id: P11172
gene_symbol: UMPS
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  UMPS is the bifunctional uridine 5'-monophosphate synthase (UMP synthase) that catalyzes the final
  two steps of the de novo pyrimidine biosynthesis pathway on a single polypeptide. Its N-terminal
  orotate phosphoribosyltransferase (OPRT; EC 2.4.2.10) activity condenses orotate with
  5-phospho-alpha-D-ribose 1-diphosphate (PRPP) to form orotidine-5'-monophosphate (OMP), and its
  C-terminal orotidine-5'-phosphate decarboxylase (ODC / OMP decarboxylase; EC 4.1.1.23) activity
  decarboxylates OMP to uridine monophosphate (UMP), the parent pyrimidine ribonucleotide from which
  all other pyrimidine nucleotides are subsequently derived. The enzyme is cytosolic and functions as
  a homodimer. Loss of either catalytic activity causes hereditary orotic aciduria (orotic aciduria 1),
  an autosomal recessive disorder presenting with megaloblastic anemia, failure to thrive, and massive
  urinary orotic acid excretion that responds to uridine supplementation.
alternative_products:
- name: '1'
  id: P11172-1
- name: '2'
  id: P11172-2
  sequence_note: VSP_009273
- name: '3'
  id: P11172-3
  sequence_note: VSP_047611
- name: '4'
  id: P11172-4
  sequence_note: VSP_009273, VSP_047612
existing_annotations:
- term:
    id: GO:0004588
    label: orotate phosphoribosyltransferase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: >-
      This is a core molecular function of UMPS, supported experimentally in human and consistent with
      the phylogenetic inference.
    supported_by:
    - reference_id: PMID:9042911
      supporting_text: >-
        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)
- term:
    id: GO:0004590
    label: orotidine-5'-phosphate decarboxylase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: >-
      Core molecular function of UMPS, supported experimentally in human and consistent with the
      phylogenetic inference.
    supported_by:
    - reference_id: PMID:18184586
      supporting_text: >-
        The C-terminal domain of UMPS is orotidine-5'-monophosphate decarboxylase (OMPD), a
        cofactor-less yet extremely efficient enzyme
- term:
    id: GO:0006222
    label: UMP biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: >-
      UMP is the direct product of the ODC step catalyzed by UMPS; this BP directly captures the
      pathway role.
    supported_by:
    - reference_id: PMID:6893554
      supporting_text: >-
        the last two enzyme activities of de novo UMP biosynthesis occur on a single polypeptide
        chain of approximately 51500 daltons
- term:
    id: GO:0019856
    label: pyrimidine nucleobase biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:9042911
      supporting_text: >-
        Uridine monophosphate (UMP) synthase is a bifunctional enzyme catalyzing the last two steps
        of de novo pyrimidine biosynthesis
- term:
    id: GO:0004588
    label: orotate phosphoribosyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      IEA support (ARBA/RHEA/EC 2.4.2.10) for the OPRT activity, matching the experimentally and
      phylogenetically supported core function.
    action: ACCEPT
    reason: Correct MF mapping to the OPRT activity, redundant with the IDA/IBA annotations.
    supported_by:
    - reference_id: PMID:9042911
      supporting_text: >-
        orotate phosphoribosyltransferase (OPRT) and orotidine-5'-monophosphate decarboxylase (ODC)
- term:
    id: GO:0004590
    label: orotidine-5'-phosphate decarboxylase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      IEA support (ARBA/RHEA/EC 4.1.1.23) for the ODC activity, matching the experimentally and
      phylogenetically supported core function.
    action: ACCEPT
    reason: Correct MF mapping to the ODC activity, redundant with the IDA/IBA annotations.
    supported_by:
    - reference_id: PMID:18184586
      supporting_text: >-
        The C-terminal domain of UMPS is orotidine-5'-monophosphate decarboxylase (OMPD)
- term:
    id: GO:0006207
    label: '''de novo'' pyrimidine nucleobase biosynthetic process'
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: >-
      Accurate representation of the de novo pyrimidine pathway role; a legitimate parent of the
      UMP-specific process terms.
    supported_by:
    - reference_id: PMID:18184586
      supporting_text: >-
        UMP synthase (UMPS) catalyzes the last two steps of de novo pyrimidine nucleotide synthesis
- term:
    id: GO:0006221
    label: pyrimidine nucleotide biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct but general; retained as non-core in favor of the more specific UMP biosynthetic
      process terms.
