Update of the human secretoglobin (SCGB) gene superfamily and an example of 'evolutionary bloom' of androgen-binding protein genes within the mouse Scgb gene superfamily

Abstract

The secretoglobins (SCGBs) comprise a family of small, secreted proteins found in animals exclusively of mammalian lineage. There are 11 human SCGB genes and five pseudogenes. Interestingly, mice have 68 Scgb genes, four of which are highly orthologous to human SCGB genes; the remainder represent an ‘evolutionary bloom’ and make up a large gene family represented by only six counterparts in humans. SCGBs are found in high concentrations in many mammalian secretions, including fluids of the lung, lacrimal gland, salivary gland, prostate and uterus. Whereas the biological activities of most individual SCGBs have not been fully characterised, what already has been discovered suggests that this family has an important role in the modulation of inflammation, tissue repair and tumorigenesis. In mice, the large Scgb1b and Scgb2b gene families encode the androgen-binding proteins, which have been shown to play a role in mate selection. Although much has been learned about SCGBs in recent years, clearly more research remains to be done to allow a better understanding of the roles of these proteins in human health and disease. Such information is predicted to reveal valuable novel drug targets for the treatment of inflammation, as well as designing biomarkers that might identify tissue damage or cancer.

Single-Nucleotide Polymorphisms on theRYD5Gene in Nasal Polyposis

“…It has been known that the cytokine-driven regulation of expression in the SCGB superfamily in the airways plays a role in the pathogenesis of some diseases, such as asthma, rhinitis, and NP (Dear et al, 1991;Mukherjee et al, 1999;Jackson et al, 2011;Lu et al, 2011;Pala et al, 2014). Similar to other secretory proteins, RYD5 protein is a member of the SCGB superfamily and it has a hydrophobic N-terminal region with a 14 amino acid signal peptide sequence, which is required for its channeling into the target organelle (Dear et al, 1991;Lu et al, 2011).…”

“…They have been indicated as candidates for a new cytokine family owing to their anti-inflammatory and immunomodulatory functions. The SCGB superfamily has been rapidly expanding with the discovery of many new human genes (Mukherjee et al, 1999;Jackson et al, 2011;Lu et al, 2011). Some SCGBs have been associated with a number of disease states involving airways, including asthma, cystic fibrosis, bronchopulmonary dysplasia, and chronic obstructive pulmonary disease, either as contributing agents or biomarkers (Reynolds et al, 2002).…”

Significant association between SCGB1D4 gene polymorphisms and susceptibility to adenoid hypertrophy in a pediatric population*

“…Studies suggested that gene interaction is not only possible but is probably ubiquitous for determining susceptibility to complex human diseases (11). Further studies on the interactions are therefore warranted to elucidate their possible underlying role in the pathogenesis and delineation of pathways leading to AH.…”

“…Various genetic factors and their combinations can affect the association with various disease phenotypes, and change the severity of chronic inflammatory diseases through altering the levels of gene expression (9)(10)(11).…”

Mammaglobin A

“…All these proteins belong to the gene family of the uteroglobin/CC10, that is, the secretoglobin superfamily [6][7][8]. The suffix "globin" refers to hemoglobin and has a structural meaning in the term globin-fold, which is a bundle of eight alpha-helices connected by rather short loop regions and arranged so that the helices form a pocket for binding of the heme group.…”