Ureide pathway - nitrogen recovery from allantoin via urea to ammonia

The ureide pathway recovers the four nitrogen atoms of the purine ring as ammonium. In organisms that keep urate oxidase, urate made by purine catabolism is oxidised to 5-hydroxyisourate, which 5-hydroxyisourate hydrolase and 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU) decarboxylase convert to (S)-allantoin. Organisms without these enzymes, such as budding yeasts, can import allantoin from outside and enter the pathway at this point. Allantoinase opens the hydantoin ring to give allantoate. The allantoate is then split along one of two chemical routes. In the first, allantoicase releases urea and (S)-ureidoglycolate, and ureidoglycolate lyase releases a second urea and glyoxylate. In the second, used by plants and many bacteria, allantoate amidohydrolase and ureidoglycine aminohydrolase release ammonium directly, and ureidoglycolate is either split by the lyase or fully hydrolysed by ureidoglycolate amidohydrolase without making urea. The urea is then broken down in one of two ways. Most fungi, plants and many bacteria use a nickel-dependent urease, which hydrolyses urea in one step. Saccharomycetes yeasts instead use urea amidolyase, a biotin-dependent enzyme with two domains: urea carboxylase makes allophanate from urea, bicarbonate and ATP, and allophanate hydrolase converts allophanate to ammonium and CO2. The glyoxylate carbon goes to the glyoxylate cycle. In fungi and animals the enzymes are soluble, and in some organisms the urate oxidase steps are peroxisomal; in plants the steps after allantoin take place in the endoplasmic reticulum.

