MOCS2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred cytosolic localization. Consistent with direct experimental evidence that the human MPT synthase subunits are cytosolic. Reason: IBA cytosol is corroborated by IDA evidence for cytosolic localization of the MPT synthase machinery in humans, so the phylogenetic inference is sound. Supporting Evidence: PMID:15073332 MOCS3 in addition to the subunits of MPT synthase are localized in the cytosol.
GO:0005634 nucleus	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Electronic (UniProt-SubCell) nuclear localization. UniProt lists Nucleus as a secondary location, associated with the moonlighting PKR/ATAC role reported in PubMed:26705305 rather than the core cytosolic MoCo-biosynthesis function. Reason: Nuclear localization is experimentally reported (IDA in PubMed:26705305) and tied to the secondary PKR/translation-regulation role, not the core molybdopterin synthase activity, which is cytosolic.
GO:0005829 cytosol	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assignment of cytosolic localization (InterPro/UniRule). Correct and consistent with experimental data. Reason: Redundant with the IDA cytosol annotations but accurate; cytosol is the established site of MPT synthase in humans.
GO:0006777 Mo-molybdopterin cofactor biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assignment of the core biological process. Accurate: MOCS2B catalyzes the second (sulfur-insertion) step of MoCo biosynthesis. Reason: This is the core biological process; also supported by multiple experimental IDA annotations.
GO:0030366 molybdopterin synthase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assignment of the core catalytic activity (mapped from EC 2.8.1.12 / RHEA:26333). Accurate and corroborated experimentally. Reason: This is the core molecular function of MOCS2B; strongly supported by direct experimental evidence.
GO:0032324 molybdopterin cofactor biosynthetic process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ARBA electronic annotation to a broader molybdopterin-cofactor biosynthesis term. Not wrong, but less specific than the co-annotated GO:0006777 Mo-molybdopterin cofactor biosynthetic process. Reason: Redundant with and less precise than GO:0006777; retained as a valid but non-core, higher-level process annotation.
GO:1990140 molybdopterin synthase complex	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assignment of the molybdopterin synthase complex. Accurate: MOCS2B is the large catalytic subunit of the (MOCS2A)2(MOCS2B)2 heterotetramer. Reason: Core cellular component; also supported by experimental IDA/IPI evidence.
GO:0005515 protein binding	IPI PMID:12732628 Mechanistic studies of human molybdopterin synthase reaction...	MARK AS OVER ANNOTATED	Summary: IPI protein-binding annotation against MOCS2A (O96033). This captures the MOCS2B-MOCS2A subunit interaction within MPT synthase, but the bare protein-binding term is uninformative; the specific interaction is already represented by the molybdopterin synthase complex CC. Reason: Bare protein binding conveys no functional specificity; the biologically meaningful interaction (MOCS2B with the sulfur-carrier subunit MOCS2A) is captured by GO:1990140 molybdopterin synthase complex.
GO:0005515 protein binding	IPI PMID:16021469 Ten novel mutations in the molybdenum cofactor genes MOCS1 a...	MARK AS OVER ANNOTATED	Summary: IPI protein-binding annotation against MOCS2A (O96033), from the paper showing a MOCS2B variant abolishes binding of both precursor Z and MOCS2A. Same subunit-subunit interaction; bare protein binding is uninformative. Reason: Uninformative bare protein-binding term; the specific MOCS2B-MOCS2A interaction is captured by the molybdopterin synthase complex CC.
GO:0030366 molybdopterin synthase activity	TAS Reactome:R-HSA-947541	ACCEPT	Summary: Reactome traceable-author-statement for the core catalytic activity (sulfhydrylation and ring cleavage of precursor Z by the MOCS2B half of the tetramer). Accurate. Reason: Reactome pathway annotation of the core molybdopterin synthase activity; consistent with experimental evidence.
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: HPA immunofluorescence IDA for cytosolic localization. Consistent with the established cytosolic site of MPT synthase. Reason: Direct immunofluorescence evidence for the core subcellular location.
GO:0005829 cytosol	IDA PMID:26705305 Moco biosynthesis and the ATAC acetyltransferase engage tran...	ACCEPT	Summary: IDA cytosolic localization from the PKR/ATAC study. Consistent with the core cytosolic location of MPT synthase. Reason: Direct experimental evidence for cytosolic localization.