    supported_by:
    - reference_id: PMID:18184586
      supporting_text: >-
        UMP synthase (UMPS) catalyzes the last two steps of de novo pyrimidine nucleotide synthesis
- term:
    id: GO:0006222
    label: UMP biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      IEA (ARBA) support for UMP biosynthetic process, matching the core biological-process role of
      producing UMP.
    action: ACCEPT
    reason: Correct BP mapping, redundant with the IBA/IDA UMP-biosynthesis annotations.
    supported_by:
    - reference_id: PMID:6893554
      supporting_text: >-
        the last two enzyme activities of de novo UMP biosynthesis occur on a single polypeptide chain
- term:
    id: GO:0044205
    label: '''de novo'' UMP biosynthetic process'
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: >-
      Best-fitting, most specific BP term for the core function; captures both the pathway (de novo
      UMP biosynthesis) and the terminal product (UMP).
    supported_by:
    - reference_id: PMID:9042911
      supporting_text: >-
        Uridine monophosphate (UMP) synthase is a bifunctional enzyme catalyzing the last two steps
        of de novo pyrimidine biosynthesis
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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).
    supported_by:
    - reference_id: PMID:28514442
      supporting_text: >-
        BioPlex 2.0 (Biophysical Interactions of ORFeome-derived complexes), which uses robust
        affinity purification-mass spectrometry methodology
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative 'protein binding' term from a proteome-scale interactome screen; retained but
      flagged as over-annotation per curation policy.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: >-
        we have created two proteome-scale, cell-line-specific interaction networks
- term:
    id: GO:0006225
    label: UDP biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:9042911
      supporting_text: >-
        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)
- term:
    id: GO:0044210
    label: '''de novo'' CTP biosynthetic process'
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:6893554
      supporting_text: >-
        the last two enzyme activities of de novo UMP biosynthesis occur on a single polypeptide chain
        of approximately 51500 daltons
- term:
    id: GO:0004588
    label: orotate phosphoribosyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:9042911
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: >-
      Direct human experimental evidence for the OPRT activity; a core molecular function. ORAC1
      variants reduce this activity.
    supported_by:
    - reference_id: PMID:9042911
      supporting_text: >-
        orotate phosphoribosyltransferase (OPRT) and orotidine-5'-monophosphate decarboxylase (ODC)
- term:
    id: GO:0004590
    label: orotidine-5'-phosphate decarboxylase activity
  evidence_type: IDA
  original_reference_id: PMID:18184586
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: >-
      Direct human structural and enzymatic evidence for the ODC activity; a core molecular function.
    supported_by:
    - reference_id: PMID:18184586
      supporting_text: >-
        The C-terminal domain of UMPS is orotidine-5'-monophosphate decarboxylase (OMPD), a
        cofactor-less yet extremely efficient enzyme
- term:
    id: GO:0004590
    label: orotidine-5'-phosphate decarboxylase activity
  evidence_type: IDA
  original_reference_id: PMID:9042911
  qualifier: enables
  review:
    summary: >-
      Direct experimental evidence from characterization of the human UMP synthase gene, including
      ORAC1 variants that reduce ODC activity, supports the ODC molecular function.
    action: ACCEPT
    reason: Direct human experimental evidence for the ODC activity; a core molecular function.
    supported_by:
    - reference_id: PMID:9042911
      supporting_text: >-
        orotate phosphoribosyltransferase (OPRT) and orotidine-5'-monophosphate decarboxylase (ODC)
- term:
    id: GO:0006222
    label: UMP biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:18184586
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: Direct experimental support for the core UMP-biosynthesis process role.
    supported_by:
    - reference_id: PMID:18184586
      supporting_text: >-
        UMP synthase (UMPS) catalyzes the last two steps of de novo pyrimidine nucleotide synthesis
- term:
    id: GO:0006222
    label: UMP biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:9042911
  qualifier: involved_in
  review:
    summary: >-
      Characterization of the human enzyme and disease variants demonstrates its role in producing UMP
      via the last two de novo pyrimidine biosynthesis steps.
    action: ACCEPT
    reason: Direct human experimental support for the core UMP-biosynthesis process role.
    supported_by:
    - reference_id: PMID:9042911
      supporting_text: >-
        Uridine monophosphate (UMP) synthase is a bifunctional enzyme catalyzing the last two steps
        of de novo pyrimidine biosynthesis
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-73564
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    reason: Correct core cellular-component annotation; UMPS is a cytosolic enzyme.