MODULE:ureide_urea_catabolismDRAFTMetabolic Pathwaymodules/ureide_urea_catabolism.yaml
allantoin catabolic processGO:0000256 urea catabolic processGO:0043419
YeastPathways:ALLANTOINDEG-PWY
superpathway of allantoin degradation in yeast
Source superpathway (five reactions): DAL1 allantoinase, DAL2 allantoicase, DAL3 ureidoglycolate lyase, and DUR1,2 urea carboxylase and allophanate hydrolase. All gene assignments are kept. The pathway starts at allantoin because S. cerevisiae has no urate oxidase.
YeastPathways:PWY-5694
allantoin degradation to glyoxylate I
DAL1, DAL2 and DAL3 subpathway (allantoin to glyoxylate plus two urea).
YeastPathways:PWY-5697
allantoin degradation to ureidoglycolate I (urea producing)
DAL1 and DAL2 subpathway (allantoin to ureidoglycolate plus urea).
YeastPathways:PWY-5703
urea degradation I
DUR1,2 urea carboxylase plus allophanate hydrolase (urea amidolyase).
GO:0000256
allantoin catabolic process
Module-level process for the core steps from allantoin to urea, glyoxylate and ammonium.
GO:0043419
urea catabolic process
Module-level process for the urea-cleavage part (urease or urea amidolyase).
GO:0019628
urate catabolic process
Process for the optional urate-to-allantoin entry part.
PMID:4604238
Clustering of the genes for allantoin degradation in Saccharomyces cerevisiae.
S. cerevisiae degrades allantoin through allantoate, urea and allophanate.
We have shown that allantoin degradation in Saccharomyces cerevisiae proceeds exclusively through the intermediate formation of allantoic acid, urea, and allophanic acid.
PMID:6105114
Structural analysis of the dur loci in S. cerevisiae: two domains of a single multifunctional gene.
Urea carboxylase and allophanate hydrolase are two domains of the single DUR1,2 polypeptide.
In Saccharomyces cerevisiae, the degradation of urea to carbon dioxide and ammonia is catalyzed by urea carboxylase and allophanate hydrolase.
PMID:21447149
Molecular evolution of urea amidolyase and urea carboxylase in fungi.
Urea amidolyase (DUR1,2) is found in Saccharomycetes, which lack urease; other fungi, including S. pombe, have urease. This supports the urea cleavage variant set.
Consistent with the earlier observation [1], the urease protein was present in all the fungal species examined except for those of the Saccharomycotina.
PMID:9339351
Identification of the ure1+ gene encoding urease in fission yeast.
S. pombe urease is a single-chain, plant-like urease needed for urea metabolism.
The fission yeast urease has a one-subunit structure like those from plants but different from bacterial ureases which are composed of two or three distinct subunits.
PMID:16462750
Completing the uric acid degradation pathway through phylogenetic comparison of whole genomes.
HIU hydrolase and OHCU decarboxylase complete the conversion of urate to (S)-allantoin after urate oxidase.
We show that the two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU): hydrolysis of HIU to give 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU) and decarboxylation of OHCU to give S-(+)-allantoin.
PMID:19935661
Ureide catabolism in Arabidopsis thaliana and Escherichia coli.
Identifies ureidoglycine aminohydrolase and ureidoglycolate amidohydrolase as the final plant ureide enzymes and a similar route in E. coli. This supports the amidohydrolase variants.
A cross-organism protein association analysis allowed us to identify two enzymes, ureidoglycine aminohydrolase and ureidoglycolate amidohydrolase, that catalyze the final reactions of purine degradation in the model plant Arabidopsis thaliana.
PMID:21482173
The biochemistry of nitrogen mobilization: purine ring catabolism.
Review of plant purine ring catabolism, including its peroxisome and ER compartments.
Xanthine is oxidized to urate in the cytosol, followed by three enzymatic steps taking place in the peroxisome and four reactions in the endoplasmic reticulum releasing the four ring nitrogen as ammonia.
PMID:1803816
The allantoinase (DAL1) gene of Saccharomyces cerevisiae.
Cloning and sequence of DAL1 allantoinase.
The allantoinase (DAL1) gene from Saccharomyces cerevisiae has been cloned, sequenced, and found to encode a 472 amino acid protein with a Mr of 52,028.
PMID:1916277
Sequences of two adjacent genes, one (DAL2) encoding allantoicase and another (DCG1) sensitive to nitrogen-catabolite repression in Saccharomyces cerevisiae.
Sequence of DAL2 allantoicase.
Reported are the nucleotide sequences of the yeast allantoicase-encoding gene (DAL2)
PMID:3915539
Identification of the ureidoglycolate hydrolase gene in the DAL gene cluster of Saccharomyces cerevisiae.
Isolation of DAL2 and DAL3 ("ureidoglycolate hydrolase", now known to be the urea-releasing lyase).
This report describes the isolation of the genes encoding allantoicase (DAL2) and ureidoglycolate hydrolase (DAL3)
19Nodes
12Parts
3Variant Sets
6Variants
12Annotons
9Connections

Derived QC

Recommended-field compliance

80.0% recommended fields populated
  • knowledge_gaps[0] · provenance (0/1)

Module deep research

✗ none found

No MODULE:ureide_urea_catabolism deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Reaction chaining (advisory)

✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.

  • urate_to_allantoin → allantoinase_step [NOT_CHECKED]
    (S)-allantoin from OHCU decarboxylase is the allantoinase substrate. Organisms without the entry part import allantoin.
  • allantoinase_step → allantoate_breakdown_step [NOT_CHECKED]
    Allantoate is the allantoinase product and the substrate of both allantoate routes.
  • allantoate_breakdown_step → ureidoglycolate_breakdown_step [NOT_CHECKED]
    Both allantoate routes end in (S)-ureidoglycolate.

