ST1E1_MOUSE
ID ST1E1_MOUSE Reviewed; 295 AA.
AC P49891;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 2.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Sulfotransferase 1E1;
DE Short=ST1E1;
DE EC=2.8.2.4 {ECO:0000269|PubMed:9765259};
DE AltName: Full=Estrogen sulfotransferase, testis isoform;
DE AltName: Full=Sulfotransferase, estrogen-preferring;
GN Name=Sult1e1; Synonyms=Est {ECO:0000303|PubMed:9765259}, Ste;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/KSJ-DB/DB; TISSUE=Testis;
RX PubMed=7750469; DOI=10.1210/endo.136.6.7750469;
RA Song W.-C., Moore R., McLachlan J.A., Negishi M.;
RT "Molecular characterization of a testis-specific estrogen sulfotransferase
RT and aberrant liver expression in obese and diabetogenic C57BL/KsJ-db/db
RT mice.";
RL Endocrinology 136:2477-2484(1995).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH ADENOSINE
RP 3',5'-BISPHOSPHATE (PAP) AND 17-BETA-ESTRADIOL, AND SEQUENCE REVISION TO
RP 113.
RC STRAIN=C57BL/KSJ-DB/DB; TISSUE=Testis;
RX PubMed=9360604; DOI=10.1038/nsb1197-904;
RA Kakuta Y., Pedersen L.G., Carter C.W., Negishi M., Pedersen L.C.;
RT "Crystal structure of estrogen sulfotransferase.";
RL Nat. Struct. Biol. 4:904-908(1997).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH ADENOSINE
RP 3',5'BISPHOSPHATE AND VANADATE, CATALYTIC ACTIVITY, FUNCTION, ACTIVE SITE,
RP MUTAGENESIS OF LYS-48; LYS-106; HIS-108 AND TYR-240, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=9765259; DOI=10.1074/jbc.273.42.27325;
RA Kakuta Y., Petrotchenko E.V., Pedersen L.C., Negishi M.;
RT "The sulfuryl transfer mechanism. Crystal structure of a vanadate complex
RT of estrogen sulfotransferase and mutational analysis.";
RL J. Biol. Chem. 273:27325-27330(1998).
CC -!- FUNCTION: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate
CC (PAPS) as sulfonate donor to catalyze the sulfate conjugation of
CC estradiol and estrone (By similarity) (PubMed:9765259). Is a key enzyme
CC in estrogen homeostasis, the sulfation of estrogens leads to their
CC inactivation. Also sulfates dehydroepiandrosterone, pregnenolone,
CC (24S)-hydroxycholesterol and xenobiotic compounds like
CC ethinylestradiol, equalenin, diethyl stilbesterol and 1-naphthol at
CC significantly lower efficiency. Does not sulfonate cortisol,
CC testosterone and dopamine (By similarity). May play a role in gut
CC microbiota-host metabolic interaction. O-sulfonates 4-ethylphenol (4-
CC EP), a dietary tyrosine-derived metabolite produced by gut bacteria.
