IGFBP4

IGFBP4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1WQJ, 2DSP, 2DSQ, 2DSR
Identifiers
Aliases	IGFBP4, BP-4, HT29-IGFBP, IBP4, IGFBP-4, insulin like growth factor binding protein 4
External IDs	OMIM: 146733 MGI: 96439 HomoloGene: 1192 GeneCards: IGFBP4
Gene location (Human) Chr. Chromosome 17 (human) Band 17q21.2 Start 40,443,450 bp End 40,457,725 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11|11 D Start 98,932,070 bp End 98,945,218 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in stromal cell of endometrium left uterine tube right lobe of liver right lobe of thyroid gland canal of the cervix smooth muscle tissue gallbladder left lobe of thyroid gland pericardium gastric mucosa Top expressed in external carotid artery internal carotid artery calvaria aortic valve ascending aorta molar atrium left lobe of liver carotid body vas deferens More reference expression data BioGPS More reference expression data
Gene ontology Molecular function insulin-like growth factor I binding insulin-like growth factor II binding signaling receptor binding insulin-like growth factor binding growth factor binding protein binding Cellular component extracellular region extracellular space endoplasmic reticulum lumen Biological process skeletal system development regulation of growth DNA metabolic process regulation of insulin-like growth factor receptor signaling pathway regulation of glucose metabolic process cell population proliferation inflammatory response positive regulation of insulin-like growth factor receptor signaling pathway type B pancreatic cell proliferation negative regulation of canonical Wnt signaling pathway regulation of cell growth signal transduction positive regulation of MAPK cascade post-translational protein modification Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3487 16010 Ensembl ENSG00000141753 ENSMUSG00000017493 UniProt P22692 P47879 RefSeq (mRNA) NM_001552 NM_010517 RefSeq (protein) NP_001543 NP_034647 Location (UCSC) Chr 17: 40.44 – 40.46 Mb Chr 11: 98.93 – 98.95 Mb PubMed search
Wikidata
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Insulin-like growth factor-binding protein 4 is a protein that in humans is encoded by the IGFBP4 gene.

Function

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 binds both insulin-like growth factors (IGFs) I and II and circulates in the plasma in both glycosylated and non-glycosylated forms. Binding of this protein prolongs the half-life of the IGFs and alters their interaction with cell surface receptors. IGFBP-4 is a unique protein and it consistently inhibits several cancer cells in vivo and in vitro. Its inhibitory action has been shown in vivo in prostate and colon. It is secreted by all colon cancer cells.

Clinical significance

The protein itself does not prevent the formation of cancer. However it may reduce the growth of cancer and act as an apoptotic factor.

Interactions

IGFBP4 has been shown to interact with Insulin-like growth factor 1 and 2.

