Osteoactivin bioinformatic analysis: prediction of novel functions, structural features, and modes of action
Abdulhafez A. Selim
Med Sci Monit 2009; 15(2): MT19-33
Available online: 2009-01-29
The initial identification of osteoactivin (OA) came from studies using an animal model of osteopetrosis in rats. Several recent studies suggested roles for OA in osteoblast differentiation, fibroblast differentiation, cancer metastasis, and attenuation of muscle, liver, and kidney injury-induced degeneration.
Material and Method: Several bioinformatic tools were utilized, including ArrayExpress, Pfam, SMART, Prosite, ELM, ProFun, PFP, Consensus Secondary Structure Prediction server, and Geno3D.
Results: 1) Novel OA functions and biological roles were predicted, including roles in cell envelope formation, enzyme activities, immune response activities, negative regulation of B-cell activation, antigen processing, heme catabolism, endothelial cell differentiation, establishment of protein localization, melanin biosynthesis from tyrosine, regulation of blood pressure, response to light, and lung development. 2) Novel OA functional motifs were predicted, including N-Arg dibasic convertase cleavage site, NEC1/NEC2 cleavage site, peptide C-terminal amidation, glycosaminoglycan attachment site, and generic motif for N-glycosylation, and substrate recognition sites that interact with different cytosolic proteins, including cyclin, MAPK, Class III PDZ domains, GSK3, phosphorylase kinase, tyrosine-based sorting signal, and internalization signal. 3) OA's secondary and tertiary structural models were predicted.
Conclusions: bioinformatic structural analysis predicted that OA has three major structural domains: two helical structures on its termini and beta sheets as a sandwich-like structure in the middle. Several functional motifs have been predicted suggesting different modes for OA functions (receptor, ligand, and enzyme). Combined data from OA's expression array and function prediction data suggest that OA might play a role in several pathologic conditions, including hypertension, diabetes, and immune system disorders.
Keywords: Software, Rats, Protein Structure, Secondary, Oligonucleotide Array Sequence Analysis, Molecular Sequence Data, Models, Molecular, Membrane Glycoproteins - metabolism, Internet, Gene Expression Regulation, Gene Expression Profiling, Protein Structure, Tertiary, Computational Biology - methods, Animals, Amino Acid Sequence, Amino Acid Motifs