Tst

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004792 thiosulfate-cyanide sulfurtransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: thiosulfate-cyanide sulfurtransferase activity (EC 2.8.1.1) is the defining catalytic activity of Tst/rhodanese, transferring sulfane sulfur from thiosulfate to cyanide; this is the core molecular function (IEA, GO_REF:0000120). Reason: GO:0004792 is the specific EC 2.8.1.1 rhodanese reaction (thiosulfate + cyanide to thiocyanate + sulfite) catalyzed by Tst, directly supported by the UniProt CATALYTIC ACTIVITY entry and the falcon deep research; this is the core molecular function. Supporting Evidence: UniProtKB:P24329 Reaction=thiosulfate + hydrogen cyanide = thiocyanate + sulfite + 2 H(+) file:rat/Tst/Tst-deep-research-falcon.md In the historical and most widely cited assay reaction for TST, the enzyme catalyzes detoxification of cyanide: Thiosulfate + CN− ⇄ sulfite + thiocyanate
GO:0005739 mitochondrion	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: mitochondrion is retained as contextual support for Tst, but it is not the core function (IEA, GO_REF:0000044). Reason: mitochondrion records localization or complex context for Tst, not the defining molecular function. GOA no longer carries this GO_REF:0000044 row; mitochondrion is still asserted by the IBA, ISO and ARBA (GO_REF:0000120) rows. Supporting Evidence: UniProtKB:P24329 SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269\|PubMed:8702895}. Mitochondrion matrix {ECO:0000250\|UniProtKB:Q16762}. file:rat/Tst/Tst-deep-research-falcon.md TST is consistently described as mitochondrial in mammalian cells—often discussed in the context of mitochondrial matrix sulfur metabolism
GO:0005759 mitochondrial matrix	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: mitochondrial matrix is retained as contextual support for Tst, but it is not the core function (IEA, GO_REF:0000044). Reason: mitochondrial matrix records localization or complex context for Tst, not the defining molecular function. Supporting Evidence: UniProtKB:P24329 SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269\|PubMed:8702895}. Mitochondrion matrix {ECO:0000250\|UniProtKB:Q16762}. file:rat/Tst/Tst-deep-research-falcon.md TST is consistently described as mitochondrial in mammalian cells—often discussed in the context of mitochondrial matrix sulfur metabolism
GO:0016783 sulfurtransferase activity	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: sulfurtransferase activity is the direct parent of the more specific GO:0004792 (thiosulfate-cyanide sulfurtransferase activity) that is already ACCEPTed for Tst; it is retained as non-core because the specific child term already captures the molecular function (IEA, GO_REF:0000120). Reason: GO:0016783 is the direct GO parent of GO:0004792 (thiosulfate-cyanide sulfurtransferase activity), which is already ACCEPTed as the core molecular function; the more specific child covers this by transitivity, so the generic parent is kept only as non-core. Supporting Evidence: file:rat/Tst/Tst-deep-research-falcon.md Rhodanese-family sulfurtransferases operate via formation of an enzyme persulfide intermediate on the active-site cysteine, enabling transfer of “sulfane sulfur” from a donor to a nucleophilic acceptor
GO:0004792 thiosulfate-cyanide sulfurtransferase activity	ISS GO_REF:0000024	ACCEPT	Summary: thiosulfate-cyanide sulfurtransferase activity (EC 2.8.1.1) is the defining catalytic activity of Tst/rhodanese, a two-domain rhodanese-fold enzyme acting via an active-site cysteine persulfide intermediate; this is the core molecular function (ISS, GO_REF:0000024). Reason: GO:0004792 is the specific rhodanese reaction catalyzed by Tst, supported by UniProt and by the falcon deep research describing the two-domain rhodanese fold with a single catalytic cysteine; this is the core molecular function. The ISS transfer is from bovine rhodanese (UniProtKB:P00586), the classic biochemically characterized enzyme, and rat Tst retains the catalytic cysteine at the equivalent position. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P00586 · bovine thiosulfate sulfurtransferase (rhodanese) SUPPORTS TRANSFER The ISS WITH source is bovine rhodanese, the founding biochemically and structurally characterized thiosulfate-cyanide sulfurtransferase; rat Tst is its 297-aa ortholog and retains the active-site cysteine, so the transfer is sound. Supporting Evidence: UniProtKB:P24329 FUNCTION: Catalyzes the transfer of sulfur ion from thiosulfate to cyanide, although other thiol compounds, besides cyanide, can act as sulfur ion acceptors file:rat/Tst/Tst-deep-research-falcon.md TST is described as a two-domain rhodanese-fold protein with one catalytically active cysteine located in the C-terminal domain
