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.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | 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. 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. Supporting Evidence: file:human/UROD/UROD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol Reactome:R-HSA-189425 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) file:human/UROD/UROD-uniprot.txt PANTHER; PTHR21091:SF169; UROPORPHYRINOGEN DECARBOXYLASE; 1. |
| GO:0006783 heme biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) assertion that UROD is involved in heme biosynthesis. UROD catalyzes the fifth step of the heme biosynthetic pathway. Reason: PAINT IBA (GO_REF:0000033) from the uroporphyrinogen decarboxylase subfamily of PANTHER PTHR21091. UROD performs the fifth step of heme biosynthesis itself (decarboxylation of uroporphyrinogen III to coproporphyrinogen III); core process. Supporting Evidence: file:human/UROD/UROD-uniprot.txt Catalyzes the sequential decarboxylation of the four acetate side chains of uroporphyrinogen to form coproporphyrinogen and participates in the fifth step in the heme biosynthetic pathway PMID:1634232 A deficiency in the activity of uroporphyrinogen decarboxylase (UROD), the fifth enzyme of the haem biosynthetic pathway, is found in familial porphyria cutanea tarda (F-PCT) and hepatoerythropoietic porphyria (HEP). file:human/UROD/UROD-uniprot.txt PANTHER; PTHR21091:SF169; UROPORPHYRINOGEN DECARBOXYLASE; 1. |
| GO:0004853 uroporphyrinogen decarboxylase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) assertion of uroporphyrinogen decarboxylase activity. This is the defining molecular function of UROD, supported experimentally and structurally. Reason: PAINT IBA (GO_REF:0000033) from PANTHER PTHR21091 (subfamily SF169, uroporphyrinogen decarboxylase). This is the defining molecular function of UROD, matching the activity assayed on the human recombinant enzyme and its crystal structures. Supporting Evidence: PMID:14633982 Uroporphyrinogen decarboxylase (URO-D), an essential enzyme that functions in the heme biosynthetic pathway, catalyzes decarboxylation of all four acetate groups of uroporphyrinogen to form coproporphyrinogen. file:human/UROD/UROD-uniprot.txt Reaction=uroporphyrinogen III + 4 H(+) = coproporphyrinogen III + 4 CO2 file:human/UROD/UROD-uniprot.txt PANTHER; PTHR21091:SF169; UROPORPHYRINOGEN DECARBOXYLASE; 1. |
| GO:0004853 uroporphyrinogen decarboxylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated electronic annotation (GO_REF:0000120; family signatures and the EC/Rhea catalytic-activity annotation) of uroporphyrinogen decarboxylase activity. Reason: Correct core catalytic function; the curated catalytic-activity line rests on experiments on the human enzyme, and the HAMAP/InterPro URO-D signatures place the protein in the family. Supporting Evidence: file:human/UROD/UROD-uniprot.txt Reaction=uroporphyrinogen III + 4 H(+) = coproporphyrinogen III + 4 CO2 file:human/UROD/UROD-uniprot.txt HAMAP; MF_00218; URO_D; 1. file:human/UROD/UROD-uniprot.txt InterPro; IPR000257; Uroporphyrinogen_deCOase. |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic (IEA) location in cytosol derived from the UniProt subcellular-location vocabulary mapping. Matches the established cytosolic localization. Reason: Correct; the UniProt SubCell mapping reproduces the experimentally supported cytosolic localization of this soluble enzyme. Supporting Evidence: file:human/UROD/UROD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0006779 porphyrin-containing compound biosynthetic process | IEA GO_REF:0000120 | MODIFY | 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). Reason: Correct but more general than the evidence supports. UROD's product, coproporphyrinogen III, is committed to heme in human cells, so the specific descendant heme biosynthetic process (GO:0006783), already carried by the gene (IBA, IC), is the appropriate replacement. Proposed replacements: heme biosynthetic process Supporting Evidence: file:human/UROD/UROD-uniprot.txt Catalyzes the sequential decarboxylation of the four acetate side chains of uroporphyrinogen to form coproporphyrinogen and participates in the fifth step in the heme biosynthetic pathway file:human/UROD/UROD-uniprot.txt PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 4/4. