Human cytosolic sulfotransferase database mining: identification of seven novel genes and pseudogenes

Abstract

A total of 10 SULT genes are presently known to be expressed in human tissues. We performed a comprehensive genome-wide search for novel SULT genes using two different but complementary approaches, and developed a novel graphical display to aid in the annotation of the hits. Seven novel human SULT genes were identified, five of which were predicted to be pseudogenes, including two processed pseudogenes and three pseudogenes that contained introns. Those five pseudogenes represent the first unambiguous SULT pseudogenes described in any species. Expression-profiling studies were conducted for one novel gene, SULT6B1, and a series of alternatively spliced transcripts were identified in the human testis. SULT6B1 was also present in chimpanzee and gorilla, differing at only seven encoded amino-acid residues among the three species. The results of these database mining studies will aid in studies of the regulation of these SULT genes, provide insights into the evolution of this gene family in humans, and serve as a starting point for comparative genomic studies of SULT genes.

Regulation of Human Cytosolic Sulfotransferases 1C2 and 1C3 by Nuclear Signaling Pathways in LS180 Colorectal Adenocarcinoma Cells

“…SULT1C2 and SULT1C4 both exhibited sulfonation activity toward p-nitrophenol and the promutagen N-hydroxy-2-acetylaminofluorene, suggesting a role in carcinogen activation (Sakakibara et al, 1998). Freimuth et al (2004) later predicted the existence of a third enzyme, SULT1C3, with three plausible splice variants (a, b, d) based on the arrangements of duplicated exons 7 and 8. Despite demonstrations that recombinant SULT1C3d exhibited sulfotransferase activity (Allali-Hassani et al, 2007;Meinl et al, 2008), neither SULT1C3 mRNA nor protein (Meinl et al, 2008) was detectable in human tissues.…”

Arylsulfatase B Mediates the Sulfonation-Transport Interplay in Human Embryonic Kidney 293 Cells Overexpressing Sulfotransferase 1A3

“…In addition to their roles in drug metabolism and detoxification, SULTs have been implicated in the activity regulation of hormones (e.g., estradiol) and neurotransmitters (e.g., dopamine) (Falany and Falany, 2007;Hempel et al, 2007). Human SULTs are divided into the following four families: SULT1, SULT2, SULT4, and SULT6 (Blanchard et al, 2004;Freimuth et al, 2004). SULT1 and SULT2 enzymes (with a total of 12 members) are well characterized and are the main contributors to chemical sulfonation (Allali-Hassani et al, 2007).…”

Multidrug Resistance-Associated Protein 4 (MRP4/ABCC4) Controls Efflux Transport of Hesperetin Sulfates in Sulfotransferase 1A3–Overexpressing Human Embryonic Kidney 293 Cells

“…The sulfonation reaction represents an important mechanism in activity regulation and elimination of numerous endobiotics and xenobiotics, including dietary polyphenols (e.g., flavonoids) (Chapman et al, 2004;Allali-Hassani et al, 2007). Human SULTs (with a total of 14 enzymes) are divided into four families, namely, SULT1, SULT2, SULT4, and SULT6 (Blanchard et al, 2004;Freimuth et al, 2004). Enzymes of SULT1 and SULT2 families, with abundant expression in the liver and intestine, play a dominant role in catalyzing sulfonation reactions (AllaliHassani et al, 2007;Teubner et al, 2007;Riches et al, 2009).…”