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Insulin-like growth factor binding protein 3
Symbols IGFBP3; BP-53; IBP3
External IDs OMIM146732 MGI96438 HomoloGene500 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 Q3UR87
RefSeq (mRNA) NM_000598 XM_001001532
RefSeq (protein) NP_000589 XP_001001532
Location (UCSC) Chr 7:
45.92 - 45.93 Mb
Chr 11:
7.11 - 7.11 Mb
PubMed search [1] [2]

Insulin-like growth factor binding protein 3, also known as IGFBP3, is a protein which 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

IGFBP3 protein levels decrease during the progression of prostate cancer from benign prostatic hyperplasia (BPH) to its metastatic form.[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


IGFBP3 has been shown to interact with Collagen, type I, alpha 1,[5] IGFALS,[6][7] Insulin-like growth factor 1,[5][8][9][10][6][7] Insulin-like growth factor 2,[11][9][6][7] ADAM12,[12][13] Transferrin,[14] Fibronectin,[15][16] Plasmin[17] and Retinoid X receptor alpha.[18]


  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.  
  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. PMID 7520932.  
  5. ^ a b Liu, Bingrong; Weinzimer Stuart A, Gibson Tara Beers, Mascarenhas Desmond, Cohen Pinchas. "Type Ialpha collagen is an IGFBP-3 binding protein". Growth Horm. IGF Res. (Scotland) 13 (2-3): 89–97. ISSN 1096-6374. PMID 12735930.  
  6. ^ a b c Twigg, S M; Baxter R C (Mar. 1998). "Insulin-like growth factor (IGF)-binding protein 5 forms an alternative ternary complex with IGFs and the acid-labile subunit". J. Biol. Chem. (UNITED STATES) 273 (11): 6074–9. ISSN 0021-9258. PMID 9497324.  
  7. ^ a b c Firth, S M; Ganeshprasad U, Baxter R C (Jan. 1998). "Structural determinants of ligand and cell surface binding of insulin-like growth factor-binding protein-3". J. Biol. Chem. (UNITED STATES) 273 (5): 2631–8. ISSN 0021-9258. PMID 9446566.  
  8. ^ Ueki, I; Ooi G T, Tremblay M L, Hurst K R, Bach L A, Boisclair Y R (Jun. 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. (UNITED STATES) 97 (12): 6868–73. doi:10.1073/pnas.120172697. ISSN 0027-8424. PMID 10823924.  
  9. ^ a b Buckway, C K; Wilson E M, Ahlsén M, Bang P, Oh Y, Rosenfeld R G (Oct. 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. (United States) 86 (10): 4943–50. ISSN 0021-972X. PMID 11600567.  
  10. ^ Cohen, P; Graves H C, Peehl D M, Kamarei M, Giudice L C, Rosenfeld R G (Oct. 1992). "Prostate-specific antigen (PSA) is an insulin-like growth factor binding protein-3 protease found in seminal plasma". J. Clin. Endocrinol. Metab. (UNITED STATES) 75 (4): 1046–53. ISSN 0021-972X. PMID 1383255.  
  11. ^ Storch, S; Kübler B, Höning S, Ackmann M, Zapf J, Blum W, Braulke T (Dec. 2001). "Transferrin binds insulin-like growth factors and affects binding properties of insulin-like growth factor binding protein-3". FEBS Lett. (Netherlands) 509 (3): 395–8. ISSN 0014-5793. PMID 11749962.  
  12. ^ Shi, Z; Xu W, Loechel F, Wewer U M, Murphy L J (Jun. 2000). "ADAM 12, a disintegrin metalloprotease, interacts with insulin-like growth factor-binding protein-3". J. Biol. Chem. (UNITED STATES) 275 (24): 18574–80. doi:10.1074/jbc.M002172200. ISSN 0021-9258. PMID 10849447.  
  13. ^ Loechel, F; Fox J W, Murphy G, Albrechtsen R, Wewer U M (Nov. 2000). "ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3". Biochem. Biophys. Res. Commun. (UNITED STATES) 278 (3): 511–5. doi:10.1006/bbrc.2000.3835. ISSN 0006-291X. PMID 11095942.  
  14. ^ Weinzimer, S A; Gibson T B, Collett-Solberg P F, Khare A, Liu B, Cohen P (Apr. 2001). "Transferrin is an insulin-like growth factor-binding protein-3 binding protein". J. Clin. Endocrinol. Metab. (United States) 86 (4): 1806–13. ISSN 0021-972X. PMID 11297622.  
  15. ^ Martin, J A; Miller B A, Scherb M B, Lembke L A, Buckwalter J A (Jul. 2002). "Co-localization of insulin-like growth factor binding protein 3 and fibronectin in human articular cartilage". Osteoarthr. Cartil. (England) 10 (7): 556–63. ISSN 1063-4584. PMID 12127836.  
  16. ^ Gui, Y; Murphy L J (May. 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. (United States) 86 (5): 2104–10. ISSN 0021-972X. PMID 11344214.  
  17. ^ Campbell, P G; Durham S K, Suwanichkul A, Hayes J D, Powell D R (Aug. 1998). "Plasminogen binds the heparin-binding domain of insulin-like growth factor-binding protein-3". Am. J. Physiol. (UNITED STATES) 275 (2 Pt 1): E321-31. ISSN 0002-9513. PMID 9688635.  
  18. ^ Liu, B; Lee H Y, Weinzimer S A, Powell D R, Clifford J L, Kurie J M, Cohen P (Oct. 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. (UNITED STATES) 275 (43): 33607–13. doi:10.1074/jbc.M002547200. ISSN 0021-9258. PMID 10874028.  

Further reading

  • 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.  


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