title: Characterization of the Tetraspan Junctional Complex (4JC) superfamily.
abstract: Connexins or innexins form gap junctions, while claudins and occludins form tight junctions. In this study, statistical data, derived using novel software, indicate that these four junctional protein families and eleven other families of channel and channel auxiliary proteins are related by common descent and comprise the Tetraspan (4 TMS) Junctional Complex (4JC) Superfamily. These proteins all share similar 4 transmembrane α-helical (TMS) topologies. Evidence is presented that they arose via an intragenic duplication event, whereby a 2 TMS-encoding genetic element duplicated tandemly to give 4 TMS proteins. In cases where high resolution structural data were available, the conclusion of homology was supported by conducting structural comparisons. Phylogenetic trees reveal the probable relationships of these 15 families to each other. Long homologues containing fusions to other recognizable domains as well as internally duplicated or fused domains are reported. Large "fusion" proteins containing 4JC domains proved to fall predominantly into family-specific patterns as follows: (1) the 4JC domain was N-terminal; (2) the 4JC domain was C-terminal; (3) the 4JC domain was duplicated or occasionally triplicated and (4) mixed fusion types were present. Our observations provide insight into the evolutionary origins and subfunctions of these proteins as well as guides concerning their structural and functional relationships.
authors.affiliation: Department of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0116, United States.
authors.forename: Amy
authors.initials: A
authors.lastname: Chou
authors.affiliation: Department of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0116, United States.
authors.forename: Andre
authors.initials: A
authors.lastname: Lee
authors.affiliation: Department of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0116, United States.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Hendargo
authors.affiliation: Department of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0116, United States.
authors.forename: Vamsee S
authors.initials: VS
authors.lastname: Reddy
authors.affiliation: Department of Orthopaedic Surgery, Medical School, University of Michigan, Ann Arbor, MI 48109-5624, United States.
authors.forename: Maksim A
authors.initials: MA
authors.lastname: Shlykov
authors.affiliation: Department of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0116, United States.
authors.forename: Harikrishnan
authors.initials: H
authors.lastname: Kuppusamykrishnan
authors.affiliation: Department of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0116, United States.
authors.forename: Arturo
authors.initials: A
authors.lastname: Medrano-Soto
authors.affiliation: Department of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0116, United States. Electronic address: msaier@ucsd.edu.
authors.forename: Milton H
authors.initials: MH
authors.lastname: Saier
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D057167:Claudins / Q000737:chemistry / Q000145:classification; D017630:Connexins / Q000737:chemistry / Q000145:classification; D017629:Gap Junctions / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000145:classification; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins / Q000737:chemistry / Q000145:classification; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D019108:Tight Junctions / Q000378:metabolism
chemical_list: D057167:Claudins; D017630:Connexins; D008565:Membrane Proteins; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins
keywords: Ca(2+) channels; Connexins; Gap junctions; Occludins; Superfamily; Tight junctions