PXD020602

PXD020602 is an original dataset announced via ProteomeXchange.

Title	Identification of small molecule activators of the ubiquitin ligase E6AP/UBE3A and Angelman syndrome-derived E6AP/UBE3A variants
Description	Genetic aberrations of the UBE3A gene encoding the E3 ubiquitin ligase E6AP underlie the development of Angelman syndrome (AS). Approximately 10 percent of AS individuals harbor UBE3A genes with point mutations, frequently resulting in the expression of full-length E6AP variants with defective E3 activity. Since E6AP exists in two states, an inactive and an active one, we hypothesized that distinct small molecules can stabilize the active state and that such molecules may rescue the E3 activity of AS-derived E6AP variants. Therefore, we established an assay that allows identifying modulators of E6AP in a high-throughput format. We identified several compounds that not only stimulate wild-type E6AP but also rescue the E3 activity of certain E6AP variants. Moreover, by chemical crosslinking coupled to mass spectrometry we provide evidence that the compounds stabilize an active conformation of E6AP. Thus, these compounds represent potential lead structures for the design of drugs for AS treatment.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:12:58.288.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Florian Stengel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-28 01:37:40	ID requested
1	2020-09-28 00:43:04	announced
⏵ 2	2024-10-22 05:13:06	announced	2024-10-22: Updated project metadata.

Offensperger F, M, ü, ller F, Jansen J, Hammler D, G, ö, tz KH, Marx A, Sirois CL, Chamberlain SJ, Stengel F, Scheffner M, Identification of Small-Molecule Activators of the Ubiquitin Ligase E6AP/UBE3A and Angelman Syndrome-Derived E6AP/UBE3A Variants. Cell Chem Biol, 27(12):1510-1520.e6(2020) [pubmed]

10.1016/j.chembiol.2020.08.017;

submitter keyword: UBE3A,Angelman syndrome, crosslinking coupled to mass spectrometry, E6AP, small molecule activator, fluorescence polarization, XL-MS, ubiquitin ligase, high-throughput screen

Prof. Dr. Florian Stengel
contact affiliation	Department of Biology University of Konstanz Germany
contact email	florian.stengel@uni-konstanz.de
lab head
Florian Stengel
contact affiliation	Universität Konstanz
contact email	florian.stengel@uni-konstanz.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/09/PXD020602

PRIDE project URI

• PRIDE
  1. PXD020602
     1. Label: PRIDE project
     2. Name: Identification of small molecule activators of the ubiquitin ligase E6AP/UBE3A and Angelman syndrome-derived E6AP/UBE3A variants