Characterization of a novel synGAP isoform, synGAP-beta

We cloned a cDNA encoding a novel synGAP, syn-GAP-d (GenBank(TM) accession number AB016962), from a rat brain cDNA library. The clone consisted of 480 1 nucleotides with a coding sequence of 3501 nucleotides, encoded a protein consisting of 1166 amino acids with >99% homology with 1092 amino acid ove rlaps to synGAP, and contained a 13-nucleotide insertion to the previously reported synGAP mRNAs, which suggested that the clone was a splice variant of synGAP, We also found that there are at least seven variants in the 3' p ortion of the synGAP mRNA and that they encoded five different protein isof orms, The coding sequence of these C-terminal variants were classified into alpha1, alpha2, beta1, beta2, beta3, beta4, and gamma, and synGAP-d was cl assified as the beta1 form, The previously reported synGAPs (synGAP-a, -b, and -c and p135synGAP) can be classified as the alpha1 isoform, All isoform s were expressed specifically in the brain. Unexpectedly, the beta isoform, which lacks a C-terminal PSD-95-binding motif ((ST)XV), was more restricte d to the postsynaptic density fraction than the motif-containing alpha1 iso form, The beta isoform did not interact with PSD-95 but specifically intera cted with a nonphosphorylated alpha subunit of Ca2+/calmodulin-dependent pr otein kinase II through its unique C-terminal tail.