CC The product 4-EPS crosses the blood-brain barrier and may negatively
CC regulate oligodendrocyte maturation and myelination, affecting the
CC functional connectivity of different brain regions associated with the
CC limbic system. {ECO:0000250|UniProtKB:P49888,
CC ECO:0000269|PubMed:9765259}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3'-phosphoadenylyl sulfate + estrone = adenosine 3',5'-
CC bisphosphate + estrone 3-sulfate + H(+); Xref=Rhea:RHEA:15973,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17263, ChEBI:CHEBI:58339,
CC ChEBI:CHEBI:58343, ChEBI:CHEBI:60050; EC=2.8.2.4;
CC Evidence={ECO:0000250|UniProtKB:P49888};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15974;
CC Evidence={ECO:0000250|UniProtKB:P49888};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + 3'-phosphoadenylyl sulfate = 17beta-
CC estradiol 3-sulfate + adenosine 3',5'-bisphosphate + H(+);
CC Xref=Rhea:RHEA:52372, ChEBI:CHEBI:15378, ChEBI:CHEBI:16469,
CC ChEBI:CHEBI:58339, ChEBI:CHEBI:58343, ChEBI:CHEBI:136582;
CC Evidence={ECO:0000269|PubMed:9765259};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52373;
CC Evidence={ECO:0000305|PubMed:9765259};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(24S)-hydroxycholesterol + 3'-phosphoadenylyl sulfate = (24S)-
CC hydroxycholesterol 3-sulfate + adenosine 3',5'-bisphosphate + H(+);
CC Xref=Rhea:RHEA:52348, ChEBI:CHEBI:15378, ChEBI:CHEBI:34310,
CC ChEBI:CHEBI:58339, ChEBI:CHEBI:58343, ChEBI:CHEBI:136567;
CC Evidence={ECO:0000250|UniProtKB:P49888};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52349;
CC Evidence={ECO:0000250|UniProtKB:P49888};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3'-phosphoadenylyl sulfate + 3beta-hydroxyandrost-5-en-17-one
CC = adenosine 3',5'-bisphosphate + dehydroepiandrosterone 3-sulfate +
CC H(+); Xref=Rhea:RHEA:51216, ChEBI:CHEBI:15378, ChEBI:CHEBI:28689,
CC ChEBI:CHEBI:57905, ChEBI:CHEBI:58339, ChEBI:CHEBI:58343;
CC Evidence={ECO:0000250|UniProtKB:P49888};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3'-phosphoadenylyl sulfate + 4-ethylphenol = 4-ethylphenyl
CC sulfate + adenosine 3',5'-bisphosphate + H(+); Xref=Rhea:RHEA:70607,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:49584, ChEBI:CHEBI:58339,
CC ChEBI:CHEBI:58343, ChEBI:CHEBI:133681;
CC Evidence={ECO:0000250|UniProtKB:P49888};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70608;
CC Evidence={ECO:0000250|UniProtKB:P49888};
CC -!- ACTIVITY REGULATION: Inhibited by estradiol.
CC {ECO:0000250|UniProtKB:P49888}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.3 uM for PAPS {ECO:0000269|PubMed:9765259};
CC KM=17.5 nM for estradiol {ECO:0000269|PubMed:9765259};
CC Note=kcat is 23.5 sec(-1) with estradiol as substrate.
CC {ECO:0000269|PubMed:9765259};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P49888}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P49887}.
CC -!- TISSUE SPECIFICITY: Testis and at very low level in the placenta.
CC -!- MISCELLANEOUS: Abnormal high expression in liver in obese and
CC diabetogenic C57BL/KSJ-DB/DB strain mice. Female > male. Normal level
CC in liver. {ECO:0000269|PubMed:7750469}.
CC -!- SIMILARITY: Belongs to the sulfotransferase 1 family. {ECO:0000305}.
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DR EMBL; S78182; AAB34320.1; -; mRNA.
DR CCDS; CCDS19392.1; -.
DR PIR; I53296; I53296.
DR PDB; 1AQU; X-ray; 1.60 A; A/B=1-295.
DR PDB; 1AQY; X-ray; 1.75 A; A/B=1-295.
DR PDB; 1BO6; X-ray; 2.10 A; A/B=1-295.
DR PDBsum; 1AQU; -.
DR PDBsum; 1AQY; -.
DR PDBsum; 1BO6; -.
DR AlphaFoldDB; P49891; -.
DR SMR; P49891; -.
DR IntAct; P49891; 1.
DR STRING; 10090.ENSMUSP00000031201; -.
DR BindingDB; P49891; -.
DR ChEMBL; CHEMBL3052; -.
DR iPTMnet; P49891; -.
DR PhosphoSitePlus; P49891; -.
DR PaxDb; P49891; -.
DR PRIDE; P49891; -.
DR ProteomicsDB; 257083; -.
DR MGI; MGI:98431; Sult1e1.
DR eggNOG; KOG1584; Eukaryota.
DR InParanoid; P49891; -.
DR PhylomeDB; P49891; -.
