pseudouridine degradation

MetaCyc:PWY-6019

The complete two-step pseudouridine degradation pathway phosphorylates free pseudouridine using ATP, then cleaves its C-C glycosidic bond to uracil and D-ribofuranose 5-phosphate. It follows MetaCyc PWY-6019 and both reactions of the misleadingly titled PathBank Purine Degradation map. The selected protein core is E. coli K-12, supported by reviewed annotations and direct K-12 PsuG characterization. Whole-cell utilization in the original study was in UTI89; kinase structural studies used strain B/BL21 and are not relabeled as K-12 flux or assembly experiments. PsuG is a supported homotrimer. The K-12 kinase is assigned by reviewed functional annotation; the cited dimer experiments concern strain B/BL21, so these sources do not establish the K-12 oligomeric state. Physiological PsuG cleavage is selected despite reversible chemistry and an equilibrium favoring synthesis. Its Mn, Fe and Co alternatives are retained without asserting simultaneous occupancy. The pathway ends at the two cleavage products; RNA pseudouridylation, transport, uracil salvage and downstream pyrimidine-ring degradation are outside the native boundary.

Pathway type

Organism scope

Escherichia coli K-12 NCBITaxon:83333

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Pathway network

17 nodes · 18 asserted directed edges

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Reaction / activity
Chemical / cofactor
Protein / complex
Pathway
Solid arrow: mechanistic relation
Dashed arrow: membership, location or cofactor relation

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Components and activities

Declared biological components and source reaction directions
Node	Kind or role	Source direction
Escherichia coli K-12 `NCBITaxon:83333`	taxon
pseudouridine `CHEBI:17802`	small molecule
ATP(4-) `CHEBI:30616`	small molecule
pseudouridine 5'-phosphate(2-) `CHEBI:58380`	small molecule
ADP(3-) `CHEBI:456216`	small molecule
hydron `CHEBI:15378`	small molecule
water `CHEBI:15377`	small molecule
D-ribofuranose 5-phosphate(2-) `CHEBI:78346`	small molecule
uracil `CHEBI:17568`	small molecule
manganese(2+) `CHEBI:29035`	cofactor
iron(2+) `CHEBI:29033`	cofactor
cobalt(2+) `CHEBI:48828`	cofactor
Pseudouridine kinase `UniProtKB:P30235`	protein
Pseudouridine-5'-phosphate glycosidase `UniProtKB:P33025`	protein
pseudouridine-5'-phosphate glycosidase `MetaCyc:CPLX0-8233`	complex
pseudouridine + ATP => psi-UMP + ADP + H(+) `RHEA:22449`	molecular activity	left to right
psi-UMP + H2O => D-ribose 5-phosphate + uracil `RHEA:18339`	molecular activity	right to left

