Emopamil binding protein

EBP
Identifiers
Aliases	EBP , CDPX2, CHO2, CPX, CPXD, MEND, emopamil binding protein (sterol isomerase), cholestenol delta-isomerase, EBP cholestenol delta-isomerase
External IDs	OMIM: 300205; MGI: 107822; HomoloGene: 4798; GeneCards: EBP; OMA:EBP - orthologs
EC number	5.3.3.5
Gene location (Human) Chr. X chromosome (human) [1] Band Xp11.23 Start 48,521,799 bp [1] End 48,528,716 bp [1]
Gene location (Mouse) Chr. X chromosome (mouse) [2] Band X A1.1|X 3.7 cM Start 8,051,568 bp [2] End 8,059,751 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver right adrenal gland right adrenal cortex left adrenal gland mucosa of transverse colon left adrenal cortex tendon of biceps brachii oocyte gingival epithelium buccal mucosa cell Top expressed in left lobe of liver esophagus decidua duodenum jejunum right kidney proximal tubule human kidney left colon pyloric antrum More reference expression data BioGPS n/a
Gene ontology Molecular function C-8 sterol isomerase activity isomerase activity xenobiotic transmembrane transporter activity transmembrane signaling receptor activity cholestenol delta-isomerase activity steroid delta-isomerase activity protein binding Cellular component integral component of membrane endoplasmic reticulum membrane membrane intracellular membrane-bounded organelle integral component of plasma membrane endoplasmic reticulum cytoplasmic vesicle nuclear envelope nucleus Biological process skeletal system development steroid metabolic process sterol biosynthetic process lipid metabolism cholesterol metabolic process cholesterol biosynthetic process via lathosterol sterol metabolic process cholesterol biosynthetic process via desmosterol steroid biosynthetic process cholesterol biosynthetic process xenobiotic transmembrane transport signal transduction hemopoiesis xenobiotic transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10682 13595 Ensembl ENSG00000147155 ENSMUSG00000031168 UniProt Q15125 P70245 RefSeq (mRNA) NM_006579 NM_007898 RefSeq (protein) NP_006570 NP_031924 Location (UCSC) Chr X: 48.52 – 48.53 Mb Chr X: 8.05 – 8.06 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

3-beta-hydroxysteroid-Δ8,Δ7-isomerase
Identifiers
EC no.	5.3.3.5
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

Emopamil binding protein is a protein that in humans is encoded by the EBP gene, located on the X chromosome. ^[5] EBP was discovered through its high-affinity binding to anti-ischemic drugs such as emopamil, from which it also derives its name. In addition to emopamil, EBP also bind with high affinity a variety of structurally unrelated compounds, such as amiodarone, opipramol, ifenprodil, trifluoperazine, and chlorpromazine. ^[6] EBP has a mass of 27.3 kDa and resembles the σ₂-receptor that resides in the endoplasmic reticulum of various tissues as an integral membrane protein. ^[7]

Function

EBP functions as a Δ8–Δ7 sterol isomerase, catalyzing the migration of the double bond in the sterol B-ring from the 8(9) to the 7(8) position. ^[8] In the Bloch pathway of cholesterol biosynthesis, EBP converts zymosterol to dehydrolathosterol, while in the Kandutsch–Russell pathway it converts zymostenol to lathosterol.

Clinical significance

Mutations in EBP cause Conradi–Hünermann syndrome and impairs cholesterol biosynthesis. ^[9] 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. ^[10]

Research areas

Remyelination and MS

The inhibition of EBP promotes oligodendrocyte formation, which may help remyelination and thus limit multiple sclerosis development. ^[11]

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. ^[7]

See also

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

References

1. GRCh38: Ensembl release 89: ENSG00000147155 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031168 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Guggenberger C, Ilgen D, Adamski J (May 2007). "Functional analysis of cholesterol biosynthesis by RNA interference". The Journal of Steroid Biochemistry and Molecular Biology. 104 (3–5): 105–109. doi:10.1016/j.jsbmb.2007.03.001. PMID   17498944. S2CID   20838858.
6. Moebius FF, Hanner M, Knaus HG, Weber F, Striessnig J, Glossmann H (November 1994). "Purification and amino-terminal sequencing of the high affinity phenylalkylamine Ca2+ antagonist binding protein from guinea pig liver endoplasmic reticulum". Journal of Biological Chemistry. 269 (46): 29314–29320. doi: 10.1016/s0021-9258(19)62046-6 .
7. Hanner M, Moebius FF, Weber F, Grabner M, Striessnig J, Glossmann H (March 1995). "Phenylalkylamine Ca2+ antagonist binding protein. Molecular cloning, tissue distribution, and heterologous expression". The Journal of Biological Chemistry. 270 (13): 7551–7557. doi: 10.1074/jbc.270.13.7551 . PMID   7706302.
8. Silve S, Dupuy PH, Labit-Lebouteiller C, Kaghad M, Chalon P, Rahier A, et al. (13 September 1996). "Emopamil-binding Protein, a Mammalian Protein That Binds a Series of Structurally Diverse Neuroprotective Agents, Exhibits Δ8-Δ7 Sterol Isomerase Activity in Yeast *". Journal of Biological Chemistry. 271 (37): 22434–22440. doi: 10.1074/jbc.271.37.22434 . PMID   8798407.
9. Barboza-Cerda MC, Wong LJ, Martínez-de-Villarreal LE, Zhang VW, Déctor MA (July 2014). "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. doi:10.1002/ajmg.a.36508. PMID   24700572. S2CID   6501291.
10. Krakow D (2018). "Chondrodysplasia Punctata". In Copel JA, D'Alton ME, Reapply WC, Feltovich H, Gratacós E, Krakow D, Odibo AO, Platt LD, Tutschek B (eds.). Obstetric Imaging: Fetal Diagnosis and Care (2nd ed.). Elsevier. pp. 259–261. doi:10.1016/b978-0-323-44548-1.00048-6. ISBN   978-0-323-44548-1.
11. Dorel R, Sun D, Carruthers N, Castanedo GM, Ung PM, Factor DC, et al. (March 2024). "Discovery and Optimization of Selective Brain-Penetrant EBP Inhibitors that Enhance Oligodendrocyte Formation". Journal of Medicinal Chemistry. 67 (6): 4819–4832. doi:10.1021/acs.jmedchem.3c02396. PMID   38470227.

External links

• GeneReviews/NCBI/NIH/UW entry on Chondrodysplasia Punctata 2, X-Linked, Conradi-Hünermann Syndrome, Happle Syndrome
• EBP+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)