TSTD1_HUMAN
ID TSTD1_HUMAN Reviewed; 115 AA.
AC Q8NFU3; Q5SY48; Q5SY49; Q5SY50; Q5SY51; Q8NFU2; Q9BV22;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Thiosulfate:glutathione sulfurtransferase {ECO:0000303|PubMed:24981631};
DE Short=TST {ECO:0000303|PubMed:24981631};
DE EC=2.8.1.- {ECO:0000269|PubMed:24981631};
GN Name=TSTD1; Synonyms=KAT;
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 [GENOMIC DNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RX PubMed=12817473; DOI=10.1515/bc.2003.085;
RA Wenzel K., Felix S.B., Flachmeier C., Heere P., Schulze W., Grunewald I.,
RA Pankow H., Hewelt A., Scherneck S., Bauer D., Hoehe M.R.;
RT "Identification and characterization of KAT, a novel gene preferentially
RT expressed in several human cancer cell lines.";
RL Biol. Chem. 384:763-775(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAH01699.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Lymph {ECO:0000312|EMBL:AAH01699.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4] {ECO:0000305}
RP PROTEIN SEQUENCE OF 2-13 (ISOFORMS 1/3).
RC TISSUE=Platelet {ECO:0000269|PubMed:12665801};
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [5]
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF
RP CYS-79, ACTIVITY REGULATION, AND ACTIVE SITE.
RX PubMed=24981631; DOI=10.1021/bi500650h;
RA Melideo S.L., Jackson M.R., Jorns M.S.;
RT "Biosynthesis of a central intermediate in hydrogen sulfide metabolism by a
RT novel human sulfurtransferase and its yeast ortholog.";
RL Biochemistry 53:4739-4753(2014).
CC -!- FUNCTION: Thiosulfate:glutathione sulfurtransferase (TST) required to
CC produce S-sulfanylglutathione (GSS(-)), a central intermediate in
CC hydrogen sulfide metabolism (PubMed:24981631). Provides the link
CC between the first step in mammalian H(2)S metabolism performed by the
CC sulfide:quinone oxidoreductase (SQOR) which catalyzes the conversion of
CC H(2)S to thiosulfate, and the sulfur dioxygenase (SDO) which uses
CC GSS(-) as substrate (PubMed:24981631). The thermodynamic coupling of
CC the irreversible SDO and reversible TST reactions provides a model for
CC the physiologically relevant reaction with thiosulfate as the sulfane
CC donor (PubMed:24981631). {ECO:0000269|PubMed:24981631}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glutathione + thiosulfate = H(+) + S-sulfanylglutathione +
CC sulfite; Xref=Rhea:RHEA:55976, ChEBI:CHEBI:15378, ChEBI:CHEBI:17359,
CC ChEBI:CHEBI:33542, ChEBI:CHEBI:57925, ChEBI:CHEBI:58905;
CC Evidence={ECO:0000269|PubMed:24981631};
CC -!- ACTIVITY REGULATION: GSS(-) is a potent inhibitor of TSTD1, since the
CC presence of the sulfur dioxygenase (SDO) strongly increases the TSTD1
CC catalytic activity (PubMed:24981631). {ECO:0000269|PubMed:24981631}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.0 mM for glutathione {ECO:0000269|PubMed:24981631};
CC KM=14.0 mM for thiosulfate {ECO:0000269|PubMed:24981631};
CC KM=0.04 mM for glutathione (in the presence of sulfur dioxygenase)
CC {ECO:0000269|PubMed:24981631};
CC KM=10.7 mM for thiosulfate (in the presence of sulfur dioxygenase)
CC {ECO:0000269|PubMed:24981631};
CC KM=11.0 mM for thiosulfate (when glutathione is the acceptor)
CC {ECO:0000269|PubMed:24981631};
CC KM=10.4 mM for thiosulfate (when cystein is the acceptor)
CC {ECO:0000269|PubMed:24981631};
CC KM=36.0 mM for thiosulfate (when coenzyme A is the acceptor)
CC {ECO:0000269|PubMed:24981631};
CC KM=14.01 mM for thiosulfate (when DTT is the acceptor)
CC {ECO:0000269|PubMed:24981631};