Function consistency and core coverage

11 gene-function check(s) reflected in core functions · 0 conflict(s) · 13 evidence or coverage gap(s) (35 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
urate_oxidase_activity uro1 (S. pombe, SPCC1223.09)
UniProtKB:O74409
Family Representative 		urate oxidase activity
GO:0004846 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
urate_oxidase_activity Uox (mouse)
UniProtKB:P25688
Family Representative 		urate oxidase activity
GO:0004846 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hiu_hydrolase_activity SPCC285.04 (S. pombe)
UniProtKB:O74492
Family Representative 		hydroxyisourate hydrolase activity
GO:0033971 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hiu_hydrolase_activity Urah (mouse)
UniProtKB:Q9CRB3
Family Representative 		hydroxyisourate hydrolase activity
GO:0033971 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
ohcu_decarboxylase_activity Urad (mouse)
UniProtKB:Q283N4
Family Representative 		2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase activity
GO:0051997 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
allantoinase_activity DAL1 (S. cerevisiae)
UniProtKB:P32375
Family Representative 		allantoinase activity
GO:0004038 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
allantoinase_activity ALN (Arabidopsis thaliana)
UniProtKB:Q94AP0
Family Representative 		allantoinase activity
GO:0004038 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
allantoinase_activity allB (Escherichia coli K-12)
UniProtKB:P77671
Family Representative 		allantoinase activity
GO:0004038 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
allantoicase_activity DAL2 (S. cerevisiae)
UniProtKB:P25335
Family Representative 		allantoicase activity
GO:0004037 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
allantoicase_activity dal2 (S. pombe, SPAC1F7.09c)
UniProtKB:Q09913
Family Representative 		allantoicase activity
GO:0004037 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
allantoate_amidohydrolase_activity AAH (Arabidopsis thaliana)
UniProtKB:O49434
Family Representative 		allantoate deiminase activity
GO:0047652 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
allantoate_amidohydrolase_activity allC (Escherichia coli K-12)
UniProtKB:P77425
Family Representative 		allantoate deiminase activity
GO:0047652 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
ureidoglycine_aminohydrolase_activity UGLYAH (Arabidopsis thaliana)
UniProtKB:Q8GXV5
Family Representative 		ureidoglycine aminohydrolase activity
GO:0071522 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
ureidoglycine_aminohydrolase_activity allE (Escherichia coli K-12)
UniProtKB:P75713
Family Representative 		ureidoglycine aminohydrolase activity
GO:0071522 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
ureidoglycolate_lyase_activity DAL3 (S. cerevisiae)
UniProtKB:P32459
Family Representative 		ureidoglycolate lyase activity
GO:0050385 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ureidoglycolate_lyase_activity dal1 (S. pombe, SPAC19G12.04)
UniProtKB:O13843
Family Representative 		ureidoglycolate lyase activity
GO:0050385 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ureidoglycolate_lyase_activity allA (Escherichia coli K-12)
UniProtKB:P77731
Family Representative 		ureidoglycolate lyase activity
GO:0050385 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
ureidoglycolate_amidohydrolase_activity UAH (Arabidopsis thaliana)
UniProtKB:Q8VXY9
Family Representative 		ureidoglycolate hydrolase activity
GO:0004848 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
urease_activity ure2 (S. pombe, SPAC1952.11c)
UniProtKB:O00084
Family Representative 		urease activity
GO:0009039 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
urea_carboxylase_activity DUR1,2 (S. cerevisiae)
UniProtKB:P32528
Family Representative 		urea carboxylase activity
GO:0004847 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
allophanate_hydrolase_activity DUR1,2 (S. cerevisiae)
UniProtKB:P32528
Family Representative 		allophanate hydrolase activity
GO:0004039 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
urate_oxidase_activity cofactor-independent urate oxidase
PANTHER:PTHR42874
Family 		urate oxidase activity
GO:0004846 		Family Supported