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/edrv.18.6.0321. PMID 9408744.
• Zhou R, Diehl D, Hoeflich A, Lahm H, Wolf E (2003). "IGF-binding protein-4: biochemical characteristics and functional consequences". J. Endocrinol. 178 (2): 177–93. doi:10.1677/joe.0.1780177. PMID 12904166.
• Durai R, Davies M, Yang W, Yang SY, Seifalian A, Goldspink G, Winslet M (2006). "Biology of insulin-like growth factor binding protein-4 and its role in cancer (review)". Int. J. Oncol. 28 (6): 1317–25. doi:10.3892/ijo.28.6.1317. PMID 16685432.
• Giudice LC, Dsupin BA, Irwin JC, Eckert RL (1992). "Identification of insulin-like growth factor binding proteins in human oviduct". Fertil. Steril. 57 (2): 294–301. doi:10.1016/S0015-0282(16)54833-X. PMID 1370941.
• Bajalica S, Allander SV, Ehrenborg E, Brøndum-Nielsen K, Luthman H, Larsson C (1992). "Localization of the human insulin-like growth-factor-binding protein 4 gene to chromosomal region 17q12-21.1". Hum. Genet. 89 (2): 234–6. doi:10.1007/BF00217129. PMID 1375185. S2CID 22341448.
• Kiefer MC, Schmid C, Waldvogel M, Schläpfer I, Futo E, Masiarz FR, Green K, Barr PJ, Zapf J (1992). "Characterization of recombinant human insulin-like growth factor binding proteins 4, 5, and 6 produced in yeast". J. Biol. Chem. 267 (18): 12692–9. doi:10.1016/S0021-9258(18)42332-0. PMID 1377672.
• Zhou J, Bondy C (1992). "Insulin-like growth factor-II and its binding proteins in placental development". Endocrinology. 131 (3): 1230–40. doi:10.1210/en.131.3.1230. PMID 1380437.
• Kiefer MC, Masiarz FR, Bauer DM, Zapf J (1991). "Identification and molecular cloning of two new 30-kDa insulin-like growth factor binding proteins isolated from adult human serum". J. Biol. Chem. 266 (14): 9043–9. doi:10.1016/S0021-9258(18)31549-7. PMID 1709161.
• Culouscou JM, Shoyab M (1991). "Purification of a colon cancer cell growth inhibitor and its identification as an insulin-like growth factor binding protein". Cancer Res. 51 (11): 2813–9. PMID 1709585.
• Tonin P, Ehrenborg E, Lenoir G, Feunteun J, Lynch H, Morgan K, Zazzi H, Vivier A, Pollak M, Huynh H (1994). "The human insulin-like growth factor-binding protein 4 gene maps to chromosome region 17q12-q21.1 and is close to the gene for hereditary breast-ovarian cancer". Genomics. 18 (2): 414–7. doi:10.1006/geno.1993.1487. PMID 7507078.
• Ilvesmäki V, Blum WF, Voutilainen R (1994). "Insulin-like growth factor binding proteins in the human adrenal gland". Mol. Cell. Endocrinol. 97 (1–2): 71–9. doi:10.1016/0303-7207(93)90212-3. PMID 7511544. S2CID 22503525.
• Zhou J, Bondy C (1993). "Anatomy of the human ovarian insulin-like growth factor system". Biol. Reprod. 48 (3): 467–82. doi:10.1095/biolreprod48.3.467. PMID 7680905.
• Conover CA, Clarkson JT, Bale LK (1993). "Phorbol ester tumor promoters regulate insulin-like growth factor-binding protein-4 proteolysis". Endocrinology. 133 (3): 1347–51. doi:10.1210/endo.133.3.7689953. PMID 7689953.
• Fridell RA, Harding LS, Bogerd HP, Cullen BR (1995). "Identification of a novel human zinc finger protein that specifically interacts with the activation domain of lentiviral Tat proteins". Virology. 209 (2): 347–57. doi:10.1006/viro.1995.1266. PMID 7778269.
• Batch JA, Mercuri FA, Werther GA (1996). "Identification and localization of insulin-like growth factor-binding protein (IGFBP) messenger RNAs in human hair follicle dermal papilla". J. Invest. Dermatol. 106 (3): 471–5. doi:10.1111/1523-1747.ep12343649. PMID 8648179.
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Han VK, Matsell DG, Delhanty PJ, Hill DJ, Shimasaki S, Nygard K (1996). "IGF-binding protein mRNAs in the human fetus: tissue and cellular distribution of developmental expression". Horm. Res. 45 (3–5): 160–6. doi:10.1159/000184780. PMID 8964576.
• Di Battista JA, Doré S, Morin N, He Y, Pelletier JP, Martel-Pelletier J (1997). "Prostaglandin E2 stimulates insulin-like growth factor binding protein-4 expression and synthesis in cultured human articular chondrocytes: possible mediation by Ca(++)-calmodulin regulated processes". J. Cell. Biochem. 65 (3): 408–19. doi:10.1002/(SICI)1097-4644(19970601)65:3<408::AID-JCB10>3.0.CO;2-B. PMID 9138096. S2CID 9142234.