SULT1E1

Summary

SULT1E1 (sulfotransferase family 1E member 1, HGNC:11377) is a protein-coding gene on chromosome 4q13.3, encoding Sulfotransferase 1E1 (P49888). Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of estradiol and estrone.

Sulfotransferase enzymes catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. These cytosolic enzymes are different in their tissue distributions and substrate specificities. The gene structure (number and length of exons) is similar among family members. This gene encodes a protein that transfers a sulfo moiety to and from estrone, which may control levels of estrogen receptors.

Source: NCBI Gene 6783 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 50 total
• Druggable target: yes
• MANE Select transcript: NM_005420

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11377
Approved symbol	SULT1E1
Name	sulfotransferase family 1E member 1
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Aliases	EST
Ensembl gene	ENSG00000109193
Ensembl biotype	protein_coding
OMIM	600043
Entrez	6783

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 12 protein_coding, 1 retained_intron

ENST00000226444, ENST00000504002, ENST00000904212, ENST00000904213, ENST00000904214, ENST00000904215, ENST00000904216, ENST00000904217, ENST00000904218, ENST00000904219, ENST00000904220, ENST00000904221, ENST00000904222

RefSeq mRNA: 1 — MANE Select: NM_005420 NM_005420

CCDS: CCDS3531

Canonical transcript exons

ENST00000226444 — 8 exons

Exon	Start	End
ENSE00000720178	69847698	69847792
ENSE00000720182	69849437	69849563
ENSE00001180361	69841212	69842106
ENSE00002049502	69860049	69860145
ENSE00003492472	69857500	69857653
ENSE00003533339	69854217	69854314
ENSE00003675419	69855301	69855426
ENSE00003811538	69844161	69844341

Expression profiles

Bgee: expression breadth ubiquitous, 145 present calls, max score 92.69.

FANTOM5 (CAGE): breadth broad, TPM avg 4.4413 / max 849.0808, expressed in 318 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52389	4.4413	318

Top tissues by expression

242 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
penis	UBERON:0000989	92.69	gold quality
adrenal tissue	UBERON:0018303	92.23	gold quality
right adrenal gland	UBERON:0001233	88.06	gold quality
buccal mucosa cell	CL:0002336	87.88	gold quality
left adrenal gland cortex	UBERON:0035825	87.48	gold quality
left adrenal gland	UBERON:0001234	87.04	gold quality
right adrenal gland cortex	UBERON:0035827	86.92	gold quality
adrenal cortex	UBERON:0001235	86.28	gold quality
skin of leg	UBERON:0001511	86.28	gold quality
jejunal mucosa	UBERON:0000399	85.37	gold quality
skin of abdomen	UBERON:0001416	85.17	gold quality
duodenum	UBERON:0002114	85.17	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.55	gold quality
right lobe of liver	UBERON:0001114	84.06	gold quality
adrenal gland	UBERON:0002369	84.06	gold quality
liver	UBERON:0002107	82.59	gold quality
zone of skin	UBERON:0000014	81.86	gold quality
mucosa of paranasal sinus	UBERON:0005030	81.18	silver quality
vagina	UBERON:0000996	80.60	gold quality
ileal mucosa	UBERON:0000331	79.87	gold quality
right lung	UBERON:0002167	79.42	gold quality
small intestine Peyer’s patch	UBERON:0003454	78.11	gold quality
small intestine	UBERON:0002108	77.52	gold quality
nasal cavity mucosa	UBERON:0001826	75.51	gold quality
minor salivary gland	UBERON:0001830	74.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.20	gold quality
mouth mucosa	UBERON:0003729	69.97	gold quality
nasal cavity epithelium	UBERON:0005384	68.27	silver quality
jejunum	UBERON:0002115	67.72	gold quality
metanephros	UBERON:0000081	67.67	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-114530	yes	5809.28
E-GEOD-124472	yes	4702.63
E-HCAD-10	yes	2920.12
E-GEOD-125970	yes	9.67
E-GEOD-110499	no	29.30
E-ENAD-17	no	10.00
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AR, HNF4A, IRF6, NFKB, NR1I2, PPARA, RELA, TFAP2A, TFAP2C, TP63

miRNA regulators (miRDB)