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | 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. Reason: Bare protein binding from a proteome-scale interactome screen carries no functional information about UROD; per the protein-binding policy the row is removed. Removal does not mean the reported interaction is false. No partner identified in these screens implies a more informative UROD molecular function. Supporting Evidence: file:human/UROD/UROD-uniprot.txt P06132; Q96KN1: LRATD2 |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | 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. Reason: Bare protein binding from a proteome-scale interactome screen carries no functional information about UROD; per the protein-binding policy the row is removed. Removal does not mean the reported interaction is false. No partner identified in these screens implies a more informative UROD molecular function. Supporting Evidence: PMID:28514442 Here we present BioPlex 2. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Non-specific protein-binding (IPI) from a systematic interaction-perturbation screen (interaction with Q96KN1). Uninformative bare protein binding. Reason: Bare protein binding from a proteome-scale interactome screen carries no functional information about UROD; per the protein-binding policy the row is removed. Removal does not mean the reported interaction is false. No partner identified in these screens implies a more informative UROD molecular function. Supporting Evidence: PMID:31515488 we then performed yeast two-hybrid (Y2H) experiments to measure the impact of these 2009 missense SNVs across 2185 human protein–protein interactions |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | 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. Reason: Bare protein binding from a proteome-scale interactome screen carries no functional information about UROD; per the protein-binding policy the row is removed. Removal does not mean the reported interaction is false. No partner identified in these screens implies a more informative UROD molecular function. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | 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. Reason: Bare protein binding from a proteome-scale interactome screen carries no functional information about UROD; per the protein-binding policy the row is removed. Removal does not mean the reported interaction is false. No partner identified in these screens implies a more informative UROD molecular function. Supporting Evidence: PMID:33961781 In contrast, affinity-purification mass spectrometry (AP-MS) enables enrichment and detection of even low-abundance proteins, though exogenous expression of tagged baits is required |
| GO:0006785 heme B biosynthetic process | IDA PMID:11069625 Co-inheritance of mutations in the uroporphyrinogen decarbox... | ACCEPT | 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. 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. Supporting Evidence: PMID:11069625 Porphyria cutanea tarda is a skin disease caused by photosensitization by porphyrins whose accumulation is caused by deficiency of hepatic uroporphyrin- ogen decarboxylase activity. file:human/UROD/UROD-uniprot.txt Catalyzes the sequential decarboxylation of the four acetate side chains of uroporphyrinogen to form coproporphyrinogen and participates in the fifth step in the heme biosynthetic pathway |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | 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. Reason: Direct Human Protein Atlas immunofluorescence observation. UROD is a small soluble cytosolic enzyme and some nucleoplasmic signal is plausible for such a protein, but there is no evidence of a nuclear function and the curated and functional location is the cytosol. Kept as an observed, peripheral location rather than marked as over-annotated, since an antibody-based direct observation cannot be dismissed from here. Supporting Evidence: file:human/UROD/UROD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol Reactome:R-HSA-189425 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 |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence (IDA) placing UROD in the cytosol. Concordant with the established cytosolic localization of this soluble enzyme. Reason: Correct localization, directly supported by experimental immunofluorescence and consistent with all other lines of evidence. Supporting Evidence: file:human/UROD/UROD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol Reactome:R-HSA-189425 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 |