    supported_by:
    - reference_id: PMID:15890648
      supporting_text: >-
        UMP synthase, the bifunctional protein that catalyzes the last two steps in the pathway, was
        also found in both the cytoplasm and nucleus
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-73567
  qualifier: located_in
  review:
    summary: >-
      Reactome-traceable OPRT reaction (orotate + PRPP -> OMP) is annotated to the cytosol,
      consistent with UMPS being a cytosolic enzyme.
    action: ACCEPT
    reason: Correct core cellular-component annotation; UMPS acts in the cytosol.
    supported_by:
    - reference_id: PMID:15890648
      supporting_text: >-
        UMP synthase, the bifunctional protein that catalyzes the last two steps in the pathway, was
        also found in both the cytoplasm and nucleus
- term:
    id: GO:0004588
    label: orotate phosphoribosyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:11730338
  qualifier: enables
  review:
    summary: >-
      An HPLC microassay directly measured the OPRT activity of UMP synthase, confirming the OPRT
      molecular function.
    action: ACCEPT
    reason: Direct experimental measurement of the OPRT activity; a core molecular function.
    supported_by:
    - reference_id: PMID:11730338
      supporting_text: >-
        the two enzymatic activities of orotate phosphoribosyltransferase (OPRTase) and orotidine
        5'-monophosphate decarboxylase (ODCase), either as a bifunctional protein (uridine
        5'-monophosphate synthase, UMPS)
- term:
    id: GO:0004588
    label: orotate phosphoribosyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:6893554
  qualifier: enables
  review:
    summary: >-
      Purification to homogeneity of the single UMP synthase polypeptide demonstrated it carries both
      OPRT and ODC active centers, directly supporting the OPRT activity.
    action: ACCEPT
    reason: Direct biochemical evidence for the OPRT activity on the purified enzyme; a core function.
    supported_by:
    - reference_id: PMID:6893554
      supporting_text: >-
        UMP synthase, or multienzyme pyr-5,6 (orotate phosphoribosyltransferase:orotidine
        monophosphate decarboxylase), has been purified from Ehrlich ascites carcinoma to apparent
        homogeneity
- term:
    id: GO:0004590
    label: orotidine-5'-phosphate decarboxylase activity
  evidence_type: IDA
  original_reference_id: PMID:11730338
  qualifier: enables
  review:
    summary: >-
      The same HPLC microassay directly measured the ODC (ODCase) activity of UMP synthase,
      confirming the ODC molecular function.
    action: ACCEPT
    reason: Direct experimental measurement of the ODC activity; a core molecular function.
    supported_by:
    - reference_id: PMID:11730338
      supporting_text: >-
        the two enzymatic activities of orotate phosphoribosyltransferase (OPRTase) and orotidine
        5'-monophosphate decarboxylase (ODCase), either as a bifunctional protein (uridine
        5'-monophosphate synthase, UMPS)
- term:
    id: GO:0004590
    label: orotidine-5'-phosphate decarboxylase activity
  evidence_type: IDA
  original_reference_id: PMID:6893554
  qualifier: enables
  review:
    summary: >-
      The purified single polypeptide of UMP synthase was shown to contain both active centers,
      directly supporting the ODC activity.
    action: ACCEPT
    reason: Direct biochemical evidence for the ODC activity on the purified enzyme; a core function.
    supported_by:
    - reference_id: PMID:6893554
      supporting_text: >-
        Both forms have the same molecular weight of 51500 and contain both active centers
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:15890648
  qualifier: located_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      Experimentally observed but minor localization; not the primary site of UMPS catalysis. Retained
      as a non-core cellular-component annotation rather than removed.
    supported_by:
    - reference_id: PMID:15890648
      supporting_text: >-
        UMP synthase, the bifunctional protein that catalyzes the last two steps in the pathway, was
        also found in both the cytoplasm and nucleus
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:15890648
  qualifier: located_in
  review:
    summary: >-
      UMP synthase was found in the cytoplasm, consistent with its established cytosolic role in de
      novo pyrimidine biosynthesis.
    action: ACCEPT
    reason: >-
      Correct cellular-component annotation; the cytoplasm/cytosol is the primary site of UMPS
      function.
    supported_by:
    - reference_id: PMID:15890648
      supporting_text: >-
        UMP synthase, the bifunctional protein that catalyzes the last two steps in the pathway, was
        also found in both the cytoplasm and nucleus
- term:
    id: GO:0006222
    label: UMP biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:11730338
  qualifier: involved_in
  review:
    summary: >-
      The assay quantifies UMP as the product of the coupled OPRT + ODC reactions of UMP synthase,
      directly supporting involvement in UMP biosynthesis.
    action: ACCEPT
    reason: Direct experimental support for the core UMP-biosynthesis process role.