Family review supports GO:0004846 FAMILY_WIDE. Asserted by ureide_urea_catabolism; accepted by uro1 and mouse Uox.
hiu_hydrolase_activity transthyretin-related HIU hydrolase
PANTHER:PTHR10395:SF7
Family 		hydroxyisourate hydrolase activity
GO:0033971 		Family Supported
Family review supports GO:0033971 for PANTHER:PTHR10395:SF7. HIU hydrolases only (SF7, SF11), as ureide_urea_catabolism asserts. The module selects the base family, which also takes in transthyretin.
hiu_hydrolase_activity transthyretin-related HIU hydrolase
PANTHER:PTHR10395:SF11
Family 		hydroxyisourate hydrolase activity
GO:0033971 		Family Supported
Family review supports GO:0033971 for PANTHER:PTHR10395:SF11. HIU hydrolases only (SF7, SF11), as ureide_urea_catabolism asserts. The module selects the base family, which also takes in transthyretin.
ohcu_decarboxylase_activity OHCU decarboxylase (URAD)
PANTHER:PTHR43466
Family 		2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase activity
GO:0051997 		Family Supported
Family review supports GO:0051997 FAMILY_WIDE. Asserted by ureide_urea_catabolism; accepted by zebrafish urad.
allantoinase_activity amidohydrolase-superfamily allantoinase
PANTHER:PTHR43668:SF2
Family 		allantoinase activity
GO:0004038 		Family Supported
Family review supports GO:0004038 for PANTHER:PTHR43668:SF2. Asserted by ureide_urea_catabolism; accepted by DAL1.
allantoinase_activity amidohydrolase-superfamily allantoinase
PANTHER:PTHR43668:SF4
Family 		allantoinase activity
GO:0004038 		Family Supported
Family review supports GO:0004038 for PANTHER:PTHR43668:SF4. Asserted by ureide_urea_catabolism; accepted by DAL1.
allantoicase_activity allantoicase
PANTHER:PTHR12045
Family 		allantoicase activity
GO:0004037 		Family Supported
Family review supports GO:0004037 FAMILY_WIDE. Asserted by ureide_urea_catabolism; accepted by DAL2 and SPAC1F7.09c. Human ALLC is a member exception.
allantoate_amidohydrolase_activity M20-peptidase-like allantoate amidohydrolase
PANTHER:PTHR32494
Family 		allantoate deiminase activity
GO:0047652 		Family Function Unreviewed
Family review leaves GO:0047652 UNRESOLVED. Asserted by ureide_urea_catabolism for plant AAH and E. coli AllC on the base family. No reviewed member confirms which subfamilies carry it.
ureidoglycine_aminohydrolase_activity cupin ureidoglycine aminohydrolase
PANTHER:PTHR34571
Family 		ureidoglycine aminohydrolase activity
GO:0071522 		Family Supported
Family review supports GO:0071522 FAMILY_WIDE. Asserted by ureide_urea_catabolism for AllE and UGLYAH. No member gene review exists.
ureidoglycolate_lyase_activity cupin ureidoglycolate lyase
PANTHER:PTHR21221:SF1
Family 		ureidoglycolate lyase activity
GO:0050385 		Family Supported
Family review supports GO:0050385 FAMILY_WIDE. Asserted by ureide_urea_catabolism (SF1); accepted by DAL3 and SPAC19G12.04.
ureidoglycolate_amidohydrolase_activity M20-peptidase-like ureidoglycolate amidohydrolase
PANTHER:PTHR32494
Family 		ureidoglycolate hydrolase activity
GO:0004848 		Family Function Unreviewed
Family review leaves GO:0004848 UNRESOLVED. Asserted by ureide_urea_catabolism for plant UAH; not assessed by any member review.
urease_activity urease
PANTHER:PTHR33569
Family 		urease activity
GO:0009039 		Family Function Unreviewed
Family review leaves GO:0009039 UNRESOLVED. The family's link to this term depends on the qualifier, which the scope values cannot express. Contributes_to urease activity is safe family-wide, because every member is part of a urease. Enables is safe only for the fungal single-chain ureases (for example S. pombe ure1), which also carry the alpha region. Gamma, beta and fused gamma-beta chains should not receive an enables-type annotation. PANTHER has no subfamily boundary between these groups.
urea_carboxylase_activity urea amidolyase
PANTHER:PTHR18866:SF128
Family 		urea carboxylase activity
GO:0004847 		Family Supported
Family review supports GO:0004847 for PANTHER:PTHR18866:SF128. DUR1,2 (SF128), as ureide_urea_catabolism selects.
allophanate_hydrolase_activity urea amidolyase
PANTHER:PTHR18866:SF128
Family 		allophanate hydrolase activity
GO:0004039 		Family Supported
Family review supports GO:0004039 for PANTHER:PTHR18866:SF128. The allophanate hydrolase domain of DUR1,2 (SF128).

