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SULT1A1

Sulfotransferase 1A1 · UniProt P50225

Length
295 aa
Mass
34.2 kDa
Annotated
2026-06-10
100 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SULT1A1 is a cytosolic phenol sulfotransferase that transfers sulfate from the donor PAPS onto a broad range of phenolic substrates, functioning both as a phase II detoxification enzyme and as a bioactivator of procarcinogens (PMID:12471039, PMID:24318996). Its active site is structurally flexible: crystal structures show it can bind two molecules of p-nitrophenol simultaneously, providing the molecular basis for substrate inhibition, and accommodate fused-ring steroids such as estradiol in a nonproductive dead-end mode that underlies partial substrate inhibition at high concentrations (PMID:12471039, PMID:16221673). Catalysis depends on essential active-site residues Glu83 and Asp134, while Arg257 anchors the 3'-phosphate of PAPS, and position 146 (Ala146) governs discrimination between simple phenolic and monoamine substrates (PMID:10441143, PMID:11123927, PMID:12867416). The enzyme is the principal hepatic sulfotransferase for diverse physiological and pharmacological substrates including 2-methoxyestradiol, resveratrol, apomorphine, and the antiestrogen fulvestrant (PMID:11062153, PMID:16418064, PMID:14660177, PMID:22822301). Through O-sulfonation it bioactivates carcinogenic N-hydroxy arylamines, methyleugenol, and 5-hydroxymethylfurfural into DNA-reactive electrophiles, with Sult1a1-knockout mice losing nearly all methyleugenol-induced hepatic DNA adducts (PMID:24318996, PMID:22563731, PMID:11191883); it also converts the small molecule YC-1 into a protein-reactive covalent species that selectively kills SULT1A1-expressing liver cancer cells (PMID:36914816). SULT1A1 expression is controlled by Sp1/GABP transcriptional synergy, by glucocorticoid and androgen receptors through a proximal IR3 element, by the constitutive androstane receptor, and post-transcriptionally by miR-631 (PMID:15383623, PMID:14570770, PMID:17618724, PMID:20881232). Marked inter-individual variation in SULT1A1 activity is driven primarily by gene copy number and secondarily by the coding Arg213His (*2) polymorphism and 5'-/3'-regulatory SNPs, with the *2 allozyme showing reduced thermal stability and lower bioactivation capacity (PMID:9345314, PMID:17189289, PMID:11191883, PMID:15970794).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1996 Medium

    Establishing the genomic structure and chromosomal organization of SULT1A1 (STP1) was needed to define the gene and its relationship to its paralog STP2.

    Evidence gene/cosmid cloning and genomic sequencing localizing STP1 to chromosome 16p with 9 exons and a paralog 95.9% identical at the protein level

    PMID:8912648 PMID:9014197

    Open questions at the time
    • Did not establish regulatory elements or functional consequence of the two noncoding 5'-UTR exons
    • High sequence identity with STP2/SULT1A2 complicates allele- and paralog-specific attribution
  2. 1997 High

    It was unknown what genetic factors explained the wide variation in platelet phenol sulfotransferase activity; identifying the Arg213His (*2) coding SNP pinned a primary determinant.

    Evidence ORF sequencing of extreme-phenotype subjects plus platelet TS PST phenotyping in 905 individuals

    PMID:9345314

    Open questions at the time
    • Did not yet account for copy number or regulatory variation
    • Mechanistic basis for low activity/thermolability of *2 not resolved
  3. 2000 High

    The catalytic machinery of SULT1A1 was undefined; chemical modification plus mutagenesis identified the essential active-site residues for catalysis.

    Evidence Woodward's reagent K carboxyl modification and E83A/D134A mutagenesis with substrate/PAPS protection and modeling

    PMID:11123927

    Open questions at the time
    • Precise catalytic roles (general base vs structural) of Glu83/Asp134 not separated
    • Modeling relied on mouse estrogen sulfotransferase template rather than human structure
  4. 1999 High

    How SULT1A1 discriminates between phenolic and monoamine substrates was unclear; residue 146 was shown to be the specificity switch.

    Evidence A146E site-directed mutagenesis converting SULT1A1 to a SULT1A3-like kinetic profile; photoaffinity labeling mapping the substrate-binding site; allozyme characterization in liver biopsies

    PMID:10413297 PMID:10441143 PMID:10548061

    Open questions at the time
    • Did not resolve how a single residue reshapes the binding pocket structurally
    • Linkage disequilibrium with SULT1A2 complicates tissue-level allozyme attribution
  5. 2003 Medium

    The PAPS-binding determinants and transcriptional control of SULT1A1 were unknown; Arg257 was shown to anchor the cofactor, and hormone-receptor regulation was defined.

    Evidence 2,3-butanedione Arg modification and R257A/R257E mutagenesis; reporter cotransfection of GR/AR with IR3 mutagenesis (rat ortholog)

    PMID:12867416 PMID:14570770

    Open questions at the time
    • IR3-mediated GR/AR regulation demonstrated in rat ortholog, not human gene
    • Did not test whether endogenous hormones drive physiological SULT1A1 levels
  6. 2002 High

    Without a human structure the basis of substrate inhibition was speculative; crystallography revealed simultaneous binding of two substrate molecules and a flexible extended active site.

