ST1E1_CAVPO
ID ST1E1_CAVPO Reviewed; 296 AA.
AC P49887;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Sulfotransferase 1E1;
DE Short=ST1E1;
DE EC=2.8.2.4 {ECO:0000269|PubMed:7980593};
DE AltName: Full=Estrogen sulfotransferase {ECO:0000303|PubMed:1406700};
DE AltName: Full=ST1E3;
DE AltName: Full=Sulfotransferase, estrogen-preferring;
GN Name=SULT1E1; Synonyms=EST {ECO:0000303|PubMed:1406700}, STE;
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, TISSUE SPECIFICITY,
RP CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RC STRAIN=NIH 2; TISSUE=Adrenal cortex;
RX PubMed=1406700; DOI=10.1210/mend.6.8.1406700;
RA Oeda T., Lee Y.C., Driscoll W.J., Chen H.-C., Strott C.A.;
RT "Molecular cloning and expression of a full-length complementary DNA
RT encoding the guinea pig adrenocortical estrogen sulfotransferase.";
RL Mol. Endocrinol. 6:1216-1226(1992).
RN [2]
RP PAPS-BINDING SITE, MUTAGENESIS OF GLY-260; SER-262; GLY-263; ASP-264;
RP LYS-266 AND ASN-267, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES,
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=7980593; DOI=10.1006/bbrc.1994.2587;
RA Komatsu K., Driscoll W.J., Koh Y., Strott C.A.;
RT "A P-loop related motif (GxxGxxK) highly conserved in sulfotransferases is
RT required for binding the activated sulfate donor.";
RL Biochem. Biophys. Res. Commun. 204:1178-1185(1994).
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 (PubMed:1406700, PubMed:7980593). Is a key enzyme
CC in estrogen homeostasis, the sulfation of estrogens leads to their
CC inactivation. Also sulfates dehydroepiandrosterone (DHEA),
CC pregnenolone, (24S)-hydroxycholesteroland 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:1406700, ECO:0000269|PubMed:7980593}.
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:0000269|PubMed:7980593};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15974;
CC Evidence={ECO:0000305|PubMed:7980593};
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=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:1406700};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52373;
CC Evidence={ECO:0000305|PubMed:1406700};
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=5.0 uM for PAPS {ECO:0000269|PubMed:7980593};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P49888}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:1406700,
CC ECO:0000269|PubMed:7980593}.
CC -!- TISSUE SPECIFICITY: Adrenal gland and much less in liver
CC (PubMed:1406700). Detectable only during pregnancy in uterine
CC (PubMed:1406700). {ECO:0000269|PubMed:1406700}.
CC -!- PTM: The N-terminus is blocked.
CC -!- SIMILARITY: Belongs to the sulfotransferase 1 family. {ECO:0000305}.
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DR EMBL; U09552; AAA18495.1; -; mRNA.
DR PIR; A44011; A44011.
DR RefSeq; NP_001166493.1; NM_001173022.1.
DR AlphaFoldDB; P49887; -.
DR SMR; P49887; -.
DR STRING; 10141.ENSCPOP00000011973; -.
DR Ensembl; ENSCPOT00000013429; ENSCPOP00000011973; ENSCPOG00000013300.
DR GeneID; 100135625; -.
DR KEGG; cpoc:100135625; -.
DR CTD; 6783; -.
DR eggNOG; KOG1584; Eukaryota.
DR GeneTree; ENSGT00940000162261; -.
DR HOGENOM; CLU_027239_1_2_1; -.
DR InParanoid; P49887; -.
DR OMA; VIKVIQF; -.
DR OrthoDB; 780670at2759; -.
DR TreeFam; TF321745; -.
DR SABIO-RK; P49887; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR Bgee; ENSCPOG00000013300; Expressed in adrenal gland and 5 other tissues.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IEA:Ensembl.
DR GO; GO:0004304; F:estrone sulfotransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0047894; F:flavonol 3-sulfotransferase activity; IEA:Ensembl.
DR GO; GO:0005496; F:steroid binding; IEA:UniProtKB-KW.
DR GO; GO:0050294; F:steroid sulfotransferase activity; ISS:UniProtKB.
DR GO; GO:0050427; P:3'-phosphoadenosine 5'-phosphosulfate metabolic process; IEA:Ensembl.
DR GO; GO:0006711; P:estrogen catabolic process; IEA:Ensembl.
DR GO; GO:0008210; P:estrogen metabolic process; ISS:UniProtKB.
DR GO; GO:0006068; P:ethanol catabolic process; IEA:Ensembl.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IEA:Ensembl.
DR GO; GO:0051923; P:sulfation; IEA:Ensembl.
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 Cytoplasm; Direct protein sequencing; Lipid metabolism; Lipid-binding;
KW Reference proteome; Steroid-binding; Transferase.
FT CHAIN 1..296
FT /note="Sulfotransferase 1E1"
FT /id="PRO_0000085152"
FT ACT_SITE 109
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P49891"
FT BINDING 49..54
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:P49891"
FT BINDING 107..109
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P49891"
FT BINDING 131
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:P49891"
FT BINDING 139
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:P49891"
FT BINDING 194
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:P49891"
FT BINDING 228..233
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:P49891"
FT BINDING 258..260
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:P49891"
FT MUTAGEN 260
FT /note="G->A: Loss of sulfotransferase activity; when
FT associated with A-263 and A-266. Does not bind PAPS; when
FT associated with A-263 and A-266."
FT /evidence="ECO:0000269|PubMed:7980593"
FT MUTAGEN 262
FT /note="S->A: Decreased of sulfotransferase activity; when
FT associated with A-264 and A-267. Increased KM for PAPS;
FT when associated with A-264 and A-267."
FT /evidence="ECO:0000269|PubMed:7980593"
FT MUTAGEN 263
FT /note="G->A: Loss of sulfotransferase activity; when
FT associated with A-260 and A-266. Does not bind PAPS; when
FT associated with A-260 and A-266."
FT /evidence="ECO:0000269|PubMed:7980593"
FT MUTAGEN 264
FT /note="D->A: Decreased of sulfotransferase activity; when
FT associated with A-262 and A-267; Increased KM for PAPS;
FT when associated with A-262 and A-267."
FT /evidence="ECO:0000269|PubMed:7980593"
FT MUTAGEN 266
FT /note="K->A: Loss of sulfotransferase activity; when
FT associated with A-260 and A-263. Does not bind PAPS; when
FT associated with A-260 and A-263."
FT /evidence="ECO:0000269|PubMed:7980593"
FT MUTAGEN 267
FT /note="N->A: Decreased of sulfotransferase activity; when
FT associated with A-262 and A-264. Increased KM for PAPS when
FT associated with A-262 and A-264."
FT /evidence="ECO:0000269|PubMed:7980593"
SQ SEQUENCE 296 AA; 35245 MW; 019D92B95E29901D CRC64;
MMDSSEHDYY EYFDEFRGIL LYKQFIKYWD NVEAFQARPD DLVIAAYPKS GTTWISEVVC
MIYAEGDVKK CRQDAIFNRV PFLECRNDKM MNGVKQLEEM NSPRIIKTHL PPRLLPASFW
EKRCKMICIC RNAKDVAVSY YYFFLMVANH PDPGSFPEFV EKFMQGQVPY GSWYDHVKSW
WEKSTDPRIL FIFYEDMKED IRKEVLKLIH FLGRKPSEEL VDKIIKHTSF QEMKNNPSTN
YTMLPEEIMN QKVSPFMRKG ISGDWKNHFT VALNESFDKH YQQQMKGSTL QLRTEI