    supported_by:
    - reference_id: PMID:11730338
      supporting_text: >-
        Substrates (orotate for OPRTase or orotidine 5'-monophosphate for ODCase) and a product (UMP)
        of the enzymatic assay
- term:
    id: GO:0006222
    label: UMP biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:6893554
  qualifier: involved_in
  review:
    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).
    action: ACCEPT
    reason: Direct biochemical support for the core UMP-biosynthesis process role.
    supported_by:
    - reference_id: PMID:6893554
      supporting_text: >-
        the last two enzyme activities of de novo UMP biosynthesis occur on a single polypeptide chain
        of approximately 51500 daltons
core_functions:
- description: >-
    Orotate phosphoribosyltransferase (OPRT): converts orotate + PRPP to orotidine-5'-monophosphate
    (OMP), the first of the two terminal steps of de novo UMP biosynthesis.
  molecular_function:
    id: GO:0004588
    label: orotate phosphoribosyltransferase activity
  directly_involved_in:
  - id: GO:0044205
    label: '''de novo'' UMP biosynthetic process'
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:9042911
    supporting_text: >-
      orotate phosphoribosyltransferase (OPRT) and orotidine-5'-monophosphate decarboxylase (ODC)
- description: >-
    Orotidine-5'-phosphate decarboxylase (ODC / OMP decarboxylase): decarboxylates OMP to uridine
    monophosphate (UMP), the terminal step of de novo UMP biosynthesis.
  molecular_function:
    id: GO:0004590
    label: orotidine-5'-phosphate decarboxylase activity
  directly_involved_in:
  - id: GO:0044205
    label: '''de novo'' UMP biosynthetic process'
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:18184586
    supporting_text: >-
      The C-terminal domain of UMPS is orotidine-5'-monophosphate decarboxylase (OMPD), a
      cofactor-less yet extremely efficient enzyme
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:11730338
  title: A nonradioactive high-performance liquid chromatographic microassay for uridine
    5'-monophosphate synthase, orotate phosphoribosyltransferase, and orotidine 5'-monophosphate
    decarboxylase.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      HPLC microassay that measures both OPRT and ODC activities of UMPS; supports the two MF
      annotations. PubMed-verified.
- id: PMID:15890648
  title: Nuclear localization and mitogen-activated protein kinase phosphorylation
    of the multifunctional protein CAD.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Primarily about CAD, but the abstract explicitly reports UMP synthase in both the cytoplasm and
      nucleus; source of the cytoplasm/nucleus IDA localization annotations.
- id: PMID:18184586
  title: Structures of the human orotidine-5'-monophosphate decarboxylase support
    a covalent mechanism and provide a framework for drug design.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Human OMP decarboxylase crystal structures, kinetics, and mutagenesis (D312N); directly
      establishes the ODC activity. PubMed-verified.
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      BioPlex 2.0 proteome-scale AP-MS screen; source of a bare 'protein binding' IPI (partner EPHA4).
      Correctly cited but uninformative about UMPS function.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      BioPlex 3.0 proteome-scale AP-MS screen; source of a second bare 'protein binding' IPI (partner
      EPHA4). Correctly cited but uninformative about UMPS function.
- id: PMID:6893554
  title: Isolation and initial characterization of the single polypeptide that synthesizes
    uridine 5'-monophosphate from orotate in Ehrlich ascites carcinoma. Purification
    by tandem affinity chromatography of uridine-5'-monophosphate synthase.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Classic purification showing a single polypeptide carries both OPRT and ODC active centers and
      catalyzes the last two steps of de novo UMP biosynthesis. PubMed-verified.
- id: PMID:9042911
  title: Molecular cloning of the human UMP synthase gene and characterization of
    point mutations in two hereditary orotic aciduria families.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Human UMPS gene cloning, catalytic-activity characterization, and ORAC1 disease variants
      affecting OPRT/ODC activity. PubMed-verified; anchors the bifunctional-enzyme and disease framing.
- id: Reactome:R-HSA-73564
  title: UMPS dimer decarboxylates OMP to UMP
  findings: []
- id: Reactome:R-HSA-73567
  title: UMPS dimer transfers phosphoribosyl group to ORO to form OMP
  findings: []
- id: file:human/UMPS/UMPS-uniprot.txt
  title: UniProtKB P11172 (UMPS_HUMAN) record
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Curated UniProt record documenting the bifunctional OPRT (EC 2.4.2.10) and ODC (EC 4.1.1.23)
      activities, OPRTase/OMPdecase domains, homodimer requirement, cytosolic PATHWAY, and ORAC1
      disease association.