MOCS3 (also called UBA4) is a cytosolic, two-domain bifunctional enzyme that activates the C-terminal Gly-Gly motif of small Ξ²-grasp-fold sulfur-carrier proteins for two sulfur-relay pathways. Its N-terminal HesA/MoeB/ThiF (E1-like) adenylation domain forms an acyl-adenylate (-COAMP) at the C-terminus of its substrates, and its C-terminal rhodanese-like domain then transfers persulfide sulfur from a catalytic cysteine (Cys412) to convert this into a C-terminal thiocarboxylate (-COSH). Through these coupled adenylyltransferase (EC 2.7.7.80) and sulfurtransferase (EC 2.8.1.11) activities, MOCS3 thiocarboxylates MOCS2A, the small subunit of molybdopterin (MPT) synthase, driving molybdenum cofactor (Moco) biosynthesis, and it thiocarboxylates the ubiquitin-related modifier URM1, supplying the sulfur used for 2-thiolation of wobble uridine (mcm5s2U34) in cytosolic tRNA-Lys, tRNA-Glu and tRNA-Gln. The physiological sulfur donor to the MOCS3 rhodanese domain is the cytosolic L-cysteine desulfurase NFS1 rather than thiosulfate. MOCS3 binds one zinc ion per subunit and requires ATP. Loss-of-function variants cause molybdenum cofactor deficiency type B2.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: MOCS3 acts in the cytoplasm/cytosol. Location is well supported by direct biochemical fractionation and imaging, though cytosol (GO:0005829) is the more precise term and is separately annotated by IDA. Supporting Evidence: file:human/MOCS3/MOCS3-uniprot.txt Cytoplasm, cytosol |
| GO:0016779 nucleotidyltransferase activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Correct but general. MOCS3 transfers AMP onto the C-terminal Gly-Gly of its sulfur-carrier substrates; the specific child term molybdopterin-synthase adenylyltransferase activity (GO:0061605) is the informative core MF. Proposed replacements: molybdopterin-synthase adenylyltransferase activity Supporting Evidence: file:human/MOCS3/MOCS3-uniprot.txt Its N-terminus first activates URM1 and MOCS2A as acyl-adenylates (-COAMP) |
| GO:0004792 thiosulfate-cyanide sulfurtransferase activity | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: The isolated MOCS3 rhodanese-like domain can transfer sulfur from thiosulfate to cyanide in vitro, but at ~1000-fold lower activity than bovine rhodanese, and thiosulfate is explicitly not the physiological sulfur donor in humans; NFS1 is. This is an in-vitro rhodanese activity, not the biological function. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000102040 Β· MOCS3/UBA4 family node SUPPORTS SOURCE BUT NOT TARGET Supporting Evidence: PMID:17459099 in humans and most eukaryotes thiosulfate is not the physiologic sulfur donor for MOCS3 |
| GO:0042292 URM1 activating enzyme activity | IBA GO_REF:0000033 | ACCEPT | Summary: MOCS3 activates the ubiquitin-related modifier URM1 (adenylation followed by thiocarboxylation of its C-terminal glycine), the URM1-pathway counterpart of its MOCS2A activity. This is a core molecular function, also supported by IDA (PMID:19017811). Supporting Evidence: file:human/MOCS3/MOCS3-uniprot.txt Acts by mediating the C-terminal thiocarboxylation of sulfur carriers URM1 and MOCS2A |
| GO:0002143 tRNA wobble position uridine thiolation | IBA GO_REF:0000033 | ACCEPT | Summary: MOCS3 is required for 2-thiolation of wobble uridine (mcm5s2U34) of cytosolic tRNA-Lys, tRNA-Glu and tRNA-Gln, by activating URM1 as the sulfur carrier. Core biological process, also supported by IDA and IMP. Supporting Evidence: file:human/MOCS3/MOCS3-uniprot.txt Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of cytosolic tRNA(Lys), tRNA(Glu) and tRNA(Gln) |
| GO:0032447 protein urmylation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: MOCS3 is a component of the URM1 machinery (it activates URM1), and URM1 can be conjugated to lysines of target proteins including MOCS3 itself under oxidative stress. This is a downstream/secondary role rather than the core catalytic function, which is sulfur-carrier activation. Supporting Evidence: PMID:21209336 Urm1 is appended to lysine residues of three components that function in its own pathway (i.e., MOCS3, ATPBD3, and CTU2) |
