Alternative titles; symbols
HGNC Approved Gene Symbol: TGFB1I1
Cytogenetic location: 16p11.2 Genomic coordinates (GRCh38): 16:31,472,152-31,477,960 (from NCBI)
Using differential screening of a cDNA library constructed from mouse osteoblastic cells (MC3T3-E1) treated with TGFB1 (190180), Shibanuma et al. (1993) isolated several TGFB1-induced cDNAs. They stated that hydrogen peroxide was released from MC3T3-E1 cells in response to TGFB1 and was partially responsible for the TGFB1 inhibition of growth. Shibanuma et al. (1994) found that expression of one of these cDNAs was induced by hydrogen peroxide as well as by TGFB1, and therefore they designated this cDNA hic5 for 'hydrogen peroxide-inducible clone-5.' The hic5 cDNA encodes a deduced 444-amino acid protein with 4 LIM motifs of the zinc finger family.
Matsuya et al. (1998) cloned a human HIC5 cDNA from a hippocampus cDNA library. Like the mouse Hic5 protein, the deduced human protein contains 444 amino acids with 4 LIM domains. They share 97% sequence identity in the double zinc finger LIM domains and 84.3% in the N-terminal domains. Both show sequence homology with the paxillin protein (602505). Matsuya et al. (1998) determined that HIC5 localizes exclusively at focal adhesions.
Shibanuma et al. (1994) found that expression of hic5 was extremely reduced in several human tumor-derived cell lines and increased during cellular senescence of normal human diploid fibroblasts. Shibanuma et al. (1997) found that antisense hic5 expression in normal human diploid fibroblasts delayed senescence.
By coimmunoprecipitation experiments, Matsuya et al. (1998) identified interaction between TGFB1I1 and PYK2 (601212), a focal adhesion protein-tyrosine kinase. By mutation analysis, they found that the C-terminal region of PYK2 interacts with the N-terminal region of TGFB1I1. Both proteins were tyrosine-phosphorylated in parallel in rat fibroblasts exposed to hypertonic osmotic stress or stimulated with lysophosphatidic acid. Fujimoto et al. (1999) found that TGFB1I1, which they called ARA55, interacts with, and can enhance the transcriptional activity of, the androgen receptor (AR; 313700) in a ligand-dependent manner. Interaction was mediated by the C-terminal half of TGFB1I1 containing the LIM motifs.
Using a yeast 2-hybrid screen, Drori et al. (2005) found that the ligand-binding domain of mouse Pparg (601487) interacted with HIC5 in a human colon cancer cDNA library. Hic5 and Pparg colocalized to the villus epithelium of mouse small intestine, and their expression during embryonic gut development correlated with the transition from endoderm to specialized epithelium. Overexpression of HIC5 in colon cancer cells enhanced PPARG-mediated induction of several gut epithelial differentiation and maturation markers. Overexpression of HIC5 during mouse preadipocyte differentiation inhibited adipogenesis while inducing inappropriate expression of several mRNAs characteristic of gut epithelium.
Using a somatic cell hybrid panel, Shibanuma et al. (1997) mapped the TGFB1I1 gene to chromosome 16.
Mashimo et al. (2000) mapped the mouse Tgfb1i1 gene to chromosome 7 using FISH.
Drori, S., Girnun, G. D., Tou, L., Szwaya, J. D., Mueller, E., Kia Xia, Shivdasani, R. A., Spiegelman, B. M. Hic-5 regulates an epithelial program mediated by PPAR-gamma. Genes Dev. 19: 362-375, 2005. Note: Erratum: Genes Dev. 19: 875 only, 2005. [PubMed: 15687259] [Full Text: https://doi.org/10.1101/gad.1240705]
Fujimoto, N., Yeh, S., Kang, H.-Y., Inui, S., Chang, H.-C., Mizokami, A., Chang, C. Cloning and characterization of androgen receptor coactivator, ARA55, in human prostate. J. Biol. Chem. 274: 8316-8321, 1999. [PubMed: 10075738] [Full Text: https://doi.org/10.1074/jbc.274.12.8316]
Mashimo, J., Shibanuma, M., Satoh, H., Chida, K., Nose, K. Genomic structure and chromosomal mapping of the mouse hic-5 gene that encodes a focal adhesion protein. Gene 249: 99-103, 2000. [PubMed: 10831843] [Full Text: https://doi.org/10.1016/s0378-1119(00)00163-3]
Matsuya, M., Sasaki, H., Aoto, H., Mitaka, T., Nagura, K., Ohba, T., Ishino, M., Takahashi, S., Suzuki, R., Sasaki, T. Cell adhesion kinase beta forms a complex with a new member, Hic-5, of proteins localized at focal adhesions. J. Biol. Chem. 273: 1003-1014, 1998. [PubMed: 9422762] [Full Text: https://doi.org/10.1074/jbc.273.2.1003]
Shibanuma, M., Mashimo, J., Kuroki, T., Nose, K. Characterization of the TGF-beta-1-inducible hic-5 gene that encodes a putative novel zinc finger protein and its possible involvement in cellular senescence. J. Biol. Chem. 269: 26767-26744, 1994. [PubMed: 7929412]
Shibanuma, M., Mashimo, J., Mita, A., Kuroki, T., Nose, K. Cloning from a mouse osteoblastic cell line of a set of transforming-growth-factor-beta-1-regulated genes, one of which seems to encode a follistatin-related polypeptide. Europ. J. Biochem. 217: 13-19, 1993. [PubMed: 7901004] [Full Text: https://doi.org/10.1111/j.1432-1033.1993.tb18212.x]
Shibanuma, M., Mochizuki, E., Maniwa, R., Mashimo, J., Nishiya, N., Imai, S.-I., Takano, T., Oshimura, M., Nose, K. Induction of senescence-like phenotypes by forced expression of hic-5, which encodes a novel LIM motif protein, in immortalized human fibroblasts. Molec. Cell. Biol. 17: 1224-1235, 1997. [PubMed: 9032249] [Full Text: https://doi.org/10.1128/MCB.17.3.1224]