Phosphorylation dynamics of sodium-independent organic anion transporter SLCO4A1 and its role in diseases: a review.

Authors

Jaytha Thomas, Suhail Subair, Althaf Mahin, Athira Perunelly Gopalakrishnan, Prathik Basthikoppa Shivamurthy, Athira C Rajeev, Rajesh Raju

Published in

Frontiers in systems biology. Volume 6. Pages 1780024. Epub Jul 31, 2026.

Abstract

SLCO4A1, a membrane-localized organic anion transporter belonging to the solute carrier (SLC) family, mediates the sodium-independent transport of endogenous substrates, including steroid hormones, prostaglandins, and thyroid hormones. Despite increasing evidence supporting its physiological and pathological significance, a comprehensive review focusing on its phosphorylation landscape and phosphoregulation is currently lacking. Large-scale phosphoproteomic analyses have identified three predominant phosphorylation sites, T37, S40, and S43, within its N-terminal intrinsically disordered region, suggesting that phosphorylation is a potential regulator of SLCO4A1 localization, stability, and substrate specificity. Predicted upstream kinases, including MAPKs, CDKs, PAKs, and HIPK2, further link SLCO4A1 to signaling pathways governing cellular stress responses, inflammation, and cell-cycle progression. Aberrant expression of both SLCO4A1 and its antisense long non-coding RNA, SLCO4A1-AS1, has been reported in multiple malignancies, including colorectal, ovarian, lung, thyroid, and gastric cancers, where they are associated with poor clinical outcomes and activation of oncogenic signaling pathways. Beyond cancer, SLCO4A1 has also been implicated in inflammatory vascular disorders such as Behçet's disease and Kawasaki disease. This review comprehensively summarizes the structural organization, phosphoregulation, and disease relevance of SLCO4A1, with particular emphasis on phosphorylation as a central determinant of its transport activity and signaling functions.

PMID:
42601857
Bibliographic data and abstract were imported from PubMed on 15 Aug 2026.

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