ST1C3_HUMAN
ID ST1C3_HUMAN Reviewed; 304 AA.
AC Q6IMI6; Q6IMI5;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Sulfotransferase 1C3;
DE Short=ST1C3;
DE EC=2.8.2.1 {ECO:0000269|PubMed:17425406, ECO:0000269|PubMed:28992322};
DE EC=2.8.2.2 {ECO:0000269|PubMed:17425406, ECO:0000269|PubMed:17936463};
GN Name=SULT1C3;
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=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [2]
RP IDENTIFICATION, TISSUE SPECIFICITY, AND ALTERNATIVE SPLICING.
RX PubMed=14676822; DOI=10.1038/sj.tpj.6500223;
RA Freimuth R.R., Wiepert M., Chute C.G., Wieben E.D., Weinshilboum R.M.;
RT "Human cytosolic sulfotransferase database mining: identification of seven
RT novel genes and pseudogenes.";
RL Pharmacogenomics J. 4:54-65(2004).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=17936463; DOI=10.1016/j.fct.2007.08.040;
RA Meinl W., Donath C., Schneider H., Sommer Y., Glatt H.;
RT "SULT1C3, an orphan sequence of the human genome, encodes an enzyme
RT activating various promutagens.";
RL Food Chem. Toxicol. 46:1249-1256(2008).
RN [4]
RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RX PubMed=24335392; DOI=10.1124/dmd.113.055665;
RA Duniec-Dmuchowski Z., Rondini E.A., Tibbs Z.E., Falany C.N.,
RA Runge-Morris M., Kocarek T.A.;
RT "Expression of the orphan cytosolic sulfotransferase SULT1C3 in human
RT intestine: characterization of the transcript variant and implications for
RT function.";
RL Drug Metab. Dispos. 42:352-360(2014).
RN [5]
RP FUNCTION (ISOFORMS 1 AND 2), CATALYTIC ACTIVITY (ISOFORMS 1 AND 2),
RP BIOPHYSICOCHEMICAL PROPERTIES, VARIANTS ARG-179 AND THR-194, AND SUBSTRATE
RP SPECIFICITY (ISOFORMS 1 AND 2).
RX PubMed=28992322; DOI=10.1093/jb/mvx044;
RA Kurogi K., Shimohira T., Kouriki-Nagatomo H., Zhang G., Miller E.R.,
RA Sakakibara Y., Suiko M., Liu M.C.;
RT "Human Cytosolic Sulphotransferase SULT1C3: genomic analysis and functional
RT characterization of splice variant SULT1C3a and SULT1C3d.";
RL J. Biochem. 162:403-414(2017).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) IN COMPLEX WITH
RP ADENOSINE-3'-5'-DIPHOSPHATE (PAP), CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=17425406; DOI=10.1371/journal.pbio.0050097;
RA Allali-Hassani A., Pan P.W., Dombrovski L., Najmanovich R., Tempel W.,
RA Dong A., Loppnau P., Martin F., Thornton J., Edwards A.M., Bochkarev A.,
RA Plotnikov A.N., Vedadi M., Arrowsmith C.H.;
RT "Structural and chemical profiling of the human cytosolic
RT sulfotransferases.";
RL PLoS Biol. 5:E97-E97(2007).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) IN COMPLEX WITH
RP ADENOSINE-3'-5'-DIPHOSPHATE (PAP).
RG Structural genomics consortium (SGC);
RT "Crystal structure of human sulfotransferase 1C3 (SULT1C3) in complex with
RT PAP.";
RL Submitted (FEB-2009) to the PDB data bank.
CC -!- FUNCTION: [Isoform 1]: Sulfotransferase that utilizes 3'-phospho-5'-
CC adenylyl sulfate (PAPS) as sulfonate donor. Has sulfotransferase
CC activity towards various substrates, such as bile acids, thyroid
CC hormones and toward xenobiotic compounds such as chloro phenols and
CC hydroxypyrenes. Lithocholic acid appears to be the best substrate among
CC the endogenous compounds tested and 3,3',5,5'-tetrachloro-4,4'-
CC biphenyldiol shows the highest specific activity among the xenobiotic
CC compounds. {ECO:0000269|PubMed:17425406, ECO:0000269|PubMed:17936463,
CC ECO:0000269|PubMed:28992322}.
