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

The secretoglobins (SCGBs) comprise a family of secreted proteins found in mammals and marsupials. The first discovered SCGB was found in rabbits and was first called blastokinin,[1] then later uteroglobin [2] and is now designated SCGB1A1 (in some early literature, the SCGB family is referred to as the 'uteroglobin' family). Eventually, the term 'secretoglobin' was coined to refer to the characteristics that all family members have in common. The 'secreto-' portion of the name indicates that these proteins are secreted. A second reason was proposed for the suffix 'globin'; their functions had largely remained a secret (Lehrer, R., personal communication). This suffix was given because secretoglobins form dimers consisting of two four-α helix-bundle monomers, creating a hydrophobic binding pocket, reminiscent of the globin-fold, which is an eight-α-helix bundle with a pocket for a molecule such as a heme group [3].Secretoglobins are found at high levels in many secretions, including uterine, prostatic, pulmonary, lacrimal and salivary glands, with any specific secre-toglobin often being expressed in more than one tissue. For example, mRNA expression of every SCGB family member (except SCGB1D2) has been demonstrated in human airways [4]. In general, the physiological and pathophysiological functions of most individual SCGBs remain to be defined. Nevertheless, roles currently ascribed to SCGBs include lung maintenance and repair, immune modulation and, at least in rodents, mate selection. Some SCGB family members, such as mammaglobin, have been successfully used as epithelial cancer biomarkers.SCGBs are small (~10 kDa in humans) proteins that dimerise before secretion. Dimers are resistant to proteases, heat and pH [5,6]. The crystal structures of several SCGBs have been resolved, including those of rabbit and rat uteroglobin (Protein Data Bank identifiers [PDB ID]:1UTG, 2UTG, 1UTR), rat Clara-cell specific protein (CCSP) (PDB ID:1CCD) and feline CH2 (Feld-1) (PDB ID: