page_title: SLC46A3
section_title: Properties
hierarchical_section_title: SLC46A3 / Protein / Properties
caption_attribution_description: English: Blue bars enclose the MFS domain and the red brackets the transmembrane regions. i = LVIF.
context_page_description: Solute carrier family 46 member 3 is a protein that in humans is encoded by the SLC46A3 gene. Also referred to as FKSG16, the protein belongs to the major facilitator superfamily and SLC46A family. Most commonly found in the plasma membrane and endoplasmic reticulum, SLC46A3 is a multi-pass membrane protein with 11 α-helical transmembrane domains. It is mainly involved in the transport of small molecules across the membrane through the substrate translocation pores featured in the MFS domain. The protein is associated with breast and prostate cancer, hepatocellular carcinoma, papilloma, glioma, obesity, and SARS-CoV. Based on the differential expression of SLC46A3 in antibody-drug conjugate-resistant cells and certain cancer cells, current research is focused on the potential of SLC46A3 as a prognostic biomarker and therapeutic target for cancer. While protein abundance is relatively low in humans, high expression has been detected particularly in the liver, small intestine, and kidney.
context_section_description: SLC46A3 is an integral membrane protein 461 amino acids (aa) of length with a molecular weight (MW) of 51.5 kDa. The basal isoelectric point (pI) for this protein is 5.56. The protein contains 11 transmembrane domains in addition to domains MFS and MFS_1. MFS and MFS_1 domains largely overlap and contain 42 putative substrate translocation pores that are predicted to bind substrates for transmembrane transport. The substrate translocation pores have access to both sides of the membrane in an alternating fashion through a conformational change. SLC46A3 lacks charged and polar amino acids while containing an excess of nonpolar amino acids, particularly phenylalanine (Phe). The resulting hydrophobicity is mostly concentrated in the transmembrane regions for interactions with the fatty acid chains in the lipid bilayer. The transmembrane domains also have a shortage of proline (Pro), a helix breaker.
  The protein sequence contains mixed, positive, and negative charge clusters, one of each, which are high in glutamine (Glu). The clusters are located outside the transmembrane regions, and thus are solvent-exposed. Two 0 runs that run through several transmembrane domains in addition to a +/* run in between two transmembrane domains are also present. The protein contains a C-(X)₂-C motif (CLLC), which is mostly present in metal-binding proteins and oxidoreductases. A sorting-signal sequence motif, YXXphi, is also found at Tyr246 - Phe249 (YMLF) and Tyr446 - Leu449 (YELL). This Y-based sorting signal directs the trafficking within the endosomal and the secretory pathways of integral membrane proteins by interacting with the mu subunits of the adaptor protein (AP) complex. The signal-transducing adaptor protein 1 (STAP1) Src homology 2 (SH2) domain binding motif at Tyr446 - Ile450 (YELLI) is a phosphotyrosine (pTyr) pocket that serves as a docking site for the SH2 domain, which is central to tyrosine kinase signaling. Multiple periodicities typical of an α-helix (periods of 3.6 residues in the hydrophobicity) encompass transmembrane domains. 3 tandem repeats with core block lengths of 3 aa (GNYT, VSTF, STFI) are observed throughout the sequence.
caption: SLC46A3 Protein Sequence Analysis. The blue bars enclose the MFS domain and the red brackets the transmembrane regions. i = LVIF.
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