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Literature summary extracted from

  • Rizner, T.L.
    The important roles of steroid sulfatase and sulfotransferases in gynecological diseases (2016), Front. Pharmacol., 7, 30 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.8.2.2 gene SULT2A1, localized to chromosome 19 (19q13.3), different transcripts and genetic variants, overview Homo sapiens
2.8.2.2 gene SULT2B1, localized to chromosome 19 (19g13.3), isozymes SULT2B1a and SULT2B1b, different transcripts and genetic variants, overview. The SULT2B1 isoforms SULT2B1a and SULT2B1b are products of alternative transcriptional initiation and mRNA splicing of the same gene. SULT1B1a and SULT1B1b, which has an additional 23 N-terminal amino-acid residues, have been cloned and expressed in prokaryotic and eukaryotic systems Homo sapiens
2.8.2.4 gene SULT1E1, localized to chromosome 4 (4q13.2), different transcripts and genetic variants, overview Homo sapiens

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.8.2.2 crystal structure analysis of both SULT2B1a and SULT2B1b in binary complexes with PAP (PDB IDs 1Q1Q, and 1Q1Z, respectively) have been resolved, as have two ternary complexes of SULT1Bb with PAP and pregnenolone (PDB ID 1Q2O), and with PAP and DHEA (PDB ID 1Q22) Homo sapiens
2.8.2.2 several crystal structures of SULT2A1 binary complexes have been resolved, including complexes with DHEA (PDB ID 1J99) and PAPS (PDB ID 4IFB) Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.8.2.2 A261T polymorphism of SULT2A1. The SULT2A1 SNP Ala261Thr has an allele frequency of 13% in African-American populations and is located within the dimerization motif, where it prevents formation of SULT2A1 dimers. But Ala261Thr still has 93% of the wild-type enzyme activity Homo sapiens
2.8.2.2 A63P polymorphism of SULT2A1. The SULT2A1 SNP Ala63Pro has an allele frequency of 5% in African-American populations Homo sapiens
2.8.2.2 additional information more than 160 cSNPs are reported for SULT2A1. Functional analysis has revealed that the nonsynonymous SNPs Met57Thr, Glu186Val, Ala63Pro, and Lys227Glu result in decreased SULT2A1 activity when expressed in COS-1 cells Homo sapiens
2.8.2.2 R18Q polymorphism of SULT2B1 Homo sapiens
2.8.2.2 R33Q polymorphism of SULT2B1 Homo sapiens
2.8.2.4 V307I polymorphism of SULT1E1 Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.8.2.2 dehydroepiandrosterone substrate inhibition of SULT2B1a and SULT2B1b; the potent substrate inhibition can be explained by trapping PAP in a dead-end complex, which impedes the release of the nucleotide coenzyme Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.8.2.2 additional information
-
 additional information the complete kinetic mechanism of SULT2A1 has been defined, which reveals that the binding of DHEA and PAPS is random, while the rate-limiting step is nucleotide release Homo sapiens
2.8.2.2 0.0023
-
 dehydroepiandrosterone SULT2B1a, pH and temperature not specified in the publication Homo sapiens
2.8.2.2 0.0025
-
 dehydroepiandrosterone SULT2A1, pH and temperature not specified in the publication Homo sapiens
2.8.2.2 0.0044
-
 dehydroepiandrosterone SULT2B1b, pH and temperature not specified in the publication Homo sapiens
2.8.2.4 0.000029
-
 17beta-estradiol SULT1E1, pH and temperature not specified in the publication Homo sapiens
2.8.2.4 0.00011
-
 estrone SULT1E1, pH and temperature not specified in the publication Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.8.2.2 cytosol
-
 Homo sapiens 5829
-

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.8.2.2 3'-phosphoadenylyl sulfate + dehydroepiandrosterone Homo sapiens
-
 adenosine 3',5'-bisphosphate + dehydroepiandrosterone 3-O-sulfate
-
 ?
2.8.2.4 3'-phosphoadenylylsulfate + 17beta-estradiol Homo sapiens
-
 adenosine 3',5'-bisphosphate + 17beta-estradiol sulfate
-
 ?
2.8.2.4 3'-phosphoadenylylsulfate + estrone Homo sapiens
-
 adenosine 3',5'-bisphosphate + estrone sulfate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.8.2.2 Homo sapiens O00204
-
-
2.8.2.2 Homo sapiens Q06520
-
-
2.8.2.4 Homo sapiens P49888
-
-

Reaction

EC Number Reaction Comment Organism Reaction ID
2.8.2.4 3'-phosphoadenylyl sulfate + estrone = adenosine 3',5'-bisphosphate + estrone 3-sulfate the proposed reaction mechanism: upon binding of PAPS, Ser137 forms an H-bond with Lys47, thus prevents its interaction with the bridging oxygenin PAPS and its further hydrolysis; His107 attracts a proton from the substrate hydroxyl (i.e. of E2 or DHEA), and enables nucleophilic attack at the sulfur atom in PAPS. In the next step, Lys47 interacts with the 5' phosphate of PAPS, which helps in dissociation of the sulfuryl group and in its transfer to the substrate. Finally, the reaction products, PAP and E1-S, are released, which completes the catalytic cycle Homo sapiens
a

