Emopamil binding protein explained

Emopamil binding protein is a protein that in humans is encoded by the EBP gene, located on the X chromosome.^[1] The protein is shown to have a high-affinity reception for anti-ischemic drugs, such as Emopamil, resulting in its discovery and given name. EBP has a mass of 27.3 kDa and resembles a σ-receptor that resides in the endoplasmic reticulum of various tissues as an integral membrane protein.^[2]

Clinical significance

Mutations in EBP cause Conradi–Hünermann syndrome and impairs cholesterol biosynthesis.^[3] Unborn males affected with EBP mutations are not expected to be liveborn, (with up to only 5% male births). Individuals, mostly female, that are liveborn with EBP mutations experience stunted growth, limb reduction and back problems. Later in life, the individual may develop cataracts along with coarse hair and hair loss.^[4]

Research areas

Remyelination and MS

The inhibition of EBP promotes oligodendrocyte formation, which may help remyelination and thus limit multiple sclerosis development. ^[5]

Cloning

Isolation, replication and characterization of the EBP and EBP-like protein have been performed in yeast/E. Coli strains (which lack the EBP protein in nature) to study the high-affinity drug binding effects.

See also

• Emopamil
• Cholestenol Delta-isomerase
• Sigma-1 receptor
• Sigma-2 receptor

External links

• GeneReviews/NCBI/NIH/UW entry on Chondrodysplasia Punctata 2, X-Linked, Conradi-Hünermann Syndrome, Happle Syndrome

Notes and References

1. Guggenberger C, Ilgen D, Adamski J . Functional analysis of cholesterol biosynthesis by RNA interference . The Journal of Steroid Biochemistry and Molecular Biology . 104 . 3–5 . 105–109 . May 2007 . 17498944 . 10.1016/j.jsbmb.2007.03.001 . 20838858 .
2. Hanner M, Moebius FF, Weber F, Grabner M, Striessnig J, Glossmann H . Phenylalkylamine Ca2+ antagonist binding protein. Molecular cloning, tissue distribution, and heterologous expression . The Journal of Biological Chemistry . 270 . 13 . 7551–7557 . March 1995 . 7706302 . 10.1074/jbc.270.13.7551 . free .
3. Barboza-Cerda MC, Wong LJ, Martínez-de-Villarreal LE, Zhang VW, Déctor MA . A novel EBP c.224T>A mutation supports the existence of a male-specific disorder independent of CDPX2 . American Journal of Medical Genetics. Part A . 164A . 7 . 1642–1647 . July 2014 . 24700572 . 10.1002/ajmg.a.36508 . 6501291 .
4. Book: Krakow D . Chondrodysplasia Punctata . 2018 . 10.1016/b978-0-323-44548-1.00048-6 . Copel JA, D'Alton ME, Reapply WC, Feltovich H, Gratacós E, Krakow D, Odibo AO, Platt LD, Tutschek B . Obstetric Imaging: Fetal Diagnosis and Care . 2nd . 259–261 . Elsevier . 978-0-323-44548-1 .
5. Discovery and Optimization of Selective Brain-Penetrant EBP Inhibitors that Enhance Oligodendrocyte Formation. Ruth. Dorel. Dawei. Sun. Nicholas. Carruthers. Georgette M.. Castanedo. Peter M.-U.. Ung. Daniel C.. Factor. Tianbo. Li. Hannah. Baumann. Danielle. Janota. Jodie. Pang. Laurent. Salphati. Robert. Meklemburg. Allison J.. Korman. Halie E.. Harper. Samantha. Stubblefield. Jian. Payandeh. Daniel. McHugh. Bradley T.. Lang. Paul J.. Tesar. Edward. Dere. Matthieu. Masureel. Drew J.. Adams. Matthew. Volgraf. Marie-Gabrielle. Braun. March 28, 2024. Journal of Medicinal Chemistry. 67. 6. 4819–4832. PubMed. 10.1021/acs.jmedchem.3c02396. 38470227.