|Protein Name||3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase|
|Ref Sequence ID||NP_776768.1|
|Protein Existence Status||Reviewed: Experimental evidence at protein level|
|Presence in other biological fluids/tissue/cells||found in all steroidogenic tissues, including adrenal glands, testes, ovaries, and human placenta, brain, human epidermal keratinocytes, and in guinea pig kidneys; In humans, expression of the type I isoenzyme accounts for the 3 -HSD activity found in placenta and peripheral tissues, whereas the type II 3 -HSD isoenzyme is predominantly expressed in the adrenal gland, ovary, and testis|
|Protein Function||catalyzes the conversion of the 3ß-hydroxy-∆5-steroids pregnenolone and dehydroepiandrosterope to the 3-keto-∆4-steroids progesterone and androstenedione, respectively; activity is essential for the production of all steroid hormones; responsible for the oxidation and isomerization of ∆5-3ß -hydroxysteroid precursors into ∆4- ketosteroids, thus catalyzing an essential step in the formation of all classes of active steroid hormones. Human placental 3β-hydroxysteroid dehydrogenase/steroid Δ5, 4-isomerase 1 (HSD3B1), a high-affinity type I enzyme, uses pregnenolone to make progesterone, which is critical for maintenance of pregnancy.|
|Biochemical Properties||it is possible that Ca2 could affect the mitochondrial to ER ratio of 3 -HSD; bovine zona glomerulosa cells showed that neither Ca2 nor Angiotensin-II had any effect on the subcellular distribution of 3 -HSD; two-step reaction of the 3 -HSD/isomerase involves the reduction of NAD to NADH by the rate-limiting 3 - HSD activity and the requirement of this NADH for the activation of the isomerase on the same enzyme|
|Significance in milk||biosynthesis of active estrogens and androgens as found in normal human mammary epithelial cells|
| Site(s) of PTM(s) |
|Predicted Disorder Regions||134-149,366-373|
|TM Helix Prediction||No TM helices|
|Additional Comments||deficiency is responsible for a rare form of congenital adrenal hyperplasia|
|Bibliography||1. Thomas, J. L., Myers, R. P., & Strickler, R. C. (1989). Human placental 3 beta-hydroxy-5-ene-steroid dehydrogenase and steroid 5----4-ene-isomerase: purification from mitochondria and kinetic profiles, biophysical characterization of the purified mitochondrial and microsomal enzymes. Journal of Steroid Biochemistry, 33(2), 209–217. https://doi.org/10.1016/0022-4731(89)90296-3. |
2. Cherradi, N., Rossier, M. F., Vallotton, M. B., Timberg, R., Friedberg, I., Orly, J., … Capponi, A. M. (1997). Submitochondrial distribution of three key steroidogenic proteins (steroidogenic acute regulatory protein and cytochrome p450scc and 3beta-hydroxysteroid dehydrogenase isomerase enzymes) upon stimulation by intracellular calcium in adrenal glomerulosa cells. The Journal of Biological Chemistry, 272(12), 7899–7907. https://doi.org/10.1074/jbc.272.12.7899.
3. Gingras, S., Moriggl, R., Groner, B., & Simard, J. (1999). Induction of 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase type 1 gene transcription in human breast cancer cell lines and in normal mammary epithelial cells by interleukin-4 and interleukin-13. Molecular Endocrinology (Baltimore, Md.), 13(1), 66–81. https://doi.org/10.1210/mend.13.1.0221.
4. Bain, P. A., Yoo, M., Clarke, T., Hammond, S. H., & Payne, A. H. (1991). Multiple forms of mouse 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase and differential expression in gonads, adrenal glands, liver, and kidneys of both sexes. Proceedings of the National Academy of Sciences of the United States of America, 88(20), 8870–8874. https://doi.org/10.1073/pnas.88.20.8870.