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Chemico-biological Interactions Jun 1994Human tissues contain at least three well-characterized cytoplasmic sulfotransferase (ST) enzymes, dehydroepiandrosterone (DHEA) ST and two of phenol ST (PST). DHEA ST... (Review)
Review
Human tissues contain at least three well-characterized cytoplasmic sulfotransferase (ST) enzymes, dehydroepiandrosterone (DHEA) ST and two of phenol ST (PST). DHEA ST catalyzes the sulfation of DHEA and other steroids. We cloned and expressed two cDNAs for human liver DHEA ST. The cloning strategy involved the design of PCR primers directed against two conserved domains in ST proteins. These primers were used to generate a specific PCR product that was then used successfully to clone cDNAs for DHEA ST from a human liver cDNA library. Two cDNAs were isolated that were approximately 1.1 and 1.8 kb in length. These two clones had identical open reading frames. Both cDNAs produced enzymatically active DHEA ST protein in a mammalian expression system. Northern blot analysis confirmed the presence of 1.1 and 1.8 kb transcripts in human liver. cDNAs for a number of eukaryotic enzymes have now been cloned, and they share significant sequence homology. These ST cDNAs appear to fall into distinct groups on the basis of amino acid sequences of the proteins that they encode, thus demonstrating that the enzymes comprise a gene superfamily. We have also isolated, a genomic clone for human DHEA ST that contains approximately 3 kb of 5'-flanking sequence, exon 1 and 1.7 kb of intron 1. Characterization of the structure and regulatory elements of this gene should help to elucidate mechanisms involved in the regulation of DHEA ST in humans.
Topics: Amino Acid Sequence; Base Sequence; Cloning, Molecular; DNA, Complementary; Humans; Liver; Molecular Sequence Data; RNA, Messenger; Sequence Alignment; Sequence Homology, Amino Acid; Sulfotransferases
PubMed: 8033249
DOI: 10.1016/0009-2797(94)90060-4 -
Pharmacogenetics Mar 2004A nomenclature system for the cytosolic sulfotransferase (SULT) superfamily has been developed. The nomenclature guidelines were applied to 65 SULT cDNAs and 18 SULT... (Review)
Review
A nomenclature system for the cytosolic sulfotransferase (SULT) superfamily has been developed. The nomenclature guidelines were applied to 65 SULT cDNAs and 18 SULT genes that were characterized from eukaryotic organisms. SULT cDNA and gene sequences were identified by querying the GenBank databases and from published reports of their identification and characterization. These sequences were evaluated and named on the basis of encoded amino acid sequence identity and, in a few cases, a necessity to maintain historical naming convention. Family members share at least 45% amino acid sequence identity whereas subfamily members are at least 60% identical. cDNAs which encode amino acid sequences of at least 97% identity to each other were assigned identical isoform names. We also attempted to categorize orthologous enzymes between various species, where these have been identified, and the nomenclature includes a species descriptor. We present recommendations for the naming of allelic variants of SULT genes and their derived allozymes arising from single nucleotide polymorphisms and other genetic variation. The superfamily currently comprises 47 mammalian SULT isoforms, one insect isoform and eight plant enzymes, and collectively these sequences represent nine separate SULT families and 14 subfamilies. It is hoped that this nomenclature system will be widely adopted and that, as novel SULTs are identified and characterized, investigators will name their discoveries according to these guidelines.
