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Literature summary for 2.8.2.2 extracted from
- The important roles of steroid sulfatase and sulfotransferases in gynecological diseases (2016), Front. Pharmacol., 7, 30 .
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| gene SULT2A1, localized to chromosome 19 (19q13.3), different transcripts and genetic variants, overview | Homo sapiens |
| 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 |
Crystallization (Commentary)
| Crystallization (Comment) | Organism |
|---|---|
| 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 |
| 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
| Protein Variants | Comment | Organism |
|---|---|---|
| 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 |
| A63P | polymorphism of SULT2A1. The SULT2A1 SNP Ala63Pro has an allele frequency of 5% in African-American populations | Homo sapiens |
| 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 |
| R18Q | polymorphism of SULT2B1 | Homo sapiens |
| R33Q | polymorphism of SULT2B1 | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| 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]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 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 | |
| 0.0023 | - |
dehydroepiandrosterone | SULT2B1a, pH and temperature not specified in the publication | Homo sapiens | |
| 0.0025 | - |
dehydroepiandrosterone | SULT2A1, pH and temperature not specified in the publication | Homo sapiens | |
| 0.0044 | - |
dehydroepiandrosterone | SULT2B1b, pH and temperature not specified in the publication | Homo sapiens | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytosol | - |
Homo sapiens | 5829 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 3'-phosphoadenylyl sulfate + dehydroepiandrosterone | Homo sapiens | - |
adenosine 3',5'-bisphosphate + dehydroepiandrosterone 3-O-sulfate | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | O00204 | - |
- |
| Homo sapiens | Q06520 | - |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| adrenal gland | adult and fetal adrenal | Homo sapiens | - |
| brain | fetal | Homo sapiens | - |
| colon | - |
Homo sapiens | - |
| Hep-G2 cell | - |
Homo sapiens | - |
| liver | - |
Homo sapiens | - |
| liver | adult and and fetal liver | Homo sapiens | - |
| 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 | - |
| ovary | - |
Homo sapiens | - |
| placenta | - |
Homo sapiens | - |
| prostate gland | - |
Homo sapiens | - |
| small intestine | - |
Homo sapiens | - |
| uterus | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 3'-phosphoadenylyl sulfate + dehydroepiandrosterone | - |
Homo sapiens | adenosine 3',5'-bisphosphate + dehydroepiandrosterone 3-O-sulfate | - |
? | |
| additional information | isozymes SULT2B1a and SULT2B1b catalyze sulfonation of 3beta-hydroxysteroids, pregnenolone, 17alpha-hydroxypregnenolone and DHEA | Homo sapiens | ? | - |
- |
|
| 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 | ? | - |
- |
|
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| SULT2A1 | - |
Homo sapiens |
| SULT2B1 | - |
Homo sapiens |
| SULT2B1a | isozyme | Homo sapiens |
| SULT2B1b | isozyme | Homo sapiens |
Ki Value [mM]
| Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.0061 | - |
dehydroepiandrosterone | SULT2A1, pH and temperature not specified in the publication | Homo sapiens | |
| 0.022 | - |
dehydroepiandrosterone | SULT2B1b, pH and temperature not specified in the publication | Homo sapiens | |
| 0.048 | - |
dehydroepiandrosterone | SULT2B1a, pH and temperature not specified in the publication | Homo sapiens | |
Expression
| Organism | Comment | Expression |
|---|---|---|
| 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 |
| 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 |
General Information
| General Information | Comment | Organism |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
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