Molecular cloning and functional characterization of murine Transmembrane Activator and CAML Interactor (TACI) with chromosomal localization in humanand mouse

The human Taci gene (Transmembrane Activator and CAML. Interactor) encodes a recently discovered member of the Tumor Necrosis Factor Receptor family. TACI is expressed in B-lymphocytes and may act to regulate humoral immunity . To identify functionally important regions of the protein, we have isolat ed and characterized the murine homolog of the human Taci cDNA. The protein s display 61.5% similarity and 54.6% identity. Mouse TACI is a type III tra nsmembrane protein, as judged by the lack of a cleaved signal sequence and its N-terminal extracellular exposure. The intracellular domains of the mou se and human proteins share a single, defined region of high sequence conse rvation (19 of 23 residues identical). This constitutes a novel domain that may play a part in the initiation of signal transduction through TACI. In support of this notion, mouse TACI was found to activate NFAT, NFkB, and AP 1 transcription factors in a transient transfection assay. The Taci gene wa s localized to human Chromosome (Chr) 17p11 by fluorescence in situ hybridi zation. The murine homolog was localized by intraspecific backcross analysi s to the middle of Chr 11, a region that is syntenic to human Chr 17p. This work identifies concerned domains within TACI that may mediate the cellula r distribution and signal transduction function of the protein and extend t he details of homology between mouse Chr 11 and human 17p.