GO:0005515 protein binding	IPI PMID:26705305 Moco biosynthesis and the ATAC acetyltransferase engage tran...	MARK AS OVER ANNOTATED	Summary: IPI protein-binding annotation against EIF2AK2/PKR (Q9NS73), from the study showing MPT synthase and ATAC bind and inhibit PKR. Real interaction but the bare protein-binding term is uninformative; the functional consequence is captured by GO:0009968. Reason: Bare protein binding is uninformative; the biologically relevant PKR interaction and its consequence are represented by the negative-regulation-of-signal-transduction annotation.
GO:0005634 nucleus	IDA PMID:26705305 Moco biosynthesis and the ATAC acetyltransferase engage tran...	KEEP AS NON CORE	Summary: IDA nuclear localization from the PKR/ATAC study, reflecting the moonlighting role of MPT synthase with the (nuclear/cytoplasmic) ATAC complex rather than its core cytosolic biosynthetic function. Reason: Experimentally supported secondary location associated with the moonlighting PKR role; the core catalytic function occurs in the cytosol.
GO:0009968 negative regulation of signal transduction	IDA PMID:26705305 Moco biosynthesis and the ATAC acetyltransferase engage tran...	KEEP AS NON CORE	Summary: IDA for a moonlighting role: human MPT synthase and ATAC directly interact with PKR and suppress its latent autophosphorylation and downstream JNK/eIF2-alpha phosphorylation, modulating stress signaling and translation initiation. Reason: A genuine, experimentally supported secondary/moonlighting activity distinct from the core molybdopterin synthase function; retained as non-core. Supporting Evidence: PMID:26705305 MPT synthase and ATAC directly interacted with PKR and suppressed latent autophosphorylation of PKR and its downstream phosphorylation of JNK and eukaryotic initiation factor 2α (eIF2α).
GO:0005515 protein binding	IPI PMID:25709896 Investigation of molybdenum cofactor deficiency due to MOCS2...	MARK AS OVER ANNOTATED	Summary: IPI protein-binding annotation against MOCS2A (O96033) from the human recombinant study (ITC measured MOCS2B-MOCS2A Kd = 0.36 uM). Same subunit interaction; bare protein binding is uninformative. Reason: Uninformative bare protein-binding term; the MOCS2B-MOCS2A interaction is captured by GO:1990140 molybdopterin synthase complex.
GO:0006777 Mo-molybdopterin cofactor biosynthetic process	IDA PMID:25709896 Investigation of molybdenum cofactor deficiency due to MOCS2...	ACCEPT	Summary: IDA for the core biological process, from human recombinant assays showing WT MOCS2B supports MPT synthesis whereas the disease variant S140F does not. Reason: Direct experimental support for MOCS2B involvement in Mo-molybdopterin cofactor biosynthesis; this is a core annotation. Supporting Evidence: PMID:25709896 While WT MOCS2B showed an effective MPT synthesis (determined by the oxidation product FormA, Fig. 2E), MOCS2B-S140F was only able to produce low levels of MPT at high concentrations of MOCS2A.
GO:0030366 molybdopterin synthase activity	IDA PMID:25709896 Investigation of molybdenum cofactor deficiency due to MOCS2...	ACCEPT	Summary: IDA for the core catalytic activity, from human recombinant MPT synthesis assays (WT MOCS2B produces MPT; the S140F variant does not). Reason: Direct experimental evidence that MOCS2B enables molybdopterin synthase activity; core molecular function. Supporting Evidence: PMID:25709896 While WT MOCS2B showed an effective MPT synthesis (determined by the oxidation product FormA, Fig. 2E), MOCS2B-S140F was only able to produce low levels of MPT at high concentrations of MOCS2A.
GO:1990140 molybdopterin synthase complex	IDA PMID:25709896 Investigation of molybdenum cofactor deficiency due to MOCS2...	ACCEPT	Summary: IDA for the molybdopterin synthase complex, from the human recombinant study that identified MOCS2B in the MPT synthase complex and measured MOCS2B-MOCS2A binding. Reason: Direct experimental evidence that MOCS2B is a component of the molybdopterin synthase complex; core cellular component. Supporting Evidence: PMID:25709896 Note that WT MOCS2B binds MOCS2A with a Kd = 0.36 ± 0.047 μM (Fig. 2C).
GO:0006777 Mo-molybdopterin cofactor biosynthetic process	IDA PMID:16021469 Ten novel mutations in the molybdenum cofactor genes MOCS1 a...	ACCEPT	Summary: ComplexPortal IDA for the core biological process, based on characterization of a MOCS2B variant that abolishes binding of precursor Z and MOCS2A. Reason: Supports MOCS2B involvement in Mo-molybdopterin cofactor biosynthesis; core annotation. Supporting Evidence: PMID:16021469 The mutation was expressed in vitro and was found to abolish the binding affinities of the large subunit of molybdopterin synthase (MOCS2B) for both precursor Z and the small subunit of molybdopterin synthase (MOCS2A).
