Просмотр кода страницы Emopamil binding protein

{{Short description|Protein-coding gene in humans}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox gene}}
{{Infobox enzyme
| name = 3-beta-hydroxysteroid-Δ8,Δ7-isomerase
| AltNames =
| image = 
| image_size = 
| caption = 
| EC_number = 5.3.3.5
| CAS_number = 
| GO_code = 0000247
}}


'''Emopamil binding protein''' is a [[protein]] that in humans is encoded by the '''''EBP'' '''[[gene]], located on the [[X chromosome]].<ref name="pmid17498944">{{cite journal | vauthors = Guggenberger C, Ilgen D, Adamski J | title = Functional analysis of cholesterol biosynthesis by RNA interference | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 104 | issue = 3–5 | pages = 105–109 | date = May 2007 | pmid = 17498944 | doi = 10.1016/j.jsbmb.2007.03.001 | s2cid = 20838858 }}</ref> 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]].<ref>{{cite journal |last1=Moebius |first1=F F |last2=Hanner |first2=M |last3=Knaus |first3=H G |last4=Weber |first4=F |last5=Striessnig |first5=J |last6=Glossmann |first6=H |title=Purification and amino-terminal sequencing of the high affinity phenylalkylamine Ca2+ antagonist binding protein from guinea pig liver endoplasmic reticulum. |journal=Journal of Biological Chemistry |date=November 1994 |volume=269 |issue=46 |pages=29314–29320 |doi=10.1016/s0021-9258(19)62046-6 |doi-access=free }}</ref> EBP has a mass of 27.3 kDa and resembles the [[Sigma-2 receptor|σ<sub>2</sub>-receptor]] that resides in the endoplasmic reticulum of various tissues as an [[integral membrane protein]].<ref name="Hanner_1995">{{cite journal | vauthors = Hanner M, Moebius FF, Weber F, Grabner M, Striessnig J, Glossmann H | title = Phenylalkylamine Ca2+ antagonist binding protein. Molecular cloning, tissue distribution, and heterologous expression | journal = The Journal of Biological Chemistry | volume = 270 | issue = 13 | pages = 7551–7557 | date = March 1995 | pmid = 7706302 | doi = 10.1074/jbc.270.13.7551 | doi-access = free }}</ref>

== 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.<ref>{{cite journal |last1=Silve |first1=Sandra |last2=Dupuy |first2=Pascal Henry |last3=Labit-Lebouteiller |first3=Christine |last4=Kaghad |first4=Mourad |last5=Chalon |first5=Pascale |last6=Rahier |first6=Alain |last7=Taton |first7=Maryse |last8=Lupker |first8=Jan |last9=Shire |first9=David |last10=Loison |first10=Gárard |title=Emopamil-binding Protein, a Mammalian Protein That Binds a Series of Structurally Diverse Neuroprotective Agents, Exhibits Δ8-Δ7 Sterol Isomerase Activity in Yeast * |journal=Journal of Biological Chemistry |date=13 September 1996 |volume=271 |issue=37 |pages=22434–22440 |doi=10.1074/jbc.271.37.22434 |pmid=8798407 |doi-access=free }}</ref> In the Bloch pathway of cholesterol biosynthesis, EBP converts [[zymosterol]] to [[dehydrolathosterol]], while in the Kandutsch–Russell pathway it converts [[zymostenol]] to [[lathosterol]].
[[File:EBP enzymatic reaction.png|500px|EBP catalyzes the conversion of zymostenol to lathosterol]]

== Clinical significance ==
Mutations in ''EBP'' cause [[Conradi–Hünermann syndrome]] and impairs [[Cholesterol|cholesterol biosynthesis]].<ref>{{cite journal | vauthors = Barboza-Cerda MC, Wong LJ, Martínez-de-Villarreal LE, Zhang VW, Déctor MA | title = A novel EBP c.224T>A mutation supports the existence of a male-specific disorder independent of CDPX2 | journal = American Journal of Medical Genetics. Part A | volume = 164A | issue = 7 | pages = 1642–1647 | date = July 2014 | pmid = 24700572 | doi = 10.1002/ajmg.a.36508 | s2cid = 6501291 }}</ref> 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 [[cataract]]s along with coarse hair and hair loss.<ref>{{cite book | vauthors = Krakow D | chapter = Chondrodysplasia Punctata |date=2018 | doi = 10.1016/b978-0-323-44548-1.00048-6 | veditors = Copel JA, D'Alton ME, Reapply WC, Feltovich H, Gratacós E, Krakow D, Odibo AO, Platt LD, Tutschek B | title = Obstetric Imaging: Fetal Diagnosis and Care | edition = 2nd |pages=259–261 | publisher=Elsevier | isbn = 978-0-323-44548-1 }}</ref>

==Research areas==

===Remyelination and MS===
The inhibition of EBP promotes [[oligodendrocyte]] formation, which may help [[remyelination]] and thus limit [[multiple sclerosis]] development. <ref>{{cite journal | vauthors = Dorel R, Sun D, Carruthers N, Castanedo GM, Ung PM, Factor DC, Li T, Baumann H, Janota D, Pang J, Salphati L, Meklemburg R, Korman AJ, Harper HE, Stubblefield S, Payandeh J, McHugh D, Lang BT, Tesar PJ, Dere E, Masureel M, Adams DJ, Volgraf M, Braun MG | title = Discovery and Optimization of Selective Brain-Penetrant EBP Inhibitors that Enhance Oligodendrocyte Formation | journal = Journal of Medicinal Chemistry | volume = 67 | issue = 6 | pages = 4819–4832 | date = March 2024 | pmid = 38470227 | doi = 10.1021/acs.jmedchem.3c02396 }}</ref>

===Cloning ===
Isolation, replication and characterization of the EBP and EBP-like protein have been performed in [[yeast]]/[[Escherichia coli|E. Coli]] strains (which lack the EBP protein in nature) to study the high-affinity drug binding effects.<ref name="Hanner_1995" />

== See also ==
* [[Emopamil]]
*[[Cholestenol Delta-isomerase]]
*[[Sigma-1 receptor]]
*[[Sigma-2 receptor]]

== References ==
{{reflist}}

== External links ==
* [https://www.ncbi.nlm.nih.gov/books/NBK55062/  GeneReviews/NCBI/NIH/UW entry on Chondrodysplasia Punctata 2, X-Linked, Conradi-Hünermann Syndrome, Happle Syndrome]
* {{MeshName|EBP+protein,+human}}

{{Intramolecular oxidoreductases}}

[[Category:Genetics]]


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