UMPS

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004588 orotate phosphoribosyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: Orotate phosphoribosyltransferase (OPRT, EC 2.4.2.10) is one of the two defining catalytic activities of UMPS, residing in its N-terminal domain and condensing orotate with PRPP to form OMP. This IBA phylogenetic annotation is well supported across the family and corroborated by direct human experimental evidence. Reason: This is a core molecular function of UMPS, supported experimentally in human and consistent with the phylogenetic inference. Supporting Evidence: PMID:9042911 Uridine monophosphate (UMP) synthase is a bifunctional enzyme catalyzing the last two steps of de novo pyrimidine biosynthesis, orotate phosphoribosyltransferase (OPRT) and orotidine-5'-monophosphate decarboxylase (ODC)
GO:0004590 orotidine-5'-phosphate decarboxylase activity	IBA GO_REF:0000033	ACCEPT	Summary: Orotidine-5'-phosphate decarboxylase (ODC / OMPdecase, EC 4.1.1.23) is the second defining catalytic activity of UMPS, in its C-terminal domain, decarboxylating OMP to UMP. This IBA annotation is well supported and corroborated by direct human structural and enzymatic evidence. Reason: Core molecular function of UMPS, supported experimentally in human and consistent with the phylogenetic inference. Supporting Evidence: PMID:18184586 The C-terminal domain of UMPS is orotidine-5'-monophosphate decarboxylase (OMPD), a cofactor-less yet extremely efficient enzyme
GO:0006222 UMP biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: UMPS produces UMP as the end product of the two reactions it catalyzes, so involvement in UMP biosynthetic process is a core biological-process annotation. The IBA inference is consistent with the experimental human data. Reason: UMP is the direct product of the ODC step catalyzed by UMPS; this BP directly captures the pathway role. Supporting Evidence: PMID:6893554 the last two enzyme activities of de novo UMP biosynthesis occur on a single polypeptide chain of approximately 51500 daltons
GO:0019856 pyrimidine nucleobase biosynthetic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: A broad grouping term covering pyrimidine nucleobase biosynthesis. It is not incorrect for UMPS (OPRT consumes the pyrimidine nucleobase orotate), but it is less specific than the UMP / de novo UMP biosynthetic-process terms that capture the actual pathway role. Reason: Correct but general; the more specific 'de novo' UMP biosynthetic process (GO:0044205) and UMP biosynthetic process (GO:0006222) better represent the core function. Supporting Evidence: PMID:9042911 Uridine monophosphate (UMP) synthase is a bifunctional enzyme catalyzing the last two steps of de novo pyrimidine biosynthesis
GO:0004588 orotate phosphoribosyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: IEA support (ARBA/RHEA/EC 2.4.2.10) for the OPRT activity, matching the experimentally and phylogenetically supported core function. Reason: Correct MF mapping to the OPRT activity, redundant with the IDA/IBA annotations. Supporting Evidence: PMID:9042911 orotate phosphoribosyltransferase (OPRT) and orotidine-5'-monophosphate decarboxylase (ODC)
GO:0004590 orotidine-5'-phosphate decarboxylase activity	IEA GO_REF:0000120	ACCEPT	Summary: IEA support (ARBA/RHEA/EC 4.1.1.23) for the ODC activity, matching the experimentally and phylogenetically supported core function. Reason: Correct MF mapping to the ODC activity, redundant with the IDA/IBA annotations. Supporting Evidence: PMID:18184586 The C-terminal domain of UMPS is orotidine-5'-monophosphate decarboxylase (OMPD)
GO:0006207 'de novo' pyrimidine nucleobase biosynthetic process	IEA GO_REF:0000002	ACCEPT	Summary: UMPS catalyzes the last two steps of de novo pyrimidine biosynthesis, so this de novo pyrimidine biosynthesis term is correct, if slightly broader than the UMP-specific terms. Reason: Accurate representation of the de novo pyrimidine pathway role; a legitimate parent of the UMP-specific process terms. Supporting Evidence: PMID:18184586 UMP synthase (UMPS) catalyzes the last two steps of de novo pyrimidine nucleotide synthesis
