id: Q9UBR1
gene_symbol: UPB1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  UPB1 encodes beta-ureidopropionase (N-carbamoyl-beta-alanine amidohydrolase;
  beta-alanine synthase; EC 3.5.1.6), the third and final enzyme of the reductive
  pyrimidine catabolic pathway. It hydrolyses N-carbamoyl-beta-alanine
  (3-ureidopropanoate) to beta-alanine, ammonia and carbon dioxide, and likewise
  converts N-carbamoyl-beta-aminoisobutyrate (from thymine degradation) to
  beta-aminoisobutyrate, ammonia and CO2. It acts downstream of dihydropyrimidine
  dehydrogenase (DPYD) and dihydropyrimidinase (DPYS), and its product beta-alanine
  is a precursor for carnosine and other metabolites. The enzyme is a member of the
  nitrilase (carbon-nitrogen hydrolase) superfamily, using an active-site cysteine
  nucleophile (Cys233), and is cytosolic, highly expressed in liver. It assembles
  into homodimers, homotetramers, homooctamers and larger homooligomers, with
  substrate- and pH-dependent allosteric regulation of activity through oligomer
  state. Loss-of-function variants in UPB1 cause beta-ureidopropionase deficiency
  (UPB1D), an inborn error of pyrimidine degradation characterised by
  N-carbamyl-beta-amino aciduria and a highly variable phenotype ranging from
  neurological involvement (intellectual disability, seizures, hypotonia,
  microcephaly) to asymptomatic; the enzyme is also relevant to catabolism of
  fluoropyrimidine anticancer drugs.
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PAN-GO/GO_Central IBA basis for the beta-ureidopropionase activity and
      beta-alanine biosynthetic process annotations; consistent with experimental
      evidence for this gene.
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Maps UniProt subcellular location (Cytoplasm) to GO:0005737; correct but
      more general than the cytosol location supported by Reactome.
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Ensembl Compara orthology transfer from rat (Q03248) underlying the
      developmental-process annotations; mechanically valid but the transferred
      developmental roles are not established for the metabolic enzyme itself.
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      ARBA/RHEA/EC-based IEA supporting the core enzyme activity and pathway;
      concordant with the experimental annotations.
- id: PMID:10415095
  title: A radiochemical assay for beta-ureidopropionase using radiolabeled N-carbamyl-beta-alanine
    obtained via hydrolysis of [2-(14)C]5, 6-dihydrouracil.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Radiochemical assay of human beta-ureidopropionase; establishes catalytic
      activity and Km (15.5 uM) for N-carbamyl-beta-alanine.
- id: PMID:10542323
  title: cDNA cloning, genomic structure and chromosomal localization of the human
    BUP-1 gene encoding beta-ureidopropionase.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Cloning of human UPB1/BUP-1; heterologous expression confirms
      beta-ureidopropionase activity and identity of the cDNA.
- id: PMID:11508704
  title: Expression and properties of human liver beta-ureidopropionase.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Characterises recombinant human liver enzyme; reports positive cooperativity
      and 0.54 zinc atoms/subunit with a predicted zinc site (later shown by the
      crystal structure to be absent).
- id: PMID:19056867
  title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Large-scale urinary-exosome proteomics; a real high-throughput detection of
      the protein in exosomes, not evidence for the site of catalytic function.
- id: PMID:22525402
  title: 'ß-ureidopropionase deficiency: phenotype, genotype and protein structural
    consequences in 16 patients.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Defines the enzyme as the third step of pyrimidine degradation; functional
      analysis of disease mutations (all significantly decrease activity) and
      oligomer assembly; establishes involvement in pyrimidine catabolism.
- id: PMID:24526388
  title: Clinical, biochemical and molecular analysis of 13 Japanese patients with
    β-ureidopropionase deficiency demonstrates high prevalence of the c.977G > A (p.R326Q)
    mutation [corrected].
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Full-text available; details the third catabolic step reaction, nitrilase
      superfamily membership, and loss-of-function variants acting via impaired
      oligomer assembly.