| GO:0002098 tRNA wobble uridine modification | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: Correct but a broader parent of tRNA wobble position uridine thiolation (GO:0002143). MOCS3 specifically contributes the 2-thiolation (thio) step, so the more specific thiolation term is preferred as core. Proposed replacements: tRNA wobble position uridine thiolation Supporting Evidence: file:human/MOCS3/MOCS3-uniprot.txt Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of cytosolic tRNA(Lys), tRNA(Glu) and tRNA(Gln) |
| GO:0002143 tRNA wobble position uridine thiolation | IEA GO_REF:0000002 | ACCEPT | Summary: Same core biological process as the IBA/IDA/IMP annotations to this term; electronic support from InterPro is consistent with the experimental evidence. Supporting Evidence: file:human/MOCS3/MOCS3-uniprot.txt Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of cytosolic tRNA(Lys), tRNA(Glu) and tRNA(Gln) |
| GO:0005737 cytoplasm | IEA GO_REF:0000104 | ACCEPT | Summary: Consistent with the experimentally established cytosolic localization; cytosol (GO:0005829) is the more precise term also annotated by IDA. Supporting Evidence: file:human/MOCS3/MOCS3-uniprot.txt Cytoplasm, cytosol |
| GO:0005829 cytosol | IEA GO_REF:0000120 | ACCEPT | Summary: Cytosol is the experimentally verified location of MOCS3 (subcellular fractionation and confocal imaging in HeLa cells). This is the precise CC term. Supporting Evidence: file:human/MOCS3/MOCS3-uniprot.txt Cytoplasm, cytosol |
| GO:0006777 Mo-molybdopterin cofactor biosynthetic process | IEA GO_REF:0000104 | ACCEPT | Summary: MOCS3 is essential for molybdenum cofactor biosynthesis; it thiocarboxylates MOCS2A, the small MPT synthase subunit. Core BP, extensively supported by IDA/IMP. Supporting Evidence: file:human/MOCS3/MOCS3-uniprot.txt Also essential during biosynthesis of the molybdenum cofactor |
| GO:0008641 ubiquitin-like modifier activating enzyme activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Family-level (E1-like/MoeB) inference. MOCS3 does activate the ubiquitin-related modifier URM1, but as a sulfur carrier (adenylation then thiocarboxylation of the C-terminal glycine) rather than by a classic Ubl conjugation cascade; no thioester intermediate is formed with URM1/MOCS2A. The specific term URM1 activating enzyme activity (GO:0042292) is preferred. Proposed replacements: URM1 activating enzyme activity Supporting Evidence: PMID:18491921 The formation of a thioester intermediate between Uba4 and Urm1 or MOCS2A was not observed |
| GO:0016779 nucleotidyltransferase activity | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: Correct but general parent of molybdopterin-synthase adenylyltransferase activity (GO:0061605). The specific child is the informative core MF. Proposed replacements: molybdopterin-synthase adenylyltransferase activity Supporting Evidence: file:human/MOCS3/MOCS3-uniprot.txt Its N-terminus first activates URM1 and MOCS2A as acyl-adenylates (-COAMP) |
| GO:0016783 sulfurtransferase activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Correct but general parent of the specific molybdopterin-synthase sulfurtransferase activity (GO:0061604). MOCS3 forms a persulfide on Cys412 and transfers sulfur to its carrier-protein substrate. Proposed replacements: molybdopterin-synthase sulfurtransferase activity Supporting Evidence: file:human/MOCS3/MOCS3-uniprot.txt the persulfide sulfur on the catalytic cysteine is transferred to URM1 and MOCS2A to form thiocarboxylation |
| GO:0034227 tRNA thio-modification | IEA GO_REF:0000104 | ACCEPT | Summary: MOCS3 supplies the sulfur (via URM1) for thio-modification of cytosolic tRNA. Core BP, also supported by IDA/IMP. Supporting Evidence: file:human/MOCS3/MOCS3-uniprot.txt Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions |
| GO:0061604 molybdopterin-synthase sulfurtransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Specific core catalytic MF (EC 2.8.1.11): transfer of persulfide sulfur from the rhodanese-like domain onto the adenylylated MOCS2A C-terminus to form a thiocarboxylate. Strongly supported by EXP/IDA/IMP. Supporting Evidence: file:human/MOCS3/MOCS3-uniprot.txt EC=2.8.1.11 |
| GO:0061605 molybdopterin-synthase adenylyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Specific core catalytic MF (EC 2.7.7.80): ATP-dependent adenylation of the MOCS2A C-terminal Gly-Gly. Strongly supported by EXP/IDA/ISO. Supporting Evidence: file:human/MOCS3/MOCS3-uniprot.txt EC=2.7.7.80 |
| GO:0070566 adenylyltransferase activity | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Correct but general parent of molybdopterin-synthase adenylyltransferase activity (GO:0061605). The specific child is the informative core MF. Proposed replacements: molybdopterin-synthase adenylyltransferase activity Supporting Evidence: file:human/MOCS3/MOCS3-uniprot.txt Its N-terminus first activates URM1 and MOCS2A as acyl-adenylates (-COAMP) |
| GO:0005515 protein binding | IPI PMID:21209336 Role of the ubiquitin-like protein Urm1 as a noncanonical ly... | MARK AS OVER ANNOTATED | Summary: IntAct-curated interaction with URM1 (Q9BTM9), the sulfur-carrier substrate of MOCS3. Bare "protein binding" is uninformative; the functionally meaningful relationship is captured by URM1 activating enzyme activity (GO:0042292) and the adenylyl/sulfurtransferase MF terms. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Large-scale neurodegenerative-disease interactome (yeast two-hybrid) reporting candidate interactions of MOCS3 with ATXN1 (P54253) and TARDBP/TDP-43 (Q13148). Bare "protein binding" is uninformative and these high-throughput interactions have no dedicated functional follow-up for MOCS3. |
| GO:0061604 molybdopterin-synthase sulfurtransferase activity | EXP PMID:18650437 A novel role for human Nfs1 in the cytoplasm: Nfs1 acts as a... | ACCEPT | Summary: Experimental support: the sulfurated MOCS3 rhodanese-like domain, receiving sulfur from NFS1, thiocarboxylates MOCS2A. Core sulfurtransferase MF. Supporting Evidence: PMID:18650437 The two-domain protein MOCS3 catalyzes both the adenylation and the subsequent generation of a thiocarboxylate group at the C terminus of MOCS2A by its C-terminal rhodanese-like domain (RLD) |
| GO:0061604 molybdopterin-synthase sulfurtransferase activity | EXP PMID:22453920 Dual role of the molybdenum cofactor biosynthesis protein MO... | ACCEPT | Summary: Experimental support: MOCS3 forms the thiocarboxylate on the MOCS2A C-terminus via a sulfur-transfer step following adenylation. Core sulfurtransferase MF. Supporting Evidence: PMID:22453920 MOCS3 activates both MOCS2A and URM1 by adenylation and a subsequent sulfur transfer step for the formation of the thiocarboxylate group at the C terminus of each protein |
| GO:0061605 molybdopterin-synthase adenylyltransferase activity | EXP PMID:18650437 A novel role for human Nfs1 in the cytoplasm: Nfs1 acts as a... | ACCEPT | Summary: Experimental support: the two-domain MOCS3 catalyzes the ATP-dependent adenylation of the MOCS2A C-terminus. Core adenylyltransferase MF. Supporting Evidence: PMID:18650437 The two-domain protein MOCS3 catalyzes both the adenylation and the subsequent generation of a thiocarboxylate group |
| GO:0002143 tRNA wobble position uridine thiolation | IDA PMID:22453920 Dual role of the molybdenum cofactor biosynthesis protein MO... | ACCEPT | Summary: Direct evidence that MOCS3 functions in the tRNA-thiolation branch (via URM1) in human cells. Core BP. Supporting Evidence: PMID:22453920 We studied two pathways that involve the transfer of persulfide sulfur in humans, molybdenum cofactor biosynthesis and tRNA thiolation |