GO:0006221 pyrimidine nucleotide biosynthetic process	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: A broad grouping term for pyrimidine nucleotide biosynthesis. Correct in that UMPS produces the pyrimidine nucleotide UMP, but less specific than the UMP / de novo UMP terms. Reason: Correct but general; retained as non-core in favor of the more specific UMP biosynthetic process terms. Supporting Evidence: PMID:18184586 UMP synthase (UMPS) catalyzes the last two steps of de novo pyrimidine nucleotide synthesis
GO:0006222 UMP biosynthetic process	IEA GO_REF:0000117	ACCEPT	Summary: IEA (ARBA) support for UMP biosynthetic process, matching the core biological-process role of producing UMP. Reason: Correct BP mapping, redundant with the IBA/IDA UMP-biosynthesis annotations. Supporting Evidence: PMID:6893554 the last two enzyme activities of de novo UMP biosynthesis occur on a single polypeptide chain
GO:0044205 'de novo' UMP biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: The most specific and accurate biological-process term for UMPS: it carries out the final two steps of the de novo UMP biosynthetic pathway (orotate -> OMP -> UMP). Supported by UniPathway UPA00070 and experimental data. Reason: Best-fitting, most specific BP term for the core function; captures both the pathway (de novo UMP biosynthesis) and the terminal product (UMP). Supporting Evidence: PMID:9042911 Uridine monophosphate (UMP) synthase is a bifunctional enzyme catalyzing the last two steps of de novo pyrimidine biosynthesis
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: A high-throughput affinity-purification/mass-spectrometry interaction (BioPlex 2.0) reporting a binding partner (UniProtKB:P54764, EPHA4). The bare 'protein binding' term is uninformative about UMPS function and reflects a proteome-scale screen rather than a characterized functional interaction of the enzyme. Reason: Uninformative 'protein binding' term from a proteome-scale interactome screen; retained but flagged as over-annotation per curation policy (bare protein binding not removed). Supporting Evidence: PMID:28514442 BioPlex 2.0 (Biophysical Interactions of ORFeome-derived complexes), which uses robust affinity purification-mass spectrometry methodology
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: A second high-throughput AP-MS interactome dataset (BioPlex 3.0) again reporting binding to UniProtKB:P54764 (EPHA4). As above, the bare 'protein binding' term is uninformative about the molecular function of UMPS. Reason: Uninformative 'protein binding' term from a proteome-scale interactome screen; retained but flagged as over-annotation per curation policy. Supporting Evidence: PMID:33961781 we have created two proteome-scale, cell-line-specific interaction networks
GO:0006225 UDP biosynthetic process	IEA GO_REF:0000107	REMOVE	Summary: UDP biosynthesis is downstream of UMPS. UMPS produces UMP; conversion of UMP to UDP is carried out by a separate enzyme (UMP-CMP kinase). This annotation is an electronic ortholog transfer (Ensembl Compara, GO_REF:0000107) that mis-states the enzymatic product. Reason: Over-propagated IEA inference. The direct catalytic product of UMPS is UMP, not UDP; UDP is made by downstream kinases. This mapping is refutable on biochemical grounds. Per policy, REMOVE is appropriate for a demonstrably wrong electronic (IEA) inference. Supporting Evidence: PMID:9042911 Uridine monophosphate (UMP) synthase is a bifunctional enzyme catalyzing the last two steps of de novo pyrimidine biosynthesis, orotate phosphoribosyltransferase (OPRT) and orotidine-5'-monophosphate decarboxylase (ODC)
GO:0044210 'de novo' CTP biosynthetic process	IEA GO_REF:0000107	REMOVE	Summary: CTP biosynthesis is several enzymatic steps downstream of UMPS (UMP -> UDP -> UTP -> CTP). UMPS itself produces only UMP. This is an Ensembl Compara ortholog-transfer IEA that mis-states the pathway product. Reason: Over-propagated IEA inference. UMPS does not catalyze any step of CTP synthesis; its product is UMP. Refutable on biochemical grounds, so REMOVE is appropriate for this wrong electronic inference. Supporting Evidence: PMID:6893554 the last two enzyme activities of de novo UMP biosynthesis occur on a single polypeptide chain of approximately 51500 daltons