| GO:0005829 cytosol | ISS GO_REF:0000024 | ACCEPT | 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. Reason: Correct; the sequence-similarity transfer recovers the established cytosolic site of activity of UROD. Supporting Evidence: file:human/UROD/UROD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0004853 uroporphyrinogen decarboxylase activity | IDA PMID:11069625 Co-inheritance of mutations in the uroporphyrinogen decarbox... | ACCEPT | Summary: IDA for uroporphyrinogen decarboxylase activity from a study of FPCT-causing UROD mutations, in which hepatic UROD activity deficiency underlies the disease. Reason: Directly supports the core molecular function; experimental annotation curated from the full text. Supporting Evidence: PMID:11069625 Porphyria cutanea tarda is a skin disease caused by photosensitization by porphyrins whose accumulation is caused by deficiency of hepatic uroporphyrin- ogen decarboxylase activity. file:human/UROD/UROD-uniprot.txt Reaction=uroporphyrinogen III + 4 H(+) = coproporphyrinogen III + 4 CO2 |
| GO:0004853 uroporphyrinogen decarboxylase activity | IDA PMID:11719352 Functional consequences of naturally occurring mutations in ... | ACCEPT | 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). Reason: Directly supports the core molecular function via recombinant enzymatic assay of the human protein. Supporting Evidence: PMID:11719352 Enzymatic activity of soluble, recombinant mutant URO-D genes ranged from 29% to 94% of normal. |
| GO:0004853 uroporphyrinogen decarboxylase activity | IDA PMID:12071824 Description of a new mutation in hepatoerythropoietic porphy... | ACCEPT | Summary: IDA for uroporphyrinogen decarboxylase activity; HEP patient with F46L UROD showed low UROD activity and recombinant expression confirmed the deleterious effect. Reason: Supports the core molecular function; enzymatic activity measured directly and confirmed by recombinant expression. Supporting Evidence: PMID:12071824 We found low levels of UROD enzymatic activity and a new homozygous mutation of the UROD gene, a phenylanine-to-leucine substitution at codon 46 (F46L). PMID:12071824 Prokaryotic expression of the F46L mutation using a pGEX vector has been used to confirm the deleterious effect of the mutation. |
| GO:0004853 uroporphyrinogen decarboxylase activity | IDA PMID:14633982 Structural basis for tetrapyrrole coordination by uroporphyr... | ACCEPT | 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. Reason: Strong structural/biochemical support for the core molecular function. Supporting Evidence: PMID:14633982 Uroporphyrinogen decarboxylase (URO-D), an essential enzyme that functions in the heme biosynthetic pathway, catalyzes decarboxylation of all four acetate groups of uroporphyrinogen to form coproporphyrinogen. PMID:14633982 The central coordination geometry of Asp86 allows the initial substrates and the various partially decarboxylated intermediates to be bound with equivalent activating interactions, and thereby explains how all four of the substrate acetate groups can be decarboxylated at the same catalytic center. |
| GO:0004853 uroporphyrinogen decarboxylase activity | IDA PMID:21668429 Hepatoerythropoietic porphyria due to a novel mutation in th... | ACCEPT | Summary: IDA for uroporphyrinogen decarboxylase activity; recombinant UROD (wild-type and G170D HEP variant) purified and assayed against uroporphyrinogen I and III substrates. Reason: Directly supports the core molecular function with a purified-protein enzymatic assay on both isomer substrates. Supporting Evidence: PMID:21668429 Recombinant mutant UROD protein was purified and the specific activity towards both uroporphyrinogen I and uroporphyrinogen III as substrates was determined and compared with a purified recombinant wild-type UROD. PMID:21668429 Relative activity of G170D UROD was 17.3 ± 0.6% of wild-type (mean ± standard deviation, N=2 assays) towards uroporphyrinogen I and 60.6 ± 1.1% of wild-type towards uroporphyrinogen III. |
| GO:0006778 porphyrin-containing compound metabolic process | IDA PMID:12071824 Description of a new mutation in hepatoerythropoietic porphy... | MODIFY | Summary: IDA that UROD is involved in porphyrin-containing compound metabolism, from a HEP study showing UROD deficiency and abnormal (poly-carboxylated) porphyrin excretion. Reason: Correct but general. The cited HEP study shows that UROD deficiency causes accumulation and excretion of polycarboxylated porphyrins, i.e. that UROD acts in the biosynthetic route; the specific descendant heme biosynthetic process (GO:0006783), already carried by the gene, is the appropriate replacement. Proposed replacements: heme biosynthetic process Supporting Evidence: PMID:12071824 Hepatoerythropoietic porphyria (HEP) is usually a severe form of cutaneous porphyria, characterized biochemically by an increased urinary excretion of polycarboxylated porphyrins. PMID:12071824 We found low levels of UROD enzymatic activity and a new homozygous mutation of the UROD gene, a phenylanine-to-leucine substitution at codon 46 (F46L). |