GO:0070458 cellular detoxification of nitrogen compound	ISS GO_REF:0000024	ACCEPT	Summary: cellular detoxification of nitrogen compound captures Tst's role in detoxifying cyanide by converting it to thiocyanate using thiosulfate as the sulfur donor (ISS, GO_REF:0000024). Reason: GO:0070458 is the process-level term for Tst's conversion of the toxic nitrogen compound cyanide to thiocyanate, the classical basis of its detoxification function, as supported by the falcon deep research on thiosulfate-based cyanide antidote chemistry. Supporting Evidence: UniProtKB:P24329 Has a pivotal role in cyanide detoxification (By similarity). file:rat/Tst/Tst-deep-research-falcon.md Because TST catalyzes conversion of cyanide to thiocyanate using thiosulfate as sulfur donor, thiosulfate-based cyanide antidote strategies depend on sulfurtransferase activity
GO:0070458 cellular detoxification of nitrogen compound	ISO GO_REF:0000121	ACCEPT	Summary: cellular detoxification of nitrogen compound captures Tst's role in detoxifying cyanide by converting it to thiocyanate using thiosulfate as the sulfur donor (ISO, GO_REF:0000121). Reason: GO:0070458 is the process-level term for Tst's conversion of the toxic nitrogen compound cyanide to thiocyanate, the classical basis of its detoxification function; the falcon deep research describes Tst as central to mitochondrial reactive sulfur species handling that underpins this detoxification. Supporting Evidence: UniProtKB:P24329 Has a pivotal role in cyanide detoxification (By similarity). file:rat/Tst/Tst-deep-research-falcon.md TST is best understood not only as a cyanide detoxification enzyme but also as a mitochondrial sulfur-species processing enzyme central to maintaining an appropriate window of reactive sulfur species (persulfides/polysulfides) and limiting toxic H2S accumulation
GO:0005739 mitochondrion	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: mitochondrion is retained as contextual support for Tst, but it is not the core function (ISO, GO_REF:0000121). Reason: mitochondrion records localization or complex context for Tst, not the defining molecular function. Supporting Evidence: UniProtKB:P24329 SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269\|PubMed:8702895}. Mitochondrion matrix {ECO:0000250\|UniProtKB:Q16762}.
GO:0016783 sulfurtransferase activity	TAS Reactome:R-RNO-1614611	KEEP AS NON CORE	Summary: sulfurtransferase activity is the direct parent of the more specific GO:0004792 (thiosulfate-cyanide sulfurtransferase activity) already ACCEPTed for Tst; retained as non-core because the specific child captures the molecular function (TAS, Reactome:R-RNO-1614611). Reason: GO:0016783 is the direct GO parent of GO:0004792 (thiosulfate-cyanide sulfurtransferase activity), which is already ACCEPTed as the core molecular function; the generic parent is kept only as non-core. Supporting Evidence: Reactome:R-RNO-1614611 Persulfide sulfur is transferred onto sulfite
GO:0030855 epithelial cell differentiation	ISO GO_REF:0000121	MARK AS OVER ANNOTATED	Summary: epithelial cell differentiation is treated as over-annotation because it is contextual or downstream of Tst's direct role (ISO, GO_REF:0000121). Reason: epithelial cell differentiation reflects exposure, expression, phenotype, or downstream pathway context rather than the direct Tst role in rhodanese sulfur transfer, cyanide detoxification, and mitochondrial 5S rRNA import support. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH ROLE CONFLATION Sources checked: UniProtKB:Q16762 · human TST SUPPORTS SOURCE BUT NOT TARGET The human TST donor annotation reflects expression during epithelial differentiation rather than a rhodanese sulfurtransferase role in the differentiation programme itself. Supporting Evidence: UniProtKB:P24329 FUNCTION: Catalyzes the transfer of sulfur ion from thiosulfate to cyanide, although other thiol compounds, besides cyanide, can act as sulfur ion acceptors
