ST1A4_HUMAN
ID ST1A4_HUMAN Reviewed; 295 AA.
AC P0DMN0; B4DNV0; O95603; P50224; Q1ET66; Q6ZWJ5;
DT 03-SEP-2014, integrated into UniProtKB/Swiss-Prot.
DT 03-SEP-2014, sequence version 1.
DT 03-AUG-2022, entry version 54.
DE RecName: Full=Sulfotransferase 1A4;
DE Short=ST1A4;
DE EC=2.8.2.1;
DE AltName: Full=Aryl sulfotransferase 1A3/1A4;
DE AltName: Full=Sulfotransferase 1A3/1A4;
GN Name=SULT1A4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [3]
RP VARIANT ASN-234, AND CHARACTERIZATION OF VARIANT ASN-234.
RX PubMed=14622112; DOI=10.1046/j.1471-4159.2003.02027.x;
RA Thomae B.A., Rifki O.F., Theobald M.A., Eckloff B.W., Wieben E.D.,
RA Weinshilboum R.M.;
RT "Human catecholamine sulfotransferase (SULT1A3) pharmacogenetics:
RT functional genetic polymorphism.";
RL J. Neurochem. 87:809-819(2003).
RN [4]
RP VARIANTS LEU-101; HIS-101 AND CYS-144, AND CHARACTERIZATION OF VARIANTS
RP LEU-101; HIS-101 AND CYS-144.
RX PubMed=15358107; DOI=10.1016/j.bbrc.2004.07.038;
RA Hildebrandt M.A.T., Salavaggione O.E., Martin Y.N., Flynn H.C., Jalal S.,
RA Wieben E.D., Weinshilboum R.M.;
RT "Human SULT1A3 pharmacogenetics: gene duplication and functional genomic
RT studies.";
RL Biochem. Biophys. Res. Commun. 321:870-878(2004).
CC -!- FUNCTION: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate
CC (PAPS) as sulfonate donor to catalyze the sulfate conjugation of
CC phenolic monoamines (neurotransmitters such as dopamine, norepinephrine
CC and serotonin) and phenolic and catechol drugs.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3'-phosphoadenylyl sulfate + a phenol = adenosine 3',5'-
CC bisphosphate + an aryl sulfate + H(+); Xref=Rhea:RHEA:12164,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:33853, ChEBI:CHEBI:58339,
CC ChEBI:CHEBI:58343, ChEBI:CHEBI:140317; EC=2.8.2.1;
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Liver, colon, kidney, lung, brain, spleen, small
CC intestine, placenta and leukocyte.
CC -!- PTM: The N-terminus is blocked.
CC -!- SIMILARITY: Belongs to the sulfotransferase 1 family. {ECO:0000305}.
CC -!- CAUTION: Found in a segmental duplication on p arm of chromosome 16
CC giving rise to two identical copies of this gene sharing exons with
CC SLX1A and SLX1B. The ORFs of SULT1A3 and SULT1A4 differ with only a
CC single nucleotide change that does not alter the encoded amino acid. It
CC is not possible to determine whether any individual polymorphism is
CC present within SULT1A3 or SULT1A4 (PubMed:15358107).
CC {ECO:0000305|PubMed:15358107}.
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DR EMBL; AC106782; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC133555; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS32427.1; -.
DR RefSeq; NP_001017390.1; NM_001017390.2.
DR RefSeq; NP_808220.1; NM_177552.3.
DR RefSeq; XP_016855108.1; XM_016999619.1.
DR AlphaFoldDB; P0DMN0; -.
DR SMR; P0DMN0; -.
DR BioGRID; 112687; 24.
DR BioGRID; 138644; 5.
DR DrugBank; DB12471; Ibrexafungerp.
DR DrugBank; DB00968; Methyldopa.
DR DrugBank; DB00960; Pindolol.
DR DrugBank; DB00871; Terbutaline.
DR iPTMnet; P0DMN0; -.
DR PhosphoSitePlus; P0DMN0; -.
DR BioMuta; SULT1A4; -.
DR EPD; P0DMN0; -.
DR jPOST; P0DMN0; -.
DR MassIVE; P0DMN0; -.
DR PRIDE; P0DMN0; -.
DR Antibodypedia; 26725; 66 antibodies from 21 providers.
DR DNASU; 6818; -.
DR Ensembl; ENST00000360423.12; ENSP00000353600.8; ENSG00000213648.11.
DR GeneID; 445329; -.
DR GeneID; 6818; -.