| GO:0006787 porphyrin-containing compound catabolic process | IDA PMID:11069625 Co-inheritance of mutations in the uroporphyrinogen decarbox... | MODIFY | 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. Reason: Lateral correction of the process branch. The decarboxylation of uroporphyrinogen to coproporphyrinogen is a biosynthetic step on the route to heme, not the breakdown of a porphyrin-containing compound; the side reaction on the isomer I substrate yields coproporphyrinogen I, which is also not degradation. The essence (UROD acts in porphyrin metabolism via its decarboxylase activity) is right, so the row is modified to heme biosynthetic process rather than removed. The source is a PCT genetics study reporting deficient UROD activity. Proposed replacements: heme biosynthetic process Supporting Evidence: PMID:11069625 Porphyria cutanea tarda is a skin disease caused by photosensitization by porphyrins whose accumulation is caused by deficiency of hepatic uroporphyrin- ogen decarboxylase activity. file:human/UROD/UROD-uniprot.txt Catalyzes the sequential decarboxylation of the four acetate side chains of uroporphyrinogen to form coproporphyrinogen and participates in the fifth step in the heme biosynthetic pathway |
| GO:0006787 porphyrin-containing compound catabolic process | IDA PMID:11719352 Functional consequences of naturally occurring mutations in ... | MODIFY | 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. Reason: Lateral correction of the process branch. The decarboxylation of uroporphyrinogen to coproporphyrinogen is a biosynthetic step on the route to heme, not the breakdown of a porphyrin-containing compound; the side reaction on the isomer I substrate yields coproporphyrinogen I, which is also not degradation. The essence (UROD acts in porphyrin metabolism via its decarboxylase activity) is right, so the row is modified to heme biosynthetic process rather than removed. The source measures activity of recombinant mutant UROD proteins. Proposed replacements: heme biosynthetic process Supporting Evidence: PMID:11719352 Enzymatic activity of soluble, recombinant mutant URO-D genes ranged from 29% to 94% of normal. file:human/UROD/UROD-uniprot.txt Catalyzes the sequential decarboxylation of the four acetate side chains of uroporphyrinogen to form coproporphyrinogen and participates in the fifth step in the heme biosynthetic pathway |
| GO:0006787 porphyrin-containing compound catabolic process | IDA PMID:14633982 Structural basis for tetrapyrrole coordination by uroporphyr... | MODIFY | Summary: IDA annotating UROD to porphyrin-containing compound CATABOLIC process. The structural paper establishes decarboxylase activity, but the biological process direction is wrong. Reason: Lateral correction of the process branch. The decarboxylation of uroporphyrinogen to coproporphyrinogen is a biosynthetic step on the route to heme, not the breakdown of a porphyrin-containing compound; the side reaction on the isomer I substrate yields coproporphyrinogen I, which is also not degradation. The essence (UROD acts in porphyrin metabolism via its decarboxylase activity) is right, so the row is modified to heme biosynthetic process rather than removed. The source is the product-complex crystal structure. Proposed replacements: heme biosynthetic process Supporting Evidence: PMID:14633982 Uroporphyrinogen decarboxylase (URO-D), an essential enzyme that functions in the heme biosynthetic pathway, catalyzes decarboxylation of all four acetate groups of uroporphyrinogen to form coproporphyrinogen. file:human/UROD/UROD-uniprot.txt Catalyzes the sequential decarboxylation of the four acetate side chains of uroporphyrinogen to form coproporphyrinogen and participates in the fifth step in the heme biosynthetic pathway |
