UROS

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004852 uroporphyrinogen-III synthase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically-inferred core catalytic activity. This is the defining molecular function of UROS, well supported by direct experimental evidence in human and orthologs. Reason: Correct molecular function at the appropriate level of specificity; the IBA is concordant with human IDA/EXP evidence for the same term. Supporting Evidence: PMID:3174619 the cyclic tetrapyrrole, uroporphyrinogen III
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: UROS acts in the cytosol, consistent with it being one of the four cytosolic enzymes of heme biosynthesis. Reason: Correct subcellular location; concordant with UniProt subcellular location (Cytoplasm, cytosol) and Reactome. Supporting Evidence: PMID:18004775 cytosolic enzymes of heme biosynthesis
GO:0006780 uroporphyrinogen III biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: UROS produces uroporphyrinogen III, so this is the immediate biosynthetic process it drives. Reason: Directly reflects the enzyme's product; well supported experimentally. Supporting Evidence: PMID:3174619 the cyclic tetrapyrrole, uroporphyrinogen III
GO:0004852 uroporphyrinogen-III synthase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assertion of the core catalytic activity (ARBA/RHEA/EC/InterPro), matching EC 4.2.1.75 and RHEA:18965. Reason: Correct and consistent with the experimentally verified molecular function. Supporting Evidence: file:human/UROS/UROS-uniprot.txt Catalyzes cyclization of the linear tetrapyrrole,
GO:0005829 cytosol	IEA GO_REF:0000044	ACCEPT	Summary: Electronic location annotation from UniProt subcellular-location mapping; matches the curated cytosolic localization. Reason: Correct location, concordant with UniProt SUBCELLULAR LOCATION. Supporting Evidence: file:human/UROS/UROS-uniprot.txt Cytoplasm, cytosol
GO:0006785 heme B biosynthetic process	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: UROS produces uroporphyrinogen III, the branch-point precursor for ALL porphyrins (heme, chlorophyll, corrins/B12, siroheme, F430), not specifically heme b. Heme b is a distal, specific product several enzymatic steps downstream. Reason: Over-specific for an enzyme acting at the branch point upstream of the heme-specific sub-pathway; the general heme biosynthetic process (GO:0006783) and tetrapyrrole biosynthetic process (GO:0033014) capture its role more appropriately. Supporting Evidence: PMID:11689424 the fourth enzyme in the porphyrin biosynthetic pathway
GO:0033014 tetrapyrrole biosynthetic process	IEA GO_REF:0000002	ACCEPT	Summary: UROS synthesizes the cyclic tetrapyrrole uroporphyrinogen III, so this broader biosynthetic-process term is correct. Reason: Accurate parent process; uroporphyrinogen III is a tetrapyrrole and the precursor of all downstream tetrapyrroles. Supporting Evidence: PMID:3174619 the cyclic tetrapyrrole, uroporphyrinogen III
GO:0005542 folic acid binding	IEA GO_REF:0000107	REMOVE	Summary: Electronic transfer from the rat ortholog (Q5XIF2) via Ensembl Compara. UROS is a hydroxymethylbilane cyclizing lyase; its substrate is a linear tetrapyrrole, not a pterin/folate, and there is no biochemical evidence that UROS binds folic acid. Reason: Spurious electronically-transferred function unsupported by any evidence for UROS; incompatible with its characterized substrate and mechanism. Supporting Evidence: file:human/UROS/UROS-uniprot.txt Catalyzes cyclization of the linear tetrapyrrole,
GO:0006780 uroporphyrinogen III biosynthetic process	IEA GO_REF:0000107	ACCEPT	Summary: Electronic transfer of the immediate biosynthetic process from the rat ortholog; correct. Reason: Matches the enzyme's direct product; concordant with human experimental annotations to the same term. Supporting Evidence: PMID:3174619 the cyclic tetrapyrrole, uroporphyrinogen III
GO:0070541 response to platinum ion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Generic stress/perturbation-response term electronically transferred from the rat ortholog (Q5XIF2). This is not part of the characterized core molecular role of this heme-biosynthesis enzyme. Reason: Peripheral response term derived from expression-type ortholog data; does not reflect the enzyme's biosynthetic function and is not core. Supporting Evidence: file:human/UROS/UROS-uniprot.txt Catalyzes cyclization of the linear tetrapyrrole,