Mechanistic edges

Mechanistic edges and their cited evidence
Subject	Predicate and description	Object	Evidence
pseudouridine `CHEBI:17802`	consumes	pseudouridine + ATP => psi-UMP + ADP + H(+) `RHEA:22449`	RHEA:22449 Source assertion: RHEA:22449 assigns CHEBI:17802 to its substrates, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/22449 rh:substrates; http://rdf.rhea-db.org/22448_L rh:contains1 http://rdf.rhea-db.org/Participant_22448_compound_3821; http://rdf.rhea-db.org/Participant_22448_compound_3821 rh:compound http://rdf.rhea-db.org/Compound_3821; rh:chebi`
ATP(4-) `CHEBI:30616`	consumes	pseudouridine + ATP => psi-UMP + ADP + H(+) `RHEA:22449`	RHEA:22449 Source assertion: RHEA:22449 assigns CHEBI:30616 to its substrates, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/22449 rh:substrates; http://rdf.rhea-db.org/22448_L rh:contains1 http://rdf.rhea-db.org/Participant_22448_compound_6372; http://rdf.rhea-db.org/Participant_22448_compound_6372 rh:compound http://rdf.rhea-db.org/Compound_6372; rh:chebi`
pseudouridine + ATP => psi-UMP + ADP + H(+) `RHEA:22449`	produces	pseudouridine 5'-phosphate(2-) `CHEBI:58380`	RHEA:22449 Source assertion: RHEA:22449 assigns CHEBI:58380 to its products, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/22449 rh:products; http://rdf.rhea-db.org/22448_R rh:contains1 http://rdf.rhea-db.org/Participant_22448_compound_1644; http://rdf.rhea-db.org/Participant_22448_compound_1644 rh:compound http://rdf.rhea-db.org/Compound_1644; rh:chebi`
pseudouridine + ATP => psi-UMP + ADP + H(+) `RHEA:22449`	produces	ADP(3-) `CHEBI:456216`	RHEA:22449 Source assertion: RHEA:22449 assigns CHEBI:456216 to its products, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/22449 rh:products; http://rdf.rhea-db.org/22448_R rh:contains1 http://rdf.rhea-db.org/Participant_22448_compound_2710; http://rdf.rhea-db.org/Participant_22448_compound_2710 rh:compound http://rdf.rhea-db.org/Compound_2710; rh:chebi`
pseudouridine + ATP => psi-UMP + ADP + H(+) `RHEA:22449`	produces	hydron `CHEBI:15378`	RHEA:22449 Source assertion: RHEA:22449 assigns CHEBI:15378 to its products, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/22449 rh:products; http://rdf.rhea-db.org/22448_R rh:contains1 http://rdf.rhea-db.org/Participant_22448_compound_3249; http://rdf.rhea-db.org/Participant_22448_compound_3249 rh:compound http://rdf.rhea-db.org/Compound_3249; rh:chebi`
pseudouridine 5'-phosphate(2-) `CHEBI:58380`	consumes	psi-UMP + H2O => D-ribose 5-phosphate + uracil `RHEA:18339`	RHEA:18339 Source assertion: RHEA:18339 assigns CHEBI:58380 to its substrates, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/18339 rh:substrates; http://rdf.rhea-db.org/18337_R rh:contains1 http://rdf.rhea-db.org/Participant_18337_compound_1644; http://rdf.rhea-db.org/Participant_18337_compound_1644 rh:compound http://rdf.rhea-db.org/Compound_1644; rh:chebi`
water `CHEBI:15377`	consumes	psi-UMP + H2O => D-ribose 5-phosphate + uracil `RHEA:18339`	RHEA:18339 Source assertion: RHEA:18339 assigns CHEBI:15377 to its substrates, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/18339 rh:substrates; http://rdf.rhea-db.org/18337_R rh:contains1 http://rdf.rhea-db.org/Participant_18337_compound_1283; http://rdf.rhea-db.org/Participant_18337_compound_1283 rh:compound http://rdf.rhea-db.org/Compound_1283; rh:chebi`
psi-UMP + H2O => D-ribose 5-phosphate + uracil `RHEA:18339`	produces	D-ribofuranose 5-phosphate(2-) `CHEBI:78346`	RHEA:18339 Source assertion: RHEA:18339 assigns CHEBI:78346 to its products, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/18339 rh:products; http://rdf.rhea-db.org/18337_L rh:contains1 http://rdf.rhea-db.org/Participant_18337_compound_9495; http://rdf.rhea-db.org/Participant_18337_compound_9495 rh:compound http://rdf.rhea-db.org/Compound_9495; rh:chebi`
psi-UMP + H2O => D-ribose 5-phosphate + uracil `RHEA:18339`	produces	uracil `CHEBI:17568`	RHEA:18339 Source assertion: RHEA:18339 assigns CHEBI:17568 to its products, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/18339 rh:products; http://rdf.rhea-db.org/18337_L rh:contains1 http://rdf.rhea-db.org/Participant_18337_compound_4063; http://rdf.rhea-db.org/Participant_18337_compound_4063 rh:compound http://rdf.rhea-db.org/Compound_4063; rh:chebi`
