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
//