PXD055141-1

PXD055141 is an original dataset announced via ProteomeXchange.

Title	Interaction proteomics of wildtype SLC16A6 (MCT7) and phospho-variants
Description	The solute carrier (SLC) transporter superfamily are important coordinators of metabolic and cellular homeostasis. Despite their importance for cellular homeostasis, SLCs remain a largely understudied group of proteins regarding their protein interactome. Thus, we conducted a largescale interactome proteomics study to characterize the interactome of roughly 400 of the 450 superfamily members. Within this study, we found that the monocarboxylate transporter SLC16A6 (MCT7) shows a unique interaction with CUL1 subunit and two F-box adaptor proteins BTRC and FBXW11. Sequence analysis revealed a potential phospho-degron sequence in the cytosolic loop of SLC16A6 (D239 to T245), like the consensus phospho-degron sequence (DSG-X(2,3,4)-S/T) recognized by the two adaptor proteins. To validate the phospho-degron, we generated single point variants of WT SLC16A6 that either potentially mimic phosphorylation (S240D, T245E) or prevent phosphorylation (phospho-dead). By comparing the interactome of the phospho-mutants against that of WT SLC16A6, we validated that the binding of phospho-dead mutants to SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex members was reduced, whereas the T245E phospho-mutant let to a slight increase in binding to the SCF protein complex. Through additional functional validations with protein stability assays and RNAi treatment of adaptors, we showed that SLC16A6 abundance is regulated by the SCF-complex through a phospho-degron.
HostingRepository	PRIDE
AnnounceDate	2025-03-03
AnnouncementXML	Submission_2025-03-03_06:08:35.340.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fabian Frommelt
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-23 08:53:52	ID requested
⏵ 1	2025-03-03 06:08:35	announced

Dataset with its publication pending

submitter keyword: phosphodegron, SLC16A6 phsopho-variants,AP-MS

Giulio Superti-Furga
contact affiliation	CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria
contact email	gsuperti@cemm.oeaw.ac.at
lab head
Fabian Frommelt
contact affiliation	CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
contact email	fabian.frommelt@hotmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055141
     1. Label: PRIDE project
     2. Name: Interaction proteomics of wildtype SLC16A6 (MCT7) and phospho-variants