id: P06132
gene_symbol: UROD
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: UROD encodes uroporphyrinogen decarboxylase (URO-D; EC 4.1.1.37), the enzyme that catalyzes
  the fifth step of heme biosynthesis. It performs the sequential decarboxylation of the four acetate
  side chains of uroporphyrinogen III to methyl groups, releasing four molecules of CO2 and producing
  coproporphyrinogen III. The enzyme is cofactor-independent and acts as a homodimer with a single active-site
  aspartate (Asp86) that binds and activates the substrate and all partially decarboxylated intermediates
  at one catalytic center. Although either the I or III isomer of uroporphyrinogen can serve as substrate
  in vitro (the III isomer being processed more efficiently), only coproporphyrinogen III can ultimately
  be converted to heme. UROD is a soluble, cytosolic protein. Deficiency of UROD causes porphyria cutanea
  tarda (PCT), the commonest human porphyria, of which the familial form (FPCT) is autosomal dominant
  with low penetrance; complete/biallelic deficiency causes the severe childhood-onset hepatoerythropoietic
  porphyria (HEP), regarded as the homozygous form of PCT.
references:
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator
    judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- 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: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:11069625
  title: Co-inheritance of mutations in the uroporphyrinogen decarboxylase and hemochromatosis genes accelerates
    the onset of porphyria cutanea tarda.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified. Establishes that PCT results from deficiency of hepatic UROD activity
      and characterizes FPCT-causing UROD mutations; supports the disease context and (via curator full-text
      reading) the IDA activity annotation.
- id: PMID:11719352
  title: Functional consequences of naturally occurring mutations in human uroporphyrinogen decarboxylase.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified. Recombinant expression and enzymatic assay of missense URO-D variants
      (activities 29-94% of normal) plus mutant crystal structures; directly supports uroporphyrinogen
      decarboxylase activity (IDA).
- id: PMID:12071824
  title: Description of a new mutation in hepatoerythropoietic porphyria and prenatal exclusion of a homozygous
    fetus.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified. HEP case with homozygous F46L UROD mutation; low UROD activity and
      recombinant expression confirm the deleterious effect; supports the enzymatic activity annotation.
- id: PMID:14633982
  title: Structural basis for tetrapyrrole coordination by uroporphyrinogen decarboxylase.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified. Crystal structures of URO-D with coproporphyrinogen I and III products;
      defines Asp86 catalysis and how one active center decarboxylates all four acetate groups. Primary
      structural/mechanistic reference for the MF.
- id: PMID:1634232
  title: Characterization of a new mutation (R292G) and a deletion at the human uroporphyrinogen decarboxylase
    locus in two patients with hepatoerythropoietic porphyria.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified. Explicitly describes UROD as the fifth enzyme of the heme biosynthetic
      pathway; source of the TAS molecular-function annotation.
- id: PMID:18004775
  title: 'Human uroporphyrinogen III synthase: NMR-based mapping of the active site.'
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified. Primary focus is uroporphyrinogen III synthase (UROS), but the study
      developed expression/purification for the cytosolic heme biosynthesis enzymes including URO-decarboxylase
      and probed a possible URO-synthase/URO-decarboxylase complex by NMR (none detected). GOA anchors
      an IDA (GO:0004853) and an IC (GO:0006783) for UROD here; full text is not in the cache, so the
      curator reading is retained rather than overruled.
- id: PMID:21668429
  title: Hepatoerythropoietic porphyria due to a novel mutation in the uroporphyrinogen decarboxylase
    gene.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified with full text. Novel homozygous G170D HEP variant; recombinant UROD
      purified and assayed against uroporphyrinogen I and III; directly supports the enzymatic activity
      annotation and the heme-biosynthesis disease context.
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: PubMed-verified. High-throughput human interactome (HuRI/CCSB) screen; source of a non-specific
      IPI protein-binding annotation, not an informative molecular function.
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease networks.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: PubMed-verified. Proteome-scale interactome (BioPlex) analysis; source of non-specific
      IPI protein-binding annotations.
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the allele frequency
    spectrum in human populations.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: PubMed-verified. Systematic interaction-perturbation (Y2H variant) screen; source of
      a non-specific IPI protein-binding annotation.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: PubMed-verified. Binary reference interactome (HuRI) Y2H screen; source of several non-specific
      IPI protein-binding annotations.