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.8.2.2 adrenal gland adult and fetal adrenal Homo sapiens
-
2.8.2.2 brain fetal Homo sapiens
-
2.8.2.2 colon
-
 Homo sapiens
-
2.8.2.2 Hep-G2 cell
-
 Homo sapiens
-
2.8.2.2 liver
-
 Homo sapiens
-
2.8.2.2 liver adult and and fetal liver Homo sapiens
-
2.8.2.2 additional information the SULT2B1 isoforms SULT2B1a and SULT2B1b are expressed in different tissues. SULT1B1a is expressed in colon, ovary, and fetal brain, and SULT2B1b in liver, colon, small intestine, placenta, ovary, uterus, and prostate Homo sapiens
-
2.8.2.2 ovary
-
 Homo sapiens
-
2.8.2.2 placenta
-
 Homo sapiens
-
2.8.2.2 prostate gland
-
 Homo sapiens
-
2.8.2.2 small intestine
-
 Homo sapiens
-
2.8.2.2 uterus
-
 Homo sapiens
-
2.8.2.4 MCF-10A cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.8.2.2 3'-phosphoadenylyl sulfate + dehydroepiandrosterone
-
 Homo sapiens adenosine 3',5'-bisphosphate + dehydroepiandrosterone 3-O-sulfate
-
 ?
2.8.2.2 additional information isozymes SULT2B1a and SULT2B1b catalyze sulfonation of 3beta-hydroxysteroids, pregnenolone, 17alpha-hydroxypregnenolone and DHEA Homo sapiens ?
-
-
2.8.2.2 additional information SULT2A1 has broad substrate specificity, it can catalyze sulfonation of many hydroxysteroids, including DHEA, epiandrosterone, androsterone, testosterone, E2, cholesterol, various bile acids, pregnenolone, 17-ethinyl-E2 and cortisol Homo sapiens ?
-
-
2.8.2.4 3'-phosphoadenylylsulfate + 17beta-estradiol
-
 Homo sapiens adenosine 3',5'-bisphosphate + 17beta-estradiol sulfate
-
 ?
2.8.2.4 3'-phosphoadenylylsulfate + estrone
-
 Homo sapiens adenosine 3',5'-bisphosphate + estrone sulfate
-
 ?

Subunits

EC Number Subunits Comment Organism
2.8.2.4 dimer 2 * 35000, about, sequence calculation Homo sapiens
2.8.2.4 More SULT1E1 is a dimer with an alpha/beta motif that consists of five parallel beta-strands surrounded by alpha-helices and a conserved alpha-helix across this structure Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
2.8.2.2 SULT2A1
-
 Homo sapiens
2.8.2.2 SULT2B1
-
 Homo sapiens
2.8.2.2 SULT2B1a isozyme Homo sapiens
2.8.2.2 SULT2B1b isozyme Homo sapiens
2.8.2.4 estrogen SULT
-
 Homo sapiens
2.8.2.4 SULT1E1
-
 Homo sapiens

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
2.8.2.2 0.0061
-
 dehydroepiandrosterone SULT2A1, pH and temperature not specified in the publication Homo sapiens
2.8.2.2 0.022
-
 dehydroepiandrosterone SULT2B1b, pH and temperature not specified in the publication Homo sapiens
2.8.2.2 0.048
-
 dehydroepiandrosterone SULT2B1a, pH and temperature not specified in the publication Homo sapiens

Expression

EC Number Organism Comment Expression
2.8.2.2 Homo sapiens The expression of SULT2A1 is regulated at the transcriptional level by the constitutive androstane receptor and pregnane X receptor. SULT2A1 appears to be regulated also at the epigenetic level, as shown by induction of SULT2A1 expression after treatment of MCF7 cells with a histone deacetylase inhibitor. In the adrenal gland, the expression of SULT2A1 depends on two transcription factors: steroidogenic factor 1 and GATA-6 additional information
2.8.2.2 Homo sapiens the SULT2A1 gene is induced by E2 activation of estrogen receptor (ER)alpha via classical, direct binding to the estrogen response element, and via nonclassical, AP-1-mediated mechanisms up
2.8.2.4 Homo sapiens in liver SULT1E1 is repressed by xenobiotic activators of the pregnane X receptor and aryl hydrocarbon receptor peroxisome proliferator down
2.8.2.4 Homo sapiens SULT1E1 is epigenetically regulated, as its expression is induced by the histone deacetylase inhibitor trichostatin A in MCF10A cells. In endometrial cancer cell line Ishikawa SULT1E1 is induced by steroid drug tibolone via progesterone receptor. In liver, it is activated via peroxisome proliferator activated receptor alpha and the liver X receptor up

