PXD047652

PXD047652 is an original dataset announced via ProteomeXchange.

Title	Identification of TBC1D30 interactors in murine MIN6 insulinoma cells.
Description	Components of the insulin processing and secretion pathways remain incompletely understood. Here we examined a genome-wide association study (GWAS) locus associated with plasma proinsulin levels. Low-frequency GWAS variant rs150781447 encodes an Arg279Cys substitution in TBC1D30, but no role for this protein in insulin processing or secretion has been previously established. Using CRISPR/Cas9 genome editing in INS1 832/13 insulinoma cells, we generated clonal cell lines with altered TBC1D30. Compared to mock-edited cells, cell lines with reduced TBC1D30 expression or function showed significantly more secreted proinsulin, and to a lesser extent, secreted insulin. Cell lines with a partial deletion of a key functional domain showed increased expression of TBC1D30 and less secreted proinsulin. The effects on secretion corresponded to effects on intracellular proinsulin and insulin content. The interactome of TBC1D30, identified through affinity purification-mass spectrometry, was enriched in proteins involved in insulin trafficking and secretion. These findings suggest that the effects of rs150781447 on TBC1D30 are responsible for this GWAS signal and that TBC1D30 plays a critical role in the secretion of mature insulin.
HostingRepository	PRIDE
AnnounceDate	2026-06-08
AnnouncementXML	Submission_2026-06-07_17:02:27.289.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christine Mills
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-08 07:54:11	ID requested
⏵ 1	2026-06-07 17:02:28	announced

10.1007/s00125-025-06391-w;

Parsons VA, Vadlamudi S, Voos KM, Rohy AE, Moxley AH, Cannon ME, Rosen JD, Mills CA, Herring LE, Broadaway KA, Lorenzo DN, Mohlke KL, TBC1D30 regulates proinsulin and insulin secretion and is the target of a genomic association signal for proinsulin. Diabetologia, 68(6):1169-1183(2025) [pubmed]

submitter keyword: Proinsulin

insulin

secretion

genome-wide association study

Rab GTPase Activating protein, Affinity Purification-Mass Spectrometry

Karen Mohlke
contact affiliation	Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
contact email	karen_mohlke@med.unc.edu
lab head
Christine Mills
contact affiliation	University of North Carolina - Chapel Hill
contact email	allie.mills@unc.edu
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/2026/06/PXD047652

PRIDE project URI

• PRIDE
  1. PXD047652
     1. Label: PRIDE project
     2. Name: Identification of TBC1D30 interactors in murine MIN6 insulinoma cells.