- 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: PubMed-verified. BioPlex dual cell-line AP-MS interactome; source of non-specific IPI
      protein-binding annotations.
- id: Reactome:R-HSA-189425
  title: UROD decarboxylates URO3 to COPRO3
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Reactome reaction describing the physiological UROD step (uroporphyrinogen III to coproporphyrinogen
      III) in the cytosol; supports both the MF and the cytosol location.
- id: Reactome:R-HSA-190182
  title: UROD decarboxylates URO1 to COPRO1
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Reactome reaction for the less-efficient decarboxylation of the isomer I substrate (uroporphyrinogen
      I to coproporphyrinogen I) in the cytosol; corroborates the cytosolic decarboxylase activity.
- id: file:human/UROD/UROD-uniprot.txt
  title: UniProtKB P06132 (DCUP_HUMAN) uroporphyrinogen decarboxylase record
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Curated UniProt record; source of the FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBUNIT
      and SUBCELLULAR LOCATION statements used to ground this review.
existing_annotations:
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic (IBA) assertion that UROD is active in the cytosol. UROD is a soluble cytosolic
      enzyme of heme biosynthesis, consistent with the UniProt subcellular location and Reactome.
    action: ACCEPT
    reason: Correct and well supported. UROD localizes to the cytosol where the fifth step of heme biosynthesis
      occurs; the IBA is concordant with experimental and UniProt evidence.
    supported_by:
    - reference_id: file:human/UROD/UROD-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
    - reference_id: Reactome:R-HSA-189425
      supporting_text: Cytosolic uroporphyrinogen decarboxylase (UROD) catalyzes the sequntial removal
        of four carboxylic groups from the acetic acid side chains of uroporphyrinogen III (URO3) to form
        coproporphyrinogen III (COPRO3)
- term:
    id: GO:0006783
    label: heme biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic (IBA) assertion that UROD is involved in heme biosynthesis. UROD catalyzes the
      fifth step of the heme biosynthetic pathway.
    action: ACCEPT
    reason: This is the core biological process for UROD. The decarboxylation of uroporphyrinogen III
      to coproporphyrinogen III is an obligate step of heme biosynthesis.
    supported_by:
    - reference_id: file:human/UROD/UROD-uniprot.txt
      supporting_text: participates in the fifth step in the heme biosynthetic pathway
    - reference_id: PMID:1634232
      supporting_text: uroporphyrinogen decarboxylase (UROD), the fifth
- term:
    id: GO:0004853
    label: uroporphyrinogen decarboxylase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic (IBA) assertion of uroporphyrinogen decarboxylase activity. This is the defining
      molecular function of UROD, supported experimentally and structurally.
    action: ACCEPT
    reason: Core molecular function. The IBA is at the correct level of specificity and matches the EC
      4.1.1.37 activity assayed for the human enzyme and its orthologs.
    supported_by:
    - reference_id: PMID:14633982
      supporting_text: the heme biosynthetic pathway, catalyzes decarboxylation of all four acetate
- term:
    id: GO:0004853
    label: uroporphyrinogen decarboxylase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic (IEA) assertion of uroporphyrinogen decarboxylase activity from InterPro/ARBA
      family membership and the RHEA:19865 / EC 4.1.1.37 mapping. Consistent with the experimentally established
      function.
    action: ACCEPT
    reason: The IEA family/EC mapping correctly recovers the core molecular function; UROD carries the
      URO-D fold and catalytic residues.
    supported_by:
    - reference_id: file:human/UROD/UROD-uniprot.txt
      supporting_text: side chains of uroporphyrinogen to form coproporphyrinogen and
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic (IEA) location in cytosol derived from the UniProt subcellular-location vocabulary
      mapping. Matches the established cytosolic localization.
    action: ACCEPT
    reason: Correct; the UniProt SubCell mapping reproduces the experimentally supported cytosolic localization
      of this soluble enzyme.
    supported_by:
    - reference_id: file:human/UROD/UROD-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:0006779
    label: porphyrin-containing compound biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Electronic (IEA) assertion that UROD is involved in porphyrin-containing compound biosynthesis.
      This is a correct parent-level biosynthetic term (coproporphyrinogen III is a porphyrin-containing
      compound produced en route to heme).
    action: ACCEPT
    reason: Biologically correct, though more general than the specific heme biosynthetic process term.