71 targeting SULT1E1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-4516	99.61	67.78	3390

Literature-anchored findings (GeneRIF, showing 40)

• linkage to SULT1B1 and to a SULT1D1 pseudogene on chromosome 4 (PMID:11688987)
• crystal structure of human EST (hEST) in the context of the V269E mutant-PAPS complex, which is the first structure containing the active sulfate donor for any sulfotransferase (PMID:11884392)
• Levels of steroid sulfatase and STS mRNA and activity may be significantly associated with degree of atherosclerotic changes in female aorta, which may be related to cytokines produced in situ, such as IL-1beta, in human atherosclerotic lesions. (PMID:14507642)
• estrogen-dependent cell growth of the EST-transfected cell clones was found to be abolished, due to the enhanced sulfoconjugation of estrogen (PMID:14556660)
• Decreased estrogen sulfotransferase expression is associated with estrogen-dependent endometrial carcinomas (PMID:15355916)
• Women with the SULT1E1 *959 GA/AA genotype had a moderately decreased breast cancer risk compared with those with the GG genotypes. They had an increased risk of recurrence compared with the TT geonotype (PMID:15894657)
• Sulfation of resveratrol in human liver: evidence of a major role for the sulfotransferases SULT1E1. (PMID:16418064)
• EST 1E1 mRNA and protein were found to be expressed in epithelial cells bordering alveola lumen (luminal cells) as well as stroma cells in the prostate (PMID:17187396)
• Altered cellular proliferation was observed in cells stably expressing SULT1E1. (PMID:17293380)
• Down-regulation of epithelial estrogen sulfotransferase was associated with high-grade ductal carcinoma in situ in breast cancer (PMID:17661084)
• a decreased single nucleotide polymorphism of CYP1A1 and an increased single nucleotide polymorphism for SULT1A1 and SULT1E1 genes may be risk factors for endometrial cancer in Caucasians. (PMID:18318428)
• Data show higher levels for EST mRNA were obtained in polycystic ovarian syndrome endometria without treatment versus normal endometria. (PMID:18467089)
• Activation of glucocorticoid receptor by dexamethasone induced the activity of estrogen sulfotransferase (SULT1E1), an enzyme important for the metabolic deactivation of estrogens, because sulfonated estrogens fail to activate the estrogen receptor. (PMID:18794126)
• SULT1E1 mRNA is expressed in human skin, at higher levels in men than women (3-4 times greater arm and hip). No gender difference in face skin. SUL1E1 mRNA levels are not altered by topical 17-beta-estradiol treatment. (PMID:18794456)
• The enhanced SULT1E1 activity may have a role in inhibiting GH-stimulated STAT5b phosphorylation and IGF-1 synthesis via the sulfation and inactivation of E2. (PMID:18831980)
• Data show that SULT1E1 expression in HepG2 cells is inducible by sterol mediated liver-X-receptor (LXR) activation. (PMID:19429440)
• Murine SULT1E1 inhibition in vitro and in silico was investigated and compared this to data for the human enzyme. (PMID:20025931)
• Human EST (a dimer of identical protomers) presents a clear example of half-sites reactivity–only one subunit of the dimer produces product during the catalytic cycle. It is the first example of half-sites reactivity in the sulfotransferase family. (PMID:20429582)
• Recent results of STS and EST in several estrogen-dependent carcinomas, are summarised. (PMID:21073915)
• estrogen sulfotransferase is expressed in abdominal sc adipose tissue of both obese males and females in association with expression of TNF-alpha and SOCS3, suggesting potential roles in inflammation. (PMID:21543429)
• Decrease or deletion of EST in the mammary gland may be related to the development of hypertrophic breast, especially gland-associated hypertrophic breast. (PMID:21548389)
• Identification of the upstream enhancer of the SULT1E1 promoter that plays a crucial role in regulating the activity of SULT1E1 transcription. (PMID:21764778)