DR KEGG; hsa:445329; -.
DR KEGG; hsa:6818; -.
DR MANE-Select; ENST00000338971.10; ENSP00000343645.6; NM_177552.4; NP_808220.1.
DR MANE-Select; ENST00000360423.12; ENSP00000353600.8; NM_001017390.3; NP_001017390.1.
DR CTD; 445329; -.
DR CTD; 6818; -.
DR DisGeNET; 445329; -.
DR DisGeNET; 6818; -.
DR GeneCards; SULT1A4; -.
DR HGNC; HGNC:30004; SULT1A4.
DR HPA; ENSG00000213648; Tissue enhanced (intestine).
DR MIM; 615819; gene.
DR neXtProt; NX_P0DMN0; -.
DR OpenTargets; ENSG00000261052; -.
DR VEuPathDB; HostDB:ENSG00000213648; -.
DR GeneTree; ENSGT00940000164316; -.
DR HOGENOM; CLU_027239_1_2_1; -.
DR OMA; KNWDNIQ; -.
DR OrthoDB; 780670at2759; -.
DR PhylomeDB; P0DMN0; -.
DR BRENDA; 2.8.2.1; 2681.
DR PathwayCommons; P0DMN0; -.
DR Reactome; R-HSA-156584; Cytosolic sulfonation of small molecules.
DR Reactome; R-HSA-9753281; Paracetamol ADME.
DR BioGRID-ORCS; 445329; 18 hits in 583 CRISPR screens.
DR BioGRID-ORCS; 6818; 19 hits in 276 CRISPR screens.
DR Pharos; P0DMN0; Tdark.
DR PRO; PR:P0DMN0; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P0DMN0; protein.
DR Bgee; ENSG00000213648; Expressed in mucosa of transverse colon and 97 other tissues.
DR ExpressionAtlas; P0DMN0; baseline.
DR Genevisible; P0DMN0; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004062; F:aryl sulfotransferase activity; IBA:GO_Central.
DR GO; GO:0008146; F:sulfotransferase activity; IBA:GO_Central.
DR GO; GO:0006584; P:catecholamine metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0008202; P:steroid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0051923; P:sulfation; IBA:GO_Central.
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 Catecholamine metabolism; Cytoplasm; Lipid metabolism; Reference proteome;
KW Steroid metabolism; Transferase.
FT CHAIN 1..295
FT /note="Sulfotransferase 1A4"
FT /id="PRO_0000430204"
FT ACT_SITE 108
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 48..53
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT BINDING 86
FT /ligand="substrate"
FT BINDING 106..108
FT /ligand="substrate"
FT BINDING 130
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT BINDING 138
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT BINDING 146
FT /ligand="substrate"
FT BINDING 193
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT BINDING 227..232
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT BINDING 257..259
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT VARIANT 101
FT /note="P -> H (decreases levels of sulfotransferase
FT activity; dbSNP:rs1460887051)"
FT /evidence="ECO:0000269|PubMed:15358107"
FT /id="VAR_071112"
FT VARIANT 101
FT /note="P -> L (decreases levels of sulfotransferase
FT activity; dbSNP:rs1460887051)"
FT /evidence="ECO:0000269|PubMed:15358107"
FT /id="VAR_071113"
FT VARIANT 144
FT /note="R -> C (no effect on sulfotransferase activity)"
FT /evidence="ECO:0000269|PubMed:15358107"
FT /id="VAR_071114"
FT VARIANT 234
FT /note="K -> N (decreases levels of sulfotransferase
FT activity; accelerates proteasome-dependent degradation)"
FT /evidence="ECO:0000269|PubMed:14622112"
FT /id="VAR_071115"
SQ SEQUENCE 295 AA; 34196 MW; ECDDEC03DBE30D46 CRC64;
MELIQDTSRP PLEYVKGVPL IKYFAEALGP LQSFQARPDD LLINTYPKSG TTWVSQILDM
IYQGGDLEKC NRAPIYVRVP FLEVNDPGEP SGLETLKDTP PPRLIKSHLP LALLPQTLLD
QKVKVVYVAR NPKDVAVSYY HFHRMEKAHP EPGTWDSFLE KFMAGEVSYG SWYQHVQEWW
ELSRTHPVLY LFYEDMKENP KREIQKILEF VGRSLPEETM DFMVQHTSFK EMKKNPMTNY
TTVPQELMDH SISPFMRKGM AGDWKTTFTV AQNERFDADY AEKMAGCSLS FRSEL