      Acceptable as a broader IEA parent; the core, more informative term is GO:0006783 (heme biosynthetic
      process).
    supported_by:
    - reference_id: file:human/UROD/UROD-uniprot.txt
      supporting_text: 'coproporphyrinogen-III from 5-aminolevulinate: step 4/4.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Non-specific protein-binding (IPI) from a proteome-scale interactome screen (interaction
      with Q96KN1/LRATD2). Bare protein binding is uninformative and no functional partnership is established.
    action: MARK_AS_OVER_ANNOTATED
    reason: Per curation guidelines, bare 'protein binding' derived from a high-throughput interactome
      map does not convey a molecular function. Not removed (experimental IPI is retained) but flagged
      as over-annotation; not a core function.
    supported_by:
    - reference_id: file:human/UROD/UROD-uniprot.txt
      supporting_text: 'P06132; Q96KN1: LRATD2'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: Non-specific protein-binding (IPI) from a proteome-scale interactome analysis. No informative
      molecular function is conveyed and no biologically meaningful partner is established for UROD.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare 'protein binding' from a high-throughput dataset; retained as experimental IPI but flagged
      as an uninformative over-annotation, not a core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: Non-specific protein-binding (IPI) from a systematic interaction-perturbation screen (interaction
      with Q96KN1). Uninformative bare protein binding.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare 'protein binding' from a high-throughput interactome study; retained but flagged as over-annotation,
      not a core molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Non-specific protein-binding (IPI) from the HuRI binary reference interactome (several partners
      including C9JJ79/PILRA, P46019/PHKA2, Q96KN1/LRATD2, Q96PN8/TSSK3). Bare protein binding without
      functional context.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare 'protein binding' from a large-scale Y2H map; retained as experimental IPI but flagged
      as uninformative over-annotation, not a core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Non-specific protein-binding (IPI) from the BioPlex dual cell-line AP-MS interactome (partners
      including A5A3E0/POTEF, Q08752/PPID). Bare protein binding, no functional partnership established.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare 'protein binding' from a high-throughput dataset; retained but flagged as over-annotation,
      not a core molecular function.
- term:
    id: GO:0006785
    label: heme B biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:11069625
  qualifier: involved_in
  review:
    summary: IDA annotation that UROD is involved in heme B (protoheme/heme b) biosynthesis. UROD produces
      coproporphyrinogen III, an obligate intermediate on the route to heme b, so this is biologically
      correct and more specific than the parent heme biosynthetic process term.
    action: ACCEPT
    reason: Correct and appropriately specific; heme b is the standard heme produced by the pathway and
      UROD deficiency causes accumulation of upstream porphyrins (porphyria cutanea tarda), confirming
      its role in the biosynthetic route. Experimental annotation whose full text was read by the curator;
      retained.
    supported_by:
    - reference_id: PMID:11069625
      supporting_text: deficiency of hepatic uroporphyrin-
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: HPA immunofluorescence (IDA) placing UROD in the nucleoplasm. UROD is a soluble cytosolic
      heme-biosynthesis enzyme with no established nuclear function; a nucleoplasmic signal in an antibody-based
      screen most likely reflects diffuse/incidental staining rather than a functional nuclear localization.
    action: MARK_AS_OVER_ANNOTATED
    reason: Not the established or functionally relevant localization. The enzyme acts in the cytosol
      (UniProt, Reactome, IBA/ISS/TAS all agree). The HPA IDA is retained but flagged as an over-annotation;
      it is not a core localization for UROD.
    supported_by:
    - reference_id: file:human/UROD/UROD-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: HPA immunofluorescence (IDA) placing UROD in the cytosol. Concordant with the established
      cytosolic localization of this soluble enzyme.
    action: ACCEPT
    reason: Correct localization, directly supported by experimental immunofluorescence and consistent
      with all other lines of evidence.
    supported_by:
    - reference_id: file:human/UROD/UROD-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: is_active_in
  review:
    summary: ISS assertion (transferred from mouse Urod, MGI:98916) that the enzyme is active in the cytosol.