CC KM=12.0 mM for thiosulfate (when cyanide is the acceptor)
CC {ECO:0000269|PubMed:24981631};
CC KM=1.7 mM for glutathione (when thiosulfate is the acceptor)
CC {ECO:0000269|PubMed:24981631};
CC KM=2.5 mM for cystein (when thiosulfate is the acceptor)
CC {ECO:0000269|PubMed:24981631};
CC KM=0.09 mM for coenzyme A (when thiosulfate is the acceptor)
CC {ECO:0000269|PubMed:24981631};
CC KM=0.12 mM for DTT (when thiosulfate is the acceptor)
CC {ECO:0000269|PubMed:24981631};
CC KM=0.22 mM for cyanide (when thiosulfate is the acceptor)
CC {ECO:0000269|PubMed:24981631};
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:12817473}. Note=Localized around the nuclear
CC membranes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1 {ECO:0000269|PubMed:12817473};
CC IsoId=Q8NFU3-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:12817473};
CC IsoId=Q8NFU3-2; Sequence=VSP_014152;
CC Name=3 {ECO:0000303|PubMed:12817473};
CC IsoId=Q8NFU3-3; Sequence=VSP_014153;
CC Name=4;
CC IsoId=Q8NFU3-4; Sequence=VSP_014151;
CC -!- TISSUE SPECIFICITY: Highly expressed in kidney, liver and skeletal
CC muscle. Lower levels of expression in heart, colon, thymus, spleen,
CC placenta and lung. Weakly expressed in brain, small intestine and
CC peripheral blood leukocytes. Expressed at high levels in the breast
CC carcinoma cell lines MCF-7 and MDA-MB-468 and at a lower level in the
CC breast carcinoma cell line MDA-MB-231, the colon carcinoma call line
CC LoVo and the lung carcinoma cell line A-549. No expression in the cell
CC lines EFO-27 and HeLa, or the normal breast tissue cell lines MCF-10A
CC and H184A1. Detected in invasive ductal carcinoma, but not in the
CC adjacent tissues. {ECO:0000269|PubMed:12817473}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH01699.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF439442; AAM69839.1; -; Genomic_DNA.
DR EMBL; AF439442; AAM69840.1; -; Genomic_DNA.
DR EMBL; AL591806; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001699; AAH01699.1; ALT_INIT; mRNA.
DR CCDS; CCDS44257.1; -. [Q8NFU3-2]
DR CCDS; CCDS44258.1; -. [Q8NFU3-3]
DR CCDS; CCDS53400.1; -. [Q8NFU3-1]
DR RefSeq; NP_001106676.1; NM_001113205.1. [Q8NFU3-3]
DR RefSeq; NP_001106677.1; NM_001113206.1. [Q8NFU3-2]
DR RefSeq; NP_001106678.1; NM_001113207.1. [Q8NFU3-1]
DR PDB; 6BEV; X-ray; 1.04 A; A/B=1-115.
DR PDBsum; 6BEV; -.
DR AlphaFoldDB; Q8NFU3; -.
DR SMR; Q8NFU3; -.
DR BioGRID; 756073; 15.
DR STRING; 9606.ENSP00000388293; -.
DR iPTMnet; Q8NFU3; -.
DR PhosphoSitePlus; Q8NFU3; -.
DR SwissPalm; Q8NFU3; -.
DR BioMuta; TSTD1; -.
DR DMDM; 68051988; -.
DR EPD; Q8NFU3; -.
DR jPOST; Q8NFU3; -.
DR MassIVE; Q8NFU3; -.
DR MaxQB; Q8NFU3; -.
DR PaxDb; Q8NFU3; -.
DR PeptideAtlas; Q8NFU3; -.
DR PRIDE; Q8NFU3; -.
DR ProteomicsDB; 73357; -. [Q8NFU3-1]
DR ProteomicsDB; 73358; -. [Q8NFU3-2]
DR ProteomicsDB; 73359; -. [Q8NFU3-3]
DR ProteomicsDB; 73360; -. [Q8NFU3-4]
DR TopDownProteomics; Q8NFU3-1; -. [Q8NFU3-1]
DR Antibodypedia; 34285; 12 antibodies from 8 providers.
DR DNASU; 100131187; -.
DR Ensembl; ENST00000318289.14; ENSP00000325518.10; ENSG00000215845.11. [Q8NFU3-3]
DR Ensembl; ENST00000368023.7; ENSP00000357002.3; ENSG00000215845.11. [Q8NFU3-4]
DR Ensembl; ENST00000368024.5; ENSP00000357003.1; ENSG00000215845.11. [Q8NFU3-2]
DR Ensembl; ENST00000423014.3; ENSP00000388293.2; ENSG00000215845.11. [Q8NFU3-1]
DR GeneID; 100131187; -.
DR KEGG; hsa:100131187; -.
DR MANE-Select; ENST00000423014.3; ENSP00000388293.2; NM_001113207.2; NP_001106678.1.
DR UCSC; uc001fxh.5; human. [Q8NFU3-1]
DR CTD; 100131187; -.
