Hensin, the polarity reversal protein, is encoded by DMBT1, a gene frequently deleted in malignant gliomas

The band 3 anion exchanger is located in the apical membrane of a beta-inte rcalated clonal cell line, whereas the vacuolar H+-ATPase is present in the basolateral membrane. When these cells were seeded at confluent density, t hey converted to an cr-phenotype, localizing each of these proteins to the opposite cell membrane domain. The reversal of polarity is induced by hensi n, a 230-kDa extracellular matrix protein. Rabbit kidney hensin is a multid omain protein composed of eight SRCR ("scavenger receptor, cysteine rich"), two CUB ("C1r/C1s Uegf Bmp1"), and one ZP ("zona pellucida") domain. Other proteins known to have these domains include CRP-ductin, a cDNA expressed at high levels in mouse intestine (8 SRCR, 5 CUB, 1 ZP), ebnerin, a protein cloned from a rat taste bud library (4 SRCR, 3 CUB, 1 ZP), and DMBT1, a se quence in human chromosome 10q25-26 frequently deleted in malignant gliomas (9 SRCR, 2 CUB, 1 ZP). Rabbit and mouse hensin genomic clones contained a new SRCR that was not found in hensin cDNA but was homologous to the first SRCR domain in DMBT1. Furthermore, the 3'-untranslated regions and the sign al peptide of hensin were homologous to those of DMBT1. Mouse genomic hensi n was localized to chromosome 7 band F4, which is syntenic to human 10q25-2 6. These data suggest that hensin and DMBT1 are alternatively spliced forms of the same gene. The analysis of mouse hensin bacterial artificial chromo some (BAC) genomic clone by sequencing and Southern hybridization revealed that the gene also likely encodes CRP-ductin. A new antibody against the mo use SRCR1 domain recognized a protein in the mouse and rabbit brain but not in the immortalized cell line or kidney, whereas an antibody to SRCR6 and SRCR7 domains which are present in all the transcripts, recognized proteins in intestine, kidney, and brain from several species. The most likely inte rpretation of these data is that one gene produces at least three transcrip ts, namely, hensin, DMBT1, and CRP-ductin. Hensin may participate in determ ining the polarized phenotype of other epithelia and brain cells.