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Protein

Thiosulfate:glutathione sulfurtransferase

Gene

TSTD1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Thiosulfate:glutathione sulfurtransferase (TST) required to produce S-sulfanylglutathione (GSS-), a central intermediate in hydrogen sulfide metabolism (PubMed:24981631). Provides the link between the first step in mammalian H2S metabolism performed by the sulfide:quinone oxidoreductase (SQOR) which catalyzes the conversion of H2S to thiosulfate, and the sulfur dioxygenase (SDO) which uses GSS- as substrate (PubMed:24981631). The thermodynamic coupling of the irreversible SDO and reversible TST reactions provides a model for the physiologically relevant reaction with thiosulfate as the sulfane donor (PubMed:24981631).1 Publication

Catalytic activityi

Thiosulfate + glutathione = sulfite + S-sulfanylglutathione + H+.1 Publication

Enzyme regulationi

GSS- is a potent inhibitor of TSTD1, since the presence of the sulfur dioxygenase (SDO) strongly increases the TSTD1 catalytic activity (PubMed:24981631).1 Publication

Kineticsi

  1. KM=1.0 mM for glutathione1 Publication
  2. KM=14.0 mM for thiosulfate1 Publication
  3. KM=0.04 mM for glutathione (in the presence of sulfur dioxygenase)1 Publication
  4. KM=10.7 mM for thiosulfate (in the presence of sulfur dioxygenase)1 Publication
  5. KM=11.0 mM for thiosulfate (when glutathione is the acceptor)1 Publication
  6. KM=10.4 mM for thiosulfate (when cystein is the acceptor)1 Publication
  7. KM=36.0 mM for thiosulfate (when coenzyme A is the acceptor)1 Publication
  8. KM=14.01 mM for thiosulfate (when DTT is the acceptor)1 Publication
  9. KM=12.0 mM for thiosulfate (when cyanide is the acceptor)1 Publication
  10. KM=1.7 mM for glutathione (when thiosulfate is the acceptor)1 Publication
  11. KM=2.5 mM for cystein (when thiosulfate is the acceptor)1 Publication
  12. KM=0.09 mM for coenzyme A (when thiosulfate is the acceptor)1 Publication
  13. KM=0.12 mM for DTT (when thiosulfate is the acceptor)1 Publication
  14. KM=0.22 mM for cyanide (when thiosulfate is the acceptor)1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei79Cysteine persulfide intermediatePROSITE-ProRule annotation1 Publication1

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionTransferase

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-20304
    ReactomeiR-HSA-1614517 Sulfide oxidation to sulfate

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Thiosulfate:glutathione sulfurtransferase1 Publication (EC:2.8.1.-1 Publication)
    Short name:
    TST1 Publication
    Gene namesi
    Name:TSTD1
    Synonyms:KAT
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 1

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000215845.10
    HGNCiHGNC:35410 TSTD1
    MIMi616041 gene
    neXtProtiNX_Q8NFU3

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi79C → A or S: Leads to the loss of catalytic activity. 1 Publication1

    Organism-specific databases

    DisGeNETi100131187
    OpenTargetsiENSG00000215845
    PharmGKBiPA165752768

    Polymorphism and mutation databases

    BioMutaiTSTD1
    DMDMi68051988

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001394231 – 115Thiosulfate:glutathione sulfurtransferaseAdd BLAST115

    Proteomic databases

    EPDiQ8NFU3
    MaxQBiQ8NFU3
    PaxDbiQ8NFU3
    PeptideAtlasiQ8NFU3
    PRIDEiQ8NFU3
    TopDownProteomicsiQ8NFU3-1 [Q8NFU3-1]

    PTM databases

    iPTMnetiQ8NFU3
    PhosphoSitePlusiQ8NFU3
    SwissPalmiQ8NFU3

    Expressioni

    Tissue specificityi

    Highly expressed in kidney, liver and skeletal muscle. Lower levels of expression in heart, colon, thymus, spleen, placenta and lung. Weakly expressed in brain, small intestine and peripheral blood leukocytes. Expressed at high levels in the breast carcinoma cell lines MCF-7 and MDA-MB-468 and at a lower level in the breast carcinoma cell line MDA-MB-231, the colon carcinoma call line LoVo and the lung carcinoma cell line A-549. No expression in the cell lines EFO-27 and HeLa, or the normal breast tissue cell lines MCF-10A and H184A1. Detected in invasive ductal carcinoma, but not in the adjacent tissues.1 Publication

    Gene expression databases

    BgeeiENSG00000215845
    ExpressionAtlasiQ8NFU3 baseline and differential
    GenevisibleiQ8NFU3 HS

    Organism-specific databases

    HPAiHPA006518
    HPA006655

    Interactioni

    Protein-protein interaction databases

    STRINGi9606.ENSP00000388293

    Structurei

    Secondary structure

    1115
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi9 – 17Combined sources9
    Beta strandi22 – 25Combined sources4
    Helixi29 – 33Combined sources5
    Helixi45 – 53Combined sources9
    Helixi56 – 63Combined sources8
    Beta strandi75 – 78Combined sources4
    Beta strandi80 – 82Combined sources3
    Helixi83 – 94Combined sources12
    Beta strandi100 – 102Combined sources3
    Helixi106 – 113Combined sources8