GO:0071243 cellular response to arsenic-containing substance	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Generic response term electronically transferred from the rat ortholog; not a characterized function of human UROS. Reason: Peripheral perturbation-response annotation from ortholog transfer, not the enzyme's core biosynthetic role. Supporting Evidence: file:human/UROS/UROS-uniprot.txt Catalyzes cyclization of the linear tetrapyrrole,
GO:0071418 cellular response to amine stimulus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Generic response term electronically transferred from the rat ortholog; not a characterized function of human UROS. Reason: Peripheral perturbation-response annotation from ortholog transfer, not the enzyme's core biosynthetic role. Supporting Evidence: file:human/UROS/UROS-uniprot.txt Catalyzes cyclization of the linear tetrapyrrole,
GO:0006785 heme B biosynthetic process	IDA PMID:18004775 Human uroporphyrinogen III synthase: NMR-based mapping of th...	MARK AS OVER ANNOTATED	Summary: Experimental annotation placing UROS in heme biosynthesis. However heme b is a distal, specific product; UROS acts at the uroporphyrinogen III branch point upstream of the heme-specific sub-pathway and its product feeds all porphyrins, not specifically heme b. Reason: The experimental support establishes UROS's role in heme/porphyrin biosynthesis, but the heme-b-specific term is over-specific for a branch-point enzyme; the general heme biosynthetic process (GO:0006783), also annotated, is the appropriate representation. Retained rather than removed per the underlying experimental evidence. Supporting Evidence: PMID:18004775 cutaneous disorder, congenital erythropoietic porphyria
GO:0006783 heme biosynthetic process	TAS Reactome:R-HSA-189451	ACCEPT	Summary: UROS is one of the eight enzymes of heme biosynthesis (the fourth step, one of the four cytosolic steps), producing the uroporphyrinogen III precursor. Reason: Core biological process for this enzyme; well supported by literature and the Reactome heme biosynthesis pathway. Supporting Evidence: Reactome:R-HSA-189451 The next two steps convert four molecules of PBG into the cyclic tetrapyrrole uroporphyringen III
GO:0004852 uroporphyrinogen-III synthase activity	TAS Reactome:R-HSA-189488	ACCEPT	Summary: Reactome-curated statement of the core catalytic activity (HMB to uroporphyrinogen III). Reason: Correct core molecular function, concordant with experimental evidence. Supporting Evidence: Reactome:R-HSA-189488 catalyzes the conversion of HMB (hydroxymethylbilane) to uroporphyrinogen III, a reaction involving ring
GO:0004852 uroporphyrinogen-III synthase activity	EXP PMID:11689424 Crystal structure of human uroporphyrinogen III synthase.	ACCEPT	Summary: Experimental (crystal structure with catalytic activity/mutagenesis) confirmation of the uroporphyrinogen-III synthase activity, including the ring closure with D-ring flipping. Reason: Direct experimental support for the defining molecular function. Supporting Evidence: PMID:11689424 catalyzes ring closure of the linear tetrapyrrole hydroxymethylbilane (HMB), with concurrent flipping of the D ring
GO:0005829 cytosol	ISS GO_REF:0000024	ACCEPT	Summary: Cytosolic localization inferred by sequence similarity to the mouse ortholog; consistent with the curated human localization. Reason: Correct location; concordant with UniProt and Reactome. Supporting Evidence: file:human/UROS/UROS-uniprot.txt Cytoplasm, cytosol
GO:0005829 cytosol	TAS Reactome:R-HSA-189488	ACCEPT	Summary: Reactome places the UROS reaction in the cytosol. Reason: Correct location, consistent with the four cytosolic steps of heme biosynthesis. Supporting Evidence: file:human/UROS/UROS-uniprot.txt Cytoplasm, cytosol
GO:0006783 heme biosynthetic process	IC PMID:18004775 Human uroporphyrinogen III synthase: NMR-based mapping of th...	ACCEPT	Summary: Curator inference (from the GO:0004852 molecular function) that UROS participates in heme biosynthesis. Reason: Sound inference; UROS is the fourth enzyme of the heme biosynthetic pathway and this is a core biological process. Supporting Evidence: PMID:11689424 the fourth enzyme in the porphyrin biosynthetic pathway