- id: PMID:29976570
  title: Crystal structure and pH-dependent allosteric regulation of human β-ureidopropionase,
    an enzyme involved in anticancer drug metabolism.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Crystal structure (T299C variant); catalytic tetrad and Cys233 nucleophile;
      pH/oligomerization-dependent allosteric regulation; shows the enzyme lacks
      bound zinc (basis for the NOT zinc ion binding annotation).
- id: Reactome:R-HSA-73591
  title: conversion of 3-ureidopropionate to beta-alanine
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Reactome reaction for the cytosolic conversion of 3-ureidopropionate to
      beta-alanine + CO2 + NH3; supports cytosol localization.
- id: Reactome:R-HSA-73620
  title: conversion of 3-Ureidoiosbutyrate to 3-Aminoisobutyrate
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Reactome reaction for the cytosolic conversion of 3-ureidoisobutyrate to
      (R)-3-aminoisobutyrate + CO2 + NH3 (thymine branch); supports cytosol
      localization.
- id: file:human/UPB1/UPB1-uniprot.txt
  title: UniProtKB Q9UBR1 (BUP1_HUMAN) entry
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      UniProt curated record; source for the SUBUNIT (oligomerization) and CAUTION
      (lack of bound zinc) statements used as supporting text.
existing_annotations:
- term:
    id: GO:0003837
    label: beta-ureidopropionase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Phylogenetic (IBA) annotation of the core beta-ureidopropionase catalytic
      activity, concordant with direct experimental evidence in human.
    action: ACCEPT
    reason: >-
      This is the defining molecular function of UPB1 and is supported by multiple
      experimental studies of the human enzyme; the IBA is at the correct level of
      specificity.
    supported_by:
    - reference_id: PMID:24526388
      supporting_text: >-
        The third step, catalyzed by β-ureidopropionase (βUP) (EC 3.5.1.6), results
        in conversion of N-carbamyl-β-alanine and N-carbamyl-β-aminoisobutyric acid
        into β-alanine and β-aminoisobutyric acid, respectively, with concomitant
        production of ammonia and carbon dioxide.
- term:
    id: GO:0019483
    label: beta-alanine biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Phylogenetic annotation to beta-alanine biosynthesis, the biological process
      in which UPB1 produces beta-alanine as the terminal step of pyrimidine
      catabolism.
    action: ACCEPT
    reason: >-
      UPB1 generates beta-alanine directly from N-carbamoyl-beta-alanine; this is a
      correct and well-supported process annotation. Note that the UniProt DR line
      lists the more specific term GO:0033396 (beta-alanine biosynthetic process via
      3-ureidopropionate), but that term is now obsolete, so GO:0019483 is the
      appropriate level.
    supported_by:
    - reference_id: PMID:22525402
      supporting_text: >-
        ß-ureidopropionase is the third enzyme of the pyrimidine degradation pathway
        and
        catalyzes the conversion of N-carbamyl-ß-alanine and
        N-carbamyl-ß-aminoisobutyric acid to ß-alanine and ß-aminoisobutyric acid,
        ammonia and CO(2).
- term:
    id: GO:0003837
    label: beta-ureidopropionase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Automated (ARBA/RHEA/EC 3.5.1.6) inference of the core enzyme activity,
      identical to the experimentally supported molecular function.
    action: ACCEPT
    reason: >-
      Redundant with the EXP/IDA/IBA annotations to GO:0003837 and correctly mapped
      from EC 3.5.1.6 / RHEA:11184.
    supported_by:
    - reference_id: PMID:29976570
      supporting_text: >-
        β-Ureidopropionase (βUP) catalyzes the third step of the reductive pyrimidine
        catabolic pathway responsible for breakdown of uracil-, thymine- and
        pyrimidine-based antimetabolites such as 5-fluorouracil.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Automated subcellular-location mapping placing UPB1 in the cytoplasm,
      consistent with its cytosolic localization.
    action: ACCEPT
    reason: >-
      Correct but general; the more precise cytosol term (GO:0005829) is supported
      by Reactome. Keeping the cytoplasm parent is acceptable.
    supported_by:
    - reference_id: file:human/UPB1/UPB1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm.'