Topics: Animals; Cytosol; DNA, Complementary; Genome; Humans; Multigene Family; Phylogeny; Sulfotransferases; Terminology as Topic
PubMed: 15167709
DOI: 10.1097/00008571-200403000-00009 -
Glycoconjugate Journal 2002Heparan sulfate that contains antithrombin binding sites is designated as anticoagulant heparan sulfate (HS(act)) since, in vitro, it dramatically enhances the... (Review)
Review
Heparan sulfate that contains antithrombin binding sites is designated as anticoagulant heparan sulfate (HS(act)) since, in vitro, it dramatically enhances the neutralization of coagulation proteases by antithrombin. Endothelial cell production of HS(act) is controlled by the Hs3st1 gene, which encodes the rate limiting enzyme-heparan sulfate 3-O-sulfotransferase-1 (Hs3st1). It has long been proposed that levels of endothelial HS(act) may tightly regulate hemostatic tone. This potential in vivo role of HS(act) was assessed by generating Hs3st1(-/-) knockout mice. Hs3st1(-/-) and Hs3st1(+/+) mice were evaluated with a variety of methods, capable of detecting altered hemostatic tone. However, both genotypes were indistinguishable. Instead, Hs3st1(-/-) mice exhibited lethality on a specific genetic background and also showed intrauterine growth retardation. Neither phenotypes result from a gross coagulopathy. So although this enzyme produces the majority of tissue HS(act), Hs3st1(-/-) mice do not show an obvious procoagulant phenotype. These results suggest that the bulk of HS(act) is not essential for normal hemostasis and that hemostatic tone is not tightly regulated by total levels of HS(act). Moreover, the unanticipated non-thrombotic phenotypes suggest structure(s) derived from this enzyme might serve additional/alternative biologic roles.
Topics: Animals; Animals, Newborn; Anticoagulants; Binding Sites; Blood Coagulation; Carbohydrate Sequence; Hemostasis; Heparitin Sulfate; Mice; Mice, Knockout; Molecular Sequence Data; Phenotype; Sulfotransferases
PubMed: 12975616
DOI: 10.1023/A:1025377206600 -
Tanpakushitsu Kakusan Koso. Protein,... Aug 1992
Review
Topics: Amino Acid Sequence; Animals; Cloning, Molecular; Liver; Polymerase Chain Reaction; Rats; Sulfotransferases
PubMed: 1410453
DOI: No ID Found -
Journal of Experimental Botany Jul 2021Tyrosine-sulfated peptides are key regulators of plant growth and development. The disulfated pentapeptide phytosulfokine (PSK) mediates growth via leucine-rich repeat...
Tyrosine-sulfated peptides are key regulators of plant growth and development. The disulfated pentapeptide phytosulfokine (PSK) mediates growth via leucine-rich repeat receptor-like kinases, PSKR1 and PSKR2. PSK receptors (PSKRs) are part of a response module at the plasma membrane that mediates short-term growth responses, but downstream signaling of transcriptional regulation remains unexplored. In Arabidopsis, tyrosine sulfation is catalyzed by a single-copy gene (TPST; encoding tyrosylprotein sulfotransferase). We performed a microarray-based transcriptome analysis in the tpst-1 mutant background that lacks sulfated peptides to identify PSK-regulated genes and genes that are regulated by other sulfated peptides. Of the 169 PSK-regulated genes, several had functions in root growth and development, in agreement with shorter roots and a higher lateral root density in tpst-1. Further, tpst-1 roots developed higher numbers of root hairs, and PSK induced expression of WEREWOLF (WER), its paralog MYB DOMAIN PROTEIN 23 (MYB23), and At1g66800 that maintain non-hair cell fate. The tpst-1 pskr1-3 pskr2-1 mutant showed even shorter roots, and higher lateral root and root hair density than tpst-1, revealing unexpected synergistic effects of ligand and PSKR deficiencies. While residual activities may exist, overexpression of PSKR1 in the tpst-1 background induced root growth, suggesting that PSKR1 may be active in the absence of sulfated ligands.
