Uteroglobin, also known as secretoglobin family 1A member 1 (or SCGB1A1 for short) is a protein found in humans and other mammals. This protein is induced by progesterone. It binds it and inhibits the enzyme phospholipase. This steroid-inducible immunomodulatory protein is considered the founding member of the secretogoblin family, but it also identical to lung clara cell protein (CC10), and is often referred to as uteroglobin/clara. This protein has been observed to be primarily expressed in the club cells of the lungs and in renal cells.
The physiological roles of uteroglobin are not entirely known, but it has been observed to have several functions.
· Immunomodulation: regulatory adjustment of the immune system
· Binding progesterone, which plays a key role in things like pregnancy, the menstrual cycle, and embryogenesis
· Inhibiting secretory phospholipase activity, which has links to development of conditions like epilepsy, Alzheimer’s and multiple sclerosis.
· Binding Phosphatidylcholine, important in liver repair and linked to atherosclerosis
· Binds to fibronectin, which is involved in growth, cell adhesion, migration, and differentiation in all vertebrate organisms
· A target of polychlorinated biphenyl, a probable human carcinogen and causes effects such as endocrine disruption and neurotoxicity
Uteroglobin’s mechanisms are not fully understood as of yet and are still the subject of much research including trials on control rabbits and mice.
A mechanism of uteroglobin is preventing severe renal disease.
This disease is caused by an abnormal deposition of predominantly multimeric fibronectin and collagen in the glomerulus.
The molecular mechanisms by which uteroglobin prevents this disease, as shown by experiments in control mice, is attributable to its high-affinity binding to fibronectin and the formation of fibronectin-uteroglobin heteromers.
These heteromers counteract both fibronectin-fibronectin and fibronectin-collagen interactions which are both required for abnormal tissue deposition.
In addition, by inhibiting secretory phospholipase activity and decreasing the level of lysophosphatidic acid, uteroglobin may indirectly prevent the activation of integrins that enhance abnormal tissue deposition of fibronectin.
The mechanism(s) of uteroglobin action is likely to be even more complex, because it also functions through a receptor-mediated pathway that has not yet been clearly defined.
As mentioned above, the specific roles and mechanisms of uteroglobin in the human body are as-of-yet unclear. However, it is primarily understood in its role of interacting with progesterone, phospholipase, phosphatidylcholine, fibronectin, and polychlorinated biphenyl. Primarily, this steroid hormone regulates the expression of specific genes, particularly in the lungs, liver, and other organs. It has evidence of further interactions with other proteins in the body, including TRIM32, LRP2, CUBN, ACTB, ACTA2, and BLK
Uteroglobin has been discovered to be a homodimeric protein with identical 70-amino acid subunits that are joined in an antiparallel orientation by two disulfide bridges. More specifically, the two disulfide bonds connecting the two subunits are formed between Cys 3 and Cys 69′ and between Cys 3′ and Cys 69, respectively. The two pairs of cysteine residues forming the two disulfide bridges are also shown as Corey-Pauling-Koltun representations in which only the side chain atoms of cysteine residues are visible. It is clear that the disulfide bridges facilitate the stabilization of the UG dimer and the formation of a central hydrophobic cavity