Alternative titles; symbols
HGNC Approved Gene Symbol: TSC22D1
Cytogenetic location: 13q14.11 Genomic coordinates (GRCh38) : 13:44,432,143-44,577,344 (from NCBI)
TSC22D1 encodes a transcription factor and belongs to the large family of early response genes.
By screening for low-abundance clones in a 6-week embryo cDNA library, Jay et al. (1996) cloned TSC22D1, which they called TSC22. The deduced 144-amino acid protein has a calculated molecular mass of about 16.7 kD and contains a leucine zipper, a C terminus rich in glutamine and proline, and 2 potential phosphorylation sites. TSC22 shares significant homology with Tsc22 from mouse, rat, and chicken, and it shares 69% identity with porcine Dsip (300506) and 52% identity with the Drosophila shortsighted protein. Zoo blot analysis detected related sequences in all represented vertebrates and in fruit fly. No signal was detected in mussel, nematode, yeast, and bacteria.
By Southwestern screening, Ohta et al. (1996) identified rat Tsc22 by its binding to the GC-rich element of the CNP (600296) promoter. They used this sequence to design primers and cloned human TSC22 by PCR and by 3-prime and 5-prime RACE of a fetal kidney cDNA library. Human TSC22 differs from the rat protein by the insertion of 1 residue and by 1 substitution. The rat and mouse proteins are identical.
By Northern blot analysis, Jay et al. (1996) and Ohta et al. (1996) determined that TSC22 is expressed as a 1.8-kb transcript at varying amounts in all fetal and adult tissues examined, except peripheral blood leukocytes. A transcript of about 5 kb was also detected in skeletal muscle.
By mobility shift assay and by cotransfection with a reporter plasmid, Ohta et al. (1996) confirmed that rat Tsc22 binds to and can drive expression from the GC-rich sequence of the CNP promoter. In human aortic endothelial cells, TSC22 expression was stimulated by cytokines, including TGFB (190180), and was degraded quickly. Expression of TSC22 mRNA correlated with increased levels of CNP mRNA.
By yeast 2-hybrid analysis, gel shift assay, and GST pull-down experiments, Kester et al. (1999) confirmed that TSC22D1 forms homodimers via its conserved leucine zipper domain and it interacts with TSC22D4 (611914) by forming heterodimers. They demonstrated that TSC22D1 has transcriptional repressor activity.
By FISH, Jay et al. (1996) mapped the TSC22D1 gene to chromosome 13q14.
Jay, P., Ji, J. W., Marsollier, C., Taviaux, S., Berge-Lefranc, J.-L., Berta, P. Cloning of the human homologue of the TGF-beta-stimulated clone 22 gene. Biochem. Biophys. Res. Commun. 222: 821-826, 1996. [PubMed: 8651929] [Full Text: https://doi.org/10.1006/bbrc.1996.0825]
Kester, H. A., Blanchetot, C., den Hertog, J., van der Saag, P. T., van der Burg, B. Transforming growth factor-beta-stimulated clone-22 is a member of a family of leucine zipper proteins that can homo- and heterodimerize and has transcriptional repressor activity. J. Biol. Chem. 274: 27439-27447, 1999. [PubMed: 10488076] [Full Text: https://doi.org/10.1074/jbc.274.39.27439]
Ohta, S., Shimekake, Y., Nagata, K. Molecular cloning and characterization of a transcription factor for the C-type natriuretic peptide gene promoter. Europ. J. Biochem. 242: 460-466, 1996. [PubMed: 9022669] [Full Text: https://doi.org/10.1111/j.1432-1033.1996.460rr.x]