• results demonstrate that SULT1E1 expression in MCF10A breast epithelial cells cells is transcriptionally regulated by confluence through a suppressive action of the AhR, which is not mediated through a dioxin response element at nt -3476 (PMID:21828262)
• Using two iterative rounds of evolution, we generated SULT1E1 mutants with increased thermostability. (PMID:22197379)
• study showed expression patterns of SULT1E1 and PAPSS in breast and endometrial tissues; the estrogen sulfation enzymes were comparatively higher in the tumorous tissues than adjacent normal tissues; overexpression of SULT1E1 and PAPSS1 retarded MCF-7 cells growth in vivo and in vitro by arresting cell cycles and inducing apoptosis (PMID:22380844)
• Knock-down of SULT1E1 in HUVECs resulted in regulation of genes involved in inflammation and lipid metabolism. (PMID:23384540)
• Report diterpenoid extracts from Leonurus sibiricus L. with estrogen sulfotransferase inhibitory activity. (PMID:23736977)
• Data indicate that protein-ligand interaction energy by using docking Quantitative Structure-Activity Relationships(QSAR) models showed accuracy of 67.28%, 78.00% and 75.46%, for the isoforms SULT1A1, SULT1A3 and SULT1E1, respectively. (PMID:24039991)
• Authors propose that the formation of this DNA loop and protein-bound complex prevents additional binding of ETS1 and p53 R273H proteins to other proximal binding sites. (PMID:24481480)
• Overexpression of EST promoted adipogenesis. (PMID:24567372)
• Data suggest that the substrate specificities of SULT1E1 and SULT1A1*1 include metabolites of tamoxifen (endoxifen, 4-hydroxytamoxifen, and N-desmethyltamoxifen); these metabolites are weak inhibitors of sulfation of estradiol by SULT1E1/SULT1A1*1. (PMID:25819444)
• It metabolizes breast cancer drugs like afimoxifene and endoxifen by sulfation. (PMID:26169578)
• Data show that both estrogen sulfatase (STS) and estrogen sulfotransferase (EST) were highly expressed in the human umbilical vein (PMID:26458420)
• a model that enables prediction of substrates and inhibitors of SULT1E1, is reported. (PMID:26542807)
• Effects of steroid hormone on estrogen sulfotransferase and on steroid sulfatase expression in endometriosis tissue and stromal cells (PMID:26723541)
• Single nucleotide polymorphisms in SULT1E1 were significantly associated with time to treatment failure in men on abiraterone acetate therapy. The single nucleotide polymorphisms may serve as predictive markers for treatment with abiraterone acetate. (PMID:27150425)
• Resveratrol and all its derivatives reduced also SULT1E1 mRNA transcript level. The reduced expression of AhR, CYP1A1, and 1B1 was also found as a result of treatment with these compounds. (PMID:27854074)
• Galeterone and abiraterone are novel inhibitors of DHEA sulfonation, as determined in enzymatic incubations containing human tissue cytosol (liver or intestinal) or human recombinant SULT enzyme (SULT2A1, SULT2B1b, or SULT1E1). (PMID:29436390)
• Increased expression of SULT1E1 is associated with obstructive cholestasis. (PMID:29929982)
• CYP19A1 mRNA levels were lower in endometrial cancer (EC) than in controls. A novel highly sensitive and accurate protocol to assess SULT1E1 activity is presented. STS enzyme activity and the STS:SULT1E1 activity ratio seem to be lower in ECs than in controls. STS is an important route for estrogen supply in endometrial cells. (PMID:30217785)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	sult1st4	ENSDARG00000003181
danio_rerio	sult1st3	ENSDARG00000018361
danio_rerio	sult1st1	ENSDARG00000028275
danio_rerio	sult2st3	ENSDARG00000028367
danio_rerio	sult2st1	ENSDARG00000033170
danio_rerio	sult1st2	ENSDARG00000041540
danio_rerio	sult1st7	ENSDARG00000079079
danio_rerio	sult1st9	ENSDARG00000094996
danio_rerio	sult2st2	ENSDARG00000103785
mus_musculus	Sult1e1	ENSMUSG00000029272
rattus_norvegicus	Sult1e1	ENSRNOG00000001957
drosophila_melanogaster	St4	FBGN0033887
drosophila_melanogaster	St1	FBGN0034887
drosophila_melanogaster	St3	FBGN0265052