Topics: Arabidopsis; Arabidopsis Proteins; Receptors, Cell Surface; Signal Transduction; Sulfotransferases
PubMed: 34028532
DOI: 10.1093/jxb/erab233 -
Journal of the European Academy of... Jan 2021
Topics: Administration, Oral; Alopecia; Arylsulfotransferase; Female; Humans; Minoxidil; Sulfotransferases; Treatment Outcome
PubMed: 32567076
DOI: 10.1111/jdv.16765 -
Chemico-biological Interactions Feb 1998Sulfotransferases (SULTs) are Phase II drug-metabolizing enzymes that catalyze the addition of a sulfuryl moiety to both endogenous compounds, including steroids and... (Review)
Review
Sulfotransferases (SULTs) are Phase II drug-metabolizing enzymes that catalyze the addition of a sulfuryl moiety to both endogenous compounds, including steroids and neurotransmitters, and certain xenobiotics, including N-hydroxy-2-acetylaminoflourine and phenolic compounds, like alpha-naphthol. In contrast to certain Phase I drug-metabolizing enzymes, little is known about the regulation of the sulfotransferases. These series of studies were designed to analyze SULT mRNA expression and hormonal regulation in male and female rats. The hepatic expression of six different SULT isoforms was examined including three phenol SULTs and three hydroxysteroid SULTs. SULT mRNA expression was examined in adult and developing rats, as well as, in hypophysectomized (HX) and growth hormone-supplemented HX animals. SULT1A1 is thought to be important for the sulfation of simple phenols and its mRNA expression is about twice as high in adult male as in female rats. This difference in SULT1A1 mRNA levels is largely due to a greater decrease in mRNA levels after puberty in female than in male rats. Hypophysectomy resulted in a decrease in expression of SULT1A1 mRNA in both male and female rats. Replacement of growth hormone (GH) by either intermittent injection (male pattern) or infusion (female pattern) failed to restore SULT1A1 expression. Sulfotransferase SULT1C1 has been implicated in activation of N-hydroxyacetylaminoflourine. In contrast to SULT1A1, SULT1C1 mRNA expression is about 10-fold higher in adult males than in adult female rats. This male-dominant expression pattern emerges at 40-50 days of age and is due to an increase in SULT1C1 mRNA in males. Hypophysectomy abolished SULT1C1 expression in male rats. Interestingly, replacement of GH by injection (male pattern) restored SULT1C1 mRNA expression in males and enhanced SULT1C1 expression in female rats to levels observed in adult male rats. GH infusion (female pattern) did not affect SULT1C1 mRNA expression in either male or female rats. Estrogen sulfotransferase (SULT1E2) may play a role in estrogen homeostasis. Adult male rats express SULTIE2 mRNA at levels 10-fold higher than those observed in adult females and similar to SULT1C1, this is due to an increase in SULT1E2 mRNA occurring during puberty in the male rat. Hypophysectomy did not appreciably affect SULT1E2 expression in male rats, however in contrast to males, hypophysectomy markedly enhanced SULT1E2 expression in female rats. GH infusion suppressed SULT1E2 levels in HX male rats. The expression of hydroxysteroid sulfotransferases was also examined. The SULT-20/21 isoform was expressed in both male and female rats. Male expression of this isoform peaked at 30 days of age and then declined to approximately 30% of the level observed in adult females. SULT-20/21 mRNA expression increased sharply at 45 days of age in female rats and remained elevated. Expression of SULT-20/21 mRNA was decreased markedly by hypophysectomy in both male and female rats. GH injection did not affect SULT-20/21 mRNA expression in HX males, however this treatment resulted in a 4-fold increase in SULT-20/21 mRNA in HX females. GH infusion restored SULT-20/21 expression in HX-male rats. GH infusion did elevate SULT-20/21 mRNA expression in female-HX rats, but not to the level observed in intact females. Hydroxysteroid SULT isoform SULT-40/41 was expressed in adult female but not adult male rats. SULT-40/41 expression peaked at 15 days of age in both male and female rats and decreased thereafter. The decrease in expression was more pronounced in male rats. SULT-60 mRNA, like SULT-40/41, was expressed only in adult female rats. Male rats express SULT-60 at 30 days of age, but SULT-60 mRNA is undetectable at 60 days. SULT-60 mRNA was expressed in females only after day 30 and female SULT-60 mRNA expression remains high thereafter. SULT-40/41 and SULT-60 mRNA expression was increased by HX in male rats and decreased by HX in female rats. (ABSTRACT TRUNCATED)
Topics: Aging; Animals; Female; Male; RNA, Messenger; Rats; Sex Factors; Sulfotransferases
PubMed: 9566754
DOI: 10.1016/s0009-2797(97)00141-5 -
Nature Communications Oct 2018Polyphenism, the extreme form of developmental plasticity, is the ability of a genotype to produce discrete morphologies matched to alternative environments. Because...
