Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this review, we highlight the physical and enzymatic properties of the novel human sulfotransferase, SULT4A1. The gene is most highly expressed in selective regions of the brain, although work to date has failed to identify any specific endogenous substrate for the enzyme. SULT4A1 shares low homology with other human sulfotransferases. Nevertheless, it is highly conserved between species. Despite the low homology, it is structurally very similar to other cytosolic sulfotransferases with a conserved substrate binding domain, dimerization site and partial cofactor binding sites. However, the catalytic cavity is much smaller, and it has been suggested that the cofactor may not be accommodated within it. A recent link between variability in the 5'UTR of the SULT4A1 gene and schizophrenia has heightened interest in the endogenous function of the enzyme and its possible role in human disease.
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PMID:Sulfotransferase 4A1. 1824 44

The cytosolic sulfotransferase SULT4A1 is highly conserved between mammalian species but its function remains unknown. Polymorphisms in the SULT4A1 gene have been linked to susceptibility to schizophrenia. There are 2 major SULT4A1 transcripts in humans, one that encodes full length protein (wild-type) and one that encodes a truncated protein (variant). Here, we investigated the expression of SULT4A1 in human tissues by RT-PCR and found the wild-type mRNA to be expressed mainly in the brain, gastrointestinal tract and prostate while the splice variant was more widely expressed. In human cell-lines, the wild-type transcript was found in neuronal cells, but the variant transcript was expressed in nearly all other lines examined. Western blot analysis only identified SULT4A1 protein in cells that expressed the wild-type mRNA. No variant protein was detected in cells that expressed the variant mRNA. Ectopically expressed full length SULT4A1 protein was stable while the truncated protein was not, having a half-life of approximately 3 hr. SULT4A1 was also shown to homodimerize, consistent with other SULTs that contain the consensus dimerization motif. Mutation of the dimerization motif resulted in a monomeric form of SULT4A1 that was rapidly degraded by polyubiquitination on the lysine located within the dimerization motif. These results show that SULT4A1 is widely expressed in human tissues, but mostly as a splice variant that produces a rapidly degraded protein. Dimerization protects the protein from degradation. Since many other cytosolic sulfotransferases possess the conserved lysine within the dimerization motif, homodimerization may serve, in part, to stabilize these enzymes in vivo.
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PMID:Expression of the orphan cytosolic sulfotransferase SULT4A1 and its major splice variant in human tissues and cells: dimerization, degradation and polyubiquitination. 2498 29