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    6BEVX-ray1.04A/B1-115[»]
    ProteinModelPortaliQ8NFU3
    SMRiQ8NFU3
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini17 – 115RhodanesePROSITE-ProRule annotationAdd BLAST99

    Phylogenomic databases

    eggNOGiKOG1530 Eukaryota
    COG0607 LUCA
    GeneTreeiENSGT00510000047949
    HOVERGENiHBG107354
    InParanoidiQ8NFU3
    OMAiIFFCQMG
    OrthoDBiEOG091G124L
    PhylomeDBiQ8NFU3
    TreeFamiTF323321

    Family and domain databases

    Gene3Di3.40.250.10, 1 hit
    InterProiView protein in InterPro
    IPR001763 Rhodanese-like_dom
    IPR036873 Rhodanese-like_dom_sf
    PfamiView protein in Pfam
    PF00581 Rhodanese, 1 hit
    SMARTiView protein in SMART
    SM00450 RHOD, 1 hit
    SUPFAMiSSF52821 SSF52821, 1 hit
    PROSITEiView protein in PROSITE
    PS50206 RHODANESE_3, 1 hit

    Sequences (4)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 11 Publication (identifier: Q8NFU3-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MAGAPTVSLP ELRSLLASGR ARLFDVRSRE EAAAGTIPGA LNIPVSELES
    60 70 80 90 100
    ALQMEPAAFQ ALYSAEKPKL EDEHLVFFCQ MGKRGLQATQ LARSLGYTGA
    110
    RNYAGAYREW LEKES
    Length:115
    Mass (Da):12,530
    Last modified:January 23, 2007 - v3
    Checksum:i01963F5B8186B3A2
    GO
    Isoform 21 Publication (identifier: Q8NFU3-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         4-44: Missing.

    Show »
    Length:74
    Mass (Da):8,274
    Checksum:iE6BF433F3A12274B
    GO
    Isoform 31 Publication (identifier: Q8NFU3-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         100-115: ARNYAGAYREWLEKES → YGEVWLLAGR

    Show »
    Length:109
    Mass (Da):11,750
    Checksum:i8BB14CF3EA5223F4
    GO
    Isoform 4 (identifier: Q8NFU3-4) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         3-3: G → GGCRAPSS

    Note: No experimental confirmation available.Curated
    Show »
    Length:122
    Mass (Da):13,189
    Checksum:iE86B87A07C62B477
    GO

    Sequence cautioni

    The sequence AAH01699 differs from that shown. Reason: Erroneous initiation.Curated
    The sequence CAI15368 differs from that shown. Reason: Erroneous gene model prediction.Curated
    The sequence CAI15369 differs from that shown. Reason: Erroneous initiation.Curated

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0141513G → GGCRAPSS in isoform 4. Curated1
    Alternative sequenceiVSP_0141524 – 44Missing in isoform 2. CuratedAdd BLAST41
    Alternative sequenceiVSP_014153100 – 115ARNYA…LEKES → YGEVWLLAGR in isoform 3. 1 PublicationAdd BLAST16

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF439442 Genomic DNA Translation: AAM69839.1
    AF439442 Genomic DNA Translation: AAM69840.1
    AL591806 Genomic DNA Translation: CAI15367.1
    AL591806 Genomic DNA Translation: CAI15368.1 Sequence problems.
    AL591806 Genomic DNA Translation: CAI15369.1 Different initiation.
    AL591806 Genomic DNA Translation: CAI15370.1
    BC001699 mRNA Translation: AAH01699.1 Different initiation.
    CCDSiCCDS44257.1 [Q8NFU3-2]
    CCDS44258.1 [Q8NFU3-3]
    CCDS53400.1 [Q8NFU3-1]
    RefSeqiNP_001106676.1, NM_001113205.1 [Q8NFU3-3]
    NP_001106677.1, NM_001113206.1 [Q8NFU3-2]
    NP_001106678.1, NM_001113207.1 [Q8NFU3-1]
    UniGeneiHs.720030

    Genome annotation databases

    EnsembliENST00000318289; ENSP00000325518; ENSG00000215845 [Q8NFU3-3]
    ENST00000368023; ENSP00000357002; ENSG00000215845 [Q8NFU3-4]
    ENST00000368024; ENSP00000357003; ENSG00000215845 [Q8NFU3-2]
    ENST00000423014; ENSP00000388293; ENSG00000215845 [Q8NFU3-1]
    GeneIDi100131187
    KEGGihsa:100131187
    UCSCiuc001fxh.5 human [Q8NFU3-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    Entry informationi

    Entry nameiTSTD1_HUMAN
    AccessioniPrimary (citable) accession number: Q8NFU3
    Secondary accession number(s): Q5SY48
    , Q5SY49, Q5SY50, Q5SY51, Q8NFU2, Q9BV22
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 21, 2005
    Last sequence update: January 23, 2007
    Last modified: April 25, 2018
    This is version 122 of the entry and version 3 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health