GO:0005759 mitochondrial matrix	TAS Reactome:R-RNO-1614611	KEEP AS NON CORE	Summary: mitochondrial matrix is retained as contextual support for Tst, but it is not the core function (TAS, Reactome:R-RNO-1614611). Reason: mitochondrial matrix records localization or complex context for Tst, not the defining molecular function. Supporting Evidence: Reactome:R-RNO-1614611 Persulfide sulfur is transferred onto sulfite
GO:0035928 rRNA import into mitochondrion	ISS GO_REF:0000024	ACCEPT	Summary: rRNA import into mitochondrion is the most specific term for Tst's UniProt-asserted role, together with MRPL18, as a mitochondrial import factor for cytosolic 5S rRNA; retained as the core process for this role (ISS, GO_REF:0000024). Note this is a By-similarity assertion not corroborated by the falcon deep research. Reason: GO:0035928 is the most specific GO term matching the UniProt FUNCTION statement that Tst, with MRPL18, imports cytosolic 5S rRNA into the mitochondrion; it is preferred over the generic parents GO:0051029 (rRNA transport) and GO:0008097-related terms. Supporting Evidence: UniProtKB:P24329 Together with MRPL18, it acts as a mitochondrial import factor for the cytosolic 5S rRNA. Only the nascent unfolded cytoplasmic form is able to bind to the 5S rRNA (By similarity).
GO:0035928 rRNA import into mitochondrion	ISO GO_REF:0000121	ACCEPT	Summary: rRNA import into mitochondrion is the most specific term for Tst's UniProt-asserted role, together with MRPL18, as a mitochondrial import factor for cytosolic 5S rRNA; retained as the core process for this role (ISO, GO_REF:0000121). Note this is a By-similarity assertion not corroborated by the falcon deep research. Reason: GO:0035928 is the most specific GO term matching the UniProt FUNCTION statement that Tst, with MRPL18, imports cytosolic 5S rRNA into the mitochondrion; it is preferred over the generic parent GO:0051029 (rRNA transport). Supporting Evidence: UniProtKB:P24329 Together with MRPL18, it acts as a mitochondrial import factor for the cytosolic 5S rRNA. Only the nascent unfolded cytoplasmic form is able to bind to the 5S rRNA (By similarity).
GO:0008097 5S rRNA binding	ISS GO_REF:0000024	ACCEPT	Summary: 5S rRNA binding matches the UniProt assertion that the nascent unfolded cytoplasmic form of Tst binds the cytosolic 5S rRNA as part of its mitochondrial import role (ISS, GO_REF:0000024). This is a By-similarity assertion not corroborated by the falcon deep research. Reason: GO:0008097 matches the UniProt FUNCTION statement that the nascent unfolded cytoplasmic form of Tst binds the cytosolic 5S rRNA; this is the molecular-function basis for the 5S rRNA mitochondrial import role. Supporting Evidence: UniProtKB:P24329 Together with MRPL18, it acts as a mitochondrial import factor for the cytosolic 5S rRNA. Only the nascent unfolded cytoplasmic form is able to bind to the 5S rRNA (By similarity).
GO:0051029 rRNA transport	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: rRNA transport is the GO parent of the more specific GO:0035928 (rRNA import into mitochondrion), which is already ACCEPTed for Tst; the parent is retained only as non-core (ISS, GO_REF:0000024). This whole role derives from a UniProt By-similarity assertion (5S rRNA import with MRPL18) and was not corroborated by the falcon deep research. Reason: GO:0051029 (rRNA transport) is the direct GO parent of GO:0035928 (rRNA import into mitochondrion), which is already ACCEPTed; the more specific child captures the process by transitivity, so the generic parent is kept only as non-core. Supporting Evidence: UniProtKB:P24329 Together with MRPL18, it acts as a mitochondrial import factor for the cytosolic 5S rRNA. Only the nascent unfolded cytoplasmic form is able to bind to the 5S rRNA (By similarity).
