The Phylogeny of Osteopontin—Analysis of the Protein Sequence

Abstract

Osteopontin (OPN) is important for tissue remodeling, cellular immune responses, and calcium homeostasis in milk and urine. In pathophysiology, the biomolecule contributes to the progression of multiple cancers. Phylogenetic analysis of 202 osteopontin protein sequences identifies a core block of integrin-binding sites in the center of the protein, which is well conserved. Remarkably, the length of this block varies among species, resulting in differing distances between motifs within. The amino acid sequence SSEE is a candidate phosphorylation site. Two copies of it reside in the far N-terminus and are variably affected by alternative splicing in humans. Between those motifs, birds and reptiles have a histidine-rich domain, which is absent from other species. Just downstream from the thrombin cleavage site, the common motif (Q/I)(Y/S/V)(P/H/Y)D(A/V)(T/S)EED(L/E)(-/S)T has been hitherto unrecognized. While well preserved, it is yet without assigned function. The far C-terminus, although very different between Reptilia/Aves on the one hand and Mammals on the other, is highly conserved within each group of species, suggesting important functional roles that remain to be mapped. Taxonomic variations in the osteopontin sequence include a lack of about 20 amino acids in the downstream portion, a small unique sequence stretch C-terminally, a lack of six amino acids just upstream of the RGD motifs, and variable length insertions far C-terminally.