PXD016948

PXD016948 is an original dataset announced via ProteomeXchange.

Title	A highly conserved luminal ER exit motif in the pseudoproteases iRhom1 and iRhom2 is indispensable for TNF������ and EGF receptor ligand release
Description	Membrane-tethered signalling proteins such as TNF������ and many EGF receptor ligands undergo shedding by the metalloproteinase ADAM17 to get released. The pseudoproteases iRhom1 and iRhom2 are important for the ER exit and activity of ADAM17. Yet, their structural requirements to promote ER exit remained unexplored. Utilising in silico and in vitro methods, we here map the conserved iRhom homology domain (IRHD) and provide insights into its structure and function. We identified a highly conserved motif within the IRHD, which is indispensable for the ER exit of iRhoms and termed it CERES (conserved ER exit sequence). Strikingly, single point mutations in CERES abrogate the ER exit without disrupting other iRhom functions. We confirmed the physiological significance of CERES by inactivating it in mice which abrogates ADAM17-mediated shedding ex vivo and in vivo. This demonstrates a crucial role of CERES in the ADAM17-dependent release of various growth factor and cytokine signals.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:22:16.846.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Preisinger
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-01-06 02:15:30	ID requested
1	2021-05-25 08:33:45	announced
⏵ 2	2024-10-22 05:22:17	announced	2024-10-22: Updated project metadata.

10.1007/s00018-021-03845-3;

D, ü, sterh, ö, ft S, Kahveci-T, ü, rk, ö, z S, Wozniak J, Seifert A, Kasparek P, Ohm H, Liu S, Kopkanova J, Lokau J, Garbers C, Preisinger C, Sedlacek R, Freeman M, Ludwig A, and EGF receptor ligand release. Cell Mol Life Sci, 78(11):5015-5040(2021) [pubmed]

curator keyword: Biological

submitter keyword: TNF������, receptors,Cell biology, EGF

Stefan D������sterh������ft
contact affiliation	Institute of Pharmacology and Toxicology, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany
contact email	sduesterhoeft@ukaachen.de
lab head
Christian Preisinger
contact affiliation	Proteomics Facility, IZKF Aachen, University Clinic RWTH Aachen
contact email	cpreisinger@ukaachen.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/2021/05/PXD016948

PRIDE project URI

• PRIDE
  1. PXD016948
     1. Label: PRIDE project
     2. Name: A highly conserved luminal ER exit motif in the pseudoproteases iRhom1 and iRhom2 is indispensable for TNF������ and EGF receptor ligand release