Pseudouridine kinase `UniProtKB:P30235`	enables This gene-product/activity assertion does not establish an independently sufficient monomer. The cited dimer experiments concern strain B/BL21; K-12 oligomeric state remains unestablished by these sources. Assay MgATP does not separately establish free-Mg cofactor binding.	pseudouridine + ATP => psi-UMP + ADP + H(+) `RHEA:22449`	UniProtKB:P30235 Source assertion: Reviewed K-12 PsuK annotates pseudouridine phosphorylation and RHEA:22448 with ECO:0000269 PMID:18591240. The original physiological study used UTI89; this edge retains the curated K-12 gene-product assignment. Source location `/organism/taxonId; /comments/0; /comments/1/reaction` RHEA:22449 Source assertion: Master RHEA:22448 explicitly links directionalReaction RHEA:22449. Source location `http://rdf.rhea-db.org/22448 rh:directionalReaction http://rdf.rhea-db.org/22449` PMID:18591240 specifically phosphorylates pseudouridine to pseudouridine 5'-phosphate Source location `/resultList/result[id="18591240"]/abstractText` PMID:35783380 Source assertion: The BL21-derived PsuK protein forms a homodimer by solution SEC and crystallography; the construct is A0A140N873, not the selected K-12 accession. Assays contain MgCl2 and KCl; the putative Mg sites were not modeled. Source location `PMC9247573: Results/Dimeric Structure of EcPsuK; Materials and Methods/Protein Expression and Purification; Activity Assay; Discussion`
pseudouridine-5'-phosphate glycosidase `MetaCyc:CPLX0-8233`	catalyzes PsuG is reversible; selecting degradation does not make the reverse synthesis impossible. The 2012 kinetic assay favors the reverse reaction and must not be read as a measured forward physiological flux.	psi-UMP + H2O => D-ribose 5-phosphate + uracil `RHEA:18339`	MetaCyc:CPLX0-8233 Source assertion: CPLX0-8233 catalyzes RXN0-5398 through ENZRXN0-6547; the pathway selects the cleavage direction. Source location `Protein[@frameid="CPLX0-8233"]/catalyzes/Enzymatic-Reaction[@frameid="ENZRXN0-6547"]/reaction` UniProtKB:P33025 Source assertion: Reviewed K-12 PsuG annotates reversible PsiMP cleavage, physiological cleavage direction and RHEA:18337, citing experimental PMIDs 18591240/23066817 plus HAMAP MF_01876 inference. Source location `/organism/taxonId; /comments/0; /comments/1/reaction` PMID:23066817 Source assertion: The study amplified yeiN from K12 DNA and characterized recombinant enzyme in BL21. Structures and covalent-adduct experiments support C-C bond cleavage; steady-state kinetic parameters were measured in the reverse synthetic direction. Source location `PMC3526674 BioC passages offsets6100,6949,23258,24413,34501` RHEA:18339 Source assertion: Master RHEA:18337 explicitly links directionalReaction RHEA:18339, the right-to-left cleavage member. Source location `http://rdf.rhea-db.org/18337 rh:directionalReaction http://rdf.rhea-db.org/18339`
Pseudouridine-5'-phosphate glycosidase `UniProtKB:P33025`	part_of Three copies form the native trimer. The monomer node is a subunit and is not independently assigned catalytic sufficiency.	pseudouridine-5'-phosphate glycosidase `MetaCyc:CPLX0-8233`	MetaCyc:CPLX0-8233 Source assertion: The native complex has three EG12033-MONOMER components. Source location `Protein[@frameid="CPLX0-8233"]/component/Protein; component/coefficient` MetaCyc:EG12033-MONOMER Source assertion: EG12033-MONOMER has explicit UNIPROT P33025 unification and MG1655 native taxonomy. Source location `Protein[@frameid="EG12033-MONOMER"]/dblink[dblink-db="UNIPROT"]; species/Organism` UniProtKB:P33025 Source assertion: SUBUNIT specifies homotrimer with ECO:0000269 PMID:23066817 and HAMAP MF_01876. Source location `/comments/5` PMID:23066817 ΨMP glycosidase is a homotrimer Source location `PMC3526674 BioC passage offset17266`
pseudouridine-5'-phosphate glycosidase `MetaCyc:CPLX0-8233`	has_cofactor Alternative metal-supported activity is retained; this does not assert simultaneous occupancy by all three metals or establish the dominant in vivo metal. Structural manganese occupancy is one per subunit.	manganese(2+) `CHEBI:29035`	UniProtKB:P33025 Source assertion: PsuG COFACTOR explicitly includes Mn(2+); the annotation states one manganese per subunit and allows Fe(2+) and Co(2+) alternatives, with experimental citations 18591240/23066817. Source location `/comments/2/cofactors; /comments/2/note` PMID:23066817 Source assertion: The hydrated Mn site has one Asp ligand and five water ligands; the paper reports highest activity with Fe(II), Co(II) and Mn(II), while Zn and, less strongly, Ni inhibit. Source location `PMC3526674 BioC passages offsets18370,31636`