GO:0004588 orotate phosphoribosyltransferase activity	IDA PMID:9042911 Molecular cloning of the human UMP synthase gene and charact...	ACCEPT	Summary: Direct experimental evidence (cloning and characterization of the human UMP synthase gene; ORAC1 variants shown to reduce OPRT activity) supports the OPRT molecular function. Reason: Direct human experimental evidence for the OPRT activity; a core molecular function. ORAC1 variants reduce this activity. Supporting Evidence: PMID:9042911 orotate phosphoribosyltransferase (OPRT) and orotidine-5'-monophosphate decarboxylase (ODC)
GO:0004590 orotidine-5'-phosphate decarboxylase activity	IDA PMID:18184586 Structures of the human orotidine-5'-monophosphate decarboxy...	ACCEPT	Summary: Nine crystal structures of the human OMP decarboxylase domain with substrate/product/inhibitors, kinetics (KM for OMP), and the D312N loss-of-activity mutant directly establish the ODC activity. Reason: Direct human structural and enzymatic evidence for the ODC activity; a core molecular function. Supporting Evidence: PMID:18184586 The C-terminal domain of UMPS is orotidine-5'-monophosphate decarboxylase (OMPD), a cofactor-less yet extremely efficient enzyme
GO:0004590 orotidine-5'-phosphate decarboxylase activity	IDA PMID:9042911 Molecular cloning of the human UMP synthase gene and charact...	ACCEPT	Summary: Direct experimental evidence from characterization of the human UMP synthase gene, including ORAC1 variants that reduce ODC activity, supports the ODC molecular function. Reason: Direct human experimental evidence for the ODC activity; a core molecular function. Supporting Evidence: PMID:9042911 orotate phosphoribosyltransferase (OPRT) and orotidine-5'-monophosphate decarboxylase (ODC)
GO:0006222 UMP biosynthetic process	IDA PMID:18184586 Structures of the human orotidine-5'-monophosphate decarboxy...	ACCEPT	Summary: The decarboxylation of OMP by UMPS yields UMP, the terminal product of the de novo pyrimidine pathway; structural/enzymatic characterization directly supports involvement in UMP biosynthesis. Reason: Direct experimental support for the core UMP-biosynthesis process role. Supporting Evidence: PMID:18184586 UMP synthase (UMPS) catalyzes the last two steps of de novo pyrimidine nucleotide synthesis
GO:0006222 UMP biosynthetic process	IDA PMID:9042911 Molecular cloning of the human UMP synthase gene and charact...	ACCEPT	Summary: Characterization of the human enzyme and disease variants demonstrates its role in producing UMP via the last two de novo pyrimidine biosynthesis steps. Reason: Direct human experimental support for the core UMP-biosynthesis process role. Supporting Evidence: PMID:9042911 Uridine monophosphate (UMP) synthase is a bifunctional enzyme catalyzing the last two steps of de novo pyrimidine biosynthesis
GO:0005829 cytosol	TAS Reactome:R-HSA-73564	ACCEPT	Summary: UMPS acts in the cytosol; the Reactome-traceable decarboxylation reaction (OMP -> UMP) is annotated to the cytosol. This is the primary subcellular location of the enzyme's catalysis. Reason: Correct core cellular-component annotation; UMPS is a cytosolic enzyme. Supporting Evidence: PMID:15890648 UMP synthase, the bifunctional protein that catalyzes the last two steps in the pathway, was also found in both the cytoplasm and nucleus
GO:0005829 cytosol	TAS Reactome:R-HSA-73567	ACCEPT	Summary: Reactome-traceable OPRT reaction (orotate + PRPP -> OMP) is annotated to the cytosol, consistent with UMPS being a cytosolic enzyme. Reason: Correct core cellular-component annotation; UMPS acts in the cytosol. Supporting Evidence: PMID:15890648 UMP synthase, the bifunctional protein that catalyzes the last two steps in the pathway, was also found in both the cytoplasm and nucleus
GO:0004588 orotate phosphoribosyltransferase activity	IDA PMID:11730338 A nonradioactive high-performance liquid chromatographic mic...	ACCEPT	Summary: An HPLC microassay directly measured the OPRT activity of UMP synthase, confirming the OPRT molecular function. Reason: Direct experimental measurement of the OPRT activity; a core molecular function. Supporting Evidence: PMID:11730338 the two enzymatic activities of orotate phosphoribosyltransferase (OPRTase) and orotidine 5'-monophosphate decarboxylase (ODCase), either as a bifunctional protein (uridine 5'-monophosphate synthase, UMPS)