      Consistent with the cytosolic localization of the mammalian enzyme.
    action: ACCEPT
    reason: Correct; the sequence-similarity transfer recovers the established cytosolic site of activity
      of UROD.
    supported_by:
    - reference_id: file:human/UROD/UROD-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol'
- term:
    id: GO:0004853
    label: uroporphyrinogen decarboxylase activity
  evidence_type: IDA
  original_reference_id: PMID:11069625
  qualifier: enables
  review:
    summary: IDA for uroporphyrinogen decarboxylase activity from a study of FPCT-causing UROD mutations,
      in which hepatic UROD activity deficiency underlies the disease.
    action: ACCEPT
    reason: Directly supports the core molecular function; experimental annotation curated from the full
      text.
    supported_by:
    - reference_id: PMID:11069625
      supporting_text: deficiency of hepatic uroporphyrin-
- term:
    id: GO:0004853
    label: uroporphyrinogen decarboxylase activity
  evidence_type: IDA
  original_reference_id: PMID:11719352
  qualifier: enables
  review:
    summary: IDA for uroporphyrinogen decarboxylase activity; recombinant wild-type and mutant URO-D proteins
      were expressed and their enzymatic activity measured (29-94% of normal for missense mutants).
    action: ACCEPT
    reason: Directly supports the core molecular function via recombinant enzymatic assay of the human
      protein.
    supported_by:
    - reference_id: PMID:11719352
      supporting_text: ranged from 29% to 94% of normal
- term:
    id: GO:0004853
    label: uroporphyrinogen decarboxylase activity
  evidence_type: IDA
  original_reference_id: PMID:12071824
  qualifier: enables
  review:
    summary: IDA for uroporphyrinogen decarboxylase activity; HEP patient with F46L UROD showed low UROD
      activity and recombinant expression confirmed the deleterious effect.
    action: ACCEPT
    reason: Supports the core molecular function; enzymatic activity measured directly and confirmed by
      recombinant expression.
    supported_by:
    - reference_id: PMID:12071824
      supporting_text: We found low levels of UROD enzymatic activity
- term:
    id: GO:0004853
    label: uroporphyrinogen decarboxylase activity
  evidence_type: IDA
  original_reference_id: PMID:14633982
  qualifier: enables
  review:
    summary: IDA for uroporphyrinogen decarboxylase activity backed by crystal structures of URO-D in
      complex with its coproporphyrinogen I and III products, defining how one catalytic center decarboxylates
      all four acetate groups.
    action: ACCEPT
    reason: Strong structural/biochemical support for the core molecular function.
    supported_by:
    - reference_id: PMID:14633982
      supporting_text: the heme biosynthetic pathway, catalyzes decarboxylation of all four acetate
- term:
    id: GO:0004853
    label: uroporphyrinogen decarboxylase activity
  evidence_type: IDA
  original_reference_id: PMID:21668429
  qualifier: enables
  review:
    summary: IDA for uroporphyrinogen decarboxylase activity; recombinant UROD (wild-type and G170D HEP
      variant) purified and assayed against uroporphyrinogen I and III substrates.
    action: ACCEPT
    reason: Directly supports the core molecular function with a purified-protein enzymatic assay on both
      isomer substrates.
    supported_by:
    - reference_id: PMID:21668429
      supporting_text: The recombinant UROD protein showed a relative activity of 17% and 60%
- term:
    id: GO:0006778
    label: porphyrin-containing compound metabolic process
  evidence_type: IDA
  original_reference_id: PMID:12071824
  qualifier: involved_in
  review:
    summary: IDA that UROD is involved in porphyrin-containing compound metabolism, from a HEP study showing
      UROD deficiency and abnormal (poly-carboxylated) porphyrin excretion.
    action: ACCEPT
    reason: Biologically correct, though this is a high-level parent (metabolic) term. The more informative
      and core biological process is heme biosynthesis (GO:0006783); this parent is acceptable and retained.
    supported_by:
    - reference_id: PMID:12071824
      supporting_text: profound deficiency (<10% of normal activity) of uroporphyrinogen decarboxylase
- term:
    id: GO:0006787
    label: porphyrin-containing compound catabolic process
  evidence_type: IDA
  original_reference_id: PMID:11069625
  qualifier: involved_in
  review:
    summary: 'IDA annotating UROD to porphyrin-containing compound CATABOLIC process. This is directionally
      incorrect: UROD is an anabolic enzyme. Its decarboxylation of uroporphyrinogen III to coproporphyrinogen
      III is a heme-biosynthetic step, not degradation of a porphyrin-containing compound.'
    action: MODIFY
    reason: The enzymatic reaction is genuine, but the process branch is wrong. UROD contributes to biosynthesis
      (production of coproporphyrinogen III on the route to heme), not catabolism. This appears to be
      a systematic mis-mapping applied to several UROD disease/structural papers. Replace with the biosynthetic
      terms that the reaction actually supports.