pseudouridine-5'-phosphate glycosidase `MetaCyc:CPLX0-8233`	has_cofactor Alternative metal-supported activity is retained; this does not assert simultaneous occupancy by all three metals or establish the dominant in vivo metal. Structural manganese occupancy is one per subunit.	iron(2+) `CHEBI:29033`	UniProtKB:P33025 Source assertion: PsuG COFACTOR explicitly includes Fe(2+); the annotation states one manganese per subunit and allows Fe(2+) and Co(2+) alternatives, with experimental citations 18591240/23066817. Source location `/comments/2/cofactors; /comments/2/note` PMID:23066817 Source assertion: The hydrated Mn site has one Asp ligand and five water ligands; the paper reports highest activity with Fe(II), Co(II) and Mn(II), while Zn and, less strongly, Ni inhibit. Source location `PMC3526674 BioC passages offsets18370,31636`
pseudouridine-5'-phosphate glycosidase `MetaCyc:CPLX0-8233`	has_cofactor Alternative metal-supported activity is retained; this does not assert simultaneous occupancy by all three metals or establish the dominant in vivo metal. Structural manganese occupancy is one per subunit.	cobalt(2+) `CHEBI:48828`	UniProtKB:P33025 Source assertion: PsuG COFACTOR explicitly includes Co(2+); the annotation states one manganese per subunit and allows Fe(2+) and Co(2+) alternatives, with experimental citations 18591240/23066817. Source location `/comments/2/cofactors; /comments/2/note` PMID:23066817 Source assertion: The hydrated Mn site has one Asp ligand and five water ligands; the paper reports highest activity with Fe(II), Co(II) and Mn(II), while Zn and, less strongly, Ni inhibit. Source location `PMC3526674 BioC passages offsets18370,31636`
pseudouridine + ATP => psi-UMP + ADP + H(+) `RHEA:22449`	part_of	`MetaCyc:PWY-6019`	MetaCyc:PWY-6019 Source assertion: PWY-6019 explicitly lists PSEUDOURIDINE-KINASE-RXN; reaction-layout selects L2R phosphorylation. Source location `Pathway[@frameid="PWY-6019"]/reaction-list; reaction-layout[Reaction/@frameid="PSEUDOURIDINE-KINASE-RXN"]/direction` MetaCyc:PSEUDOURIDINE-KINASE-RXN Source assertion: PSEUDOURIDINE-KINASE-RXN has explicit RHEA 22449 unification cross-reference. Source location `Reaction[@frameid="PSEUDOURIDINE-KINASE-RXN"]/dblink[dblink-db="RHEA"]/dblink-oid; dblink-relationship`
psi-UMP + H2O => D-ribose 5-phosphate + uracil `RHEA:18339`	part_of	`MetaCyc:PWY-6019`	MetaCyc:PWY-6019 Source assertion: PWY-6019 explicitly lists RXN0-5398; reaction-layout selects R2L cleavage. Source location `Pathway[@frameid="PWY-6019"]/reaction-list; reaction-layout[Reaction/@frameid="RXN0-5398"]/direction` MetaCyc:RXN0-5398 Source assertion: RXN0-5398 has explicit RHEA 18340 unification cross-reference. Source location `Reaction[@frameid="RXN0-5398"]/dblink[dblink-db="RHEA"]/dblink-oid; dblink-relationship` RHEA:18339 Source assertion: Master RHEA:18337 links bidirectionalReaction RHEA:18340 and directionalReaction RHEA:18339; the latter is the selected cleavage variant. Source location `http://rdf.rhea-db.org/18337 rh:bidirectionalReaction http://rdf.rhea-db.org/18340; rh:directionalReaction http://rdf.rhea-db.org/18339`
pseudouridine + ATP => psi-UMP + ADP + H(+) `RHEA:22449`	provides_input_for The shared PsiMP is chemically identical across the two selected Rhea sides. ATP phosphorylation precedes reversible glycosidic-bond cleavage; downstream uracil utilization is not appended.	psi-UMP + H2O => D-ribose 5-phosphate + uracil `RHEA:18339`	MetaCyc:PWY-6019 Source assertion: RXN0-5398 has PSEUDOURIDINE-KINASE-RXN as its explicit predecessor; the two reaction-layouts share PSEUDOURIDINE-5-P. Source location `Pathway[@frameid="PWY-6019"]/reaction-ordering; reaction-layout` RHEA:22449 Source assertion: RHEA:22449 produces CHEBI:58380, the substrate of the selected PsuG cleavage reaction. Source location `http://rdf.rhea-db.org/22449 rh:products; http://rdf.rhea-db.org/22448_R rh:contains1` RHEA:18339 Source assertion: RHEA:18339 consumes CHEBI:58380 and water, producing uracil and D-ribofuranose 5-phosphate. Source location `http://rdf.rhea-db.org/18339 rh:substrates; rh:products` PMID:18591240 Source assertion: The indexed primary abstract describes both sequential enzymes and reports failure of yeiC(-) UTI89 mutants to metabolize pseudouridine. This is direct UTI89 physiology, not a K-12 whole-cell flux measurement. Source location `/resultList/result[id="18591240"]/abstractText`