Polyphenism, the extreme form of developmental plasticity, is the ability of a genotype to produce discrete morphologies matched to alternative environments. Because polyphenism is likely to be under switch-like molecular control, a comparative genetic approach could reveal the molecular targets of plasticity evolution. Here we report that the lineage-specific sulfotransferase SEUD-1, which responds to environmental cues, dosage-dependently regulates polyphenism of mouthparts in the nematode Pristionchus pacificus. SEUD-1 is expressed in cells producing dimorphic morphologies, thereby integrating an intercellular signalling mechanism at its ultimate target. Additionally, multiple alterations of seud-1 support it as a potential target for plasticity evolution. First, a recent duplication of seud-1 in a sister species reveals a direct correlation between genomic dosage and polyphenism threshold. Second, inbreeding to produce divergent polyphenism thresholds resulted in changes in transcriptional dosage of seud-1. Our study thus offers a genetic explanation for how plastic responses evolve.
Topics: Animals; Animals, Genetically Modified; Environment; Gene Expression Regulation; Genotype; Helminth Proteins; Mouth; Phenotype; Phylogeny; Polymorphism, Genetic; Rhabditida; Sulfotransferases
PubMed: 30297689
DOI: 10.1038/s41467-018-05612-8 -
The International Journal of... 1994Sulfation is an important conjugation reaction in the metabolism of various xenobiotics and endogenous compounds and is catalyzed by sulfotransferase (ST) present in... (Review)
Review
Sulfation is an important conjugation reaction in the metabolism of various xenobiotics and endogenous compounds and is catalyzed by sulfotransferase (ST) present in cytosols. The cloning studies on STs have provided the basis for the understanding of the ST multigene family. STs are classified into hydroxysteroid (or alcohol), aryl (or phenol), estrogen, flavonol and polysaccharide STs and recent developments in the molecular characterization of these isoforms are reviewed. Regulation and localization of ST isoforms in various tissues are characterized at the molecular level by virtue of the specific antibodies and the corresponding cDNA probes. The recent developments are summarized. ST inhibitors are potent tools for the study on ST multiplicity and for the characterization of the enzyme structure. It also appears to be important to understand exogenous and endogenous ST inhibitors in clinical environment. The recent developments are reviewed.
Topics: Animals; Cloning, Molecular; Enzyme Activation; Humans; Isoenzymes; Organ Specificity; Pharmaceutical Preparations; Sulfotransferases
PubMed: 7851628
DOI: 10.1016/0020-711x(94)90093-0 -
The Journal of Biological Chemistry Sep 2014Human cytosolic sulfotransferases (SULTs) regulate the activities of thousands of signaling small molecules via transfer of the sulfuryl moiety (-SO3) from...
Human cytosolic sulfotransferases (SULTs) regulate the activities of thousands of signaling small molecules via transfer of the sulfuryl moiety (-SO3) from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to the hydroxyls and primary amines of acceptors. Sulfonation controls the affinities of ligands for their targets, and thereby regulates numerous receptors, which, in turn, regulate complex cellular responses. Despite their biological and medical relevance, basic SULT mechanism issues remain unresolved. To settle these issues, and to create an in-depth model of SULT catalysis, the complete kinetic mechanism of a representative member of the human SULT family, SULT2A1, was determined. The mechanism is composed of eight enzyme forms that interconvert via 22 rate constants, each of which was determined independently. The result is a complete quantitative description of the mechanism that accurately predicts complex enzymatic behavior. This is the first description of a SULT mechanism at this resolution, and it reveals numerous principles of SULT catalysis and resolves previously ambiguous issues. The structures and catalytic behaviors SULTs are highly conserved; hence, the mechanism presented here should prove paradigmatic for the family.
Topics: Biocatalysis; Dehydroepiandrosterone; Humans; Kinetics; Models, Chemical; Phosphoadenosine Phosphosulfate; Protein Binding; Sulfotransferases
PubMed: 25056952
DOI: 10.1074/jbc.M114.573501