Dataset Information

Interaction proteomics of wildtype SLC16A6 (MCT7) and phospho-variants

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Kidney Cell

SUBMITTER: Fabian Frommelt

LAB HEAD: Giulio Superti-Furga

PROVIDER: PXD055141 | Pride | 2025-03-03

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	2021-04-01-decoys-reviewed-contam-UP000005640.fas	Other
	RC_PPi_01-M1184-A01-SM13EZ-V-P13200-1.mzML	Mzml
	RC_PPi_01-M1184-A01-SM13EZ-V-P13200-1.pepXML	Pepxml
	RC_PPi_01-M1184-A01-SM13EZ-V-P13200-1.raw	Raw
	RC_PPi_01-M1184-A01-SM13EZ-V-P13200-2.mzML	Mzml

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Publications

The solute carrier superfamily interactome.

Frommelt Fabian F Ladurner Rene R Goldmann Ulrich U Wolf Gernot G Ingles-Prieto Alvaro A Lineiro-Retes Eva E Gelová Zuzana Z Hopp Ann-Katrin AK Christodoulaki Eirini E Teoh Shao Thing ST Leippe Philipp P Santini Brianda L BL Rebsamen Manuele M Lindinger Sabrina S Serrano Iciar I Onstein Svenja S Klimek Christoph C Barbosa Barbara B Pantielieieva Anastasiia A Dvorak Vojtech V Hannich Thomas J TJ Schoenbett Julian J Sansig Gilles G Mocking Tamara A M TAM Ooms Jasper F JF IJzerman Adriaan P AP Heitman Laura H LH Sykacek Peter P Reinhardt Juergen J Müller André C AC Wiedmer Tabea T Superti-Furga Giulio G

Molecular systems biology 20250512 6

Solute carrier (SLC) transporters form a protein superfamily that enables transmembrane transport of diverse substrates including nutrients, ions and drugs. There are about 450 different SLCs, residing in a variety of subcellular membranes. Loss-of-function of an unusually high proportion of SLC transporters is genetically associated with a plethora of human diseases, making SLCs a rapidly emerging but challenging drug target class. Knowledge of their protein environment may elucidate the molecu ...[more]

PMID: 40355756

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