| GO:0005829 cytosol | IDA PMID:22453920 Dual role of the molybdenum cofactor biosynthesis protein MO... | ACCEPT | Summary: MOCS3 is localized to the cytosol; C-terminal extension of its substrates relocalizes MOCS3 from cytosol to nucleus, confirming cytosolic steady-state localization. Core CC. Supporting Evidence: PMID:22453920 altered the localization of MOCS3 from the cytosol to the nucleus |
| GO:0006777 Mo-molybdopterin cofactor biosynthetic process | IDA PMID:22453920 Dual role of the molybdenum cofactor biosynthesis protein MO... | ACCEPT | Summary: Direct evidence that MOCS3 functions in molybdenum cofactor biosynthesis in human cells. Core BP. Supporting Evidence: PMID:22453920 molybdenum cofactor biosynthesis and tRNA thiolation |
| GO:0061605 molybdopterin-synthase adenylyltransferase activity | IDA PMID:22453920 Dual role of the molybdenum cofactor biosynthesis protein MO... | ACCEPT | Summary: Direct experimental support for the adenylyltransferase activity on MOCS2A (and URM1). Core MF. Supporting Evidence: PMID:22453920 MOCS3 activates both MOCS2A and URM1 by adenylation |
| GO:0070566 adenylyltransferase activity | IDA PMID:22453920 Dual role of the molybdenum cofactor biosynthesis protein MO... | KEEP AS NON CORE | Summary: Correct but general parent of molybdopterin-synthase adenylyltransferase activity (GO:0061605); the specific child is the core MF. Proposed replacements: molybdopterin-synthase adenylyltransferase activity Supporting Evidence: PMID:22453920 MOCS3 activates both MOCS2A and URM1 by adenylation |
| GO:0005829 cytosol | IDA PMID:23593335 The L-cysteine desulfurase NFS1 is localized in the cytosol ... | ACCEPT | Summary: Subcellular fractionation and confocal imaging place MOCS3 (and its interaction with NFS1) in the cytosol of HeLa cells. Core CC. Supporting Evidence: PMID:23593335 these results show that NFS1 interacts with MOCS3 in the cytosol |
| GO:0006777 Mo-molybdopterin cofactor biosynthetic process | IDA PMID:18650437 A novel role for human Nfs1 in the cytoplasm: Nfs1 acts as a... | ACCEPT | Summary: Direct evidence for MOCS3's role in Moco biosynthesis, with NFS1 supplying the sulfur to the MOCS3 rhodanese domain in the cytosol. Core BP. Supporting Evidence: PMID:18650437 cytosolic Nfs1 has an important role in sulfur transfer for the biosynthesis of Moco |
| GO:0061605 molybdopterin-synthase adenylyltransferase activity | ISO PMID:18491921 The sulfurtransferase activity of Uba4 presents a link betwe... | ACCEPT | Summary: Orthology-based support from yeast Uba4 (UniProtKB:P38820), whose N-terminal domain adenylates MOCS2A/Urm1 as an acyl-adenylate; consistent with the human EXP/IDA evidence. Core MF. Supporting Evidence: PMID:18491921 The N-terminal domain of Uba4 catalyzes the activation of either MOCS2A or Urm1 by formation of an acyl-adenylate bond |
| GO:0061604 molybdopterin-synthase sulfurtransferase activity | IMP PMID:15073332 Evidence for the physiological role of a rhodanese-like prot... | ACCEPT | Summary: Mutation of the persulfide-forming active-site cysteine (Cys412) abolishes MOCS3-RLD sulfurtransferase activity, and the sulfurated RLD provides sulfur for MOCS2A thiocarboxylation. Core MF. Supporting Evidence: PMID:15073332 Mutation of the putative persulfide-forming active-site cysteine residue C412 abolished the sulfurtransferase activity of MOCS3-RLD completely |
| GO:0016783 sulfurtransferase activity | IMP PMID:17459099 Site-directed mutagenesis of the active site loop of the rho... | KEEP AS NON CORE | Summary: Active-site loop mutagenesis of the MOCS3 rhodanese domain characterizes its sulfurtransferase activity, but this general term is superseded by the specific molybdopterin-synthase sulfurtransferase activity (GO:0061604). Proposed replacements: molybdopterin-synthase sulfurtransferase activity Supporting Evidence: PMID:17459099 the charge of the last amino acid determines thiosulfate sulfurtransferase activity |