    Evidence X-ray crystallography of SULT1A1 with p-nitrophenol plus kinetic analysis of substrate inhibition

    PMID:12471039

    Open questions at the time
    • Did not capture the catalytically productive Michaelis complex
    • Implications for steroid substrates inferred, not directly resolved
  7. 2005 High

    The mechanism of estradiol partial inhibition was unresolved; structure with sulfated estradiol/PAP defined a dead-end complex, and the Sp1/GABP transcriptional logic was established.

    Evidence X-ray crystallography of E2/PAP complex with kinetic modeling; promoter-reporter, EMSA and hepatocyte assays of Sp1/GABP synergy

    PMID:15383623 PMID:16221673

    Open questions at the time
    • Did not quantify in vivo contribution of E2 dead-end complex to physiological estrogen handling
    • Upstream signals that modulate Sp1/GABP occupancy not identified
  8. 2000 Medium

    Whether the Arg213His polymorphism affects carcinogen bioactivation was untested; allozyme assays showed the *1 (Arg213) form bioactivates N-hydroxy arylamines far more efficiently.

    Evidence recombinant SULT1A1*1 vs *2 DNA-adduct formation with N-OH-ABP and N-OH-PhIP; identification of SULT1A1 as the 2-methoxyestradiol- and apomorphine-sulfonating enzyme

    PMID:11062153 PMID:11191883 PMID:14660177

    Open questions at the time
    • In vitro adduct assays do not establish in vivo cancer risk
    • Substrate overlap with SULT1A3/1E1 for some substrates limits sole-enzyme attribution
  9. 2006 High

    The dominant source of activity variation was debated; copy number was shown to outweigh coding and regulatory SNPs, while 5'- and 3'-regulatory variants and miR-631 add further modulation.

    Evidence quantitative multiplex PCR copy-number measurement, 5'-FR and 3'-UTR haplotype/reporter analysis, and functional miR-631 characterization across large platelet and liver cohorts

    PMID:15970794 PMID:17189289 PMID:20881232

    Open questions at the time
    • Mechanistic link between copy number and protein dosage not directly traced
    • Population-specific haplotype effects not fully generalized
  10. 2013 High

    In vitro bioactivation evidence lacked in vivo proof; genetic mouse models established SULT1A1 as the essential mediator of procarcinogen activation, and engineered cells confirmed activation of HMF and YC-1.

    Evidence Sult1a1-knockout and humanized transgenic mice with hepatic DNA-adduct quantification; V79-hSULT1A1 mutagenicity/adduct assays for HMF; proteomics-based YC-1 covalent-targeting screen in liver cancer cells

    PMID:22563731 PMID:24318996 PMID:36914816

    Open questions at the time
    • Tissue- and dose-specific thresholds for human carcinogenic risk not defined
    • YC-1 protein-target consequences and therapeutic window not fully characterized
  11. 2010 Medium

    Whether SULT1A1 activity influences drug cytotoxicity was unclear; ectopic expression showed it potentiates 4-hydroxytamoxifen-induced apoptosis.

    Evidence stable SULT1A1 transfection of MCF-7 cells with proliferation, apoptosis and endonuclease G readouts; fulvestrant sulfation panel and liver-cytosol correlation

    PMID:21537383 PMID:22822301

    Open questions at the time
    • Causal sulfonated metabolite of 4-OHT not directly identified
    • Single-cell-line context limits generalization to patient tumors

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SULT1A1 substrate selectivity, regulation, and copy-number dosage integrate to determine individual carcinogen-activation and drug-response phenotypes in vivo remains incompletely defined.
  • No high-resolution structure of a catalytically productive complex for diverse drug substrates
  • Quantitative mapping from genotype/copy number to in vivo bioactivation flux not established
  • Physiological signals governing human transcriptional regulators (Sp1/GABP, CAR) not delineated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 8 GO:0140096 catalytic activity, acting on a protein 4
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-1643685 Disease 3