- term:
    id: GO:0001701
    label: in utero embryonic development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Developmental-process annotation transferred by Ensembl Compara orthology from
      rat; not supported by any direct evidence that UPB1 has a role in embryonic
      development beyond its metabolic function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This is an electronic orthology transfer (GO_REF:0000107) from rat Q03248, not
      evidence about human UPB1. UPB1 is a pyrimidine-catabolic enzyme; there is no
      literature support for a specific role in in utero embryonic development. The
      phenotype associated with loss of function is a metabolic/neurological inborn
      error, not an embryonic-development defect. Flagging as over-annotated rather
      than removing, as it is an automated inference rather than a clearly wrong
      mapping.
    supported_by:
    - reference_id: file:human/UPB1/UPB1-uniprot.txt
      supporting_text: >-
        Catalyzes a late step in pyrimidine degradation
- term:
    id: GO:0001889
    label: liver development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Liver-development annotation transferred by Ensembl Compara orthology from
      rat; UPB1 is highly expressed in liver but there is no evidence it participates
      in liver morphogenesis/development.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Electronic orthology transfer from rat (GO_REF:0000107). High hepatic
      expression reflects where pyrimidine catabolism occurs, not a role in the
      developmental process of the liver. No experimental evidence links UPB1 to
      liver development. Marked as over-annotated rather than removed since it is an
      automated inference.
    supported_by:
    - reference_id: file:human/UPB1/UPB1-uniprot.txt
      supporting_text: 'TISSUE SPECIFICITY: Detected in liver (at protein level).'
- term:
    id: GO:0019483
    label: beta-alanine biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: >-
      Automated (UniPathway UPA00131 / orthology) annotation to beta-alanine
      biosynthesis, redundant with the experimental and IBA annotations.
    action: ACCEPT
    reason: >-
      Correct process annotation supported by UniPathway (beta-alanine biosynthesis)
      and by the experimental IDA annotations to the same term.
    supported_by:
    - reference_id: file:human/UPB1/UPB1-uniprot.txt
      supporting_text: 'PATHWAY: Amino-acid biosynthesis; beta-alanine biosynthesis.'
- term:
    id: GO:0019483
    label: beta-alanine biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:22525402
  qualifier: involved_in
  review:
    summary: >-
      Direct experimental evidence that UPB1 produces beta-alanine as the terminal
      step of the pyrimidine degradation pathway.
    action: ACCEPT
    reason: >-
      Experimental study of the human enzyme and disease mutants establishes its
      role in converting N-carbamyl-beta-alanine to beta-alanine.
    supported_by:
    - reference_id: PMID:22525402
      supporting_text: >-
        ß-ureidopropionase is the third enzyme of the pyrimidine degradation pathway
        and
        catalyzes the conversion of N-carbamyl-ß-alanine and
        N-carbamyl-ß-aminoisobutyric acid to ß-alanine and ß-aminoisobutyric acid,
        ammonia and CO(2).
- term:
    id: GO:0019483
    label: beta-alanine biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:29976570
  qualifier: involved_in
  review:
    summary: >-
      Direct experimental evidence (biochemical/structural characterisation of the
      human enzyme) for beta-alanine production from N-carbamoyl-beta-alanine.
    action: ACCEPT
    reason: >-
      The crystal-structure paper biochemically characterises the human enzyme's
      conversion of N-carbamoyl-beta-alanine, the reaction that generates
      beta-alanine.
    supported_by:
    - reference_id: PMID:29976570
      supporting_text: >-
        β-Ureidopropionase (βUP) catalyzes the third step of the reductive pyrimidine
        catabolic pathway responsible for breakdown of uracil-, thymine- and
        pyrimidine-based antimetabolites such as 5-fluorouracil.
- term:
    id: GO:0003837
    label: beta-ureidopropionase activity
  evidence_type: EXP
  original_reference_id: PMID:10415095
  qualifier: enables
  review:
    summary: >-
      Experimental radiochemical assay measuring human beta-ureidopropionase
      activity on N-carbamyl-beta-alanine.
    action: ACCEPT
    reason: >-
      Direct enzymatic assay of the human protein with kinetic characterisation (Km
      15.5 uM), establishing the core molecular function.
    supported_by:
    - reference_id: PMID:10415095
      supporting_text: >-
        Human beta-ureidopropionase
        obeyed Michaelis-Menten kinetics with an apparent Km for N-carbamyl-beta-alanine
        of 15.5 +/- 1.9 microM.