References

MetaCyc:PWY-6019 pseudouridine degradation (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)
MetaCyc:CPLX0-8233 pseudouridine-5'-phosphate glycosidase trimer (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)
MetaCyc:EG12033-MONOMER PsuG subunit native cross-reference (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)
MetaCyc:PSEUDOURIDINE-KINASE-RXN pseudouridine kinase reaction (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)
MetaCyc:RXN0-5398 pseudouridine-5-phosphate glycosidase reversible reaction (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)
UniProtKB:P30235 Reviewed K-12 Pseudouridine kinase (source version: UniProt 2026_03; retrieved 2026-10-11 UTC)
UniProtKB:P33025 Reviewed K-12 Pseudouridine-5'-phosphate glycosidase (source version: UniProt 2026_03; retrieved 2026-10-11 UTC)
PMID:18591240 Molecular identification of pseudouridine-metabolizing enzymes. (source version: 2008; indexed abstract in Europe PMC core response; body digest covers retained JSON, not inaccessible full article)
PMID:23066817 Pseudouridine monophosphate glycosidase: a new glycosidase mechanism. (source version: 2012; complete primary article via PMC BioC XML; retrieved 2026-10-11 UTC)
PMID:35783380 Structure Characterization of Escherichia coli Pseudouridine Kinase PsuK. (source version: 2022; complete PMC9247573 JATS XML; retrieved 2026-10-11 UTC)
RHEA:22449 Rhea directional reaction 22449 (source version: Rhea 142, 2026-09-02; digest covers complete compressed RDF; named exact reaction and related triples selected by locators)
RHEA:18339 Rhea directional reaction 18339 (source version: Rhea 142, 2026-09-02; digest covers complete compressed RDF; named exact reaction and related triples selected by locators)

Curation history

2026-10-11T01:52:48Z Codex
- CREATE — Add the complete two-reaction pseudouridine degradation pathway.
  Curated exact MetaCyc:PWY-6019 with PsuK, the PsuG trimer, native reaction direction bridges and experimental versus inferred metal and strain limits. Resolved the misleading PathBank title against its exact chemistry. Source and duplicate-search dossiers are retained in research/pathway_additions/2026-10-11-next-pathways. Shared identifier authorities, generated pages, validation and independent reviews are recorded separately.
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