Evolution of Transmembrane and Gel-forming Mucins Studied with Bioinformatic Methods

.............................................................................................................................................................3 List of Publications ............................................................................................................................................4 Table of contents................................................................................................................................................5 Introduction........................................................................................................................................................6 Mucin proteins ...........................................................................................................................................6 Domain structure of mucins.....................................................................................................................11 Materials and methods .....................................................................................................................................14 Sources of protein and nucleotide sequences...........................................................................................14 Bioinformatic tools ..................................................................................................................................15 PTSpred............................................................................................................................................15 Mpred...............................................................................................................................................15 Other bioinformatics software .........................................................................................................17 Genome sequencing projects ...................................................................................................................18 Results..............................................................................................................................................................23 Mucins and related proteins with multiple VWD domains .....................................................................23 MUC2 ..............................................................................................................................................25 MUC5 ..............................................................................................................................................26 MUC6 and MUC19..........................................................................................................................27 Ovomucin.........................................................................................................................................27 MUC6-MUC2-MUC5AC-MUC5B gene cluster.............................................................................28 MucMV (Multiple VWDs) ..............................................................................................................28 Otogelin and VWF...........................................................................................................................28 Insect hemolectin and gel-forming mucin ancestor .........................................................................29 MUC4 and related proteins......................................................................................................................30 Mucins and related proteins with SEA domains......................................................................................30 MUC3 group ....................................................................................................................................32 MUC1, MUC13 and MUC16 ..........................................................................................................34 MucMS (Multiple SEAs).................................................................................................................35 Cleavage site of mucins ...........................................................................................................................35 Information presented at mucin web site .................................................................................................36 Discussion........................................................................................................................................................37 Prediction of mucin proteins....................................................................................................................37 Prediction of the PTS domain ..........................................................................................................37 The use of domain structure in the prediction of mucin proteins ....................................................38 Synteny and the prediction of mucin genes .....................................................................................39 Study of mucin evolution with a phylogenetic analysis of protein domains ...........................................40 Acknowledgements..........................................................................................................................................42 References........................................................................................................................................................43