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Crystal structure of human SULT1A1 complexed with the xenobiotic substrate p-nitrophenol revealed that the enzyme accommodates two molecules of p-nitrophenol in the active site simultaneously, providing the molecular basis for substrate inhibition. The extended active site is consistent with binding of diiodothyronine but not easily beta-estradiol, suggesting an active site flexibility that allows accommodation of diverse hydrophobic substrates. X-ray crystallography; kinetic analysis of substrate inhibition The Journal of biological chemistry High 12471039
2005 Crystal structure of SULT1A1 co-crystallized with sulfated estradiol and PAP showed that beta-estradiol binds in a nonproductive mode in the active site; the structure reveals conformational changes in the binding site to accommodate fused-ring steroids and supports formation of an enzyme·PAP·E2 dead-end complex as the mechanism of partial substrate inhibition at high E2 concentrations. X-ray crystallography; kinetic modeling The Journal of biological chemistry High 16221673
1999 Site-directed mutagenesis of residue 146 showed that Ala146 in SULT1A1 is a key determinant of substrate specificity: the A146E mutation converted SULT1A1 to a SULT1A3-like kinetic profile for simple phenols, demonstrating that position 146 controls discrimination between simple phenolic and monoamine substrates. Site-directed mutagenesis; kinetic assays with multiple phenolic and monoamine substrates Biochemistry High 10441143
2000 Carboxyl-specific modification with Woodward's reagent K and site-directed mutagenesis identified Glu83 and Asp134 as essential catalytic residues in the active site of SULT1A1; E83A and D134A mutants lost nearly 100% catalytic activity. Both substrate and PAPS protected against inactivation, placing these residues in the active site. Chemical modification (Woodward's reagent K); site-directed mutagenesis (E83A, D134A, E246A, D263A, E151A); activity assays; computer modeling based on mouse estrogen sulfotransferase crystal structure Biochemistry High 11123927
2003 Arg-specific modification and site-directed mutagenesis identified Arg257 as critical for SULT1A1 catalytic activity (R257A and R257E both inactive), likely through ionic interaction with the 3'-phosphate of PAPS. Arg78 contributes to activity through charge (R78E inactivated; R78A active). Arg130 was not critical despite proximity to PAPS 3'-phosphate. Chemical modification (2,3-butanedione); site-directed mutagenesis; computer structure modeling; activity assays The Journal of biological chemistry High 12867416
1999 Photoaffinity labeling with 7-azido-4-methylcoumarin (AzMC) covalently labeled the substrate-binding site of SULT1A1; labeling was protected by phenolic substrate but not PAPS, identifying the substrate binding site as distinct and accessible. The probe competitively inhibited sulfation (Ki = 0.47 mM) and inactivated SULT1A1 in a concentration- and time-dependent manner. Photoaffinity labeling; competitive inhibition kinetics; recombinant SULT1A1 expressed in E. coli as MBP fusion Protein science Medium 10548061
1997 Common SULT1A1 alleles (notably SULT1A1*2, encoding Arg213His) were identified by sequencing the ORF of subjects with extreme platelet TS PST phenotypes; SULT1A1*2 was uniformly associated with very low TS PST activity and low thermal stability, establishing this coding SNP as the primary genetic determinant of platelet phenol sulfotransferase activity variation. PCR amplification and sequencing; phenotyping of platelet TS PST activity and thermal stability in 905 subjects; genotyping of 33 extreme-phenotype subjects Biochemical and biophysical research communications High 9345314
1999 Allozyme characterization of SULT1A1*1 and SULT1A1*2 in human liver biopsy samples showed that SULT1A1 is primarily responsible for the thermostable phenol sulfotransferase (TS PST) phenotype in the liver, while SULT1A2 contributes less. SULT1A1 and SULT1A2 alleles are in linkage disequilibrium. Phenotyping (TS PST thermal stability and activity) of 61 liver biopsies; PCR sequencing of SULT1A1 and SULT1A2 ORFs; biochemical characterization of allozymes Biochemical pharmacology Medium 10413297
2006 SULT1A1 gene copy number (ranging 1–5 copies) is the dominant source of inter-individual variation in platelet and liver SULT1A1 enzymatic activity; reporter assays showed 5'-flanking region SNP haplotypes also contribute to activity, but copy number was the best predictor. African-Americans had more frequent gene duplications (≥3 copies in 63%) than Caucasians (26%). Quantitative multiplex PCR to measure copy number; reporter assays for 5'-FR SNP haplotypes; activity measurements in 23 platelet and 267 liver samples; statistical modeling Human molecular genetics High 17189289
1996 Cloning and structural characterization of the STP1 (SULT1A1) gene showed it spans ~4.4 kb, contains 9 exons (including two noncoding exons IA and IB with alternative 5'-UTRs), lacks a canonical TATA box in the 5'-flanking region, and is located ~45 kb upstream of STP2 on chromosome 16p. Gene cloning; 5'-RACE with human liver cDNA; long PCR; genomic sequencing Pharmacogenetics Medium 9014197