Gene-review completeness (10/20 grounded genes reviewed)

8 complete review(s) · 5 with deep research · 10 missing review · 5 reviewed but lacking deep research

Gene Review Complete Deep research
DAL1 P32375 ✓ ✓ ✓
DAL2 P25335 ✓ ✓ ✓
DAL3 P32459 ✓ 12/13 ✓
DUR1,2 P32528 ✓ ✓ ✓
AAH (Arabidopsis thaliana) O49434 ✗ — —
allE (Escherichia coli K-12) P75713 ✗ — —
allC (Escherichia coli K-12) P77425 ✗ — —
allB (Escherichia coli K-12) P77671 ✗ — —
allA (Escherichia coli K-12) P77731 ✗ — —
Urad (mouse) Q283N4 ✗ — —
UGLYAH (Arabidopsis thaliana) Q8GXV5 ✗ — —
UAH (Arabidopsis thaliana) Q8VXY9 ✗ — —
ALN (Arabidopsis thaliana) Q94AP0 ✗ — —
Urah (mouse) Q9CRB3 ✗ — —
SPAC19G12.04 O13843 ✓ ✓ ✗
SPAC1F7.09c Q09913 ✓ ✓ ✗
SPCC1223.09 O74409 ✓ ✓ ✗
SPCC285.04 O74492 ✓ ✓ ✗
Uox P25688 ✓ 34/35 ✓
ure1 O00084 ✓ ✓ ✗

Details

Context
cytosolGO:0005829
Ureide pathway (allantoin to urea to ammonia), with urease or urea amidolyase variantsMetabolic Pathwayureide_urea_catabolism

[urate -> 5-hydroxyisourate -> OHCU ->] (S)-allantoin -> allantoate -> (S)-ureidoglycolate (+ urea or NH4+) -> glyoxylate (+ urea or NH4+/CO2); urea -> NH4+ + CO2 (urease, or urea carboxylase + allophanate hydrolase).

allantoin catabolic processGO:0000256 urea catabolic processGO:0043419
Context
cytosolGO:0005829

Boundary: starts at urate (optional entry) or allantoin, and ends with ammonium, CO2 and glyoxylate. Purine nucleotide breakdown to urate is in purine_nucleotide_catabolism (animals) and bacterial_purine_base_oxidation_to_urate. Urease nickel-centre assembly is in urease_biogenesis_urea_hydrolysis. Uptake of allantoin, allantoate and urea (S. cerevisiae DAL4, DAL5, DUR3), the fate of glyoxylate (DAL7 malate synthase), and nitrogen catabolite repression and induction (GATA factors and DAL81/DAL82) are outside the module. YeastCyc assessment: all five S. cerevisiae reactions and genes (DAL1, DAL2, DAL3, DUR1,2) are kept, all cytosolic. DAL3 was historically called "ureidoglycolate hydrolase" (PMID:3915539, PMID:1776360). The reaction YeastCyc, UniProt and the GO-CAMs assign it is the urea-releasing lyase (EC 4.3.2.3, GO:0050385), not the plant amidohydrolase (GO:0004848). This fits with S. cerevisiae degrading allantoin through urea and allophanate (PMID:4604238). No enzyme is missing from the SGD summary. S. cerevisiae lacks the urate oxidase entry part and urease (PMID:21447149; no member of PTHR42874, PTHR10395, PTHR43466 or PTHR33569 in the PANTHER 19.0 yeast proteome). Generalisation: the crosswalk asked for an entry variant (urate oxidase route present or absent) and a urea-cleavage variant (urease or urea amidolyase). The entry is an optional part rather than a variant set, because allantoin import is a transport step, not an alternative enzyme. Two more lineage variant sets were added from the literature: plant and E. coli allantoate amidohydrolase plus ureidoglycine aminohydrolase in place of allantoicase, and plant ureidoglycolate amidohydrolase in place of the lyase (PMID:19935661, PMID:21482173). GO-CAM notes: (1) PomBase model gomodel:665912ed00002626 is a broader nitrogen-cycle model. Its urea-cycle, arginase, agmatinase, ornithine transport, glutaminase and spermidine synthase activities are outside this module, apart from noting that arginase-derived urea also feeds urease. (2) In that model the allantoinase (66e382fb00001783) and OHCU decarboxylase (69c59f8a00003378) activities are enabled by a generic "protein" (CHEBI:36080), so no S. pombe gene is assigned. (3) S. pombe dal1 (SPAC19G12.04) ureidoglycolate lyase is placed in GO:0019627 urea metabolic process, while the other ureide steps are in GO:0019628 urate catabolic process. (4) The model has a separate urease activator complex activity (GO:0150006) that positively regulates ure2. The S. pombe accessory proteins are ure4 (UreD-like, P87125), ure6 (UreF-like, O14016) and ure7 (UreG-like, Q96WV0); they belong to the urease biogenesis module and are not exemplars here. (5) The YeastPathways models put all five activities in GO:0000256 allantoin catabolic process (PWY-5703 in GO:0043419), which agrees with this module.