DR BRENDA; 2.8.2.4; 3474.
DR Reactome; R-MMU-156584; Cytosolic sulfonation of small molecules.
DR Reactome; R-MMU-9753281; Paracetamol ADME.
DR SABIO-RK; P49891; -.
DR ChiTaRS; Map7; mouse.
DR EvolutionaryTrace; P49891; -.
DR PRO; PR:P49891; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P49891; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0004062; F:aryl sulfotransferase activity; IBA:GO_Central.
DR GO; GO:0004304; F:estrone sulfotransferase activity; ISO:MGI.
DR GO; GO:0047894; F:flavonol 3-sulfotransferase activity; ISO:MGI.
DR GO; GO:0005496; F:steroid binding; IEA:UniProtKB-KW.
DR GO; GO:0050294; F:steroid sulfotransferase activity; IDA:UniProtKB.
DR GO; GO:0008146; F:sulfotransferase activity; ISO:MGI.
DR GO; GO:0050427; P:3'-phosphoadenosine 5'-phosphosulfate metabolic process; ISO:MGI.
DR GO; GO:0006711; P:estrogen catabolic process; ISO:MGI.
DR GO; GO:0008210; P:estrogen metabolic process; IDA:UniProtKB.
DR GO; GO:0006068; P:ethanol catabolic process; ISO:MGI.
DR GO; GO:0007565; P:female pregnancy; IMP:MGI.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISO:MGI.
DR GO; GO:0051923; P:sulfation; ISO:MGI.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000863; Sulfotransferase_dom.
DR Pfam; PF00685; Sulfotransfer_1; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Lipid metabolism; Lipid-binding; Phosphoprotein;
KW Reference proteome; Steroid-binding; Transferase.
FT CHAIN 1..295
FT /note="Sulfotransferase 1E1"
FT /id="PRO_0000085154"
FT ACT_SITE 108
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:9765259"
FT BINDING 48..53
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000269|PubMed:9360604,
FT ECO:0000269|PubMed:9765259, ECO:0007744|PDB:1AQU,
FT ECO:0007744|PDB:1AQY, ECO:0007744|PDB:1BO6"
FT BINDING 106..108
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:9360604,
FT ECO:0007744|PDB:1AQU"
FT BINDING 130
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000269|PubMed:9360604,
FT ECO:0000269|PubMed:9765259, ECO:0007744|PDB:1AQU,
FT ECO:0007744|PDB:1AQY, ECO:0007744|PDB:1BO6"
FT BINDING 138
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000269|PubMed:9360604,
FT ECO:0000269|PubMed:9765259, ECO:0007744|PDB:1AQU,
FT ECO:0007744|PDB:1AQY, ECO:0007744|PDB:1BO6"
FT BINDING 193
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000269|PubMed:9360604,
FT ECO:0000269|PubMed:9765259, ECO:0007744|PDB:1AQU,
FT ECO:0007744|PDB:1AQY, ECO:0007744|PDB:1BO6"
FT BINDING 227..232
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000269|PubMed:9360604,
FT ECO:0000269|PubMed:9765259, ECO:0007744|PDB:1AQU,
FT ECO:0007744|PDB:1AQY, ECO:0007744|PDB:1BO6"
FT BINDING 257..259
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000269|PubMed:9360604,
FT ECO:0000269|PubMed:9765259, ECO:0007744|PDB:1AQU,
FT ECO:0007744|PDB:1AQY, ECO:0007744|PDB:1BO6"
FT MOD_RES 156
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P52844"
FT MUTAGEN 48
FT /note="K->M: Loss of estrogen sulfotransferase activity."
FT /evidence="ECO:0000269|PubMed:9765259"
FT MUTAGEN 48
FT /note="K->R: Reduced estrogen sulfotransferase activity."
FT /evidence="ECO:0000269|PubMed:9765259"
FT MUTAGEN 106
FT /note="K->A: Strongly reduced estrogen sulfotransferase
FT activity. Strongly reduced affinity for estradiol."
