A review of protein structure and gene organisation for proteins associated with mineralised tissue and calcium phosphate stabilisation encoded on human chromosome 4

Abstract

Several proteins associated with mineralised tissue (teeth and bone) or involved in calcium phosphate stabilisation in the body fluids, milk and saliva have been mapped to the q arm of human chromosome 4. These include the dentine/bone proteins dentine sialophosphoprotein (DSPP), dentine matrix protein 1 (DMP1), bone sialoprotein (BSP), matrix extracellular phosphoglycoprotein, osteopontin (OPN), enamelin, ameloblastin, milk caseins, salivary statherin, and proline-rich proteins. The proposed function of those that are multiphosphorylated is: (i) the stabilisation of calcium phosphate in solution (e.g. casein, statherin) preventing spontaneous precipitation and seeded-crystal growth or (ii) promoting biomineralisation (e.g. the phosphophoryn domain of DSPP), where the protein described as a template macromolecule, is proposed to act as a nucleator/promoter of crystal growth. The genes of these proteins have been subjected to conserved chromosomal synteny during mammalian evolution. The multiphosphorylated proteins statherin, caseins, phosphophoryn, BSP and OPN have been characterised as intrinsically disordered. The codon usage patterns for the amino acid serine reveal a bias for AGC and AGT codons within the human genes dspp, dmp1 and bsp, mouse dspp and dmp1 but not significantly for statherin or caseins. This pattern was also observed in the gene encoding hen phosvitin that also contains stretches of multiphosphorylated serines and in the dmp1 gene sequences of mammalian, reptilian and avian classes. In conclusion, these intrinsically disordered multiphosphorylated proteins are the translation products of genes displaying examples of codon usage bias, internal repeats and conserved chromosomal synteny within the mammalian class.