Paralogs (12): SULT2B1 (ENSG00000088002), SULT2A1 (ENSG00000105398), SULT4A1 (ENSG00000130540), SULT6B1 (ENSG00000138068), SULT1B1 (ENSG00000173597), SULT1C3 (ENSG00000196228), SULT1A1 (ENSG00000196502), SULT1A2 (ENSG00000197165), SULT1C4 (ENSG00000198075), SULT1C2 (ENSG00000198203), SULT1A4 (ENSG00000213648), SULT1A3 (ENSG00000261052)

Protein

Protein identifiers

Sulfotransferase 1E1 — P49888 (reviewed: P49888)

Alternative names: EST-1, Estrogen sulfotransferase, Sulfotransferase, estrogen-preferring

All UniProt accessions (2): P49888, Q53X91

UniProt curated annotations — full annotation on UniProt →

Function. Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of estradiol and estrone. Is a key enzyme in estrogen homeostasis, the sulfation of estrogens leads to their inactivation. Also sulfates dehydroepiandrosterone (DHEA), pregnenolone, (24S)-hydroxycholesterol and xenobiotic compounds like ethinylestradiol, equalenin, diethyl stilbesterol and 1-naphthol at significantly lower efficiency. Does not sulfonate cortisol, testosterone and dopamine. May play a role in gut microbiota-host metabolic interaction. O-sulfonates 4-ethylphenol (4-EP), a dietary tyrosine-derived metabolite produced by gut bacteria. The product 4-EPS crosses the blood-brain barrier and may negatively regulate oligodendrocyte maturation and myelination, affecting the functional connectivity of different brain regions associated with the limbic system.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Liver, intestine and at lower level in the kidney.

Activity regulation. Inhibited by estradiol.

Similarity. Belongs to the sulfotransferase 1 family.

RefSeq proteins (1): NP_005411* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000863	Sulfotransferase_dom	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00685

Enzyme classification (BRENDA):

• EC 2.8.2.4 — estrone sulfotransferase (BRENDA: 11 organisms, 222 substrates, 221 inhibitors, 96 Km, 3 kcat entries)

Substrate kinetics (BRENDA)

43 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
17BETA-ESTRADIOL	—	10
ESTRADIOL	—	10
ESTRONE	0.0001–0.0166	10
3’-PHOSPHOADENYLYLSULFATE	0.0001–0.037	6
DEHYDROEPIANDROSTERONE	0.0001–0.0607	4
ANDROSTENEDIOL	0.0009–0.0032	3
DOPAMINE	0.2407–79.35	3
P-NITROPHENOL	0.0766–0.9372	3
QUERCETIN	0.0003–0.002	3
RESVERATROL	0.0006–0.0069	3
ADENOSINE 3’,5’-BISPHOSPHATE	—	2
APIGENIN	0.0053	2
CHRYSIN	0.0045	2
EPICATECHIN	0.962	2
ESTRIOL	—	2

Catalyzed reactions (Rhea), 5 shown:

• estrone + 3’-phosphoadenylyl sulfate = estrone 3-sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:15973)
• 3beta-hydroxyandrost-5-en-17-one + 3’-phosphoadenylyl sulfate = dehydroepiandrosterone 3-sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:51216)
• (24S)-hydroxycholesterol + 3’-phosphoadenylyl sulfate = (24S)-hydroxycholesterol 3-sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:52348)
• 17beta-estradiol + 3’-phosphoadenylyl sulfate = 17beta-estradiol 3-sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:52372)
• 4-ethylphenol + 3’-phosphoadenylyl sulfate = 4-ethylphenyl sulfate + adenosine 3’,5’-bisphosphate + H(+) (RHEA:70607)

UniProt features (47 total): helix 18, strand 7, binding site 7, mutagenesis site 6, turn 5, chain 1, active site 1, sequence conflict 1, sequence variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
1G3M	X-RAY DIFFRACTION	1.7
1HY3	X-RAY DIFFRACTION	1.8
4JVL	X-RAY DIFFRACTION	1.94
4JVM	X-RAY DIFFRACTION	1.99
4JVN	X-RAY DIFFRACTION	2.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49888-F1	97.24	0.95

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 107 (proton acceptor)

Ligand- & substrate-binding residues (7): 47–52; 105–107; 129; 137; 192; 226–231; 256–258

Mutagenesis-validated functional residues (6):

Position	Phenotype
85	does not have decreased sulfonation activity towards the estrogens and dhea.
107	complete loss of sulfonation activity towards all substrates tested.
137	decreased gradually the sulfotransferase activity.
145	substrate specificity constants for estradiol and estrone are reduced. dramatic 400-fold increase in the ability to sulf
269	does not prevent the formation of homodimer.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-156584	Cytosolic sulfonation of small molecules
R-HSA-9753281	Paracetamol ADME
R-HSA-1430728	Metabolism
R-HSA-156580	Phase II - Conjugation of compounds
R-HSA-211859	Biological oxidations
R-HSA-9748784	Drug ADME

MSigDB gene sets: 145 (showing top): GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_POSITIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_SULFATION, MODULE_404, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, chr4q13, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, FUJIWARA_PARK2_HEPATOCYTE_PROLIFERATION_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS

GO Biological Process (8): ethanol catabolic process (GO:0006068), estrogen catabolic process (GO:0006711), steroid metabolic process (GO:0008202), estrogen metabolic process (GO:0008210), positive regulation of fat cell differentiation (GO:0045600), 3’-phosphoadenosine 5’-phosphosulfate metabolic process (GO:0050427), sulfation (GO:0051923), lipid metabolic process (GO:0006629)

GO Molecular Function (9): aryl sulfotransferase activity (GO:0004062), estrone sulfotransferase activity (GO:0004304), steroid binding (GO:0005496), sulfotransferase activity (GO:0008146), flavonol 3-sulfotransferase activity (GO:0047894), steroid sulfotransferase activity (GO:0050294), protein binding (GO:0005515), lipid binding (GO:0008289), transferase activity (GO:0016740)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear membrane (GO:0031965)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Phase II - Conjugation of compounds	1
Drug ADME	1
Biological oxidations	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sulfotransferase activity	4
sulfur compound metabolic process	2
binding	2
cellular anatomical structure	2
ethanol metabolic process	1
primary alcohol catabolic process	1
steroid catabolic process	1
estrogen metabolic process	1
hormone catabolic process	1
lipid metabolic process	1
steroid metabolic process	1
hormone metabolic process	1
fat cell differentiation	1
positive regulation of cell differentiation	1
regulation of fat cell differentiation	1
purine ribonucleotide metabolic process	1
purine ribonucleoside bisphosphate metabolic process	1
oxoacid metabolic process	1
primary metabolic process	1
lipid binding	1
transferase activity, transferring sulphur-containing groups	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1
nucleus	1
nuclear envelope	1
organelle membrane	1