1996 Genomic organization of STP1 (SULT1A1) and STP2 on chromosome 16p12.1-p11.2 was established from a single cosmid clone; both genes contain 7 coding exons with conserved intron-exon boundaries, and STP1 and STP2 are 95.9% identical at the amino acid level. Cosmid cloning; genomic DNA sequencing; exon-intron boundary mapping Biochemical and biophysical research communications Medium 8912648
2004 Transcriptional regulation of SULT1A1 depends on both Sp1 and the Ets transcription factor GABP binding within −112 nucleotides of the transcriptional start site; GABP alone transactivated the SULT1A1 promoter, and co-transfection with Sp1 produced a 10-fold synergistic enhancement. A 2-bp difference in the Ets binding site accounts for the 70% lower activity of the SULT1A3 promoter versus SULT1A1 in adult liver. Promoter-reporter transfection assays (HepG2 cells, Drosophila S2 cells); cotransfection with Sp1 and GABP expression constructs; electrophoretic mobility shift assays; primary human hepatocyte experiments Molecular pharmacology High 15383623
2003 Glucocorticoid receptor (GR) and androgen receptor (AR) transactivate rat SULT1A1 gene transcription through a proximal inverted repeat with 3 intervening bases (IR3) element in the 5'-flanking region; mutation of a conserved GT in the 3' half-site of IR3 abolished GR and AR responsiveness. Reporter cotransfection assays in CV-1 cells and primary rat hepatocytes; wild-type vs. mutant GR/AR expression constructs; IR3 site-directed mutagenesis Drug metabolism and disposition Medium 14570770
2000 SULT1A1 catalyzes sulfonation of 2-methoxyestradiol (2-MeOE2) in MCF-7 breast cancer cells; correlation of SULT1A1 mRNA expression with 2-MeOE2 conjugation across nine cell lines, and heterologous expression of either SULT1A1*1 or SULT1A1*2 in MDA-MB-231 cells (which lack endogenous SULT1A1) conferred 2-MeOE2 sulfonation activity, confirming SULT1A1 as the responsible enzyme. RT-PCR expression correlation across 9 cell lines; heterologous cDNA expression in MDA-MB-231 cells; LC-MS confirmation of 2-MeOE2-3-sulfate; Km determination using SF:9 insect cell expression Carcinogenesis High 11062153
2005 SULT1A1 is the major hepatic enzyme responsible for sulfonation of resveratrol to trans-resveratrol-3-O-sulfate (M1), as demonstrated by incubation with a panel of recombinant human SULTs; SULT1A2 selectively forms M2 (resveratrol-4'-O-sulfate), while SULT1A2 and 1A3 form the disulfate M3. Incubation of resveratrol with human liver cytosol and recombinant SULTs (SULT1A1, 1A2, 1A3, 1E1); product identification by mass spectrometry and NMR; kinetic analysis Xenobiotica Medium 16418064
2003 SULT1A1 is the primary enzyme responsible for hepatic sulfonation of apomorphine; correlation of apomorphine sulfation with 4-nitrophenol sulfation (SULT1A1 marker) across 28 liver cytosols, and immunoinhibition with anti-SULT1A antibodies, confirmed SULT1A1 as the dominant contributor. SULT1A1, 1A3, and 1E1 all sulfate apomorphine in vitro with similar Vmax/Km values. Kinetic analysis with purified recombinant SULTs; substrate correlation in 28 liver cytosols; immunoinhibition with antibodies against SULT1A and SULT1E1 Xenobiotica Medium 14660177
2011 Only SULT1A1 and SULT1E1 among nine recombinant human sulfotransferases display catalytic activity toward fulvestrant (antiestrogen); fulvestrant sulfation in 104 human liver cytosols was highly correlated with β-naphthol sulfation (SULT1A1 substrate, r=0.98) but not 17β-estradiol sulfation (SULT1E1 substrate), and was significantly associated with SULT1A1 genotype and copy number, indicating SULT1A1 is the primary enzyme for hepatic fulvestrant sulfation. In vitro sulfation assays with 9 recombinant SULTs; activity correlation analysis in 104 liver cytosols; genotype and copy number association Pharmacogenomics and personalized medicine Medium 22822301
2010 Expression of SULT1A1 in MCF-7 breast cancer cells significantly increased 4-hydroxytamoxifen (4-OHT)-induced apoptosis (>80% increase within 24h) and reduced cell proliferation (>30% decrease), with increased endonuclease G expression, establishing that SULT1A1-mediated biotransformation of 4-OHT contributes to its cytotoxicity through a caspase-independent apoptotic pathway. Stable transfection of MCF-7 cells with SULT1A1; cell proliferation assays; apoptosis assays; endonuclease G protein measurement; comparison with control (pcDNA3) cells International journal of molecular epidemiology and genetics Medium 21537383
2013 Sult1a1 knockout mice showed a near-complete abolition of methyleugenol-induced hepatic DNA adduct formation (23 vs. 735 adducts/10^8 dN in ko vs. wild-type), while transgenic human SULT1A1/2 mice showed ~5-fold higher adduct levels than wild-type, demonstrating that Sult1a1/SULT1A1 enzymes are the essential mediators of methyleugenol bioactivation to DNA-reactive intermediates in vivo. Mouse knockout (Sult1a1 ko) and transgenic (human SULT1A1/2) models; adduct quantification by 32P-postlabeling in hepatic DNA; in vivo dose-response Carcinogenesis High 24318996
2012 SULT1A1 expressed in V79 cells activates 5-hydroxymethylfurfural (HMF) by sulfonation to form 5-sulfooxymethylfurfural (SMF), which forms DNA adducts N6-FFM-dAdo and N2-FFM-dGuo; HMF induced gene mutations only in V79 cells expressing SULT1A1, not in parental cells, establishing SULT1A1 as the activating enzyme for HMF mutagenicity. V79-hSULT1A1 cell mutagenicity assay; LC-MS/MS adduct identification and quantification; NMR characterization of synthetic adducts; isotope-labeled internal standards Chemical research in toxicology High 22563731