- term:
    id: GO:0003837
    label: beta-ureidopropionase activity
  evidence_type: EXP
  original_reference_id: PMID:10542323
  qualifier: enables
  review:
    summary: >-
      Experimental confirmation that the cloned human UPB1 cDNA encodes an active
      beta-ureidopropionase.
    action: ACCEPT
    reason: >-
      Heterologous expression of the human cDNA yielded high beta-ureidopropionase
      activity, confirming the enzyme's molecular function.
    supported_by:
    - reference_id: PMID:10542323
      supporting_text: >-
        Expression of the
        human cDNA in an Escherichia coli and eukaryotic COS-7 expression system
        revealed a very high beta-ureidopropionase enzymatic activity, thus confirming
        the identity of the cDNA.
- term:
    id: GO:0003837
    label: beta-ureidopropionase activity
  evidence_type: EXP
  original_reference_id: PMID:11508704
  qualifier: enables
  review:
    summary: >-
      Experimental characterisation of purified recombinant human liver
      beta-ureidopropionase, including cooperativity toward its substrate.
    action: ACCEPT
    reason: >-
      Purification and biochemical assay of the human enzyme directly establish the
      beta-ureidopropionase activity.
    supported_by:
    - reference_id: PMID:11508704
      supporting_text: >-
        exhibited positive cooperativity with N-carbamoyl-beta-alanine as the
        substrate with a Hill coefficient 2.0
- term:
    id: GO:0003837
    label: beta-ureidopropionase activity
  evidence_type: EXP
  original_reference_id: PMID:24526388
  qualifier: enables
  review:
    summary: >-
      Experimental activity measurements of wild-type and mutant human UPB1,
      confirming beta-ureidopropionase catalytic activity.
    action: ACCEPT
    reason: >-
      Functional assays of human UPB1 (EC 3.5.1.6) catalysing the third catabolic
      step directly support this molecular function.
    supported_by:
    - reference_id: PMID:24526388
      supporting_text: >-
        The third step, catalyzed by β-ureidopropionase (βUP) (EC 3.5.1.6), results
        in conversion of N-carbamyl-β-alanine and N-carbamyl-β-aminoisobutyric acid
        into β-alanine and β-aminoisobutyric acid, respectively, with concomitant
        production of ammonia and carbon dioxide.
- term:
    id: GO:0003837
    label: beta-ureidopropionase activity
  evidence_type: IDA
  original_reference_id: PMID:22525402
  qualifier: enables
  review:
    summary: >-
      Direct assay evidence that human UPB1 has beta-ureidopropionase activity, with
      disease mutants showing reduced activity.
    action: ACCEPT
    reason: >-
      Experimental measurement of enzyme activity in wild-type and mutant human UPB1
      directly supports this molecular function.
    supported_by:
    - reference_id: PMID:22525402
      supporting_text: >-
        Heterologous expression of the 6
        mutant enzymes in Escherichia coli showed that all mutations yielded mutant
        ß-ureidopropionase proteins with significantly decreased activity.
- term:
    id: GO:0003837
    label: beta-ureidopropionase activity
  evidence_type: IDA
  original_reference_id: PMID:29976570
  qualifier: enables
  review:
    summary: >-
      Direct biochemical/structural evidence for human beta-ureidopropionase
      activity, including catalytic residue and kinetic characterisation.
    action: ACCEPT
    reason: >-
      The crystal-structure study biochemically characterises the catalytic activity
      of recombinant human UPB1.
    supported_by:
    - reference_id: PMID:29976570
      supporting_text: >-
        β-Ureidopropionase (βUP) catalyzes the third step of the reductive pyrimidine
        catabolic pathway responsible for breakdown of uracil-, thymine- and
        pyrimidine-based antimetabolites such as 5-fluorouracil.
