title: Molecular characterisation of the SAND protein family: a study based on comparative genomics, structural bioinformatics and phylogeny.
abstract: The activities of vertebrate lysosomes are critical to many essential cellular processes. The yeast vacuole is analogous to the mammalian lysosome and is used as a tool to gain insights into vesicle mediated vacuolar/lysosome transport. The protein SAND, which does not contain a SAND domain (PFAM accession number PF01342), has recently been shown to function at the tethering/docking stage of vacuole fusion as a critical component of the vacuole SNARE complex. In this publication we have identified SAND in diverse eukaryotes, from single celled organisms such as the yeasts to complex multi-cellular chordates such as mammals. We have demonstrated subfamily divisions in the SAND proteins and show that in vertebrates, a duplication event gave rise to two SAND sequences. This duplication appears to have occurred during early vertebrate evolution and conceivably with the evolution of lysosomes. Using bioinformatics we predict a secondary structure, solvent accessibility profile and protein fold for the SAND proteins and determine conserved sequence motifs, present in all SAND proteins and those that are specific to subsets. A comprehensive evaluation of yeast and human functional studies in conjunction with our in silico analysis has identified potential roles for some of these motifs.
authors.affiliation: MRC Rosalind Franklin Centre for Genomic Research, Genome Campus, Hinxton, Cambridge, CB10 1SB, UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: Cottage
authors.forename: Lisa
authors.initials: L
authors.lastname: Mullan
authors.forename: Miriam B D
authors.initials: MB
authors.lastname: Portela
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hellen
authors.forename: Tim
authors.initials: T
authors.lastname: Carver
authors.forename: Sunil
authors.initials: S
authors.lastname: Patel
authors.forename: Tanya
authors.initials: T
authors.lastname: Vavouri
authors.forename: Greg
authors.initials: G
authors.lastname: Elgar
authors.forename: Yvonne J K
authors.initials: YJ
authors.lastname: Edwards
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology; D005658:Fungi / Q000235:genetics; D023281:Genomics; D006801:Humans; D008247:Lysosomes / Q000235:genetics; D008969:Molecular Sequence Data; D010802:Phylogeny; D010944:Plants / Q000235:genetics; D017433:Protein Structure, Secondary; D050600:SNARE Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014617:Vacuoles / Q000235:genetics; D033921:Vesicular Transport Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics*
chemical_list: D050600:SNARE Proteins; D033921:Vesicular Transport Proteins