Ribosomal protein SA

40S ribosomal protein SA is a ribosomal protein that in humans is encoded by the "RPSA" gene. It also acts as a cell surface receptor, in particular for laminin, and is involved in several pathogenic processes.
Function.
Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Many of the effects of laminin are mediated through interactions with cell surface receptors. These receptors include members of the integrin family, as well as non-integrin laminin-binding proteins. The RPSA gene encodes a multifunctional protein, which is both a ribosomal protein and a high-affinity, non-integrin laminin receptor. This protein has been variously called Ribosomal protein SA; RPSA; LamR; LamR1; 37 kDa Laminin Receptor Precursor; 37LRP; 67 kDa Laminin Receptor; 67LR; 37/67 kDa Laminin Receptor; LRP/LR; LBP/p40; and p40 ribosome-associated protein. Ribosomal protein SA and RPSA are the approved name and symbol. The amino acid sequence of RPSA is highly conserved through evolution, suggesting a key biological function. It has been observed that the level of RPSA transcript is higher in colon carcinoma tissue and lung cancer cell lines than their normal counterparts. Also, there is a correlation between the upregulation of this polypeptide in cancer cells and their invasive and metastatic phenotype. Multiple copies of the RPSA gene exist; however, most of them are pseudogenes thought to have arisen from retropositional events. Two alternatively spliced transcript variants encoding the same protein have been found for this gene.
Structure and stability.
The complementary DNA (cDNA) of the RPSA gene is formed by the assembly of seven exons, six of which correspond to the coding sequence. The amino acid sequence of RPSA, deduced from the sequence of its cDNA, includes 295 residues. RPSA can be sub-divided in two main domains: an N-domain (residues 1-209), which corresponds to exons 2-5 of the gene, and a C-domain (residues 210-295), which corresponds to exons 6-7. The N-domain of RPSA is homologous to the ribosomal protein S2 (RPS2) of prokaryotes. It contains a palindromic sequence 173LMWWML178 which is conserved in all metazoans. Its C-domain is highly conserved in vertebrates. The amino acid sequence of RPSA is 98% identical in all mammals. RPSA is a ribosomal protein which has acquired the function of laminin receptor during evolution. The structure of the N-domain of RPSA is similar to those of prokaryotic RPS2. The C-domain is intrinsically disordered in solution. The N-domain is monomeric in solution and unfolds according to a three state equilibrium. The folding intermediate is predominant at 37 °C.
Interactions.
Several interactions of RPSA that had originally been discovered by methods of cellular biology, have subsequently been confirmed by using recombinant derivatives and in vitro experiments. The latter have shown that the folded N-domain and disordered C-domain of RPSA have both common and specific functions.