FT /evidence="ECO:0000269|PubMed:9765259"
FT MUTAGEN 106
FT /note="K->R,S: Strongly reduced estrogen sulfotransferase
FT activity. Strongly reduced affinity for estradiol."
FT /evidence="ECO:0000269|PubMed:9765259"
FT MUTAGEN 108
FT /note="H->K,L,S,R: Loss of estrogen sulfotransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:9765259"
FT MUTAGEN 240
FT /note="Y->F: Slightly decreased estrogen sulfotransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:9765259"
FT CONFLICT 113
FT /note="L -> V (in Ref. 1; AAB34320)"
FT /evidence="ECO:0000305"
FT HELIX 8..11
FT /evidence="ECO:0007829|PDB:1AQU"
FT STRAND 12..15
FT /evidence="ECO:0007829|PDB:1AQU"
FT STRAND 18..21
FT /evidence="ECO:0007829|PDB:1AQU"
FT HELIX 22..24
FT /evidence="ECO:0007829|PDB:1AQU"
FT TURN 25..27
FT /evidence="ECO:0007829|PDB:1AQU"
FT HELIX 28..32
FT /evidence="ECO:0007829|PDB:1AQU"
FT STRAND 41..45
FT /evidence="ECO:0007829|PDB:1AQU"
FT HELIX 51..62
FT /evidence="ECO:0007829|PDB:1AQU"
FT TURN 63..65
FT /evidence="ECO:0007829|PDB:1AQY"
FT HELIX 75..78
FT /evidence="ECO:0007829|PDB:1AQU"
FT TURN 87..89
FT /evidence="ECO:0007829|PDB:1AQU"
FT HELIX 92..97
FT /evidence="ECO:0007829|PDB:1AQU"
FT STRAND 104..107
FT /evidence="ECO:0007829|PDB:1AQU"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:1AQU"
FT HELIX 116..120
FT /evidence="ECO:0007829|PDB:1AQU"
FT STRAND 124..129
FT /evidence="ECO:0007829|PDB:1AQU"
FT HELIX 132..145
FT /evidence="ECO:0007829|PDB:1AQU"
FT HELIX 155..164
FT /evidence="ECO:0007829|PDB:1AQU"
FT HELIX 172..182
FT /evidence="ECO:0007829|PDB:1AQU"
FT STRAND 188..192
FT /evidence="ECO:0007829|PDB:1AQU"
FT HELIX 193..198
FT /evidence="ECO:0007829|PDB:1AQU"
FT HELIX 200..210
FT /evidence="ECO:0007829|PDB:1AQU"
FT HELIX 217..226
FT /evidence="ECO:0007829|PDB:1AQU"
FT HELIX 229..234
FT /evidence="ECO:0007829|PDB:1AQU"
FT TURN 236..242
FT /evidence="ECO:0007829|PDB:1AQU"
FT TURN 245..247
FT /evidence="ECO:0007829|PDB:1AQU"
FT TURN 250..252
FT /evidence="ECO:0007829|PDB:1AQU"
FT HELIX 263..266
FT /evidence="ECO:0007829|PDB:1AQU"
FT HELIX 270..284
FT /evidence="ECO:0007829|PDB:1AQU"
SQ SEQUENCE 295 AA; 35590 MW; 8E85AB47952BFB1C CRC64;
METSMPEYYE VFGEFRGVLM DKRFTKYWED VEMFLARPDD LVIATYPKSG TTWISEVVYM
IYKEGDVEKC KEDAIFNRIP YLECRNEDLI NGIKQLKEKE SPRIVKTHLP PKLLPASFWE
KNCKMIYLCR NAKDVAVSYY YFLLMITSYP NPKSFSEFVE KFMQGQVPYG SWYDHVKAWW
EKSKNSRVLF MFYEDMKEDI RREVVKLIEF LERKPSAELV DRIIQHTSFQ EMKNNPSTNY
TMMPEEMMNQ KVSPFMRKGI IGDWKNHFPE ALRERFDEHY KQQMKDCTVK FRMEL
