PXD065789

PXD065789 is an original dataset announced via ProteomeXchange.

Title	The intracellular localization and the ionic permeation of TRPV6 triggers chronic pancreatitis, skeletal dysplasia and is connected to mucolipidosis type II (data part II)
Description	Heterozygous TRPV6 mutations, which reduce significantly the Ca2+-permeability of the channel, lead to chronic pancreatitis and, if both TRPV6-alleles are affected, to skeletal dysplasia with neonatal transient hyperparathyroidism (TNHP) of newborns. We show that TRPV6 channels are localized in intracellular vesicles in pancreatic acinar cells, in the syncytiotrophoblast layer of the placenta and, after overexpression, in HEK293 cells. We identify three motifs within the TRPV6 sequence a N-glycosylation site, an ER- and a sorting motif which in concerted action leads to an intracellular localisation. The transport to vesicles depends on the N-glycosylation site of TRPV6. We found that the channel interacts with the cation independent mannose-6-phosphate receptor (CI-M6PR/IGF2R) indicating that TRPV6 is a target of the GNPTAB enzyme which targets proteins for endosomes/lysosomes by generating a mannose-6-phosphate residue at the N-glykosyl site chain of TRPV6. Defects in the GNTPAB enzyme cause mucolipidosis type II and patients show at the time of birth overlapping defects with patients with TRPV6 mutations. We show that a TRPV6 mutation, I223T, frequently found in patients with pancreatitis/skeletal dysplasia sticks to the ER but shows not reduced channel activity. The I223T mutation causes the diseases because the TRPV6 channel is not transferred to intracellular vesicles.
HostingRepository	PRIDE
AnnounceDate	2026-02-02
AnnouncementXML	Submission_2026-02-01_17:32:51.800.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD065789
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Claudia Fecher-Trost
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-04 06:57:37	ID requested
⏵ 1	2026-02-01 17:32:52	announced

Fecher-Trost C, Gehl AL, Trunk A, Hellmich J, Wesely C, L, ö, hr H, Buchholz S, Cole M, Beck A, Meyer MR, Wissenbach U, The intracellular localization and the ionic permeation of TRPV6 triggers chronic pancreatitis, skeletal dysplasia and is connected to mucolipidosis type II. Cell Commun Signal, 24(1):44(2025) [pubmed]

10.6019/PXD065789;

10.1186/s12964-025-02613-1;

submitter keyword: Transient Receptor Potential, I-cell disease, TRPV6,Mucolipidosis type II, Skeletal Dysplasia, Calcium Channel, GNPTAB, Chronic Pancreatitis, Mannose-6-phosphate

Ulrich Wissenbach
contact affiliation	Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, PZMS, Universität des Saarlandes, Geb. 46, 66421 Homburg, Germany
contact email	ulrich.wissenbach@uks.eu
lab head
Claudia Fecher-Trost
contact affiliation	PZMS
contact email	claudia.fecher-trost@uks.eu
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/2026/02/PXD065789

PRIDE project URI

• PRIDE
  1. PXD065789
     1. Label: PRIDE project
     2. Name: The intracellular localization and the ionic permeation of TRPV6 triggers chronic pancreatitis, skeletal dysplasia and is connected to mucolipidosis type II (data part II)