GO:0008097 5S rRNA binding	ISO GO_REF:0000121	ACCEPT	Summary: 5S rRNA binding matches the UniProt assertion that the nascent unfolded cytoplasmic form of Tst binds the cytosolic 5S rRNA as part of its mitochondrial import role (ISO, GO_REF:0000121). This is a By-similarity assertion not corroborated by the falcon deep research. Reason: GO:0008097 matches the UniProt FUNCTION statement that the nascent unfolded cytoplasmic form of Tst binds the cytosolic 5S rRNA; this is the molecular-function basis for the 5S rRNA mitochondrial import role. Supporting Evidence: UniProtKB:P24329 Together with MRPL18, it acts as a mitochondrial import factor for the cytosolic 5S rRNA. Only the nascent unfolded cytoplasmic form is able to bind to the 5S rRNA (By similarity).
GO:0051029 rRNA transport	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: rRNA transport is the GO parent of the more specific GO:0035928 (rRNA import into mitochondrion), which is already ACCEPTed for Tst; the parent is retained only as non-core (ISO, GO_REF:0000121). This whole role derives from a UniProt By-similarity assertion (5S rRNA import with MRPL18) and was not corroborated by the falcon deep research. Reason: GO:0051029 (rRNA transport) is the direct GO parent of GO:0035928 (rRNA import into mitochondrion), which is already ACCEPTed; the more specific child captures the process by transitivity, so the generic parent is kept only as non-core. Supporting Evidence: UniProtKB:P24329 Together with MRPL18, it acts as a mitochondrial import factor for the cytosolic 5S rRNA. Only the nascent unfolded cytoplasmic form is able to bind to the 5S rRNA (By similarity).
GO:0016226 iron-sulfur cluster assembly	NAS PMID:2018478 Molecular cloning, sequencing and characterization of cDNA t...	MARK AS OVER ANNOTATED	Summary: iron-sulfur cluster assembly is likely an over-annotation for Tst. The support is an NAS introduction statement (PMID:2018478, 1991) plus in vitro Fe-S reconstitution/sulfur-extraction literature, and UniProt has dropped the Fe-S wording from the FUNCTION comment. Reason: The participation test is not met. In vitro sulfane-sulfur donation and the ability to extract/insert labile sulfur from Fe-S centers do not establish that Tst performs a step of the cellular iron-sulfur cluster assembly process; that process is carried out by the dedicated ISC machinery (cysteine desulfurase NFS1 as the physiological sulfur donor, the ISCU scaffold, and associated factors), which are the gene products that enable GO:0016226. The evidence here is NAS (a 1991 cDNA-characterization introduction statement, PMID:2018478) and in vitro reconstitution, not demonstration of Tst as a component of the cellular assembly pathway, and UniProt has since removed the Fe-S wording from FUNCTION. The annotation is not retained in core_functions; Tst's core role is sulfur transfer / sulfide metabolism (GO:0004792, GO:0070813). Supporting Evidence: PMID:2018478 Rhodanese (EC 2.8.1.1), a mitochondrial thiosulphate sulphurtransferase, is involved in the formation of iron-sulphur complexes and cyanide detoxification. file:rat/Tst/Tst-deep-research-falcon.md TST interacts functionally with iron–sulfur centers in mitochondrial redox proteins and can form enzyme persulfides by extracting labile sulfur from Fe–S centers
GO:0070813 hydrogen sulfide metabolic process	TAS Reactome:R-RNO-1614611	NEW	Summary: NEW annotation. Tst/rhodanese is a component of the mitochondrial sulfide oxidation (H2S catabolism) pathway: sulfide:quinone oxidoreductase generates a persulfide that is processed by ETHE1 and TST, with TST transferring persulfide sulfur onto sulfite to form thiosulfate (the rat Reactome reaction R-RNO-1614611). This places Tst directly in hydrogen sulfide metabolic process: Tst itself catalyzes a sulfur-transfer step of sulfide catabolism, rather than merely being required for it. Reason: The falcon deep research and the reviews it synthesizes describe TST as a component of mitochondrial H2S catabolism (the SQOR/ETHE1/TST pathway) that limits toxic H2S accumulation, and the corresponding rat Reactome reaction (persulfide sulfur transferred onto sulfite) is already cited in this review. GO:0070813 (hydrogen sulfide metabolic process) is the term that captures this core sulfur-species processing role, complementing the accepted thiosulfate-cyanide sulfurtransferase