CHARACTERIZATION OF THE HUMAN SYNAPTOGYRIN GENE FAMILY

Genomic sequencing was combined with searches of databases for identif ication of active genes on human chromosome 22. A cosmid from 22q13, l ocated in the telomeric vicinity of the PDGFB (platelet-derived growth factor B-chain) gene, was fully sequenced. Using an expressed sequenc e tag-based approach we characterized human (SYNGR1) and mouse (Syngr1 ) orthologs of the previously cloned rat synaptogyrin gene (RATSYNGR1) . The human SYNGR1 gene reveals three (SYNGR1a, SYNGR1b, SYNGR1c) alte rnative transcript forms of 4.5, 1.3 and 0.9 kb, respectively. The tra nscription of SYNGR1 stares from two different promoters, and leads to predicted proteins with different N- and C-terminal ends. The most ab undant SYNGR1a transcript, the 4.5-kb form, which corresponds to RATSY NGR1, is highly expressed in neurons of the central nervous system and at much lower levels in other tissues, as determined by in situ hybri dization histochemistry. The levels of SYNGR1b and SYNGR1c transcripts are low and limited to heart, skeletal muscle, ovary and fetal liver. We also characterized two additional members of this novel synaptogyr in gene family in human (SYNGR2 and SYNGR3), and one in mouse (Syngr2) . The human SYNGR2 gene transcript of 1.6 kb is expressed at high leve ls in all tissues, except brain. The 2.2-kb SYNGR3 transcript was dete cted in brain and placenta only. The human SYNGR2 and SYNGR3 genes wer e mapped by fluorescence in situ hybridization to 17qtel and 16ptel, r espectively. The human SYNGR2 gene has a processed pseudogene localize d in 15q11. All predicted synaptogyrin proteins contain four strongly conserved transmembrane domains, which is consistent with the M-shaped topology. The C-terminal polypeptide ends are variable in length, dis play a low degree of sequence similarity between family members, and a re therefore likely to convey the functional specificity of each prote in.