2015 SULT1A1 activity and expression in rat liver intestine is upregulated by ethanol ingestion; two weeks of ethanol significantly increased SULT1A1 at the enzyme activity and protein levels in rat intestine, and increased hSULT1A1 protein expression approximately 2-fold in human Hep-G2 cells. Western blot; enzyme activity assays; rat in vivo ethanol treatment model; Hep-G2 cell culture Archives of physiology and biochemistry Low 25720860
2007 Pyrene-induced SULT1A1 expression and associated 1-hydroxypyrene sulfation activity are regulated by the constitutive androstane receptor (CAR), not by the aryl hydrocarbon receptor (AhR), based on equivalent induction in both AhR(+/+) and AhR(-/-) mice alongside CAR and CYP2B10 co-induction. AhR knockout vs. wild-type mouse comparison; mRNA and protein expression analysis; enzyme activity assays; CAR and CYP2B10 expression as markers Toxicology Medium 17618724
2000 SULT1A1*1 (Arg213) allozyme catalyzes N-hydroxy-aminobiphenyl (N-OH-ABP) DNA adduct formation with substantially greater efficiency than SULT1A1*2 (His213) (5.4 vs. 0.4 pmol/mg DNA/20 min), and N-OH-PhIP adduct formation similarly (4.6 vs. 1.8 pmol/mg DNA/20 min), establishing that the Arg213His polymorphism reduces SULT1A1's capacity to bioactivate carcinogenic N-hydroxy arylamines. Recombinant SULT1A1*1 and SULT1A1*2 DNA binding assays with 32P-postlabeling or direct measurement; comparison of two allozymes Pharmacogenetics Medium 11191883
2010 Two SNPs in the 3'-UTR of SULT1A1 (rs6839 and rs1042157) are significantly associated with SULT1A1 mRNA levels and enzyme activity in liver samples, and functional characterization revealed that miR-631 regulates SULT1A1 expression in a genotype-specific manner, identifying 3'-UTR variation as an additional source of activity variation. Direct sequencing of 97 liver samples; haplotype analysis across 498 Caucasians and 127 African-Americans; mRNA and activity correlation; functional miR-631 characterization Toxicological sciences Medium 20881232
2005 Common SNPs in the 5'-flanking region of SULT1A1 account for 4–13% of inter-individual variability in platelet SULT1A1 activity, with specific haplotypes (GAACT and GGACT) significantly associated with activity in Caucasians; the coding region *1/*2 polymorphism showed no independent effect on activity when 5'-FR polymorphisms were included in the model. Promoter region sequencing; haplotype analysis; platelet enzyme activity correlation in Caucasian, African-American, and Chinese populations Pharmacogenetics and genomics Medium 15970794
2023 SULT1A1 sulfonates the small molecule YC-1, and this sulfonation event stimulates covalent binding of YC-1 to lysine residues in target proteins enriched for RNA-binding factors, conferring selective cytotoxicity against SULT1A1-expressing liver cancer cells. This identifies SULT1A1 as a bioactivating enzyme that converts structurally related small molecules into protein-reactive covalent species. High-throughput cell viability screens; proteomics; in vitro sulfonation assays; in vitro resistance models; computational analysis of structurally related compounds Nature cancer Medium 36914816
2004 A single nucleotide polymorphism (A546G) in porcine SULT1A1 causes a significant decrease in sulfation activity toward skatole metabolites, establishing that this SNP is responsible for reduced hepatic clearance of skatole in pigs. Cloning and expression of porcine SULT1A1 confirmed its role in phase II metabolism of skatole. cDNA cloning and expression; in vitro sulfation activity assays; comparison of wild-type and variant allozymes Mammalian genome Medium 15014971
2001 Natural xanthones from Calophyllum brasiliense reversibly inhibit SULT1A1 with IC50 values of 1.6–7 μM, while coumarins from the same plant inhibit SULT1A1 at picomolar concentrations (IC50 47–185 pM), demonstrating that SULT1A1 is particularly sensitive to inhibition by these natural product classes. In vitro inhibition assays with recombinant SULT1A1 and SULT2A1; IC50 determination; substrate assays Phytomedicine Medium 11824526
2019 Molecular dynamics simulation of the SULT1A1 R213H (Arg213His) variant showed that this mutation induces local conformational changes in the substrate-binding loop (residues 235–263), converting loop to helix/bridge conformations that reduce active site volume and hydrophobicity, thereby decreasing substrate binding affinity as quantified by MM-PBSA analysis. Molecular dynamics simulation; MM-PBSA binding energy analysis of wild-type and R213H mutant SULT1A1 International journal of molecular sciences Low 31835852
2002 Canine SULT1A1 (cSULT1A1) was cloned and expressed in E. coli; the recombinant enzyme sulfates p-nitrophenol (nanomolar Km), alpha-naphthol, dopamine, minoxidil, and beta-estradiol but not dehydroepiandrosterone, and Western blot showed ubiquitous expression in canine tissues with highest levels in liver. cDNA cloning; recombinant expression in E. coli; kinetic substrate characterization; Western blot of tissue distribution Archives of biochemistry and biophysics Medium 12054462

