An alternatively spliced region of the human hexabrachion contains a repeat of potential N-glycosylation sites.

Abstract

We have cloned and sequenced two cDNA molecules that code for parts of two forms of human hexabrachion. The smaller clone has a sequence that corresponds to the previously published sequence of a cDNA clone coding for a part of chicken hexabrachion [Jones, F. S., Burgoon, M. P., Hoffman, S., Crossin, K. L., Cunningham, B. A. & Edelman, G. M. (1988) Proc. Natl. Acad. Sci. USA 85, 2186USA 85, -2190. It has eight consecutive domains similar to the type m homology units from fibronectin, several epidermal growth factor repeats, and a domain similar to the 13 and y chains offibrinogen. The larger clone has 5' and 3' ends that are identical to the smaller clone but also has an alternatively spliced 1.9-kilobase internal segment. The unique segment contains remarkable repeats of potential glycosylation sites and an additional seven type III homology units.We have previously described a pair of large glycosylated polypeptides that we isolated from human fetal brain and called gplSO/225 (1). Both polypeptides form homomultimers linked by disulfide bonds, both contain a significant amount of N-linked oligosaccharides, and both have the HNK-1 epitope that may be a marker for adhesion molecules (2). Recently it has become clear that one and the same protein or a family of closely related proteins has been described under several names, including hexabrachion (3), tenascin (4), myotendinous antigen (5), glioma mesenchymal extracellular matrix antigen (6), J1 glycoprotein (2), and cytotactin (7). The gplSO/225 also belongs to this family (see below).Rotary shadowed electron micrographs of this protein(s) reveal a characteristic structure, which lead Erickson and Inglesias (3) to come up with the name hexabrachion. The typical molecule consists of a pair of three arms that are connected through a central globular particle (8). In this paper we have, for clarity and convenience, elected to use the name hexabrachion for all of the above-mentioned proteins. Although it has not been unequivocally proven that they are all the same protein, the circumstantial evidence is compelling (9). The name hexabrachion describes the typical structure without implying anything about function or localization, both of which are still somewhat controversial.Most reports on the hexabrachions indicate that they are polypeptides of 200 kDa or more, but there are also reports on smaller polypeptides in the family, including our own on the gplSO (1). It has, however, been debated whether or not these smaller polypeptides are authentic hexabrachions (9, 10). We believe that some of that data presented below support the opinion that they are.Recently, Jones et al. (11) reported on the sequence of a cDNA clone (AC801) coding for a part of one of the hexabrachions from the chicken. The deduced amino acid sequence contained several epidermal growth factor (EGF) repeats, fibronectin type III homology units, and a domain with a sequence similar to the 3 and y chains of fibrinogen. Here we report on the sequence of two cDNA clones coding for a part of...

Tenascin-C: Form versus function

“…22 The first human tenascin-C exon sequence was published using cDNA clones isolated from U-373MG glioblastoma cells, identifying a clone with 8 consecutive FNIII like repeats, and another clone containing the same repeats but with a 1.9 kb insert between FNIII 5 and 6; providing clear genetic evidence of alternative splicing within the tenascin-C transcript. 23 Transcriptional regulators of tenascin-C expression Expression of tenascin-C is regulated in a stimulus specific manner in humans, mice, rats and chickens; the promoter elements of which are well conserved up to around 250 bp upstream of the transcription start site (TSS), including a TATA box located 21 nucleotides downstream of the TSS. 24 Regulation of the tenascin-C promoter is influenced by many transcription factors ( Table 2)(reviewed in 21 ).…”

“…As a result this moderate number of genes is able to produce >290,000 non-redundant peptide combinations. 26 Following on from the first observations by Jones et al 22 and Gulcher et al 23 that tenascin-C is subject to alternative splicing, many studies have expanded on this theme revealing that post transcriptional modification of tenascin-C has a profound effect on tenascin biology.…”

Tenascin variants: differential binding to fibronectin and distinct distribution in cell cultures and tissues.

“…The different types of subunits are disulfide-linked to homo-oligomers . Mouse and human tenascin contain even more of these alternatively spliced extra repeats (Gulcher et aL, 1989;Siri et a!., 1991;Weller et Localization of the epitopes of the anti-tenascin antibodies. This model of chicken tenascin was derived from the primary sequence (Spring et al, 1989).…”

Expression of the extracellular matrix protein tenascin in malignant and benign ovarian tumours

“…Several different isoforms of the monomeric protein have been identified ranging in molecular weight from 150 to 320 kDa. These isoforms are produced by alternative splicing of the primary RNA transcript of the domain with fibronectin type III repeats (Jones et al, 1989;Gulcher et al, 1989). In cultured human cell lines, eight different mRNA species, containing varying numbers of fibronectin type III repeats, have been identified (Siri et al, 1991;Sriramarao and Bourdon, 1993).…”