SLC46A3
Description
The SLC46A3 (solute carrier family 46 member 3) is a protein-coding gene located on chromosome 13.
SLC46A3, also known as FKSG16, is a protein encoded by the SLC46A3 gene. It belongs to the major facilitator superfamily (MFS) and SLC46A family. Found primarily in the plasma membrane and endoplasmic reticulum (ER), SLC46A3 is a multi-pass membrane protein with 11 α-helical transmembrane domains. Its primary function is the transport of small molecules across the membrane through the substrate translocation pores present in the MFS domain. SLC46A3 is associated with various diseases, including breast and prostate cancer, hepatocellular carcinoma (HCC), papilloma, glioma, obesity, and SARS-CoV. Current research focuses on its potential as a prognostic biomarker and therapeutic target for cancer due to its differential expression in antibody-drug conjugate (ADC)-resistant cells and certain cancer cells. While its abundance is relatively low in humans, high expression is observed in the liver, small intestine, and kidney. The SLC46A3 gene is located at 13q12.3 on the reverse strand in humans. It spans 18,950 bases, flanked by POMP upstream and CYP51A1P2 downstream. The gene contains 6 exons and 5 introns. Two paralogs, SLC46A1 and SLC46A2, and orthologs as distant as fungi exist for this gene.
SLC46A3 acts as a lysosomal transporter, mediating the movement of various molecules across the lysosomal membrane. It preferentially transports lipophilic steroid conjugates and bile acids from lysosomes to the cytoplasm. Additionally, it plays a role in copper homeostasis within the liver, potentially functioning as a lysosomal copper transporter. SLC46A3 also transports catabolites of non-cleavable antibody-drug conjugates from lysosomes to the cytoplasm, facilitating their escape from lysosomal degradation. Furthermore, it is involved in innate immunity by delivering pathogen-associated molecular patterns (PAMPs) to cytosolic pattern recognition receptors, triggering inflammatory responses. Specifically, it transports bacterial muramyl dipeptide (MDP) into the cytosol, leading to NOD2 activation. SLC46A3 may also act as a redundant importer of cyclic GMP-AMP dinucleotides (cGAMPs) in monocyte and macrophage cell lineages. The exact transport mechanism, electrogenicity, and stoichiometry of SLC46A3 remain to be fully elucidated.
SLC46A3 is also known as FKSG16.
Associated Diseases
- prostate cancer
- cholesterol-ester transfer protein deficiency
- hemochromatosis type 5
- hypertriglyceridemia 2
- microcytic anemia with liver iron overload
- sitosterolemia
- thyroid hormone metabolism, abnormal, 2
- homozygous familial hypercholesterolemia
- dehydrated hereditary stomatocytosis
