Alternative titles; symbols
HGNC Approved Gene Symbol: IGFBP2
Cytogenetic location: 2q35 Genomic coordinates (GRCh38): 2:216,632,828-216,664,436 (from NCBI)
Unlike most other peptide hormones, insulin-like growth factors I and II are complexed to specific binding proteins in plasma. Two major classes of IGF-BPs have been identified in man. The quantitatively predominant form in plasma has a molecular weight of about 150 kD. It contains an IGF-binding subunit (IGF-BP53) with an apparent molecular mass of 53 kD. Molecular cloning of this subunit showed a cysteine-rich protein with 264 amino acids (Wood et al., 1988). Comparison of the encoded protein sequence of each exon in IGFBP1 (146730), IGFBP2, and IGFBP3 (146732) shows that the highest amino acid identity (28%) is in exon 1, while the lowest is in exon 2. However, pairwise sequence comparisons demonstrated 50% identity between the protein sequences encoded by exon 4 in IGFBP1 and IGFBP2, whereas their respective identities with IGFBP3 were only 25 and 30%.
By structural analysis, Ehrenborg et al. (1991) showed that the IGFBP2 gene consists of 4 exons with 3 introns of lengths 27.0, 1.0, and 1.9 kb.
Allander et al. (1994) showed that the IGFBP5 gene (146734) is separated from the IGFBP2 gene by approximately 20 to 40 kb of DNA and are in opposite transcriptional orientation.
By somatic cell hybrid analysis and in situ hybridization, Ehrenborg et al. (1991) showed that the IGFBP2 gene is located in region 2q33-q34.
Agarwal et al. (1991) confirmed the assignment to 2q33-qter by Southern blot analysis of DNA from human/rodent cell hybrids. By comparable studies of mouse/rodent somatic cell hybrids, they assigned the homologous gene to mouse chromosome 1 in a region of known conservation of synteny.
Png et al. (2012) demonstrated that endogenous miR126 (611767), a miRNA silenced in a variety of human cancers, non-cell-autonomously regulates endothelial cell recruitment to metastatic breast cancer cells, in vitro and in vivo. It suppresses metastatic endothelial recruitment, metastatic angiogenesis, and metastatic colonization through coordinate targeting of IGFBP2, PITPNC1 (605134), and MERTK (604705), novel proangiogenic genes and biomarkers of human metastasis. Insulin-like growth factor binding protein-2 (IGFBP2) secreted by metastatic cells recruits endothelia by modulating IGF1 (147440)-mediated activation of the IGF type-I receptor (147370) on endothelial cells, whereas c-Mer tyrosine kinase (MERTK) receptor cleaved from metastatic cells promotes endothelial recruitment by competitively antagonizing the binding of its ligand GAS6 (600441) to endothelial MERTK receptors. Coinjection of endothelial cells with breast cancer cells non-cell-autonomously rescued their miR126-induced metastatic defect, revealing a novel and important role for endothelial interactions in metastatic initiation. Through loss-of-function and epistasis experiments, Png et al. (2012) delineated a miRNA regulator network's individual components as novel and cell-extrinsic regulators of endothelial recruitment, angiogenesis, and metastatic colonization. The authors also identified the IGFBP2/IGF1/IGF1R and GAS6/MERTK signaling pathways as regulators of cancer-mediated endothelial recruitment.
Agarwal, N., Hsieh, C. L., Sills, D., Swaroop, M., Desai, B., Francke, U., Swaroop, A. Sequence analysis, expression and chromosomal localization of a gene, isolated from a subtracted human retina cDNA library, that encodes an insulin-like growth factor binding protein (IGFBP2). Exp. Eye Res. 52: 549-561, 1991. [PubMed: 1712312] [Full Text: https://doi.org/10.1016/0014-4835(91)90056-k]
Alitalo, T., Kontula, K., Koistinen, R., Aalto-Setala, K., Julkunen, M., Janne, O. A., Seppala, M., de la Chapelle, A. The gene encoding human low-molecular weight insulin-like growth-factor binding protein (IGF-BP25): regional localization to 7p12-p13 and description of a DNA polymorphism. Hum. Genet. 83: 335-338, 1989. [PubMed: 2478445] [Full Text: https://doi.org/10.1007/BF00291377]
Allander, S. V., Larsson, C., Ehrenborg, E., Suwanichkul, A., Weber, G., Morris, S. L., Bajalica, S., Kiefer, M. C., Luthman, H., Powell, D. R. Characterization of the chromosomal gene and promoter for human insulin-like growth factor binding protein-5. J. Biol. Chem. 269: 10891-10898, 1994. [PubMed: 7511611] [Full Text: https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(17)34142-X]
Ehrenborg, E., Vilhelmsdotter, S., Bajalica, S., Larsson, C., Stern, I., Koch, J., Brondum-Nielsen, K., Luthman, H. Structure and localization of the human insulin-like growth factor-binding protein 2 gene. Biochem. Biophys. Res. Commun. 176: 1250-1255, 1991. [PubMed: 1710112] [Full Text: https://doi.org/10.1016/0006-291x(91)90420-c]
Png, K. J., Halberg, N., Yoshida, M., Tavazoie, S. F. A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature 481: 190-194, 2012.
Wood, W. I., Cachianes, G., Henzel, W. J., Winslow, G. A., Spencer, S. A., Hellmiss, R., Martin, J. L., Baxter, R. C. Cloning and expression of the growth hormone-dependent insulin-like growth factor-binding protein. Molec. Endocr. 2: 1176-1185, 1988. [PubMed: 2464130] [Full Text: https://doi.org/10.1210/mend-2-12-1176]