title: Structure and evolution of RIM-BP genes: identification of a novel family member.
abstract: RIM-binding proteins (RIM-BPs) were identified as binding partners of the presynaptic active zone proteins RIMs as well as for voltage-gated Ca(2+)-channels. They were suggested to form a functional link between the synaptic-vesicle fusion apparatus and Ca(2+)-channels. Here we show that the RIM-BP gene family diversified in different stages during evolution, but retained their unique domain structure. While invertebrate genomes contain one, and vertebrates include at least two RIM-BPs, we identified an additional gene, RIM-BP3, which is exclusively expressed in mammals. RIM-BP3 is encoded by a single exon of which three copies are present in the human genome. All RIM-BP genes encode proteins with three SH3-domains and two to three fibronectin III repeats. The flanking regions diverge in size and sequence and are alternatively spliced in RIM-BP1 and -2. Quantitative real-time RT-PCR and in situ hybridization analyses revealed overlapping but distinct expression patterns throughout the brain for RIM-BP1 and -2, while RIM-BP3 was detected at high levels outside the nervous system. The modular domain structure of RIM-BPs, their expression pattern and the conservative expansion during evolution shown here support their potential role as important molecular adaptors.
authors.affiliation: Department of Neuropathology and Epileptology, University of Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Mittelstaedt
authors.forename: Susanne
authors.initials: S
authors.lastname: Schoch
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D019143:Evolution, Molecular; D005091:Exons; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D007438:Introns; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011392:Proline / Q000737:chemistry; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000737:chemistry
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C524445:RIMBP3 protein, human; D012333:RNA, Messenger; D012694:Serine; D001120:Arginine; D011392:Proline