- term:
    id: GO:0008270
    label: zinc ion binding
  evidence_type: IDA
  original_reference_id: PMID:29976570
  qualifier: enables
  negated: true
  review:
    summary: >-
      NOT annotation correctly asserting that human UPB1 does not bind zinc, refuting
      an earlier sequence-based prediction.
    action: ACCEPT
    reason: >-
      Although early work reported ~0.5 zinc atoms/subunit and predicted a zinc site,
      the crystal structure shows no bound zinc and that the predicted residues are
      too far apart to form a site. The negated annotation is correct and should be
      retained to prevent erroneous propagation of a zinc-binding function.
    supported_by:
    - reference_id: file:human/UPB1/UPB1-uniprot.txt
      supporting_text: >-
        The crystal structure indicates a lack of bound
        zinc ions, and shows that the residues that were predicted to bind zinc
        are too far apart in space to form a zinc binding site
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:29976570
  qualifier: enables
  review:
    summary: >-
      UPB1 forms homodimers, the basic building block of its higher-order
      oligomeric assemblies.
    action: KEEP_AS_NON_CORE
    reason: >-
      Homodimerization is experimentally established and structurally important, but
      it is a means of assembling the active oligomer rather than the core catalytic
      function of the enzyme. Retained as non-core supporting activity.
    supported_by:
    - reference_id: PMID:29976570
      supporting_text: >-
        Existing as a homodimer at pH 9, the enzyme increasingly associates to
        form octamers and larger oligomers with decreasing pH.
- term:
    id: GO:0046135
    label: pyrimidine nucleoside catabolic process
  evidence_type: IMP
  original_reference_id: PMID:22525402
  qualifier: involved_in
  review:
    summary: >-
      Annotation to pyrimidine catabolism based on disease-mutation analysis, but the
      chosen term (nucleoside catabolism) is inaccurate: UPB1 acts on
      N-carbamoyl-beta-alanine, a nucleobase-degradation intermediate, not a
      nucleoside.
    action: MODIFY
    reason: >-
      The gene is genuinely involved in pyrimidine catabolism (loss of function
      causes accumulation of N-carbamyl-beta-amino acids), so the essence is correct,
      but nucleoside catabolism is the wrong branch. UPB1 acts downstream of base
      ring-opening on the ureido acid, so the appropriate terms are uracil catabolic
      process (GO:0006212) and, more generally, pyrimidine nucleobase catabolic
      process (GO:0006208).
    proposed_replacement_terms:
    - id: GO:0006212
      label: uracil catabolic process
    - id: GO:0006208
      label: pyrimidine nucleobase catabolic process
    supported_by:
    - reference_id: PMID:22525402
      supporting_text: >-
        markedly elevated levels
        of N-carbamyl-ß-alanine and N-carbamyl-ß-aminoisobutyric acid in urine and
        plasma.
- term:
    id: GO:0051260
    label: protein homooligomerization
  evidence_type: IDA
  original_reference_id: PMID:22525402
  qualifier: involved_in
  review:
    summary: >-
      UPB1 assembles into higher-order homooligomers, which underlies its
      substrate/pH-dependent allosteric regulation.
    action: KEEP_AS_NON_CORE
    reason: >-
      Homooligomerization is experimentally supported and mechanistically relevant to
      activity regulation, but it is a supporting structural property rather than the
      core biological function (pyrimidine catabolism / beta-alanine biosynthesis).
    supported_by:
    - reference_id: PMID:29976570
      supporting_text: >-
        Existing as a homodimer at pH 9, the enzyme increasingly associates to
        form octamers and larger oligomers with decreasing pH.
- term:
    id: GO:0051289
    label: protein homotetramerization
  evidence_type: IDA
  original_reference_id: PMID:29976570
  qualifier: involved_in
  review:
    summary: >-
      UPB1 forms homotetramers as part of its progression from dimers to larger
      oligomeric states.
    action: KEEP_AS_NON_CORE
    reason: >-
      Homotetramerization is part of the experimentally observed oligomerization
      series; retained as a non-core supporting property rather than the core
      function.
    supported_by:
    - reference_id: PMID:29976570
      supporting_text: >-
        Existing as a homodimer at pH 9, the enzyme increasingly associates to
        form octamers and larger oligomers with decreasing pH.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:19056867
  qualifier: located_in
  review:
    summary: >-
      High-throughput detection of UPB1 in urinary exosomes; a real proteomic
      observation but not the site of catalytic function.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is a large-scale mass-spectrometry detection in urinary exosomes, not
      evidence for the functional localization of the enzyme, which is cytosolic.
