The 3'-terminal exon of the family of steroid and phenol sulfotransferase genes is spliced at the N-terminal glycine of the universally conserved GXXGXXK motif that forms the sulfonate donor binding site.
The guinea pig estrogen sulfotransferase gene has been cloned and compared to three other cloned steroid and phenol sulfotransferase genes (human estrogen sulfotransferase, human phenol sulfotransferase, and guinea pig 3 alpha-hydroxysteroid sulfotransferase). The four sulfotransferase genes demonstrate a common outstanding feature: the splice sites for their 3'-terminal exons are identically located. That is, the 3'-terminal exon splice sites involve a glycine that constitutes the N-terminal glycine of an invariably conserved GXXGXXK motif present in all steroid and phenol sulfotransferases for which primary structures are known. This consistency strongly suggests that all steroid and phenol sulfotransferase genes will be similarly spliced. The GXXGXXK motif forms the active binding site for the universal sulfonate donor 3'-phosphoadenosine 5'-phosphosulfate. Amino acid sequence alignment of 19 cloned steroid and phenol sulfotransferases starting with the GXXGXXK motif indicates that the 3'-terminal exon for each steroid and phenol sulfotransferase gene encodes a similarly sized C-terminal fragment of the protein. Interestingly, on further analysis of the alignment, three distinct amino acid sequence patterns emerge. The presence of the conserved functional GXXGXXK motif suggests that the protein domains encoded by steroid and phenol sulfotransferase 3'-terminal exons have evolved from a common ancestor. Furthermore, it is hypothesized that during the course of evolution, the 3'-terminal exon further diverged into at least three sulfotransferase subdivisions: a phenol or aryl group, an estrogen or phenolic steroid group, and a neutral steroid group.
Chiba
H
H
Section on Steroid Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-4510, USA.
Komatsu
K
K
Lee
Y C
YC
Tomizuka
T
T
Strott
C A
CA
D000595:Amino Acid Sequence; D000818:Animals; D015239:Arylsulfotransferase / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D017931:DNA Primers; D005091:Exons; D005998:Glycine / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D008969:Molecular Sequence Data; D012326:RNA Splicing; D017386:Sequence Homology, Amino Acid; D013451:Sulfonic Acids / Q000378:metabolism*; D015238:Sulfotransferases / Q000235:genetics* / Q000378:metabolism
D017931:DNA Primers; D013451:Sulfonic Acids; D015238:Sulfotransferases; D015239:Arylsulfotransferase; C044251:steroid sulfotransferase; D005998:Glycine