CC -!- FUNCTION: [Isoform 2]: Exhibits weak sulphating activity and only
CC toward chloro phenols (pentachlorophenol and 3,3',5,5'-tetrachloro-
CC 4,4'-biphenyldiol). {ECO:0000269|PubMed:28992322}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3'-phosphoadenylyl sulfate + an alcohol = adenosine 3',5'-
CC bisphosphate + an alkyl sulfate + H(+); Xref=Rhea:RHEA:22552,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30879, ChEBI:CHEBI:58339,
CC ChEBI:CHEBI:58343, ChEBI:CHEBI:83414; EC=2.8.2.2;
CC Evidence={ECO:0000269|PubMed:17425406, ECO:0000269|PubMed:17936463};
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 Evidence={ECO:0000269|PubMed:17425406, ECO:0000269|PubMed:28992322};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3'-phosphoadenylyl sulfate + lithocholate = adenosine 3',5'-
CC bisphosphate + H(+) + lithocholate sulfate; Xref=Rhea:RHEA:51064,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29744, ChEBI:CHEBI:58339,
CC ChEBI:CHEBI:58343, ChEBI:CHEBI:133940;
CC Evidence={ECO:0000269|PubMed:17425406, ECO:0000269|PubMed:28992322};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51065;
CC Evidence={ECO:0000305};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=11.29 uM for 3,3',5,5'-tetrachloro-4,4'-biphenyldiol
CC {ECO:0000269|PubMed:28992322};
CC KM=35.17 uM for lithocholate {ECO:0000269|PubMed:28992322};
CC Vmax=5.45 nmol/min/mg enzyme for 3,3',5,5'-tetrachloro-4,4'-
CC biphenyldiol {ECO:0000269|PubMed:28992322};
CC Vmax=0.52 nmol/min/mg enzyme for lithocholate
CC {ECO:0000269|PubMed:28992322};
CC -!- INTERACTION:
CC Q6IMI6; O00204: SULT2B1; NbExp=3; IntAct=EBI-12837366, EBI-749441;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q80VR3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Contains alternative exons 7 (7b) and 8 (8b) which may
CC generate three possible splice variants containing sequences
CC corresponding respectively to exons 7a and 8a (SULT1C3a), exons 7a
CC and 8b (SULT1C3c) and exons 7b and 8b (SULT1C3d). So far, it is not
CC known which isoforms are expressed. {ECO:0000269|PubMed:28992322};
CC Name=1; Synonyms=D, SULT1C3d {ECO:0000303|PubMed:14676822};
CC IsoId=Q6IMI6-1; Sequence=Displayed;
CC Name=2; Synonyms=A, SULT1C3a {ECO:0000303|PubMed:14676822};
CC IsoId=Q6IMI6-2; Sequence=VSP_020583;
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Not detectable in any of the tissues
CC tested. {ECO:0000269|PubMed:14676822}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in the small intestine.
CC {ECO:0000269|PubMed:24335392}.
CC -!- MISCELLANEOUS: SULT1C3 gene appears to be present only in humans and
CC other primates. {ECO:0000305|PubMed:28992322}.
CC -!- SIMILARITY: Belongs to the sulfotransferase 1 family. {ECO:0000305}.
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DR EMBL; AC019100; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BK001432; DAA01770.1; -; Genomic_DNA.
DR EMBL; BK001432; DAA01771.1; -; Genomic_DNA.
DR CCDS; CCDS33267.1; -. [Q6IMI6-1]
DR RefSeq; NP_001008743.1; NM_001008743.2. [Q6IMI6-1]
DR RefSeq; NP_001307807.1; NM_001320878.1. [Q6IMI6-2]
DR PDB; 2H8K; X-ray; 3.20 A; A/B=1-304.
DR PDB; 2REO; X-ray; 2.65 A; A=1-304.
DR PDBsum; 2H8K; -.
DR PDBsum; 2REO; -.
DR AlphaFoldDB; Q6IMI6; -.
DR SMR; Q6IMI6; -.
DR BioGRID; 137954; 9.
DR IntAct; Q6IMI6; 1.
DR STRING; 9606.ENSP00000333310; -.
DR DrugBank; DB12471; Ibrexafungerp.
DR DrugBank; DB00968; Methyldopa.
DR DrugBank; DB00960; Pindolol.
DR DrugBank; DB00871; Terbutaline.
DR SwissLipids; SLP:000001649; -.
DR iPTMnet; Q6IMI6; -.
DR PhosphoSitePlus; Q6IMI6; -.
DR BioMuta; SULT1C3; -.
DR DMDM; 74724707; -.