Protein interactions and networks

STRING

794 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SULT1E1	TERT	O14746	996
SULT1E1	SMG6	Q86US8	893
SULT1E1	SMG7	Q92540	875
SULT1E1	STS	P08842	864
SULT1E1	SMG5	Q9UPR3	832
SULT1E1	UPF1	Q92900	722
SULT1E1	CCR8	P51685	712
SULT1E1	HSD17B1	P14061	635
SULT1E1	TERF1	P54274	625
SULT1E1	CYP19A1	P11511	608
SULT1E1	UGT1A6	P19224	592
SULT1E1	UGT1A4	P22310	592
SULT1E1	UGT1A10	Q9HAW8	592
SULT1E1	DHRS11	Q6UWP2	584
SULT1E1	HSD17B2	P37059	582

IntAct

18 interactions, top by confidence:

A	B	Type	Score
SULT1E1	PDE9A	psi-mi:“MI:0915”(physical association)	0.560
PDE9A	SULT1E1	psi-mi:“MI:0915”(physical association)	0.560
SULT1E1	ENOX1	psi-mi:“MI:0915”(physical association)	0.370
SULT1E1	SULT2B1	psi-mi:“MI:0915”(physical association)	0.370
SULT1E1	PDE9A	psi-mi:“MI:0915”(physical association)	0.000
SULT1E1	TP53	psi-mi:“MI:0915”(physical association)	0.000
SULT1E1	UNC119	psi-mi:“MI:0915”(physical association)	0.000
SULT1E1	EEF1A1	psi-mi:“MI:0915”(physical association)	0.000
SULT1E1	RIF1	psi-mi:“MI:0915”(physical association)	0.000
SULT1E1	SETDB1	psi-mi:“MI:0915”(physical association)	0.000
SULT1E1	COPS6	psi-mi:“MI:0915”(physical association)	0.000
SULT1E1	RBM48	psi-mi:“MI:0915”(physical association)	0.000
SULT1E1	IGSF21	psi-mi:“MI:0915”(physical association)	0.000
SULT1E1	ERG28	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): SULT1E1 (Two-hybrid), ENOX1 (Two-hybrid), SULT2B1 (Two-hybrid), AGL (Co-fractionation), GK (Co-fractionation), C14orf1 (Two-hybrid), COPS6 (Two-hybrid), RBM48 (Two-hybrid), IGSF21 (Two-hybrid), PDE9A (Two-hybrid), EEF1A1 (Two-hybrid), LRIF1 (Two-hybrid), SETDB1 (Two-hybrid), TP53 (Two-hybrid), UNC119 (Two-hybrid)

ESM2 similar proteins: A0A173GP47, A0A1L8HV70, A0A2K5X3B6, B2RVI8, F1QYJ6, G3V9R3, O00338, O43704, O46503, O75897, P0CC03, P15709, P17988, P19217, P22789, P27707, P46560, P48769, P49887, P49888, P49891, P50234, P50235, P50236, P50237, P52840, P52841, P52843, P52844, P52847, Q06520, Q3T0Y3, Q3UZZ6, Q5ZJM7, Q6IMI4, Q6IMI6, Q6PH37, Q6WG17, Q6WG18, Q7T2V2

Diamond homologs: A0A173GP47, A0A2K5X3B6, G3V9R3, O00338, O35400, O43704, O46503, O46640, O75897, P0DMM9, P0DMN0, P19217, P49887, P49888, P49891, P50236, P50237, P52839, P52840, P52842, P52844, P52847, P63046, P63047, Q29476, Q3T0Y3, Q3UZZ6, Q6IMI6, Q80VR3, Q8BGL3, Q8JG30, Q95JD5, Q9BR01, Q9C9D0, Q9D939, Q9FZ80, Q9QWG7, Q9WUW8, Q9WUW9, B2RVI8

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
TFAP2A	“up-regulates quantity by expression”	SULT1E1	“transcriptional regulation”
TFAP2C	“up-regulates quantity by expression”	SULT1E1	“transcriptional regulation”
SULT1E1	“up-regulates quantity”	17beta-estradiol	“chemical modification”
SULT1E1	“up-regulates quantity”	“17beta-estradiol 3-sulfate(1-)”	“chemical modification”