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Phenol sulfotransferase pharmacogenetics in humans: association of common SULT1A1 alleles with TS PST phenotype. Biochemical and biophysical research communications 242 9345314
2007 Genetic variants of CYP3A5, CYP2D6, SULT1A1, UGT2B15 and tamoxifen response in postmenopausal patients with breast cancer. Breast cancer research : BCR 213 17244352
1999 Human phenol sulfotransferases SULT1A2 and SULT1A1: genetic polymorphisms, allozyme properties, and human liver genotype-phenotype correlations. Biochemical pharmacology 157 10413297
2002 Structure of a human carcinogen-converting enzyme, SULT1A1. Structural and kinetic implications of substrate inhibition. The Journal of biological chemistry 133 12471039
2001 Sulfation pharmacogenetics: SULT1A1 and SULT1A2 allele frequencies in Caucasian, Chinese and African-American subjects. Pharmacogenetics 120 11207031
2003 Genotype and allele frequencies of TPMT, NAT2, GST, SULT1A1 and MDR-1 in the Egyptian population. British journal of clinical pharmacology 117 12814450
2007 Effects of CYP2D6 and SULT1A1 genotypes including SULT1A1 gene copy number on tamoxifen metabolism. Annals of oncology : official journal of the European Society for Medical Oncology 115 17947222
1999 Phenol sulphotransferase SULT1A1 polymorphism: molecular diagnosis and allele frequencies in Caucasian and African populations. The Biochemical journal 113 9854023
2006 Human SULT1A1 gene: copy number differences and functional implications. Human molecular genetics 96 17189289
2005 Divergence of Stp1 and Stp2 transcription factors in Candida albicans places virulence factors required for proper nutrient acquisition under amino acid control. Molecular and cellular biology 95 16227594
2005 The structure of human SULT1A1 crystallized with estradiol. An insight into active site plasticity and substrate inhibition with multi-ring substrates. The Journal of biological chemistry 92 16221673
2012 Serine/threonine phosphatase Stp1 contributes to reduced susceptibility to vancomycin and virulence in Staphylococcus aureus. The Journal of infectious diseases 85 22492855
2005 Sulfation of resveratrol in human liver: evidence of a major role for the sulfotransferases SULT1A1 and SULT1E1. Xenobiotica; the fate of foreign compounds in biological systems 77 16418064
2008 CYP1A1, SULT1A1, and SULT1E1 polymorphisms are risk factors for endometrial cancer susceptibility. Cancer 76 18318428
2000 Relationship of phenol sulfotransferase activity (SULT1A1) genotype to sulfotransferase phenotype in platelet cytosol. Pharmacogenetics 73 11191883
2001 Phenol sulphotransferase SULT1A1*1 genotype is associated with reduced risk of colorectal cancer. Pharmacogenetics 69 11692076
2004 Association of SULT1A1 phenotype and genotype with prostate cancer risk in African-Americans and Caucasians. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 67 14973106
1989 Nucleotide sequence of the Stp-1 gene coding for rat spermatid nuclear transition protein 1 (TP1): homology with protamine P1 and assignment of the mouse Stp-1 gene to chromosome 1. Gene 66 2524424
2004 Amino acid signaling in yeast: casein kinase I and the Ssy5 endoprotease are key determinants of endoproteolytic activation of the membrane-bound Stp1 transcription factor. Molecular and cellular biology 65 15509782
2010 Functional genetic variants in the 3'-untranslated region of sulfotransferase isoform 1A1 (SULT1A1) and their effect on enzymatic activity. Toxicological sciences : an official journal of the Society of Toxicology 63 20881232
2013 Two unique phosphorylation-driven signaling pathways crosstalk in Staphylococcus aureus to modulate the cell-wall charge: Stk1/Stp1 meets GraSR. Biochemistry 62 24102310
2011 CYP2D6, SULT1A1 and UGT2B17 copy number variation: quantitative detection by multiplex PCR. Pharmacogenomics 62 22111604
2003 SULT1A1 polymorphism and esophageal cancer in males. International journal of cancer 58 12455060
2000 A simple colorimetric assay for phenotyping the major human thermostable phenol sulfotransferase (SULT1A1) using platelet cytosols. Drug metabolism and disposition: the biological fate of chemicals 58 10950850
1999 Analysis of the substrate specificity of human sulfotransferases SULT1A1 and SULT1A3: site-directed mutagenesis and kinetic studies. Biochemistry 58 10441143
2011 Association between cancer risk and drug-metabolizing enzyme gene (CYP2A6, CYP2A13, CYP4B1, SULT1A1, GSTM1, and GSTT1) polymorphisms in cases of lung cancer in Japan. Drug metabolism and pharmacokinetics 56 21791872
2003 Sulfotransferase 1A1 (SULT1A1) polymorphism and bladder cancer risk: a case-control study. Cancer letters 55 14643027
2019 Structural and Dynamic Characterizations Highlight the Deleterious Role of SULT1A1 R213H Polymorphism in Substrate Binding. International journal of molecular sciences 52 31835852
2013 Formation of hepatic DNA adducts by methyleugenol in mouse models: drastic decrease by Sult1a1 knockout and strong increase by transgenic human SULT1A1/2. Carcinogenesis 50 24318996
2006 Inner nuclear membrane proteins Asi1, Asi2, and Asi3 function in concert to maintain the latent properties of transcription factors Stp1 and Stp2. The Journal of biological chemistry 50 17085444
2012 Mutagenicity of 5-hydroxymethylfurfural in V79 cells expressing human SULT1A1: identification and mass spectrometric quantification of DNA adducts formed. Chemical research in toxicology 49 22563731
2010 Efficacy of tamoxifen based on cytochrome P450 2D6, CYP2C19 and SULT1A1 genotype in the Italian Tamoxifen Prevention Trial. The pharmacogenomics journal 49 20309015
2008 Interaction of the cytochrome P4501A2, SULT1A1 and NAT gene polymorphisms with smoking and dietary mutagen intake in modification of the risk of pancreatic cancer. Carcinogenesis 48 18499698