GO:1990140 molybdopterin synthase complex	IPI PMID:16021469 Ten novel mutations in the molybdenum cofactor genes MOCS1 a...	ACCEPT	Summary: ComplexPortal IPI for the molybdopterin synthase complex, based on the demonstrated MOCS2B-MOCS2A binding (and its loss in the disease variant). Reason: Experimental evidence that MOCS2B is part of the molybdopterin synthase complex; core cellular component. Supporting Evidence: PMID:16021469 The mutation was expressed in vitro and was found to abolish the binding affinities of the large subunit of molybdopterin synthase (MOCS2B) for both precursor Z and the small subunit of molybdopterin synthase (MOCS2A).
GO:0030366 molybdopterin synthase activity	IDA PMID:12732628 Mechanistic studies of human molybdopterin synthase reaction...	ACCEPT	Summary: IDA (contributes_to) for the core catalytic activity. Appropriate qualifier: full molybdopterin synthase activity requires the MOCS2A-MOCS2B heterotetramer, so MOCS2B contributes to the complex activity. Reason: Correct core molecular-function annotation with the appropriate contributes_to qualifier for a multi-subunit enzyme. Supporting Evidence: PMID:12732628 MOCS2A and MOCS2B were purified after heterologous expression in E. coli, and the separately purified subunits readily assemble into a functional MPT synthase tetramer.
GO:0030366 molybdopterin synthase activity	IDA PMID:15073332 Evidence for the physiological role of a rhodanese-like prot...	ACCEPT	Summary: IDA (contributes_to) for the core catalytic activity, from the in vitro MPT generation system in which sulfurated MOCS3 provides sulfur to MOCS2A for MPT synthesis by MPT synthase. Reason: Correct core molecular-function annotation with the appropriate contributes_to qualifier. Supporting Evidence: PMID:15073332 the sulfurated form of MOCS3-RLD was able to provide the sulfur for the thiocarboxylation of MOCS2A, the small MPT synthase subunit in humans.
GO:0032324 molybdopterin cofactor biosynthetic process	TAS Reactome:R-HSA-947581	KEEP AS NON CORE	Summary: Reactome TAS to the broader molybdopterin-cofactor biosynthesis term. Valid but less specific than GO:0006777. Reason: Higher-level, less precise process term relative to GO:0006777; retained as non-core.
GO:0005829 cytosol	TAS Reactome:R-HSA-947541	ACCEPT	Summary: Reactome TAS for cytosolic localization. Consistent with the established cytosolic site of MPT synthase. Reason: Accurate core subcellular localization.
GO:0005829 cytosol	IDA PMID:15073332 Evidence for the physiological role of a rhodanese-like prot...	ACCEPT	Summary: IDA cytosolic localization, from the study reporting that the MPT synthase subunits (with MOCS3) are localized in the cytosol. Reason: Direct experimental evidence for the core cytosolic location. 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:12732628 Mechanistic studies of human molybdopterin synthase reaction...	ACCEPT	Summary: IDA for the core biological process, from mechanistic studies of the human MPT synthase reaction and its disease mutants. Reason: Direct experimental support for MOCS2B involvement in Mo-molybdopterin cofactor biosynthesis; core annotation. Supporting Evidence: PMID:12732628 The sulfur used for the formation of the dithiolene group of MPT exists in the form of a thiocarboxylate group at the C terminus of the smaller subunit of MPT synthase.
GO:0006777 Mo-molybdopterin cofactor biosynthetic process	IDA PMID:15073332 Evidence for the physiological role of a rhodanese-like prot...	ACCEPT	Summary: IDA for the core biological process, from the in vitro reconstitution of MPT generation from precursor Z in the human system. Reason: Direct experimental support for MOCS2B involvement in Mo-molybdopterin cofactor biosynthesis; core annotation. Supporting Evidence: PMID:15073332 the sulfurated form of MOCS3-RLD was able to provide the sulfur for the thiocarboxylation of MOCS2A, the small MPT synthase subunit in humans.
GO:1990140 molybdopterin synthase complex	IPI PMID:12732628 Mechanistic studies of human molybdopterin synthase reaction...	ACCEPT	Summary: IPI for the molybdopterin synthase complex, based on the demonstration that purified MOCS2A and MOCS2B assemble into a functional MPT synthase tetramer. Reason: Experimental evidence that MOCS2B is part of the molybdopterin synthase complex; core cellular component. Supporting Evidence: PMID:12732628 the separately purified subunits readily assemble into a functional MPT synthase tetramer.

Gene Description

Existing Annotations Review

Core Functions

Catalytic (large) subunit of molybdopterin synthase, which catalyzes the second step of molybdenum cofactor biosynthesis by inserting two sulfur atoms into cyclic pyranopterin monophosphate (precursor Z) to form the dithiolene group of molybdopterin.

References

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Notes

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