Thiosulfate:glutathione sulfurtransferase (TSTD1)
The protein contains 115 amino acids for an estimated molecular weight of 12530 Da.
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 H(2)S metabolism performed by the sulfide:quinone oxidoreductase (SQOR) which catalyzes the conversion of H(2)S 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). (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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No binding partner found
Cellular Component
Cytoplasm
Cytoplasmic ribonucleoprotein granule
Cytosol
Perinuclear region of cytoplasm
The reference OMIM entry for this protein is 616041
Thiosulfate sulfurtransferase (rhodanese)-like domain-containing protein 1; tstd1
Kat
DESCRIPTION
Hydrogen sulfide (H2S) signaling is particularly important in the cardiovascular and nervous systems and is mediated, at least in part, by covalent protein sulfhydration on cysteine residues. TSTD1 catalyzes the intermediate step of H2S metabolism, converting thiosulfate and glutathione to sulfite and glutathione persulfide (Melideo et al., 2014).CLONING
While analyzing exons of the JAM1 gene (605721), Wenzel et al. (2003) identified an exon of the TSTD1 gene, which they called KAT. By RT-PCR analysis of human cell lines, they obtained a full-length KAT clone. The deduced 115-amino acid protein has a calculated molecular mass of approximately 12.5 kD and contains a potential amidation site. Wenzel et al. (2003) also cloned a splice variant that lacks exon 2 and encodes a deduced 74-amino acid protein with a calculated molecular mass of 8.4 kD. EST database analysis identified a KAT splice variant that retains intron 3 and encodes a 109-amino acid protein. Northern blot analysis detected KAT expression in all 12 tissues examined, with highest expression in kidney, liver, and skeletal muscle. Western blot analysis of human cell lines detected KAT proteins at apparent molecular masses of approximately 12.5, 26, and 32 kD. The apparent masses of the proteins were unaffected by deglycosylation. Database analysis revealed KAT orthologs in gorilla, chimpanzee, orangutan, rat, and mouse. Human KAT shares 100% amino acid identity with the gorilla protein, and 84.3% identity with the mouse and rat proteins. By searching databases for sequences homologous to yeast Rdl1, a thiosulfate:glutathione sulfurtransferase (TST), Melideo et al. (2014) identified full-length human TSTD1. They found that all 3 isoforms of TSTD1 reported by Wenzel et al. (2003) share a common 55-amino acid rhodanese (TST; 180370) homology domain with a putative catalytic cysteine (C79). Full-length TSTD1 shares 34% amino acid identity with yeast Rdl1.GENE FUNCTION
Using synthetic cDNAs designed to optimize expression in bacteria, Melideo et al. (2014) purified all 3 recombinant TSTD1 isoforms. Full-length TSTD1, but not the 2 shorter isoforms, catalyzed the conversion of thiosulfate to sulfite in a glutathione-dependent reaction in vitro at pH 9.0. The TST reaction was accompanied by the formation of stoichiometric amounts of glutathione persulfide, which acted as a competitive inhibitor. Addition of the next enzyme in the metabolism of H2S, sulfur dioxygenase (ETHE1; 608451), removed glutathione persulfide and stimulated TSTD1 activity. L-cysteine, coenzyme A, dithiothreitol, or cyanide could substitute for glutathione as sulfur acceptor. Mutation of C79 within the rhodanese homology domain of TSTD1 abrogated its catalytic activity. Catalysis appeared to occur via a double-displacement mechanism involving transfer of sulfur from thiosulfate to the active-site cysteine, followed by transfer of sulfur from the cysteine persulfide intermediate to glutathione.GENE STRUCTURE
Wenzel et al. (2003) determined that the TSTD1 gene has 4 exons and spans 1.6 kb. Using 5-prime RACE of human placenta and cell line cDNAs, they identified multiple transcription initiation sites within a region approximately 80 bp upstream of the translation start site.MAPPING
By genomic sequence analysis, Wenzel et al. (2003) mapped the TSTD1 gene to chromosome 1q23.3, where it lies between the USF1 (191523) and JAM1 genes. ... More on the omim web site
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 616041 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).