    proposed_replacement_terms:
    - id: GO:0006783
      label: heme biosynthetic process
    - id: GO:0006779
      label: porphyrin-containing compound biosynthetic process
    supported_by:
    - reference_id: file:human/UROD/UROD-uniprot.txt
      supporting_text: participates in the fifth step in the heme biosynthetic pathway
    - reference_id: PMID:11069625
      supporting_text: deficiency of hepatic uroporphyrin-
- term:
    id: GO:0006787
    label: porphyrin-containing compound catabolic process
  evidence_type: IDA
  original_reference_id: PMID:11719352
  qualifier: involved_in
  review:
    summary: IDA annotating UROD to porphyrin-containing compound CATABOLIC process. As above, this is
      directionally wrong for an enzyme whose reaction is part of heme biosynthesis.
    action: MODIFY
    reason: The recombinant enzymatic-activity data in this paper support decarboxylase activity, but
      the correct process is biosynthetic, not catabolic. Replace with heme / porphyrin biosynthetic process.
    proposed_replacement_terms:
    - id: GO:0006783
      label: heme biosynthetic process
    - id: GO:0006779
      label: porphyrin-containing compound biosynthetic process
    supported_by:
    - reference_id: PMID:11719352
      supporting_text: ranged from 29% to 94% of normal
- term:
    id: GO:0006787
    label: porphyrin-containing compound catabolic process
  evidence_type: IDA
  original_reference_id: PMID:14633982
  qualifier: involved_in
  review:
    summary: IDA annotating UROD to porphyrin-containing compound CATABOLIC process. The structural paper
      establishes decarboxylase activity, but the biological process direction is wrong.
    action: MODIFY
    reason: Decarboxylation of uroporphyrinogen to coproporphyrinogen is a biosynthetic step of heme synthesis,
      not porphyrin catabolism. Replace with the biosynthetic process terms.
    proposed_replacement_terms:
    - id: GO:0006783
      label: heme biosynthetic process
    - id: GO:0006779
      label: porphyrin-containing compound biosynthetic process
    supported_by:
    - reference_id: PMID:14633982
      supporting_text: the heme biosynthetic pathway, catalyzes decarboxylation of all four acetate
- term:
    id: GO:0006787
    label: porphyrin-containing compound catabolic process
  evidence_type: IDA
  original_reference_id: PMID:21668429
  qualifier: involved_in
  review:
    summary: IDA annotating UROD to porphyrin-containing compound CATABOLIC process. The HEP study supports
      decarboxylase activity, but this catabolic BP is directionally incorrect.
    action: MODIFY
    reason: UROD acts in heme biosynthesis; the reaction produces coproporphyrinogen III on the route
      to heme rather than degrading a porphyrin. Replace with heme / porphyrin biosynthetic process.
    proposed_replacement_terms:
    - id: GO:0006783
      label: heme biosynthetic process
    - id: GO:0006779
      label: porphyrin-containing compound biosynthetic process
    supported_by:
    - reference_id: PMID:21668429
      supporting_text: results from a deficiency of uroporphyrinogen decarboxylase (UROD)
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-189425
  qualifier: located_in
  review:
    summary: TAS (Reactome) location in cytosol for the UROD reaction converting uroporphyrinogen III
      to coproporphyrinogen III. Consistent with the established cytosolic localization.
    action: ACCEPT
    reason: Correct; Reactome explicitly describes cytosolic UROD.
    supported_by:
    - reference_id: Reactome:R-HSA-189425
      supporting_text: Cytosolic uroporphyrinogen decarboxylase (UROD) catalyzes the sequntial removal
        of four carboxylic groups from the acetic acid side chains of uroporphyrinogen III (URO3) to form
        coproporphyrinogen III (COPRO3)
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-190182
  qualifier: located_in
  review:
    summary: TAS (Reactome) location in cytosol for the UROD reaction converting uroporphyrinogen I to
      coproporphyrinogen I (the less-efficient isomer I reaction). Consistent with the established cytosolic
      localization.
    action: ACCEPT
    reason: Correct; Reactome describes cytosolic UROD activity on the isomer I substrate.