| GO:0006787 porphyrin-containing compound catabolic process | IDA PMID:21668429 Hepatoerythropoietic porphyria due to a novel mutation in th... | MODIFY | Summary: IDA annotating UROD to porphyrin-containing compound CATABOLIC process. The HEP study supports decarboxylase activity, but this catabolic BP is directionally incorrect. Reason: Lateral correction of the process branch. The decarboxylation of uroporphyrinogen to coproporphyrinogen is a biosynthetic step on the route to heme, not the breakdown of a porphyrin-containing compound; the side reaction on the isomer I substrate yields coproporphyrinogen I, which is also not degradation. The essence (UROD acts in porphyrin metabolism via its decarboxylase activity) is right, so the row is modified to heme biosynthetic process rather than removed. The source assays purified recombinant UROD on both isomer substrates. Proposed replacements: heme biosynthetic process Supporting Evidence: PMID:21668429 Recombinant mutant UROD protein was purified and the specific activity towards both uroporphyrinogen I and uroporphyrinogen III as substrates was determined and compared with a purified recombinant wild-type UROD. file:human/UROD/UROD-uniprot.txt Catalyzes the sequential decarboxylation of the four acetate side chains of uroporphyrinogen to form coproporphyrinogen and participates in the fifth step in the heme biosynthetic pathway |
| GO:0005829 cytosol | TAS Reactome:R-HSA-189425 | ACCEPT | Summary: TAS (Reactome) location in cytosol for the UROD reaction converting uroporphyrinogen III to coproporphyrinogen III. Consistent with the established cytosolic localization. Reason: Correct; Reactome explicitly describes cytosolic UROD. Supporting Evidence: Reactome:R-HSA-189425 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 file:human/UROD/UROD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-190182 | ACCEPT | 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. Reason: Correct; Reactome describes cytosolic UROD activity on the isomer I substrate. Supporting Evidence: Reactome:R-HSA-190182 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 file:human/UROD/UROD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0006783 heme biosynthetic process | IC PMID:18004775 Human uroporphyrinogen III synthase: NMR-based mapping of th... | ACCEPT | 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. 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. Supporting Evidence: PMID:18004775 an efficient expression and purification procedure was developed for these cytosolic enzymes of heme biosynthesis file:human/UROD/UROD-uniprot.txt Catalyzes the sequential decarboxylation of the four acetate side chains of uroporphyrinogen to form coproporphyrinogen and participates in the fifth step in the heme biosynthetic pathway |
| GO:0004853 uroporphyrinogen decarboxylase activity | IDA PMID:18004775 Human uroporphyrinogen III synthase: NMR-based mapping of th... | ACCEPT | 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. 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. Supporting Evidence: PMID:18004775 an efficient expression and purification procedure was developed for these cytosolic enzymes of heme biosynthesis PMID:18004775 The absence of chemical shift changes in the (15)N spectrum of URO-synthase mixed with the homogeneous HMB-synthase holoenzyme or URO-decarboxylase precluded occurrence of a stable cytosolic enzyme complex. file:human/UROD/UROD-uniprot.txt Catalyzes the sequential decarboxylation of the four acetate side chains of uroporphyrinogen to form coproporphyrinogen and participates in the fifth step in the heme biosynthetic pathway |
| GO:0004853 uroporphyrinogen decarboxylase activity | TAS PMID:1634232 Characterization of a new mutation (R292G) and a deletion at... | ACCEPT | Summary: TAS for uroporphyrinogen decarboxylase activity; the paper describes UROD as the fifth enzyme of the heme biosynthetic pathway and studies HEP-causing mutations. Reason: Supports the core molecular function; author statement (TAS) that UROD is the fifth heme biosynthetic enzyme. Supporting Evidence: PMID:1634232 A deficiency in the activity of uroporphyrinogen decarboxylase (UROD), the fifth enzyme of the haem biosynthetic pathway, is found in familial porphyria cutanea tarda (F-PCT) and hepatoerythropoietic porphyria (HEP). |
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Download this section (compressed HTML)Q: Does UROD have any biologically meaningful non-cytosolic (e.g. nuclear) pool or moonlighting function, or is the HPA nucleoplasmic immunofluorescence signal purely incidental?
Q: 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?
Experiment: 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.
Experiment: 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.
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