DR jPOST; Q6IMI6; -.
DR MassIVE; Q6IMI6; -.
DR PaxDb; Q6IMI6; -.
DR PeptideAtlas; Q6IMI6; -.
DR PRIDE; Q6IMI6; -.
DR ProteomicsDB; 66429; -. [Q6IMI6-1]
DR Antibodypedia; 54777; 63 antibodies from 11 providers.
DR DNASU; 442038; -.
DR Ensembl; ENST00000329106.3; ENSP00000333310.2; ENSG00000196228.5. [Q6IMI6-1]
DR Ensembl; ENST00000681802.2; ENSP00000505748.1; ENSG00000196228.5. [Q6IMI6-2]
DR GeneID; 442038; -.
DR KEGG; hsa:442038; -.
DR MANE-Select; ENST00000681802.2; ENSP00000505748.1; NM_001320878.2; NP_001307807.1. [Q6IMI6-2]
DR UCSC; uc010ywo.2; human. [Q6IMI6-1]
DR CTD; 442038; -.
DR DisGeNET; 442038; -.
DR GeneCards; SULT1C3; -.
DR HGNC; HGNC:33543; SULT1C3.
DR HPA; ENSG00000196228; Tissue enriched (breast).
DR MIM; 617151; gene.
DR neXtProt; NX_Q6IMI6; -.
DR OpenTargets; ENSG00000196228; -.
DR PharmGKB; PA162405069; -.
DR VEuPathDB; HostDB:ENSG00000196228; -.
DR eggNOG; KOG1584; Eukaryota.
DR GeneTree; ENSGT00940000160996; -.
DR HOGENOM; CLU_027239_1_2_1; -.
DR InParanoid; Q6IMI6; -.
DR OMA; VGKYIQP; -.
DR OrthoDB; 780670at2759; -.
DR PhylomeDB; Q6IMI6; -.
DR TreeFam; TF321745; -.
DR PathwayCommons; Q6IMI6; -.
DR SignaLink; Q6IMI6; -.
DR BioGRID-ORCS; 442038; 12 hits in 1062 CRISPR screens.
DR ChiTaRS; SULT1C3; human.
DR EvolutionaryTrace; Q6IMI6; -.
DR GeneWiki; SULT1C3; -.
DR GenomeRNAi; 442038; -.
DR Pharos; Q6IMI6; Tbio.
DR PRO; PR:Q6IMI6; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q6IMI6; protein.
DR Bgee; ENSG00000196228; Expressed in duodenum and 24 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0050656; F:3'-phosphoadenosine 5'-phosphosulfate binding; IDA:UniProtKB.
DR GO; GO:0004027; F:alcohol sulfotransferase activity; IDA:UniProtKB.
DR GO; GO:0004062; F:aryl sulfotransferase activity; IDA:UniProtKB.
DR GO; GO:0047704; F:bile-salt sulfotransferase activity; IDA:UniProtKB.
DR GO; GO:0008146; F:sulfotransferase activity; IBA:GO_Central.
DR GO; GO:0050427; P:3'-phosphoadenosine 5'-phosphosulfate metabolic process; IDA:UniProtKB.
DR GO; GO:0008203; P:cholesterol metabolic process; IDA:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0051923; P:sulfation; IBA:GO_Central.
DR GO; GO:0006790; P:sulfur compound metabolic process; IDA:UniProtKB.
DR GO; GO:0006805; P:xenobiotic metabolic process; IDA:UniProtKB.
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; Alternative splicing; Cytoplasm; Lipid metabolism;
KW Reference proteome; Transferase.