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

50 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1181 predictions. Top by Δscore:

Variant	Effect	Δscore
4:69842103:ATTC:A	acceptor_gain	1.0000
4:69842104:TTC:T	acceptor_gain	1.0000
4:69842105:TC:T	acceptor_gain	1.0000
4:69842106:CC:C	acceptor_gain	1.0000
4:69842107:C:CC	acceptor_gain	1.0000
4:69842113:C:CT	acceptor_gain	1.0000
4:69844157:TCA:T	donor_loss	1.0000
4:69844159:A:AG	donor_loss	1.0000
4:69844159:AC:A	donor_gain	1.0000
4:69844160:C:CA	donor_loss	1.0000
4:69844160:CC:C	donor_gain	1.0000
4:69844337:ATATC:A	acceptor_gain	1.0000
4:69844338:TATC:T	acceptor_gain	1.0000
4:69844339:ATC:A	acceptor_gain	1.0000
4:69844340:TC:T	acceptor_gain	1.0000
4:69844341:CC:C	acceptor_gain	1.0000
4:69844342:C:CC	acceptor_gain	1.0000
4:69844342:C:T	acceptor_gain	1.0000
4:69844342:CTAG:C	acceptor_loss	1.0000
4:69844343:T:C	acceptor_loss	1.0000
4:69847793:C:CC	acceptor_gain	1.0000
4:69857541:G:A	donor_gain	1.0000
4:69842102:AATTC:A	acceptor_gain	0.9900
4:69842114:A:T	acceptor_gain	0.9900
4:69844126:T:TA	donor_gain	0.9900
4:69844159:A:AC	donor_gain	0.9900
4:69844160:C:CC	donor_gain	0.9900
4:69849435:AC:A	donor_gain	0.9900
4:69849436:CC:C	donor_gain	0.9900
4:69855291:TGA:T	donor_gain	0.9900

AlphaMissense

1980 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:69844171:G:C	F254L	0.991
4:69844171:G:T	F254L	0.991
4:69844173:A:G	F254L	0.991
4:69844165:T:A	R256S	0.990
4:69844165:T:G	R256S	0.990
4:69857505:T:A	K47I	0.990
4:69849537:C:A	K132N	0.989
4:69849537:C:G	K132N	0.989
4:69857504:T:A	K47N	0.989
4:69857504:T:G	K47N	0.989
4:69855426:C:A	G49V	0.987
4:69842092:A:G	W263R	0.986
4:69842092:A:T	W263R	0.986
4:69849536:C:G	D133H	0.986
4:69844166:C:G	R256T	0.985
4:69847778:A:G	W171R	0.985
4:69847778:A:T	W171R	0.985
4:69844161:C:G	G258R	0.984
4:69844161:C:T	G258R	0.984
4:69857523:A:T	V41D	0.984
4:69855426:C:T	G49D	0.983
4:69849547:C:G	R129P	0.982
4:69855418:A:G	W52R	0.982
4:69855418:A:T	W52R	0.982
4:69844240:C:A	M231I	0.980
4:69844240:C:G	M231I	0.980
4:69844240:C:T	M231I	0.980
4:69854280:T:A	R102S	0.980
4:69854280:T:G	R102S	0.980
4:69844241:A:G	M231T	0.979

dbSNP variants (sampled 300 via entrez): RS1000032643 (4:69841529 A>C,G,T), RS1000051817 (4:69840207 C>A,T), RS1000075840 (4:69857262 G>C), RS1000120216 (4:69845916 A>T), RS1000198801 (4:69840797 A>G), RS1000246687 (4:69829801 G>A,T), RS1000249853 (4:69834900 G>T), RS1000308076 (4:69835015 A>C,T), RS1000386777 (4:69821356 G>A), RS1000388659 (4:69858624 G>A), RS1000558994 (4:69851026 T>C), RS1000575474 (4:69845618 T>C), RS1000603121 (4:69850752 C>T), RS1000635653 (4:69833774 C>T), RS1000654155 (4:69840975 G>A,T)