| GO:0061604 molybdopterin-synthase sulfurtransferase activity | IDA PMID:15073332 Evidence for the physiological role of a rhodanese-like prot... | ACCEPT | Summary: Direct in-vitro demonstration that sulfurated MOCS3-RLD provides sulfur for MOCS2A thiocarboxylation. Core MF. Supporting Evidence: PMID:15073332 the sulfurated form of MOCS3-RLD was able to provide the sulfur for the thiocarboxylation of MOCS2A |
| GO:0005515 protein binding | IPI PMID:23593335 The L-cysteine desulfurase NFS1 is localized in the cytosol ... | MARK AS OVER ANNOTATED | Summary: IntAct/UniProt-curated interaction with NFS1 (Q9Y697), the cytosolic sulfur donor, via the MOCS3 rhodanese-like domain. Bare "protein binding" is uninformative; the functional relationship (NFS1 as sulfur donor) is captured in the sulfurtransferase MF and Moco/tRNA BP terms. |
| GO:0006777 Mo-molybdopterin cofactor biosynthetic process | IMP PMID:30817134 Analysis of the Cellular Roles of MOCS3 Identifies a MOCS3-I... | ACCEPT | Summary: CRISPR MOCS3 knockout in HEK293T cells abolishes sulfite oxidase activity due to absence of Moco, demonstrating an essential in-vivo role in Moco biosynthesis. Core BP. Supporting Evidence: PMID:30817134 sulfite oxidase activity was almost completely abolished, on the basis of the absence of Moco in these cells |
| GO:0034227 tRNA thio-modification | IMP PMID:30817134 Analysis of the Cellular Roles of MOCS3 Identifies a MOCS3-I... | ACCEPT | Summary: In the MOCS3 knockout, mcm5s2U thio-modified tRNAs are undetectable, showing MOCS3 is required for cytosolic tRNA thio-modification. Core BP. Supporting Evidence: PMID:30817134 mcm5s2U thio-modified tRNAs were not detectable |
| GO:0005829 cytosol | TAS Reactome:R-HSA-947514 | ACCEPT | Summary: Reactome traceable-author statement for the cytosolic NFS1-to-MOCS3 sulfur transfer reaction. Consistent with the experimentally established cytosolic localization. Supporting Evidence: file:human/MOCS3/MOCS3-uniprot.txt Cytoplasm, cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-947538 | ACCEPT | Summary: Reactome traceable-author statement for the cytosolic MOCS3-to-MOCS2A sulfur transfer reaction. Consistent with the experimentally established cytosolic localization. Supporting Evidence: file:human/MOCS3/MOCS3-uniprot.txt Cytoplasm, cytosol |
| GO:0016783 sulfurtransferase activity | IDA PMID:18650437 A novel role for human Nfs1 in the cytoplasm: Nfs1 acts as a... | KEEP AS NON CORE | Summary: Direct evidence for the rhodanese-domain sulfurtransferase activity; superseded by the specific molybdopterin-synthase sulfurtransferase activity (GO:0061604) as core. Proposed replacements: molybdopterin-synthase sulfurtransferase activity Supporting Evidence: PMID:18650437 the subsequent generation of a thiocarboxylate group at the C terminus of MOCS2A by its C-terminal rhodanese-like domain (RLD) |
| GO:0002098 tRNA wobble uridine modification | IDA PMID:19017811 A functional proteomics approach links the ubiquitin-related... | KEEP AS NON CORE | Summary: Direct evidence linking the URM1 pathway (activated by MOCS3) to tRNA modification. Broader parent of tRNA wobble position uridine thiolation (GO:0002143), which is the more specific core term. Proposed replacements: tRNA wobble position uridine thiolation Supporting Evidence: PMID:19017811 an enzymatic activity that links Urm1 to a tRNA modification pathway |
| GO:0005515 protein binding | IPI PMID:18650437 A novel role for human Nfs1 in the cytoplasm: Nfs1 acts as a... | MARK AS OVER ANNOTATED | Summary: IntAct/UniProt-curated interaction with NFS1 (Q9Y697), the sulfur donor that interacts specifically with the MOCS3 rhodanese-like domain. Bare "protein binding" is uninformative; the specific MF/BP terms capture the biology. |
| GO:0005829 cytosol | IDA PMID:15073332 Evidence for the physiological role of a rhodanese-like prot... | ACCEPT | Summary: MOCS3 and the MPT synthase subunits are localized in the cytosol, unlike most mammalian rhodaneses which are mitochondrial. Core CC. Supporting Evidence: PMID:15073332 MOCS3 in addition to the subunits of MPT synthase are localized in the cytosol |