FT CHAIN 1..304
FT /note="Sulfotransferase 1C3"
FT /id="PRO_0000249887"
FT ACT_SITE 117
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q06520"
FT BINDING 56..61
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000269|PubMed:17425406, ECO:0000269|Ref.7,
FT ECO:0007744|PDB:2H8K, ECO:0007744|PDB:2REO"
FT BINDING 115..117
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 139
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000269|PubMed:17425406, ECO:0000269|Ref.7,
FT ECO:0007744|PDB:2H8K, ECO:0007744|PDB:2REO"
FT BINDING 147
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000269|PubMed:17425406, ECO:0000269|Ref.7,
FT ECO:0007744|PDB:2H8K, ECO:0007744|PDB:2REO"
FT BINDING 202
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000269|PubMed:17425406, ECO:0000269|Ref.7,
FT ECO:0007744|PDB:2H8K, ECO:0007744|PDB:2REO"
FT BINDING 236..241
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000269|PubMed:17425406, ECO:0000269|Ref.7,
FT ECO:0007744|PDB:2H8K, ECO:0007744|PDB:2REO"
FT BINDING 264..268
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000269|PubMed:17425406, ECO:0000269|Ref.7,
FT ECO:0007744|PDB:2H8K, ECO:0007744|PDB:2REO"
FT VAR_SEQ 208..304
FT /note="DPKREIEKILKFLEKDISEEILNKIIYHTSFDVMKQNPMTNYTTLPTSIMDH
FT SISPFMRKGMPGDWKNYFTVAQNEEFDKDYQKKMAGSTLTFRTEI -> NPKHEIHKVL
FT EFLEKTWSGDVINKIVHHTSFDVMKDNPMANHTAVPAHIFNHSISKFMRKGMPGDWKNH
FT FTVALNENFDKHYEKKMAGSTLNFCLEI (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_020583"
FT VARIANT 88
FT /note="A -> T (in dbSNP:rs11903659)"
FT /id="VAR_052519"
FT VARIANT 148
FT /note="Y -> C (in dbSNP:rs17035911)"
FT /id="VAR_033732"
FT VARIANT 179
FT /note="G -> R (in dbSNP:rs2219078)"
FT /evidence="ECO:0000269|PubMed:28992322"
FT /id="VAR_033733"
FT VARIANT 194
FT /note="M -> T (in dbSNP:rs6722745)"
FT /evidence="ECO:0000269|PubMed:28992322"
FT /id="VAR_033734"
FT STRAND 21..23
FT /evidence="ECO:0007829|PDB:2H8K"
FT TURN 24..27
FT /evidence="ECO:0007829|PDB:2H8K"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:2H8K"
FT HELIX 32..39
FT /evidence="ECO:0007829|PDB:2H8K"
FT STRAND 49..53
FT /evidence="ECO:0007829|PDB:2REO"
FT HELIX 59..70
FT /evidence="ECO:0007829|PDB:2REO"
FT STRAND 113..116
FT /evidence="ECO:0007829|PDB:2REO"
FT HELIX 120..122
FT /evidence="ECO:0007829|PDB:2REO"
FT HELIX 125..129
FT /evidence="ECO:0007829|PDB:2REO"
FT STRAND 133..138
FT /evidence="ECO:0007829|PDB:2REO"
FT HELIX 141..154
FT /evidence="ECO:0007829|PDB:2REO"
FT HELIX 164..173
FT /evidence="ECO:0007829|PDB:2REO"
FT HELIX 181..191
FT /evidence="ECO:0007829|PDB:2REO"
FT TURN 192..194
FT /evidence="ECO:0007829|PDB:2REO"
FT STRAND 197..201
FT /evidence="ECO:0007829|PDB:2REO"
FT HELIX 202..207
FT /evidence="ECO:0007829|PDB:2REO"
FT HELIX 209..220
FT /evidence="ECO:0007829|PDB:2REO"
FT HELIX 226..235
FT /evidence="ECO:0007829|PDB:2REO"
FT HELIX 238..242
FT /evidence="ECO:0007829|PDB:2REO"
FT TURN 245..247
FT /evidence="ECO:0007829|PDB:2REO"
FT TURN 254..256
FT /evidence="ECO:0007829|PDB:2REO"
FT TURN 259..261
FT /evidence="ECO:0007829|PDB:2REO"
FT HELIX 272..275
FT /evidence="ECO:0007829|PDB:2REO"
FT HELIX 279..292
FT /evidence="ECO:0007829|PDB:2REO"
SQ SEQUENCE 304 AA; 35889 MW; 5510C869578BB70C CRC64;
MAKIEKNAPT MEKKPELFNI MEVDGVPTLI LSKEWWEKVC NFQAKPDDLI LATYPKSGTT
WMHEILDMIL NDGDVEKCKR AQTLDRHAFL ELKFPHKEKP DLEFVLEMSS PQLIKTHLPS
HLIPPSIWKE NCKIVYVARN PKDCLVSYYH FHRMASFMPD PQNLEEFYEK FMSGKVVGGS
WFDHVKGWWA AKDMHRILYL FYEDIKKDPK REIEKILKFL EKDISEEILN KIIYHTSFDV
MKQNPMTNYT TLPTSIMDHS ISPFMRKGMP GDWKNYFTVA QNEEFDKDYQ KKMAGSTLTF
RTEI