DR DisGeNET; 100131187; -.
DR GeneCards; TSTD1; -.
DR HGNC; HGNC:35410; TSTD1.
DR HPA; ENSG00000215845; Low tissue specificity.
DR MIM; 616041; gene.
DR neXtProt; NX_Q8NFU3; -.
DR OpenTargets; ENSG00000215845; -.
DR PharmGKB; PA165752768; -.
DR VEuPathDB; HostDB:ENSG00000215845; -.
DR eggNOG; KOG1530; Eukaryota.
DR GeneTree; ENSGT00940000161394; -.
DR HOGENOM; CLU_2903509_0_0_1; -.
DR InParanoid; Q8NFU3; -.
DR OMA; FFCQMGR; -.
DR OrthoDB; 1478958at2759; -.
DR PhylomeDB; Q8NFU3; -.
DR TreeFam; TF323321; -.
DR BioCyc; MetaCyc:MON-20304; -.
DR BRENDA; 2.8.1.1; 2681.
DR BRENDA; 2.8.1.3; 2681.
DR PathwayCommons; Q8NFU3; -.
DR Reactome; R-HSA-1614517; Sulfide oxidation to sulfate.
DR BioGRID-ORCS; 100131187; 7 hits in 1070 CRISPR screens.
DR ChiTaRS; TSTD1; human.
DR GenomeRNAi; 100131187; -.
DR Pharos; Q8NFU3; Tdark.
DR PRO; PR:Q8NFU3; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q8NFU3; protein.
DR Bgee; ENSG00000215845; Expressed in parotid gland and 175 other tissues.
DR ExpressionAtlas; Q8NFU3; baseline and differential.
DR Genevisible; Q8NFU3; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0003690; F:double-stranded DNA binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0050337; F:thiosulfate-thiol sulfurtransferase activity; TAS:Reactome.
DR GO; GO:0006006; P:glucose metabolic process; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0070221; P:sulfide oxidation, using sulfide:quinone oxidoreductase; TAS:Reactome.
DR Gene3D; 3.40.250.10; -; 1.
DR InterPro; IPR001763; Rhodanese-like_dom.
DR InterPro; IPR036873; Rhodanese-like_dom_sf.
DR InterPro; IPR042457; TSTD1_mammal.
DR PANTHER; PTHR45544; PTHR45544; 1.
DR Pfam; PF00581; Rhodanese; 1.
DR SMART; SM00450; RHOD; 1.
DR SUPFAM; SSF52821; SSF52821; 1.
DR PROSITE; PS50206; RHODANESE_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Direct protein sequencing;
KW Reference proteome; Transferase.
FT CHAIN 1..115
FT /note="Thiosulfate:glutathione sulfurtransferase"
FT /id="PRO_0000139423"
FT DOMAIN 17..115
FT /note="Rhodanese"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00173"
FT ACT_SITE 79
FT /note="Cysteine persulfide intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00173,
FT ECO:0000269|PubMed:24981631"
FT VAR_SEQ 3
FT /note="G -> GGCRAPSS (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_014151"
FT VAR_SEQ 4..44
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_014152"
FT VAR_SEQ 100..115
FT /note="ARNYAGAYREWLEKES -> YGEVWLLAGR (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_014153"
FT MUTAGEN 79
FT /note="C->A,S: Leads to the loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:24981631"
FT HELIX 9..17
FT /evidence="ECO:0007829|PDB:6BEV"
FT STRAND 22..25
FT /evidence="ECO:0007829|PDB:6BEV"
FT HELIX 29..33
FT /evidence="ECO:0007829|PDB:6BEV"
FT HELIX 45..53
FT /evidence="ECO:0007829|PDB:6BEV"
FT HELIX 56..63
FT /evidence="ECO:0007829|PDB:6BEV"
FT STRAND 75..78
FT /evidence="ECO:0007829|PDB:6BEV"
FT STRAND 80..82
FT /evidence="ECO:0007829|PDB:6BEV"
FT HELIX 83..94
FT /evidence="ECO:0007829|PDB:6BEV"
FT STRAND 100..102
FT /evidence="ECO:0007829|PDB:6BEV"
FT HELIX 106..113
FT /evidence="ECO:0007829|PDB:6BEV"
SQ SEQUENCE 115 AA; 12530 MW; 01963F5B8186B3A2 CRC64;
MAGAPTVSLP ELRSLLASGR ARLFDVRSRE EAAAGTIPGA LNIPVSELES ALQMEPAAFQ
ALYSAEKPKL EDEHLVFFCQ MGKRGLQATQ LARSLGYTGA RNYAGAYREW LEKES
