HGNC Approved Gene Symbol: SLC10A4
Cytogenetic location: 4p11 Genomic coordinates (GRCh38): 4:48,483,343-48,489,526 (from NCBI)
SLC10A4 is a protease-activated transporter involved in uptake of bile acid (Abe et al., 2013).
Using a bioinformatic approach, Splinter et al. (2006) identified human SLC10A4, which encodes a predicted 437-amino acid protein with a calculated molecular mass of 46.5 kD. SLC10A4 contains 8 putative transmembrane domains and 3 potential N-linked glycosylation sites. Human SLC10A4 protein shares 89% and 73% amino acid identity with its rat and mouse orthologs, respectively, and 24 to 30% identity with other members of the human SLC10 family. RT-PCR analysis identified SLC10A4 transcripts in human T84 colon cells, H69 human cholangiocyte cells, and human cholangiocarcinoma cell lines. Northern blot analysis of human tissues showed highest SLC10A4 expression in brain, placenta, and pancreas, with lower expression in liver and kidney. The major SLC10A4 transcript was 2.4 kb, but pancreas expressed an additional prominent transcript of 0.7 kb, and liver and kidney expressed an additional minor transcript of 1.4 kb. Immunofluorescence analysis of transfected CHO cells revealed that epitope-tagged SLC10A4 localized primarily in intracellular compartments and, to a lesser degree, on the plasma membrane. Immunoblot analysis detected a 49-kD protein in transfected CHO cells.
Using Western blot analysis, Abe et al. (2013) detected SLC10A4 as approximately 90- and 35-kD proteins in TE671 human medulloblastoma cells. Further analysis suggested that the 90-kD protein represented a glycosylated form of SLC10A4 and that the 35-kD protein represented the C terminus of SLC10A4 following cleavage by thrombin (F2; 176910). Immunofluorescence analysis detected SLC10A4 on the plasma membrane of TE671 cells.
By immunofluorescence analyses, Schmidt et al. (2015) showed that SLC10A4 was expressed in vesicular structures in human and mouse neuronal cell lines. The protein was detected along long neurite-like outgrowths, indicating sorting of the SLC10A4 protein to the synaptic direction of differentiated neuronal cells. Truncation analysis revealed that the C terminus of SLC10A4 was responsible for vesicular sorting of the protein.
Gross (2019) mapped the SLC10A4 gene to chromosome 4p11 based on an alignment of the SLC10A4 sequence (GenBank BC012048) with the genomic sequence (GRCh38).
Abe et al. (2013) found that cleavage by thrombin activated SLC10A4, resulting in enhanced uptake of taurocholic acid and lithocholic acid and increased cell death in TE671 cells.
Using immunohistochemistry, Popova and Alafuzoff (2013) showed that SLC10A4 was ubiquitously expressed in aged human brain, particularly in cholinergic and monoaminergic neurons and in the lateral geniculate body. In patients with Alzheimer disease (AD; 104300), SLC10A4 expression was decreased in the transentorhinal cortex as the severity of AD-related pathology increased.
Using in vitro transport studies, Schmidt et al. (2015) showed that SLC10A4 did not transport various neurotransmitters and neuromodulators. Moreover, they found that SLC10A4 transport activity could not be activated by thrombin treatment in transfected HEK293 cells.
Abe, T., Kanemitu, Y., Nakasone, M., Kawahata, I., Yamakuni, T., Nakajima, A., Suzuki, N., Nishikawa, M., Hishinuma, T., Tomioka, Y. SLC10A4 is a protease-activated transporter that transports bile acids. J. Biochem. 154: 93-101, 2013. [PubMed: 23589386] [Full Text: https://doi.org/10.1093/jb/mvt031]
Gross, M. B. Personal Communication. Baltimore, Md. 8/30/2019.
Popova, S. N., Alafuzoff, I. Distribution of SLC10A4, a synaptic vesicle protein in the human brain, and the association of this protein with Alzheimer's disease-related neuronal degeneration. J. Alzheimers Dis. 37: 603-610, 2013. [PubMed: 23948907] [Full Text: https://doi.org/10.3233/JAD-130548]
Schmidt, S., Moncada, M., Burger, S., Geyer, J. Expression, sorting and transport studies for the orphan carrier SLC10A4 in neuronal and non-neuronal cell lines and in Xenopus laevis oocytes. BMC Neurosci. 16: 35, 2015. Note: Electronic Article. [PubMed: 26084360] [Full Text: https://doi.org/10.1186/s12868-015-0174-2]
Splinter, P. L., Lazaridis, K. N., Dawson, P. A., LaRusso, N. F. Cloning and expression of SLC10A4, a putative organic anion transport protein. World J. Gastroent. 12: 6797-6805, 2006. [PubMed: 17106928] [Full Text: https://doi.org/10.3748/wjg.v12.i42.6797]