2006 Human cytosolic sulfotransferase SULT1A1. The international journal of biochemistry & cell biology 48 17110154
2004 Effect of SULT1A1 and NAT2 genetic polymorphism on the association between cigarette smoking and colorectal adenomas. International journal of cancer 48 14618622
2003 A functional polymorphism in the SULT1A1 gene (G638A) is associated with risk of lung cancer in relation to tobacco smoking. Carcinogenesis 48 14688021
2005 Gene-environment interaction: the role of SULT1A1 and CYP3A5 polymorphisms as risk modifiers for squamous cell carcinoma of the oesophagus. Carcinogenesis 43 16272171
2004 The external amino acid signaling pathway promotes activation of Stp1 and Uga35/Dal81 transcription factors for induction of the AGP1 gene in Saccharomyces cerevisiae. Genetics 43 15126393
2004 The human sulfotransferase SULT1A1 gene is regulated in a synergistic manner by Sp1 and GA binding protein. Molecular pharmacology 43 15383623
2000 SULT1A1 catalyzes 2-methoxyestradiol sulfonation in MCF-7 breast cancer cells. Carcinogenesis 42 11062153
2003 Sulfotransferase 1A1 (SULT1A1) polymorphism, PAH-DNA adduct levels in breast tissue and breast cancer risk in a case-control study. Breast cancer research and treatment 41 12725421
2002 Association of genotypes of carcinogen-activating enzymes, phenol sulfotransferase SULT1A1 (ST1A3) and arylamine N-acetyltransferase NAT2, with urothelial cancer in a Japanese population. International journal of cancer 39 12402313
1996 Human phenol sulfotransferase pharmacogenetics: STP1 gene cloning and structural characterization. Pharmacogenetics 39 9014197
1997 STP1, a gene involved in pre-tRNA processing in yeast, is important for amino-acid uptake and transcription of the permease gene BAP2. Current genetics 37 9065387
2011 Serine/threonine phosphatase Stp1 mediates post-transcriptional regulation of hemolysin, autolysis, and virulence of group B Streptococcus. The Journal of biological chemistry 36 22081606
2004 Sulfotransferase 1A1 (SULT1A1) polymorphism and breast cancer risk in Chinese women. Toxicology letters 34 15093672
1995 Purification and characterization of the low molecular weight protein tyrosine phosphatase, Stp1, from the fission yeast Schizosaccharomyces pombe. Biochemistry 33 7654712
2008 Case-control study and meta-analysis of SULT1A1 Arg213His polymorphism for gene, ethnicity and environment interaction for cancer risk. British journal of cancer 32 18854828
2005 Genetic polymorphisms in human SULT1A1 and UGT1A1 genes associate with breast tumor characteristics: a case-series study. Breast cancer research : BCR 32 16280036
2005 Common genetic polymorphisms in the 5'-flanking region of the SULT1A1 gene: haplotypes and their association with platelet enzymatic activity. Pharmacogenetics and genomics 31 15970794
2002 Association of the SULT1A1 R213H polymorphism with colorectal cancer. Clinical and experimental pharmacology & physiology 31 12165038
2000 Phenol sulphotransferase SULT1A1 polymorphism in prostate cancer: lack of association. Archives of toxicology 31 10959796
2010 The prodomain of Ssy5 protease controls receptor-activated proteolysis of transcription factor Stp1. Molecular and cellular biology 30 20421414
2008 Genetic polymorphisms in platelet-related proteins and coronary artery disease: investigation of candidate genes, including N-acetylgalactosaminyltransferase 4 (GALNT4) and sulphotransferase 1A1/2 (SULT1A1/2). Journal of thrombosis and thrombolysis 30 18259693
2004 Molecular cloning and functional analysis of porcine SULT1A1 gene and its variant: a single mutation SULT1A1 causes a significant decrease in sulfation activity. Mammalian genome : official journal of the International Mammalian Genome Society 30 15014971
2003 The relationship among the polymorphisms of SULT1A1, 1A2 and different types of cancers in Taiwanese. International journal of molecular medicine 30 12469224
2007 Dal81 enhances Stp1- and Stp2-dependent transcription necessitating negative modulation by inner nuclear membrane protein Asi1 in Saccharomyces cerevisiae. Genetics 29 17603098
2005 SULT1A1 genotype, active and passive smoking, and breast cancer risk by age 50 years in a German case-control study. Breast cancer research : BCR 29 15743503
1999 Photoaffinity labeling probe for the substrate binding site of human phenol sulfotransferase (SULT1A1): 7-azido-4-methylcoumarin. Protein science : a publication of the Protein Society 29 10548061
2014 Genotoxicity of 1-methylpyrene and 1-hydroxymethylpyrene in Chinese hamster V79-derived cells expressing both human CYP2E1 and SULT1A1. Environmental and molecular mutagenesis 27 25243916
2009 TORC1 controls degradation of the transcription factor Stp1, a key effector of the SPS amino-acid-sensing pathway in Saccharomyces cerevisiae. Journal of cell science 27 19494127
2007 Pyrene-induced CYP1A2 and SULT1A1 may be regulated by CAR and not by AhR. Toxicology 27 17618724
1996 Genomic organization and DNA sequences of two human phenol sulfotransferase genes (STP1 and STP2) on the short arm of chromosome 16. Biochemical and biophysical research communications 27 8912648
2010 Expression of sulfotransferase isoform 1A1 (SULT1A1) in breast cancer cells significantly increases 4-hydroxytamoxifen-induced apoptosis. International journal of molecular epidemiology and genetics 26 21537383
2000 Carboxyl residues in the active site of human phenol sulfotransferase (SULT1A1). Biochemistry 26 11123927
2007 SULT1A1 genotype and susceptibility to colorectal cancer. International journal of cancer 24 17013894
2016 Influence of SULT1A1 genetic variation on age at menopause, estrogen levels, and response to hormone therapy in recently postmenopausal white women. Menopause (New York, N.Y.) 23 27300114