General Information

EC Number General Information Comment Organism
2.8.2.2 evolution more than 160 cSNPs have been reported for SULT2A1. SULT2A1 SNPs Ala63Pro, Lys227Glu, and Ala261Thr have only been found in African-American populations, and these might explain the interethnic differences in SULT2A1 activity Homo sapiens
2.8.2.2 malfunction Functional analysis has revealed that the nonsynonymous SNPs Met57Thr, Glu186Val, Ala63Pro, and Lys227Glu result in decreased SULT2A1 activity when expressed in COS-1 cells Homo sapiens
2.8.2.2 metabolism in peripheral tissues, estrogens can be formed from the inactive precursors dehydroepiandrosterone sulfate and estrone sulfate. Sulfatase and sulfotransferases have pivotal roles in these processes, where sulfatase hydrolyzes estrone sulfate to estrone, and dehydroepiandrosterone sulfate to dehydroepiandrosterone, and sulfotransferases catalyze the reverse reactions. Further activation of estrone to the most potent estrogen, estradiol, is catalyzed by 17-ketosteroid reductases, while estradiol can also be formed from dehydroepiandrosterone by the sequential actions of 3beta-hydroxysteroid dehydrogenase-DELTA4-isomerase, aromatase, and 17-ketosteroid reductase. Roles of the STS and SULT enzymes in local estrogen biosynthesis, overview Homo sapiens
2.8.2.2 metabolism in peripheral tissues, estrogens can be formed from the inactive precursors dehydroepiandrosterone sulfate and estrone sulfate. Sulfatase and sulfotransferases have pivotal roles in these processes, where sulfatase hydrolyzes estrone sulfate to estrone, and dehydroepiandrosterone sulfate to dehydroepiandrosterone, and sulfotransferases catalyze the reverse reactions. Further activation of estrone to the most potent estrogen, estradiol, is catalyzed by 17-ketosteroid reductases, while estradiol can also be formed from dehydroepiandrosterone by the sequential actions of 3beta-hydroxysteroid dehydrogenase-DELTA4-isomerase, aromatase, and 17-ketosteroid reductase. Roles of the STS and SULT enzymes in local estrogen biosynthesis, overview. The expression of SULT2A1 is regulated at the transcriptional level by the constitutive androstane receptor and pregnane X receptor Homo sapiens
2.8.2.2 physiological function in peripheral tissues, estrogens can be formed from the inactive precursors dehydroepiandrosterone sulfate and estrone sulfate. Sulfatase and sulfotransferases have pivotal roles in these processes, where sulfatase hydrolyzes estrone sulfate to estrone, and dehydroepiandrosterone sulfate to dehydroepiandrosterone, and sulfotransferases catalyze the reverse reactions. Sulfotransferases 2A1 (SULT2A1) and SULT2B1 catalyze the conjugation of dehydroepiandrosterone (DHEA). In general, SULT2s catalyze sulfonation of the hydroxyl groups of steroids (SULT2A1, SULT2B1) Homo sapiens
2.8.2.4 metabolism in peripheral tissues, estrogens can be formed from the inactive precursors dehydroepiandrosterone sulfate and estrone sulfate. Sulfatase and sulfotransferases have pivotal roles in these processes, where sulfatase hydrolyzes estrone sulfate to estrone, and dehydroepiandrosterone sulfate to dehydroepiandrosterone, and sulfotransferases catalyze the reverse reactions. Further activation of estrone to the most potent estrogen, estradiol, is catalyzed by 17-ketosteroid reductases, while estradiol can also be formed from dehydroepiandrosterone by the sequential actions of 3beta-hydroxysteroid dehydrogenase-DELTA4-isomerase, aromatase, and 17-ketosteroid reductase. Roles of the STS and SULT enzymes in local estrogen biosynthesis, overview Homo sapiens
2.8.2.4 additional information analysis of tertiary structure and reaction mechanism of the human SULT1E1 enzyme using the structure of the human SULT1E1 enzyme in complex with PAP and E2 (PDB ID 4JVL), catalytic amino acid residues His107, Lys47, and Ser137 play a role in the reaction mechanism Homo sapiens
2.8.2.4 physiological function in peripheral tissues, estrogens can be formed from the inactive precursors dehydroepiandrosterone sulfate and estrone sulfate. Sulfatase and sulfotransferases have pivotal roles in these processes, where sulfatase hydrolyzes estrone sulfate to estrone, and dehydroepiandrosterone sulfate to dehydroepiandrosterone, and sulfotransferases catalyze the reverse reactions. Enzyme SULT1E1 catalyzes the conjugation of estrone (E1) Homo sapiens