STIM2 - Gene and Protein Structure

Gene and Protein Structure

In 2001, STIM2 was identified as a new human homologue of the STIM1 gene, representing the second member of a two-gene family in vertebrates. The STIM2 gene contains 12 exons and 11 introns located on the human chromosome 4p15.1, and on the large arm of the mouse chromosome 5, close to the centromere. The members of STIM family most probably have evolved from a single gene in lower multicellular eukaryotes into two related genes in vertebrates, since human STIM1 and STIM2 as well as Drosophila melanogaster Stim (D-Stim) have a conserved genomic organization. The D-STIM protein of 570 aas exhibits equal similarity to both STIM1 (33% identical; 50% of amino acid sequence conserved) and STIM2 (31% identical; 46% of amino acid sequence conserved). No STIM-like genes have been identified in prokaryotes or unicellular eukaryotes. No additional STIM-like proteins have been identified until now in vertebrates. STIM2 protein is a type I transmembrane protein located in the S/ER. Human STIM2 consists of 833 amino acid residues (aas) (105-115 kDa) (Fig. 1), 148 additional aas compared to human STIM1. Their N-termina regions share 66% similarity over 577 aas (85% of the amino acid sequence of STIM1). Only the extreme of the C-terminal region shows a significant sequence divergence. The domain architecture of both isoforms is highly conserved in vertebrates (Fig. 1). Mouse STIM2 shares a 92% identity with human STIM2 in the aminoacid sequence according the pairwise alignment generated by BLAST. Their domain structure is also highly conserved (Fig. 1). Human STIM2 is post-translationally modified in vivo, such as maturation by cleavage of N-terminal S/ER signaling peptide (14 aas), glycosylation and variable degrees of phosphorylation, but the phosphorylated sites are still unknown (Fig. 1).