    supported_by:
    - reference_id: Reactome:R-HSA-190182
      supporting_text: Cytosolic uroporphyrinogen decarboxylase (UROD) catalyzes the sequential removal
        of four carboxylic groups from the acetic acid side chains of uroporphyrinogen I (URO1) to form
        coproporphyrinogen I (COPRO1)
- term:
    id: GO:0006783
    label: heme biosynthetic process
  evidence_type: IC
  original_reference_id: PMID:18004775
  qualifier: involved_in
  review:
    summary: IC (inferred by curator) that UROD is involved in heme biosynthesis, based on its uroporphyrinogen
      decarboxylase activity (with:GO:0004853). UROD is one of the cytosolic heme-biosynthesis enzymes.
    action: ACCEPT
    reason: Core biological process, correctly inferred from the enzymatic activity. Although this paper's
      primary subject is uroporphyrinogen III synthase, it treats UROD as one of the cytosolic heme-biosynthesis
      enzymes; the curator inference to heme biosynthesis is sound.
    supported_by:
    - reference_id: PMID:18004775
      supporting_text: cytosolic enzymes of heme biosynthesis
    - reference_id: file:human/UROD/UROD-uniprot.txt
      supporting_text: participates in the fifth step in the heme biosynthetic pathway
- term:
    id: GO:0004853
    label: uroporphyrinogen decarboxylase activity
  evidence_type: IDA
  original_reference_id: PMID:18004775
  qualifier: enables
  review:
    summary: IDA for uroporphyrinogen decarboxylase activity anchored to a study that expressed and purified
      the cytosolic heme-biosynthesis enzymes (including URO-decarboxylase) and probed a possible URO-synthase/URO-decarboxylase
      complex.
    action: ACCEPT
    reason: Supports the core molecular function. The paper foregrounds uroporphyrinogen III synthase
      in its title, but per policy an experimental annotation whose full text the curator read is not
      overruled from the abstract alone; the abstract confirms preparation of purified URO-decarboxylase.
      Retained as supporting the enzymatic activity.
    supported_by:
    - reference_id: PMID:18004775
      supporting_text: cytosolic enzymes of heme biosynthesis
- term:
    id: GO:0004853
    label: uroporphyrinogen decarboxylase activity
  evidence_type: TAS
  original_reference_id: PMID:1634232
  qualifier: enables
  review:
    summary: TAS for uroporphyrinogen decarboxylase activity; the paper describes UROD as the fifth enzyme
      of the heme biosynthetic pathway and studies HEP-causing mutations.
    action: ACCEPT
    reason: Supports the core molecular function; author statement (TAS) that UROD is the fifth heme biosynthetic
      enzyme.
    supported_by:
    - reference_id: PMID:1634232
      supporting_text: uroporphyrinogen decarboxylase (UROD), the fifth
core_functions:
- description: 'Uroporphyrinogen decarboxylase: catalyzes the fifth step of heme biosynthesis, the sequential,
    cofactor-independent decarboxylation of the four acetate side chains of uroporphyrinogen III to methyl
    groups, yielding coproporphyrinogen III (and 4 CO2), in the cytosol.'
  molecular_function:
    id: GO:0004853
    label: uroporphyrinogen decarboxylase activity
  directly_involved_in:
  - id: GO:0006783
    label: heme biosynthetic process
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:14633982
    supporting_text: the heme biosynthetic pathway, catalyzes decarboxylation of all four acetate
  - reference_id: file:human/UROD/UROD-uniprot.txt
    supporting_text: participates in the fifth step in the heme biosynthetic pathway
proposed_new_terms: []
suggested_questions:
- question: Does UROD have any biologically meaningful non-cytosolic (e.g. nuclear) pool or moonlighting
    function, or is the HPA nucleoplasmic immunofluorescence signal purely incidental?
- question: Are any of the high-throughput interactome partners (e.g. PPID, PHKA2, LRATD2) reproducible
    and functionally relevant to UROD folding, stability, or heme-pathway channeling?
suggested_experiments:
- description: Metabolic-channeling / complex-formation assays (co-IP, proximity labeling, size-exclusion
    with purified proteins) to test whether UROD physically associates with adjacent cytosolic heme-biosynthesis
    enzymes (UROS, HMBS) under physiological conditions, given that NMR did not detect a stable URO-synthase/URO-decarboxylase
    complex.
- description: Quantitative subcellular fractionation and validated-antibody immunofluorescence to confirm
    that endogenous UROD is essentially confined to the cytosol and to assess the reported nucleoplasmic
    signal.