Tenascin-X: a novel extracellular matrix protein encoded by the human XB gene overlapping P450c21B

Abstract

Abstract.A human gene termed XB overlaps the P450c21B gene encoding steroid 21-hydroxylase and encodes a protein that closely resembles extracellular matrix proteins. Sequencing of phage and cosmid clones and of cDNA fragments shows that the XB gene spans 65 kb of DNA, consisting of 39 exons that encode a 12-kb mRNA. The predicted protein of over 400 kD consists of five distinct domains: a signal peptide, a hydrophobic domain containing three heptad repeats, a series of 18.5 EGF-like repeats, 29 fibronectin type HI repeats, and a carboxy-terminal fibrinogenlike domain. Because the structure of the protein encoded by the XB gene closely resembles tenascin, we term this protein tenascin-X (TN-X), and propose a simplified nomenclature system for the family of tenascins. RNase protection experiments show that the TN-X transcript is expressed ubiquitously in human fetal tissues, with the greatest expression in the fetal testis and in fetal skeletal, cardiac, and smooth muscle. Two adrenal-specific transcripts, P450c21B (steroid 21-hydroxylase) and Y (an untranslated transcrip0 overlap the XB gene on the complementary strand of DNA, yielding a unique array of overlapping transcripts: a "polygene: In situ hybridization histochemistry experiments show that the TN-X transcript and the P450c21 and Y transcripts encoded on the complementary DNA strand are all expressed in the same cells of the human adrenal cortex. Genetic data suggest that TN-X may be essential for life.

Embryonic expression of tenascin‐X suggests a role in limb, muscle, and heart development

“…This work confirms the earlier analysis of TN-X expression in the human and mouse (Bristow et al, 1993b;Matsumoto et al, 19941, while extending them to define the cell type responsible for TN-X synthesis, and the temporal pattern of expression during development. These new findings invite speculation as to the possible functions of TN-X.…”

“…Longer exposure of this autoradiograph did show low level expression at E16. As expected from our previous work in the human fetus (Gitelman et al, 1992;Bristow et al, 1993b), TN-X expression was greatest in developing heart, prenatal limb, and postnatal leg muscle. With longer exposure, a low level signal was also detected in all E20 and P2 RNA samples examined.…”

“…The recent observation that homozygous TN-C deficient mice develop normally (Saga et al, 1992) has cast some doubt on the paramount importance of this protein during development, and has led to intensified interest in other family members that might compensate for deficiency of TN-C. TN-R, initially identified as restrictin in the chick and J160l180 in the rat (Norenberg et al, 1992;Fuss et al, 1993), has expression confined to the central nervous system, and is thus unlikely to fulfill this role. TN-X on the other hand, is more widely expressed during human development (Gitelman et al, 1992;Bristow et al, 1993b).…”

“…Detailed analysis of this locus revealed that the human TN-X gene was partially duplicated in tandem with the P450c21 and C4 genes. Extensive genomic sequencing (Matsumoto et al, 1992;Bristow et al, 1993b) demonstrated that the TN-X gene is larger than those of other family members, encoding a n mRNA of a t least 13 kb that is highly expressed in muscular tissues. Recently TN-X was shown to be conserved in the mouse and analysis of the TN-X protein confirmed the size of TN-X subunits to be 500 kD .…”

Shining a light on CNTNAP2: complex functions to complex disorders

“…35 These domains mediate cell-cell adhesions and extracellular matrix interactions. 36,37 The large extracellular region of CASPR2 also features four laminin G domains and two epidermal growth factor-like (EGF-like) domains predicted to be involved in receptor-ligand interactions, cell adhesion, migration, and differentiation. The small intracellular portion of the protein is largely involved in protein-protein interactions, and contains a type-II PDZ domain and a protein 4.1B binding site (Figure 1b).…”