2014 Latency of transcription factor Stp1 depends on a modular regulatory motif that functions as cytoplasmic retention determinant and nuclear degron. Molecular biology of the cell 23 25253722
2007 Phenol sulfotransferase SULT1A1*2 allele and enhanced risk of upper urinary tract urothelial cell carcinoma. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 23 18006944
2007 Comparison of 2-aminophenol and 4-nitrophenol as in vitro probe substrates for the major human hepatic sulfotransferase, SULT1A1, demonstrates improved selectivity with 2-aminophenol. Biochemical pharmacology 22 17506995
2018 Genetic polymorphisms of 3'-untranslated region of SULT1A1 and their impact on tamoxifen metabolism and efficacy. Breast cancer research and treatment 21 30120701
2015 5,5'-Methylenedisalicylic Acid (MDSA) Modulates SarA/MgrA Phosphorylation by Targeting Ser/Thr Phosphatase Stp1. Chembiochem : a European journal of chemical biology 21 25810089
2011 Sulfation of fulvestrant by human liver cytosols and recombinant SULT1A1 and SULT1E1. Pharmacogenomics and personalized medicine 21 22822301
2009 Amino acid signaling in yeast: post-genome duplication divergence of the Stp1 and Stp2 transcription factors. The Journal of biological chemistry 21 19906648
2004 CYP17 and SULT1A1 gene polymorphisms in Indian breast cancer. Breast cancer (Tokyo, Japan) 21 15604994
2001 Natural products isolated from Mexican medicinal plants: novel inhibitors of sulfotransferases, SULT1A1 and SULT2A1. Phytomedicine : international journal of phytotherapy and phytopharmacology 21 11824526
1992 STP1, a gene involved in pre-tRNA processing, encodes a nuclear protein containing zinc finger motifs. Molecular and cellular biology 20 1588961
2015 Ethanol up-regulates phenol sulfotransferase (SULT1A1) and hydroxysteroid sulfotransferase (SULT2A1) in rat liver and intestine. Archives of physiology and biochemistry 19 25720860
2015 Yeast Cyc8p and Tup1p proteins function as coactivators for transcription of Stp1/2p-dependent amino acid transporter genes. Biochemical and biophysical research communications 19 26546823
2010 Differential regulation of transcription factors Stp1 and Stp2 in the Ssy1-Ptr3-Ssy5 amino acid sensing pathway. The Journal of biological chemistry 19 21127045
2009 An investigation of the relationship between SULT1A1 Arg(213)His polymorphism and lung cancer susceptibility in a Turkish population. Cell biochemistry and function 18 19350537
2006 Genotypic and allelic frequencies of SULT1A1 polymorphisms in women receiving adjuvant tamoxifen therapy. Breast cancer research and treatment 18 16317586
2003 Transactivation of glucocorticoid-inducible rat aryl sulfotransferase (SULT1A1) gene transcription. Drug metabolism and disposition: the biological fate of chemicals 18 14570770
2021 Insights into the substrate binding mechanism of SULT1A1 through molecular dynamics with excited normal modes simulations. Scientific reports 17 34162941
2020 Stp1 Loss of Function Promotes β-Lactam Resistance in Staphylococcus aureus That Is Independent of Classical Genes. Antimicrobial agents and chemotherapy 17 32179529
2015 Polymorphisms in CYP1B1, CYP3A5, GSTT1, and SULT1A1 Are Associated with Early Age Acute Leukemia. PloS one 17 25992585
2003 Arginine residues in the active site of human phenol sulfotransferase (SULT1A1). The Journal of biological chemistry 16 12867416
2003 Sulfation of apomorphine by human sulfotransferases: evidence of a major role for the polymorphic phenol sulfotransferase, SULT1A1. Xenobiotica; the fate of foreign compounds in biological systems 16 14660177
2023 SULT1A1-dependent sulfonation of alkylators is a lineage-dependent vulnerability of liver cancers. Nature cancer 15 36914816
2023 A 21-bp InDel in the promoter of STP1 selected during tomato improvement accounts for soluble solid content in fruits. Horticulture research 15 36960428
2019 Metallopeptidase Stp1 activates the transcription factor Sre1 in the carotenogenic yeast Xanthophyllomyces dendrorhous. Journal of lipid research 15 31806730
2007 Genetic polymorphisms in CYP1A1, CYP2D6, UGT1A6, UGT1A7, and SULT1A1 genes and correlation with benzene exposure in a Chinese occupational population. Journal of toxicology and environmental health. Part A 15 17479406
2005 Genetic polymorphism in the sulfotransferase SULT1A1 gene in cancer. Cancer genetics and cytogenetics 15 15949571
2020 The Paralogous Transcription Factors Stp1 and Stp2 of Candida albicans Have Distinct Functions in Nutrient Acquisition and Host Interaction. Infection and immunity 14 32094252
2016 Role of exposure/recovery schedule in micronuclei induction by several promutagens in V79-derived cells expressing human CYP2E1 and SULT1A1. Mutation research. Genetic toxicology and environmental mutagenesis 14 27637483
2001 Expression of the small tyrosine phosphatase (Stp1) in Saccharomyces cerevisiae: a study on protein tyrosine phosphorylation. Electrophoresis 14 11258771
2020 Insight into the Dual inhibitory Mechanism of verbascoside targeting serine/threonine phosphatase Stp1 against Staphylococcus aureus. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 13 33115673
2020 Stk and Stp1 participate in Streptococcus suis serotype 2 pathogenesis by regulating capsule thickness and translocation of certain virulence factors. Microbial pathogenesis 13 33161059
2009 Trans-resveratrol-mediated inhibition of beta-oestradiol conjugation in MCF-7 cells stably expressing human sulfotransferases SULT1A1 or SULT1E1, and human liver microsomes. Xenobiotica; the fate of foreign compounds in biological systems 13 19219749
2002 Canine sulfotransferase SULT1A1: molecular cloning, expression, and characterization. Archives of biochemistry and biophysics 13 12054462

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