title: Conservation of the TRAPPII-specific subunits of a Ypt/Rab exchanger complex.
abstract: BACKGROUND
  Ypt/Rab GTPases and their GEF activators regulate intra-cellular trafficking in all eukaryotic cells. In S. cerivisiae, the modular TRAPP complex acts as a GEF for the Golgi gatekeepers: Ypt1 and the functional pair Ypt31/32. While TRAPPI, which acts in early Golgi, is conserved from fungi to animals, not much is known about TRAPPII, which acts in late Golgi and consists of TRAPPI plus three additional subunits.
  
  
  RESULTS
  Here, we show a phylogenetic analysis of the three TRAPPII-specific subunits. One copy of each of the two essential subunits, Trs120 and Trs130, is present in almost every fully sequenced eukaryotic genome. Moreover, the primary, as well as the predicted secondary, structure of the Trs120- and Trs130-related sequences are conserved from fungi to animals. The mammalian orthologs of Trs120 and Trs130, NIBP and TMEM1, respectively, are candidates for human disorders. Currently, NIBP is implicated in signaling, and TMEM1 is suggested to have trans-membrane domains (TMDs) and to function as a membrane channel. However, we show here that the yeast Trs130 does not function as a trans-membrane protein, and the human TMEM1 does not contain putative TMDs. The non-essential subunit, Trs65, is conserved only among many fungi and some unicellular eukaryotes. Multiple alignment analysis of each TRAPPII-specific subunit revealed conserved domains that include highly conserved amino acids.
  
  
  CONCLUSIONS
  We suggest that the function of both NIBP and TMEM1 in the regulation of intra-cellular trafficking is conserved from yeast to man. The conserved domains and amino acids discovered here can be used for functional analysis that should help to resolve the differences in the assigned functions of these proteins in fungi and animals.
authors.affiliation: Department of Biological Sciences, Laboratory for Molecular Biology, University of Illinois at Chicago, Chicago, IL 60607, USA. randal@randalcox.net <randal@randalcox.net>
authors.forename: Randal
authors.initials: R
authors.lastname: Cox
authors.forename: Shu Hui
authors.initials: SH
authors.lastname: Chen
authors.forename: Eunice
authors.initials: E
authors.lastname: Yoo
authors.forename: Nava
authors.initials: N
authors.lastname: Segev
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D006801:Humans; D008322:Mammals; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D017433:Protein Structure, Secondary; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D033921:Vesicular Transport Proteins / Q000235:genetics* / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; C406327:transport protein particle, TRAPP; C060755:YPT1 protein, S cerevisiae; D020691:rab GTP-Binding Proteins