HGNC Approved Gene Symbol: DPT
Cytogenetic location: 1q24.2 Genomic coordinates (GRCh38) : 1:168,695,468-168,729,206 (from NCBI)
Superti-Furga et al. (1993) noticed the presence of a protein with a molecular weight of approximately 22 kD in proteoglycan preparations from human fibroblast cultures and speculated that it might be related to a 22-kD protein from bovine skin with proteoglycan- and cell-binding properties. Using degenerated oligomers designed from the amino acid sequence of the bovine protein, they amplified and subcloned the sequences from human fibroblast and fibrosarcoma cDNA. The 3 clones that were characterized contained an open reading frame (603 bp) coding for 201 amino acids comprising a secretory leader peptide of 18 amino acids and a secreted portion of 183 amino acids with 96% identity to the bovine sequence, indicating that they code for the human homolog, dermatopontin. Expression of dermatopontin was not limited to connective tissue, as Northern blots showed specific mRNAs in cultured fibroblasts, muscle, heart, pancreas, and lung. Two species of mRNA (1.0 and 2.2 kb) were present, indicating alternative polyadenylation or alternative splicing. Because the protein was first identified in skin extracts and because of its ability to bind both to cells and to dermatan sulfate proteoglycans, Superti-Furga et al. (1993) proposed that the protein be called dermatopontin, in analogy to bone osteopontin, which binds both to cellular integrins and to hydroxyapatite crystals in bone.
By study of a cell hybrid panel containing specific chromosomal deletions, Superti-Furga et al. (1993) mapped the DPT gene to chromosome 1q12-q23.
Uterine leiomyomas (150699) are prevalent estrogen-responsive clonal tumors. To identify genes involved in the formation of leiomyomas, Catherino et al. (2004) used global expression profiling to compare clonal tumors with normal myometrium. Contrary to expectation, genes involved in estrogen action were not differentially expressed between leiomyoma and normal myometrium. On the other hand, genes encoding extracellular matrix proteins were prominently featured, suggesting their involvement in formation of a myofibroblast phenotype. Analysis of the extracellular matrix in the leiomyomas showed a disordered collagen fibril orientation. Expression of dermatopontin was consistently decreased in leiomyomata, regardless of leiomyoma size, leiomyoma location, patient race, or patient age. Decreased expression of dermatopontin was also associated with keloid (148100) formation, a fibrotic disease that shares epidemiologic similarities with leiomyoma. Immunohistochemical studies of leiomyomas and keloids demonstrated reduced levels of dermatopontin in both tissues. In addition, ultrastructural analysis revealed that the orientation of the collagen fibrils in the keloid tissues strongly resembled that in the leiomyomas. Reduction in dermatopontin was associated with an increase in transforming growth factor beta-3 (TGFB3; 190230) mRNA levels in leiomyomas, whereas other genes involved in dermatopontin signaling were not differentially expressed. Catherino et al. (2004) concluded that leiomyoma development involves a myofibroblast cell phenotype characterized by dysregulation of genes encoding extracellular matrix proteins.
Catherino, W. H., Leppert, P. C., Stenmark, M. H., Payson, M., Potlog-Nahari, C., Nieman, L. K., Segars, J. H. Reduced dermatopontin expression is a molecular link between uterine leiomyomas and keloids. Genes Chromosomes Cancer 40: 204-217, 2004. [PubMed: 15139000] [Full Text: https://doi.org/10.1002/gcc.20035]
Superti-Furga, A., Rocchi, M., Schafer, B. W., Gitzelmann, R. Complementary DNA sequence and chromosomal mapping of a human proteoglycan-binding cell-adhesion protein (dermatopontin). Genomics 17: 463-467, 1993. [PubMed: 8104875] [Full Text: https://doi.org/10.1006/geno.1993.1348]