Connections

Allantoicase releases the first urea.
Ureidoglycolate lyase releases the second urea.
Part 1: urate to (S)-allantoin (entry; absent from budding yeasts) (optional)

Present where urate oxidase is kept (S. pombe, most bacteria, plants, most non-primate animals). Saccharomycetes such as S. cerevisiae have no urate oxidase, HIU hydrolase or OHCU decarboxylase family member (PANTHER 19.0 PTHR42874, PTHR10395, PTHR43466) and take up allantoin from outside.

Urate oxidation to (S)-allantoinMetabolic Pathwayurate_to_allantoin
urate catabolic processGO:0019628

Connections

Part 1: urate oxidation
urate + O2 to 5-hydroxyisourate + H2O2Reactionurate_oxidase_step

Annotons

Urate oxidase (uricase)
urate_oxidase_activity
Participant: Family: cofactor-independent urate oxidase
Family:
cofactor-independent urate oxidasePANTHER:PTHR42874
Representative Members: uro1 (S. pombe, SPCC1223.09)UniProtKB:O74409 Uox (mouse)UniProtKB:P25688
Required Function:
urate oxidase activityGO:0004846

Function

urate oxidase activityGO:0004846
Substrates: urate dioxygen
Products: 5-hydroxyisourate hydrogen peroxide

Peroxisomal in animals and plants (PMID:21482173 for plants); the PomBase model places uro1 in the cytosol.

Part 2: 5-hydroxyisourate hydrolysis
5-hydroxyisourate to OHCUReactionhiu_hydrolase_step

Annotons

5-hydroxyisourate hydrolase (transthyretin-related protein)
hiu_hydrolase_activity
Participant: Family: transthyretin-related HIU hydrolase
Family:
transthyretin-related HIU hydrolase Restricted to the HIU hydrolase subfamilies of PTHR10395: SF7 (bacterial, fungal, plant and invertebrate HIU hydrolases, including SPCC285.04) and SF11 (vertebrate URAH). The non-enzymatic vertebrate transthyretin (SF12) is left out.
Representative Members: SPCC285.04 (S. pombe)UniProtKB:O74492 Urah (mouse)UniProtKB:Q9CRB3
Required Function:
hydroxyisourate hydrolase activityGO:0033971

Function

hydroxyisourate hydrolase activityGO:0033971
Substrates: 5-hydroxyisourate water
Products: 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU)
Part 3: OHCU decarboxylation
OHCU to (S)-allantoin + CO2Reactionohcu_decarboxylase_step

Annotons

OHCU decarboxylase (allantoin synthase)
ohcu_decarboxylase_activity
Participant: Family: OHCU decarboxylase (URAD)
Family:
OHCU decarboxylase (URAD)PANTHER:PTHR43466
Representative Members: Urad (mouse)UniProtKB:Q283N4
Required Function:
2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase activityGO:0051997

Function

2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase activityGO:0051997
Substrates: 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU)
Products: (S)-allantoin CO2

No S. pombe gene has been assigned; the PomBase model types this activity with a generic protein placeholder (see knowledge gaps).

