in human articular cartilage". Osteoarthr. Cartil. 10 (7): 556–63. doi:10.1053/joca.2002.0791. PMID 12127836. 
  10. ^ Gui Y, Murphy LJ (2001). "Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) binds to fibronectin (FN): demonstration of IGF-I/IGFBP-3/fn ternary complexes in human plasma". J. Clin. Endocrinol. Metab. 86 (5): 2104–10. doi:10.1210/jcem.86.5.7472. PMID 11344214. 
  11. ^ a b c Twigg SM, Baxter RC (1998). "Insulin-like growth factor (IGF)-binding protein 5 forms an alternative ternary complex with IGFs and the acid-labile subunit". J. Biol. Chem. 273 (11): 6074–9. doi:10.1074/jbc.273.11.6074. PMID 9497324. 
  12. ^ a b c Firth SM, Ganeshprasad U, Baxter RC (1998). "Structural determinants of ligand and cell surface binding of insulin-like growth factor-binding protein-3". J. Biol. Chem. 273 (5): 2631–8. doi:10.1074/jbc.273.5.2631. PMID 9446566. 
  13. ^ Ueki I, Ooi GT, Tremblay ML, Hurst KR, Bach LA, Boisclair YR (2000). "Inactivation of the acid labile subunit gene in mice results in mild retardation of postnatal growth despite profound disruptions in the circulating insulin-like growth factor system". Proc. Natl. Acad. Sci. U.S.A. 97 (12): 6868–73. doi:10.1073/pnas.120172697. PMC 18767. PMID 10823924. 
  14. ^ a b Buckway CK, Wilson EM, Ahlsén M, Bang P, Oh Y, Rosenfeld RG (2001). "Mutation of three critical amino acids of the N-terminal domain of IGF-binding protein-3 essential for high affinity IGF binding". J. Clin. Endocrinol. Metab. 86 (10): 4943–50. doi:10.1210/jcem.86.10.7936. PMID 11600567. 
  15. ^ Cohen P, Graves HC, Peehl DM, Kamarei M, Giudice LC, Rosenfeld RG (1992). "Prostate-specific antigen (PSA) is an insulin-like growth factor binding protein-3 protease found in seminal plasma". J. Clin. Endocrinol. Metab. 75 (4): 1046–53. doi:10.1210/jcem.75.4.1383255. PMID 1383255. 
  16. ^ Storch S, Kübler B, Höning S, Ackmann M, Zapf J, Blum W, Braulke T (2001). "Transferrin binds insulin-like growth factors and affects binding properties of insulin-like growth factor binding protein-3". FEBS Lett. 509 (3): 395–8. doi:10.1016/S0014-5793(01)03204-5. PMID 11749962. 
  17. ^ Campbell PG, Durham SK, Suwanichkul A, Hayes JD, Powell DR (1998). "Plasminogen binds the heparin-binding domain of insulin-like growth factor-binding protein-3". Am. J. Physiol. 275 (2 Pt 1): E321–31. PMID 9688635. 
  18. ^ Liu B, Lee HY, Weinzimer SA, Powell DR, Clifford JL, Kurie JM, Cohen P (2000). "Direct functional interactions between insulin-like growth factor-binding protein-3 and retinoid X receptor-alpha regulate transcriptional signaling and apoptosis". J. Biol. Chem. 275 (43): 33607–13. doi:10.1074/jbc.M002547200. PMID 10874028. 
  19. ^ Weinzimer SA, Gibson TB, Collett-Solberg PF, Khare A, Liu B, Cohen P (2001). "Transferrin is an insulin-like growth factor-binding protein-3 binding protein". J. Clin. Endocrinol. Metab. 86 (4): 1806–13. doi:10.1210/jcem.86.4.7380. PMID 11297622. 

Further reading[edit]

  • Rajaram S, Baylink DJ, Mohan S (1998). "Insulin-like growth factor-binding proteins in serum and other biological fluids: regulation and functions". Endocr. Rev. 18 (6): 801–31. doi:10.1210/er.18.6.801. PMID 9408744. 
  • Ferry RJ, Cerri RW, Cohen P (1999). "Insulin-like growth factor binding proteins: new proteins, new functions". Horm. Res. 51 (2): 53–67. doi:10.1159/000023315. PMID 10352394. 
  • Schedlich LJ, Graham LD (2002). "Role of insulin-like growth factor binding protein-3 in breast cancer cell growth". Microsc. Res. Tech. 59 (1): 12–22. doi:10.1002/jemt.10173. PMID 12242693. 
  • Adham IM, Agoulnik AI (2005). "Insulin-like 3 signalling in testicular descent". Int. J. Androl. 27 (5): 257–65. doi:10.1111/j.1365-2605.2004.00481.x. PMID 15379965.