GO:0004852 uroporphyrinogen-III synthase activity	IDA PMID:3805019 Purification and properties of uroporphyrinogen III synthase...	ACCEPT	Summary: The enzyme was purified to homogeneity from human erythrocytes and shown to form uroporphyrinogen III from hydroxymethylbilane, directly demonstrating uroporphyrinogen-III synthase activity. Reason: Direct experimental demonstration of the core catalytic activity. Supporting Evidence: PMID:3805019 the purified enzyme formed uroporphyrinogen
GO:0005739 mitochondrion	ISS GO_REF:0000024	REMOVE	Summary: Mitochondrial localization asserted by an old (2009) sequence-similarity inference from UniProtKB:P51163. UROS is a cytosolic enzyme, one of the four cytosolic steps of heme biosynthesis; UniProt and Reactome both localize it to the cytosol only. Reason: Contradicted by the curated cytosolic localization; a non-experimental ISS inference that is inconsistent with current UniProt and pathway evidence. Supporting Evidence: file:human/UROS/UROS-uniprot.txt Cytoplasm, cytosol PMID:18004775 cytosolic enzymes of heme biosynthesis
GO:0005829 cytosol	NAS PMID:3805019 Purification and properties of uroporphyrinogen III synthase...	ACCEPT	Summary: Non-traceable author statement of cytosolic localization; the enzyme was purified from human erythrocyte cytosol. Reason: Consistent with the well-established cytosolic localization of UROS. Supporting Evidence: file:human/UROS/UROS-uniprot.txt Cytoplasm, cytosol
GO:0006780 uroporphyrinogen III biosynthetic process	IDA PMID:3805019 Purification and properties of uroporphyrinogen III synthase...	ACCEPT	Summary: The purified enzyme formed uroporphyrinogen III from hydroxymethylbilane, directly demonstrating its role in uroporphyrinogen III biosynthesis. Reason: Direct experimental support for the immediate biosynthetic process. Supporting Evidence: PMID:3805019 the purified enzyme formed uroporphyrinogen
GO:0006783 heme biosynthetic process	IDA PMID:3805019 Purification and properties of uroporphyrinogen III synthase...	ACCEPT	Summary: The paper characterizes UROS as the fourth enzyme in the heme biosynthetic pathway, purified from human erythrocytes. Reason: Core biological process; UROS is an essential heme-biosynthesis enzyme. Supporting Evidence: PMID:3805019 the fourth enzyme in the heme biosynthetic pathway
GO:0004852 uroporphyrinogen-III synthase activity	IDA PMID:18004775 Human uroporphyrinogen III synthase: NMR-based mapping of th...	ACCEPT	Summary: NMR active-site mapping study of URO-synthase confirming the enzyme catalyzes cyclization and D-ring isomerization of hydroxymethylbilane to uroporphyrinogen III. Reason: Direct experimental support for the core catalytic activity. Supporting Evidence: PMID:11689424 catalyzes ring closure of the linear tetrapyrrole hydroxymethylbilane (HMB), with concurrent flipping of the D ring
GO:0006780 uroporphyrinogen III biosynthetic process	IDA PMID:18004775 Human uroporphyrinogen III synthase: NMR-based mapping of th...	ACCEPT	Summary: The enzyme catalyzes the formation of uroporphyrinogen III from hydroxymethylbilane, directly implicating it in uroporphyrinogen III biosynthesis. Reason: Direct experimental support for the immediate biosynthetic process. Supporting Evidence: PMID:11689424 catalyzes ring closure of the linear tetrapyrrole hydroxymethylbilane (HMB), with concurrent flipping of the D ring
GO:0004852 uroporphyrinogen-III synthase activity	IDA PMID:3174619 Human uroporphyrinogen III synthase: molecular cloning, nucl...	ACCEPT	Summary: Molecular cloning and expression of the full-length human URO-synthase cDNA in E. coli yielded high levels of enzymatic activity, confirming the gene product's uroporphyrinogen-III synthase activity. Reason: Direct experimental support (functional expression) for the core catalytic activity. Supporting Evidence: PMID:3174619 the fourth enzyme in the heme biosynthetic pathway
GO:0006780 uroporphyrinogen III biosynthetic process	IDA PMID:3174619 Human uroporphyrinogen III synthase: molecular cloning, nucl...	ACCEPT	Summary: The cloned/expressed enzyme is responsible for conversion of hydroxymethylbilane to uroporphyrinogen III. Reason: Direct experimental support for the immediate biosynthetic process. Supporting Evidence: PMID:3174619 the cyclic tetrapyrrole, uroporphyrinogen III

Gene Description

Existing Annotations Review

Core Functions

Uroporphyrinogen-III synthase activity - catalyzes the cyclization of the linear tetrapyrrole hydroxymethylbilane into uroporphyrinogen III, with inversion of ring D, ensuring formation of the physiological III isomer.

References

📚 Additional Documentation

Notes

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