Disease associations

OMIM: gene MIM:600043 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006979_434	Heel bone mineral density	2.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2346 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3736599	SULT1E1		0.00	0
rs3775770	SULT1E1		0.00	0

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.60	IC50	250	nM	CHEMBL112118
5.52	IC50	3000	nM	CHEMBL113219

PubChem BioAssay actives

2 with measured affinity, of 19 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
6,8-dichloro-3-[(E)-5-[(E)-(3,5-dibromo-4-hydroxyphenyl)methylideneamino]oxypentoxyiminomethyl]chromen-4-one	70675: Compound was tested for inhibition against estrogen sulfotransferase (EST), a human cytosolic sulfotransferase	ic50	0.2500	uM
3-[(E)-5-[(E)-(5-bromo-2-hydroxy-3-nitrophenyl)methylideneamino]oxypentoxyiminomethyl]-6,8-dichlorochromen-4-one	70676: Compound was tested for inhibition against estrogen sulfotransferase (EST), a human cytosolic sulfotransferase.	ic50	3.0000	uM

CTD chemical–gene interactions

118 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases reaction, increases metabolic processing, decreases activity, affects sulfation, affects binding (+5 more)	7
bisphenol A	decreases response to substance, increases sulfation, decreases reaction, increases expression, decreases expression (+1 more)	5
Resveratrol	increases sulfation, decreases activity, increases abundance, increases expression	5
Estrone	decreases sulfation, decreases activity, increases sulfation, affects sulfation, affects cotreatment	4
Ethinyl Estradiol	affects sulfation, decreases activity, affects cotreatment, decreases sulfation, decreases reaction (+1 more)	4
sodium arsenite	decreases expression	3
1-hydroxypyrene	decreases activity, increases reaction, increases sulfation, decreases reaction	2
perfluorooctane sulfonic acid	decreases expression	2
2,2’,4,4’-tetrabromodiphenyl ether	decreases reaction, increases metabolic processing, affects binding, affects cotreatment, decreases activity	2
Air Pollutants	decreases expression, increases abundance	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Chenodeoxycholic Acid	decreases expression, affects cotreatment	2
Flame Retardants	decreases reaction, increases metabolic processing, decreases expression	2
Folic Acid	decreases reaction, increases activity, increases expression, decreases expression	2
Nickel	decreases expression	2
Phenobarbital	decreases expression	2
Polychlorinated Biphenyls	affects metabolic processing, decreases reaction, increases sulfation	2
Progesterone	decreases reaction, increases expression, affects expression	2
Quercetin	affects cotreatment, decreases sulfation, decreases activity, increases sulfation	2
Silicon Dioxide	decreases expression	2
Smoke	decreases expression, increases abundance	2
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Triclosan	increases sulfation, affects cotreatment, decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation, affects cotreatment	2
Cadmium Chloride	decreases expression	2
Genistein	decreases expression, decreases activity	2
Particulate Matter	decreases expression, increases abundance	2
2-hydroxyestradiol	affects sulfation	1
2,4-dichlorophenol	decreases activity	1

ChEMBL screening assays

18 unique, capped per target: 12 binding, 6 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1743309	ADMET	Major substrate of human cytosolic sulfotransferase SULT1E1	Casarett and Doull’s Toxicology The Basic Science of Poisons, 7th edition
CHEMBL4482695	Binding	Substrate activity at SULT1E1 (unknown origin) expressed in baculovirus infected Sf9 cells assessed as substrate Km incubated for 15 mins using [35S-]PAPS as sulfate donor by TLC analysis	In vivo imaging of sulfotransferases

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.