Early pregnancy factor

4PJ1333615528ENSG00000115541ENSMUSG00000073676P61604Q64433NM_002157NM_008303NP_002148NP_032329Heat shock 10 kDa protein 1 (Hsp10), also known as chaperonin 10 (cpn10) or early-pregnancy factor (EPF), is a protein that in humans is encoded by the HSPE1 gene. The homolog in E. coli is GroES that is a chaperonin which usually works in conjunction with GroEL. Heat shock 10 kDa protein 1 (Hsp10), also known as chaperonin 10 (cpn10) or early-pregnancy factor (EPF), is a protein that in humans is encoded by the HSPE1 gene. The homolog in E. coli is GroES that is a chaperonin which usually works in conjunction with GroEL. GroES exists as a ring-shaped oligomer of between six and eight identical subunits, while the 60 kDa chaperonin (cpn60 - or groEL in bacteria) forms a structure comprising 2 stacked rings, each ring containing 7 identical subunits. These ring structures assemble by self-stimulation in the presence of Mg2+-ATP. The central cavity of the cylindrical cpn60 tetradecamer provides an isolated environment for protein folding whilst cpn-10 binds to cpn-60 and synchronizes the release of the folded protein in an Mg2+-ATP dependent manner. The binding of cpn10 to cpn60 inhibits the weak ATPase activity of cpn60. Escherichia coli GroES has also been shown to bind ATP cooperatively, and with an affinity comparable to that of GroEL. Each GroEL subunit contains three structurally distinct domains: an apical, an intermediate and an equatorial domain. The apical domain contains the binding sites for both GroES and the unfolded protein substrate. The equatorial domain contains the ATP-binding site and most of the oligomeric contacts. The intermediate domain links the apical and equatorial domains and transfers allosteric information between them. The GroEL oligomer is a tetradecamer, cylindrically shaped, that is organised in two heptameric rings stacked back to back. Each GroEL ring contains a central cavity, known as the `Anfinsen cage', that provides an isolated environment for protein folding. The identical 10 kDa subunits of GroES form a dome-like heptameric oligomer in solution. ATP binding to GroES may be important in charging the seven subunits of the interacting GroEL ring with ATP, to facilitate cooperative ATP binding and hydrolysis for substrate protein release. GroES has been shown to interact with GroEL. Early pregnancy factor is tested for rosette inhibition assay. EPF is present in the maternal serum (blood plasma) shortly after fertilization; EPF is also present in cervical mucus and in amniotic fluid. EPF may be detected in sheep within 72 hours of mating, in mice within 24 hours of mating, and in samples from media surrounding human embryos fertilized in vitro within 48 hours of fertilization (although another study failed to duplicate this finding for in vitro embryos). EPF has been detected as soon as within six hours of mating. Because the rosette inhibition assay for EPF is indirect, substances that have similar effects may confound the test. Pig semen, like EPF, has been shown to inhibit rosette formation - the rosette inhibition test was positive for one day in sows mated with a vasectomized boar, but not in sows similarly stimulated without semen exposure. A number of studies in the years after the discovery of EPF were unable to reproduce the consistent detection of EPF in post-conception females, and the validity of the discovery experiments was questioned. However, progress in characterization of EPF has been made and its existence is well-accepted in the scientific community. Early embryos are not believed to directly produce EPF. Rather, embryos are believed to produce some other chemical that induces the maternal system to create EPF. After implantation, EPF may be produced by the conceptus directly. EPF is an immunosuppressant. Along with other substances associated with early embryos, EPF is believed to play a role in preventing the immune system of the pregnant female from attacking the embryo. Injecting anti-EPF antibodies into mice after mating significantly reduced the number of successful pregnancies and number of pups; no effect on growth was seen when mice embryos were cultured in media containing anti-EPF antibodies. While some actions of EPF are the same in all mammals (namely rosette inhibition), other immunosuppressant mechanism vary between species.