TENASCIN-X - A NOVEL EXTRACELLULAR-MATRIX PROTEIN ENCODED BY THE HUMAN XB GENE OVERLAPPING P450C21B

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 fr agments shows that the XB gene spans 65 kb of DNA, consisting of 39 ex ons that encode a 12-kb mRNA. The predicted protein of over 400 kD con sists of five distinct domains: a signal peptide, a hydrophobic domain containing three heptad repeats, a series of 18.5 EGF-like repeats, 2 9 fibronectin type III repeats, and a carboxy-terminal fibrinogen-like domain. Because the structure of the protein encoded by the XB gene c losely 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 express ed ubiquitously in human fetal tissues, with the greatest expression i n the fetal testis and in fetal skeletal, cardiac, and smooth muscle. Two adrenal-specific transcripts, P450c21B (steroid 21-hydroxylase) an d Y (an untranslated transcript) overlap the XB gene on the complement ary 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 t he human adrenal cortex. Genetic data suggest that TN-X may be essenti al for life.