Osteopontin (also referred to as OPN) and also known as bone sialoprotein (BSP 1 or BNSP), is a protein that is encoded by the SPP1 gene in humans. It is a sibling glycoprotein that was first identified in 1986.
The word’s prefix ‘osteo’ states that the protein is expressed in bone, in addition to being expressed in other tissues. While the suffix ‘pontin’ comes from the word ‘pons’, the Latin meaning for the term bridge, which signifies OPN’s role as a linking protein. Osteopontin is known as an extracellular structural protein, and because of this, it is thus an organic component of bone.
Home to 7 exons, the OPN gene also spans 5 kilobases in length; in humans, it is located on the long arm of chromosome 4, region 22. It is composed of 300 amino acid residues and also has 30 carbohydrate residues that are attached to it, including 10 sialic acid residues. These are attached to the protein during the post-translational modification within the Golgi apparatus. Rich in acidic residues, this protein has 30-36% that are either aspartic or glutamic.
OPN is a gene that is negatively charged and is an extracellular matrix protein that is missing an extensive secondary structure. It is made up of 300 amino acids and can be expressed as a 33-kDa nascent protein. OPN goes through post-transitional modifications, which increase its molecular weight to around 44 kDa. Out of the 7 exons that OPN is composed of, 6 contain a coding sequence. The initial two exons contain the 5 untranslated region ( 5 UTR). While exons 2,3,4,5,6, and 7 code for 17,13,27,14,108, and 134 amino acids.
Full-length OPN is able to be modified by thrombin cleavage, which creates a cryptic sequence, known as ‘SVVGLR’ on the cleaved form of the protein, this area is known as OPN-R. What this does is creates an epitope for integrin receptors, these integrin receptors are visible on various immune cells, like mast cells, T cells, and neutrophils, for instance. This can also be expressed by macrophages and monocytes. When these receptors are bound, the cells use various signal transduction routes to create immune responses within these cells. OPN-R can be cleaved further by Carboxypeptidase B by the removal of the C-terminal arginine, meaning it becomes OPN-L. However, the function of OPN-L is largely unknown.
It has been suggested that OPN-L is an intracellular variant of OPN and is involved in various cellular processes, including fusion, migration and motility. Intracellular OPN is created using an alternative translation site of the same mRNA species which is used to generate the extracellular isoform. This alternative start site is located downstream of the N-terminal endoplasmic reticulum which targets signal sequence, therefore allowing cytoplasmic translation of OPN. It has been observed that various cancers in humans, including breast cancer, have expressed spliced variants of OPN. The cancer-specific splice variants include OSN-a, OSN-b, OSN-c. Exon 5 is lacking from OSN-b, whereas OSN-c does not have exon 4. It has been suggested that OSN-c facilitates the anchorage-independent phenotype of some breast cancer cells in humans, because of its inability to associate the extracellular matrix.