40S ribosomal protein SA is a ribosomal protein that in humans is encoded by the RPSA gene. [5] [6] It also acts as a cell surface receptor, in particular for laminin, and is involved in several pathogenic processes.
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. [7]
The complementary DNA (cDNA) of the RPSA gene is formed by the assembly of seven exons, six of which correspond to the coding sequence. [6] 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. [8] [9] The structure of the N-domain of RPSA is similar to those of prokaryotic RPS2. [10] 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. [11]
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. [12]
Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, organization of the intracellular cytoskeleton, and movement of new receptors to the cell membrane. The presence of integrins allows rapid and flexible responses to events at the cell surface.
A poliovirus, the causative agent of polio, is a serotype of the species Enterovirus C, in the family of Picornaviridae. There are three poliovirus serotypes: types 1, 2, and 3.
Laminins are a family of glycoproteins of the extracellular matrix of all animals. They are major components of the basal lamina, the protein network foundation for most cells and organs. The laminins are an important and biologically active part of the basal lamina, influencing cell differentiation, migration, and adhesion.
Thrombospondin 1, abbreviated as THBS1, is a protein that in humans is encoded by the THBS1 gene.
Heparin-binding EGF-like growth factor (HB-EGF) is a member of the EGF family of proteins that in humans is encoded by the HBEGF gene.
Syndecan-2 is a protein that in humans is encoded by the SDC2 gene.
Receptor for activated C kinase 1 (RACK1), also known as guanine nucleotide-binding protein subunit beta-2-like 1 (GNB2L1), is a 35 kDa protein that in humans is encoded by the RACK1 gene.
Integrin, beta 4 (ITGB4) also known as CD104, is a human gene.
Laminin subunit alpha-5 is a protein that in humans is encoded by the LAMA5 gene.
Laminin subunit alpha-1 is a protein that in humans is encoded by the LAMA1 gene.
Laminin subunit beta-1 is a protein that in humans is encoded by the LAMB1 gene.
40S ribosomal protein S19 is a protein that in humans is encoded by the RPS19 gene.
Alpha-7 integrin is a protein that in humans is encoded by the ITGA7 gene. Alpha-7 integrin is critical for modulating cell-matrix interactions. Alpha-7 integrin is highly expressed in cardiac muscle, skeletal muscle and smooth muscle cells, and localizes to Z-disc and costamere structures. Mutations in ITGA7 have been associated with congenital myopathies and noncompaction cardiomyopathy, and altered expression levels of alpha-7 integrin have been identified in various forms of muscular dystrophy.
Syndecan-3 is a protein that in humans is encoded by the SDC3 gene.
60S ribosomal protein L10 is a protein that in humans is encoded by the RPL10 gene.
Eukaryotic translation initiation factor 6 (EIF6), also known as Integrin beta 4 binding protein (ITGB4BP), is a human gene.
Fibulin-2 is a protein that in humans is encoded by the FBLN2 gene.
60S ribosomal protein L6 is a protein that in humans is encoded by the RPL6 gene.
60S ribosomal protein L22 is a protein that in humans is encoded by the RPL22 gene on Chromosome 1.
Tensin-like C1 domain-containing phosphatase is an enzyme that in humans is encoded by the TENC1 gene.