activity annotations. Under the participation test, Tst performs the persulfide-to-sulfite transfer step itself (Reactome R-RNO-1614611). Comparator check (QuickGO, human/mouse/rat, 2026-10-10) shows that the other enzymes of the same pathway carry this term or the related sulfide-oxidation term (ETHE1 GO:0070813 ISO; SQOR and ETHE1 GO:0019418 sulfide oxidation IDA; the paralogous sulfurtransferase TSTD1 GO:0019418 TAS), so the absence for Tst is a gap, not a convention. The broader GO:0070813 is retained rather than GO:0019418 because Tst's product is thiosulfate rather than sulfite or sulfate. Supporting Evidence: file:rat/Tst/Tst-deep-research-falcon.md TST is a component of mitochondrial H2S catabolism (SQOR/ETHE1/TST) and a node that can couple sulfur flux to respiratory function and redox homeostasis Reactome:R-RNO-1614611 Persulfide sulfur is transferred onto sulfite
GO:0005739 mitochondrion	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetically inferred mitochondrial localization (IBA, PANTHER:PTN000146244); consistent with the experimentally determined mitochondrial location of rat Tst and kept as non-core localization context, like the other mitochondrion rows. Reason: The PAINT node places mitochondrial activity at the ancestor of the vertebrate and plant mitochondrial rhodaneses; rat Tst is inside that clade and UniProt records an experimental (PubMed:8702895) mitochondrial location. RGD:620065 in WITH/FROM is rat Tst's own experimental grounding, as expected for an IBA. Localization is context for the sulfurtransferase function rather than the core function. Supporting Evidence: UniProtKB:P24329 SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269\|PubMed:8702895}. Mitochondrion matrix {ECO:0000250\|UniProtKB:Q16762}. file:rat/Tst/Tst-deep-research-falcon.md TST is consistently described as mitochondrial in mammalian cells—often discussed in the context of mitochondrial matrix sulfur metabolism
GO:0005739 mitochondrion	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: ARBA rule-based mitochondrion annotation (IEA, GO_REF:0000120); correct and kept as non-core localization context, consistent with the other mitochondrion rows. Reason: Rat Tst is experimentally mitochondrial (UniProt, PubMed:8702895), so the ARBA-derived location is correct; the more specific mitochondrial matrix location is also carried. Localization is context rather than the core function. Supporting Evidence: UniProtKB:P24329 SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269\|PubMed:8702895}. Mitochondrion matrix {ECO:0000250\|UniProtKB:Q16762}.
GO:0016783 sulfurtransferase activity	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetically inferred sulfurtransferase activity (IBA, PANTHER:PTN000146159); correct for rat Tst but the generic parent of the accepted GO:0004792 thiosulfate-cyanide sulfurtransferase activity, so kept as non-core like the IEA and TAS sulfurtransferase rows. Reason: The PAINT node covers the rhodanese sulfurtransferase family across bacteria, fungi, plants and animals, and rat Tst retains the catalytic cysteine; there is no evidence of divergence. Rat Tst (RGD:620065) and bovine rhodanese (UniProtKB:P00586) among the WITH/FROM sources reflect experimental grounding on the target and its ortholog. The specific child GO:0004792 already captures the activity. Supporting Evidence: UniProtKB:P24329 FUNCTION: Catalyzes the transfer of sulfur ion from thiosulfate to cyanide, although other thiol compounds, besides cyanide, can act as sulfur ion acceptors file:rat/Tst/Tst-deep-research-falcon.md Rhodanese-family sulfurtransferases operate via formation of an enzyme persulfide intermediate on the active-site cysteine, enabling transfer of “sulfane sulfur” from a donor to a nucleophilic acceptor

Gene Description

Existing Annotations Review

Core Functions

By similarity (propagated from the human ortholog and not corroborated by the falcon deep research), the nascent unfolded cytoplasmic form of Tst binds cytosolic 5S rRNA and, together with MRPL18, acts as a mitochondrial import factor for the 5S rRNA.

References

Deep Research

Falcon

📚 Additional Documentation

Notes

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