GO:0004588 orotate phosphoribosyltransferase activity	IDA PMID:6893554 Isolation and initial characterization of the single polypep...	ACCEPT	Summary: Purification to homogeneity of the single UMP synthase polypeptide demonstrated it carries both OPRT and ODC active centers, directly supporting the OPRT activity. Reason: Direct biochemical evidence for the OPRT activity on the purified enzyme; a core function. Supporting Evidence: PMID:6893554 UMP synthase, or multienzyme pyr-5,6 (orotate phosphoribosyltransferase:orotidine monophosphate decarboxylase), has been purified from Ehrlich ascites carcinoma to apparent homogeneity
GO:0004590 orotidine-5'-phosphate decarboxylase activity	IDA PMID:11730338 A nonradioactive high-performance liquid chromatographic mic...	ACCEPT	Summary: The same HPLC microassay directly measured the ODC (ODCase) activity of UMP synthase, confirming the ODC molecular function. Reason: Direct experimental measurement of the ODC activity; a core molecular function. Supporting Evidence: PMID:11730338 the two enzymatic activities of orotate phosphoribosyltransferase (OPRTase) and orotidine 5'-monophosphate decarboxylase (ODCase), either as a bifunctional protein (uridine 5'-monophosphate synthase, UMPS)
GO:0004590 orotidine-5'-phosphate decarboxylase activity	IDA PMID:6893554 Isolation and initial characterization of the single polypep...	ACCEPT	Summary: The purified single polypeptide of UMP synthase was shown to contain both active centers, directly supporting the ODC activity. Reason: Direct biochemical evidence for the ODC activity on the purified enzyme; a core function. Supporting Evidence: PMID:6893554 Both forms have the same molecular weight of 51500 and contain both active centers
GO:0005634 nucleus	IDA PMID:15890648 Nuclear localization and mitogen-activated protein kinase ph...	KEEP AS NON CORE	Summary: A minor nuclear pool of UMP synthase was observed alongside the multifunctional CAD protein. However, the enzyme is predominantly cytosolic and the de novo pyrimidine reactions it catalyzes occur in the cytosol; the nuclear pool is a secondary/non-core localization. Reason: Experimentally observed but minor localization; not the primary site of UMPS catalysis. Retained as a non-core cellular-component annotation rather than removed. Supporting Evidence: PMID:15890648 UMP synthase, the bifunctional protein that catalyzes the last two steps in the pathway, was also found in both the cytoplasm and nucleus
GO:0005737 cytoplasm	IDA PMID:15890648 Nuclear localization and mitogen-activated protein kinase ph...	ACCEPT	Summary: UMP synthase was found in the cytoplasm, consistent with its established cytosolic role in de novo pyrimidine biosynthesis. Reason: Correct cellular-component annotation; the cytoplasm/cytosol is the primary site of UMPS function. Supporting Evidence: PMID:15890648 UMP synthase, the bifunctional protein that catalyzes the last two steps in the pathway, was also found in both the cytoplasm and nucleus
GO:0006222 UMP biosynthetic process	IDA PMID:11730338 A nonradioactive high-performance liquid chromatographic mic...	ACCEPT	Summary: The assay quantifies UMP as the product of the coupled OPRT + ODC reactions of UMP synthase, directly supporting involvement in UMP biosynthesis. Reason: Direct experimental support for the core UMP-biosynthesis process role. Supporting Evidence: PMID:11730338 Substrates (orotate for OPRTase or orotidine 5'-monophosphate for ODCase) and a product (UMP) of the enzymatic assay
GO:0006222 UMP biosynthetic process	IDA PMID:6893554 Isolation and initial characterization of the single polypep...	ACCEPT	Summary: Purification of the single polypeptide that synthesizes UMP from orotate directly demonstrates involvement in UMP biosynthesis (the last two steps of de novo UMP biosynthesis). Reason: Direct biochemical support for the core UMP-biosynthesis process role. Supporting Evidence: PMID:6893554 the last two enzyme activities of de novo UMP biosynthesis occur on a single polypeptide chain of approximately 51500 daltons

Gene Description

Existing Annotations Review

Core Functions

Orotate phosphoribosyltransferase (OPRT): converts orotate + PRPP to orotidine-5'-monophosphate (OMP), the first of the two terminal steps of de novo UMP biosynthesis.

Orotidine-5'-phosphate decarboxylase (ODC / OMP decarboxylase): decarboxylates OMP to uridine monophosphate (UMP), the terminal step of de novo UMP biosynthesis.

References

📚 Additional Documentation

Notes

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