Secretoglobins are relatively small, secreted, disulphide-bridged dimeric proteins with encoding genes sharing substantial sequence similarity. Their family subunits may be grouped into five subfamilies, A-E. Uteroglobin (subfamily A), which is identical to Clara cell protein (CC10), forms a globular shaped homodimer with a large hydrophobic pocket located between the two dimers. The uteroglobin monomer structure is composed of four alpha helices that do not form a canonical four helix-bundle motif but rather a boomerang-shaped structure in which helices H1, H3, and H4 are able to bind a homodimeric partner. The hydrophobic pocket binds steroids, particularly progesterone, with high specificity. However, the true biological function of uteroglobin is poorly understood. In mammals, uteroglobin has immunosuppressive and anti-inflammatory properties through the inhibition of phospholipase A2. The other four main subfamilies of secretoglobins are found in heterodimeric combinations, with B and C subfamilies disulphide-bridged to the E and D subfamilies, respectively. [See review by Laukaitis C.M. & Karn R.C. (2005). Biological Journal of the Linnean Society 84, 493]. These include rat prostatic steroid-binding protein (PBP or prostatein), human mammaglobin (or heteroglobin), lipophilins, major cat allergen Fel dI, the hamster Harderian gland proteins and mouse salivary androgen-binding protein (ABP). Example of such a heterodimer: ABPalpha-like sequences are closely related to cat Fel dI chain 1, whereas ABPbeta-gamma-like sequences are closely related to Fel dI chain 2. Thus, the heterodimeric structure of ABPalpha-beta and ABPalpha-gamma is recapitulated by the sequence-similar Fel dI chains 1 and 2. This conservation of primary and quaternary structure indicates that the genome of the eutherian common ancestor of cats, rodents, and primates contained a similar gene pair.
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