Pathways & interactions
Short name: Secretoglobin
Overlapping homologous superfamilies
- Secretoglobin superfamily (IPR035960)
Secretoglobins are relatively small, secreted, disulphide-bridged dimeric proteins with encoding genes sharing substantial sequence similarity [PMID: 7868811,PMID: 11193777]. Members of this family include:
- Uteroglobin, a mammalian, steroid-inducible, secreted anti-inflammatory/immunomodulatory protein [PMID: 17916741].
- Mammaglobin, expressed in ovarian cancer cells [PMID: 18021217].
- Lipophilin B, which exists as a complex with mammary-specific mammaglobin A [PMID: 17163411].
- Clara cell 17 kDa protein, which inhibits phospholipase A2 and papain, and also binds to progesterone [PMID: 1560460,PMID: 11193778].
- Allergen Fel d 1 (Felis silvestris catus (Cat) allergen 1) chains 1 and 2, a tetrameric glycoprotein formed by two heterodimers that elicit IgE responses in people with allergy to cats [PMID: 17543334,PMID: 12851385].
Secretoglobin proteins have a four-helical structure, and in the case of uteroglobin, form homodimers, whereas allergen Fel d 1 forms a tetramer of two heterodimers (chains 1 and 2). The conservation of this primary and quaternary structure indicates that the genome of the eutherian common ancestor of cats, rodents, and primates contained a similar gene pair.
Uteroglobin (blastokinin or Clara cell protein CC10) is a mammalian steroid-inducible secreted protein originally isolated from the uterus of rabbits during early pregnancy [PMID: 2378892]. The mucosal epithelia of several organs that communicate with the external environment express uteroglobin. Its tissue-specific expression is regulated by steroid hormones, and is augmented in the uterus by non-steroidal prolactin. Uteroglobin may be a multi-functional protein with anti-inflammatory/immunomodulatory properties, acting to inhibit phospholipase A2 activity [PMID: 3319534,PMID: 11193767], and binding to (and possibly sequestering) several hydrophobic ligands such as progesterone, retinols, polychlorinated biphenyls, phospholipids and prostaglandins [PMID: 11193782,PMID: 11193750]. In addition, uteroglobin has anti-chemotactic, anti-allergic, anti-tumourigenic and embryo growth-stimulatory properties. Uteroglobin may have a homeostatic role against oxidative damage, inflammation, autoimmunity and cancer [PMID: 17916741, PMID: 17928103, PMID: 11193760, PMID: 7770456]. However, the true biological function of uteroglobin is poorly understood. Uteroglobin consists of a disulphide-linked homodimer with a large hydrophobic pocket located between the two dimers [PMID: 3656405]. Each monomer being composed of four 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 [PMID: 11193783]. The hydrophobic pocket binds steroids, particularly progesterone, with high specificity. It is a member of the secretoglobin superfamily.