      Retained as non-core to reflect the proteomic observation without implying an
      extracellular functional role.
    supported_by:
    - reference_id: PMID:19056867
      supporting_text: >-
        Normal human urine contains large numbers of exosomes
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-73591
  qualifier: located_in
  review:
    summary: >-
      Cytosolic localization inferred from the Reactome reaction for conversion of
      3-ureidopropionate to beta-alanine.
    action: ACCEPT
    reason: >-
      Consistent with UniProt (Cytoplasm) and the known cytosolic site of pyrimidine
      catabolism; this is the functionally relevant location.
    supported_by:
    - reference_id: Reactome:R-HSA-73591
      supporting_text: >-
        Cytosolic 3-ureidopropionase catalyzes the reaction of 3-ureidopropionate
        and water to form beta-alanine, CO2, and NH3
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-73620
  qualifier: located_in
  review:
    summary: >-
      Cytosolic localization inferred from the Reactome reaction for conversion of
      3-ureidoisobutyrate to 3-aminoisobutyrate (thymine branch).
    action: ACCEPT
    reason: >-
      Consistent with the cytosolic function of UPB1 in both the uracil- and
      thymine-derived branches of pyrimidine catabolism.
    supported_by:
    - reference_id: Reactome:R-HSA-73620
      supporting_text: >-
        Cytosolic UPB1 (beta-ureidopropionase) catalyzes the reaction of 3-ureidoisobutyrate
        and H2O to form (R)-3-aminoisobutyrate, CO2, and NH3
core_functions:
- description: >-
    Beta-ureidopropionase catalytic activity: hydrolyses N-carbamoyl-beta-alanine to
    beta-alanine, ammonia and CO2 (and N-carbamoyl-beta-aminoisobutyrate to
    beta-aminoisobutyrate), the third and final step of reductive pyrimidine
    catabolism.
  molecular_function:
    id: GO:0003837
    label: beta-ureidopropionase activity
  directly_involved_in:
  - id: GO:0006212
    label: uracil catabolic process
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:24526388
    supporting_text: >-
      The third step, catalyzed by β-ureidopropionase (βUP) (EC 3.5.1.6), results
      in conversion of N-carbamyl-β-alanine and N-carbamyl-β-aminoisobutyric acid
      into β-alanine and β-aminoisobutyric acid, respectively, with concomitant
      production of ammonia and carbon dioxide.
- description: >-
    Production of beta-alanine (and beta-aminoisobutyrate) as the terminal metabolic
    output of the pyrimidine degradation pathway, in the cytosol.
  molecular_function:
    id: GO:0003837
    label: beta-ureidopropionase activity
  directly_involved_in:
  - id: GO:0019483
    label: beta-alanine biosynthetic process
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:22525402
    supporting_text: >-
      ß-ureidopropionase is the third enzyme of the pyrimidine degradation pathway
      and
      catalyzes the conversion of N-carbamyl-ß-alanine and
      N-carbamyl-ß-aminoisobutyric acid to ß-alanine and ß-aminoisobutyric acid,
      ammonia and CO(2).
proposed_new_terms: []
suggested_questions:
- question: >-
    Does the substrate/pH-dependent oligomerization of human UPB1 regulate flux
    through pyrimidine catabolism in vivo, or is it primarily an in vitro phenomenon?
- question: >-
    To what extent does reduced UPB1 activity modulate systemic fluoropyrimidine
    (e.g. 5-fluorouracil) catabolism and toxicity, given that its substrates derive
    from these antimetabolites?
suggested_experiments:
- description: >-
    Determine a substrate- or product-bound crystal/cryo-EM structure of human UPB1
    to define the catalytic mechanism and the basis of allosteric activation by
    oligomer assembly.
- description: >-
    Metabolomic profiling of UPB1-deficient patient cells or knockout models to
    quantify accumulation of N-carbamyl-beta-alanine / N-carbamyl-beta-aminoisobutyrate
    and depletion of beta-alanine and downstream carnosine.