| GO:0006777 Mo-molybdopterin cofactor biosynthetic process | IDA PMID:15073332 Evidence for the physiological role of a rhodanese-like prot... | ACCEPT | Summary: Establishes the physiological role of MOCS3 in human molybdenum cofactor biosynthesis. Core BP. Supporting Evidence: PMID:15073332 the physiological role of a rhodanese-like protein for the biosynthesis of the molybdenum cofactor in humans |
| GO:0016779 nucleotidyltransferase activity | IDA PMID:19017811 A functional proteomics approach links the ubiquitin-related... | KEEP AS NON CORE | Summary: Correct but general parent of molybdopterin-synthase adenylyltransferase activity (GO:0061605); the specific child is the core MF. Proposed replacements: molybdopterin-synthase adenylyltransferase activity Supporting Evidence: PMID:19017811 Urm1 is activated by an unusual mechanism to yield a thiocarboxylate intermediate |
| GO:0016783 sulfurtransferase activity | IDA PMID:19017811 A functional proteomics approach links the ubiquitin-related... | KEEP AS NON CORE | Summary: Direct evidence for the sulfur-transfer step generating the URM1 thiocarboxylate; superseded by the specific molybdopterin-synthase sulfurtransferase activity (GO:0061604) as core. Proposed replacements: molybdopterin-synthase sulfurtransferase activity Supporting Evidence: PMID:19017811 Urm1 is activated by an unusual mechanism to yield a thiocarboxylate intermediate that serves as sulfur donor in tRNA thiolation reactions |
| GO:0034227 tRNA thio-modification | IDA PMID:19017811 A functional proteomics approach links the ubiquitin-related... | ACCEPT | Summary: Direct evidence that the URM1 thiocarboxylate (formed by MOCS3) serves as sulfur donor for tRNA thiolation. Core BP. Supporting Evidence: PMID:19017811 a thiocarboxylate intermediate that serves as sulfur donor in tRNA thiolation reactions |
| GO:0042292 URM1 activating enzyme activity | IDA PMID:19017811 A functional proteomics approach links the ubiquitin-related... | ACCEPT | Summary: Direct evidence that MOCS3 activates URM1 to its thiocarboxylate form. Core MF for the tRNA-thiolation branch. Supporting Evidence: PMID:19017811 Urm1 is activated by an unusual mechanism to yield a thiocarboxylate intermediate |
| GO:0016783 sulfurtransferase activity | IDA PMID:15910006 Molybdenum cofactor biosynthesis in humans: identification o... | KEEP AS NON CORE | Summary: Mass spectrometry directly identifies the catalytic persulfide on Cys412 of the MOCS3 rhodanese domain, the chemical basis of its sulfurtransferase activity; superseded by the specific term GO:0061604 as core. Proposed replacements: molybdopterin-synthase sulfurtransferase activity Supporting Evidence: PMID:15910006 direct evidence for the formation of a persulfide group that is exclusively formed on C412 |
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Download this section (compressed HTML)Q: What reductant regenerates oxidized MOCS3 (resolving the transient Cys316-Cys324 disulfide) between catalytic cycles in vivo? Reactome notes this reducing agent is unknown.
Q: Are the Moco-biosynthesis and tRNA-thiolation branches of MOCS3 differentially regulated or competitively partitioned in cells, and does substrate (MOCS2A vs URM1) availability control flux?
Experiment: Quantitatively partition MOCS3 activity between the MOCS2A (Moco) and URM1 (tRNA thiolation) branches in the MOCS3-knockout HEK293T background by add-back of catalytic (Cys412) and adenylation (Cys239/ACT_SITE) point mutants, measuring both sulfite oxidase activity and mcm5s2U tRNA levels.
Experiment: Test the physiological relevance and functional consequence of the MOCS3-ATXN1/TARDBP high-throughput interactions with orthogonal co-IP/proximity assays in relevant cell types, to determine whether they reflect genuine function or interactome noise.
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