Part 2: allantoin ring opening
(S)-allantoin + H2O to allantoateReactionallantoinase_step

Annotons

Allantoinase (DAL1/AllB/ALN)
allantoinase_activity
Participant: Family: amidohydrolase-superfamily allantoinase
Family:
amidohydrolase-superfamily allantoinase
Representative Members: DAL1 (S. cerevisiae)UniProtKB:P32375 ALN (Arabidopsis thaliana)UniProtKB:Q94AP0 allB (Escherichia coli K-12)UniProtKB:P77671
Required Function:
allantoinase activityGO:0004038

Function

allantoinase activityGO:0004038
Substrates: (S)-allantoin water
Products: allantoate

Locations

cytosolGO:0005829

Cytosolic in yeast (GO-CAMs); ER-resident in plants (PMID:21482173). S. pombe has no PTHR43668 member; its allantoinase is unassigned in the PomBase model.

Part 3: allantoate breakdown to ureidoglycolate
allantoate to (S)-ureidoglycolateReactionallantoate_breakdown_step
Variant set: Allantoate breakdown routes by route variant (Exactly One)
Allantoicase (urea-releasing; fungi, some animals)Reactionallantoicase_route

Annotons

Allantoicase (DAL2)
allantoicase_activity
Participant: Family: allantoicase
Family:
allantoicasePANTHER:PTHR12045 Human ALLC is in this family but is annotated as probably inactive (UniProt Q8N6M5), so it is not used as an exemplar.
Representative Members: DAL2 (S. cerevisiae)UniProtKB:P25335 dal2 (S. pombe, SPAC1F7.09c)UniProtKB:Q09913
Required Function:
allantoicase activityGO:0004037

Function

allantoicase activityGO:0004037
Substrates: allantoate water
Products: (S)-ureidoglycolate urea

Locations

cytosolGO:0005829
Allantoate amidohydrolase then ureidoglycine aminohydrolase (ammonium-releasing; plants, many bacteria)Metabolic Pathwayallantoate_amidohydrolase_route

Plants and bacteria such as E. coli hydrolyse allantoate to (S)-ureidoglycine, NH4+ and CO2, then release a second NH4+ from ureidoglycine to give (S)-ureidoglycolate (PMID:19935661). No yeast representative.

Connections

Part 1: allantoate amidohydrolysis
allantoate to (S)-2-ureidoglycine + NH4+ + CO2Reactionallantoate_amidohydrolase_step

Annotons

Allantoate amidohydrolase (AAH/AllC)
allantoate_amidohydrolase_activity
Participant: Family: M20-peptidase-like allantoate amidohydrolase
Family:
M20-peptidase-like allantoate amidohydrolasePANTHER:PTHR32494
Representative Members: AAH (Arabidopsis thaliana)UniProtKB:O49434 allC (Escherichia coli K-12)UniProtKB:P77425
Required Function:
allantoate deiminase activityGO:0047652

Function

allantoate deiminase activityGO:0047652
Substrates: allantoate water
Products: (S)-2-ureidoglycine ammonium CO2

Locations

endoplasmic reticulumGO:0005783

ER-resident in plants (PMID:21482173).

Part 2: ureidoglycine deamination
(S)-2-ureidoglycine to (S)-ureidoglycolate + NH4+Reactionureidoglycine_aminohydrolase_step

Annotons

Ureidoglycine aminohydrolase (UGLYAH/AllE)
ureidoglycine_aminohydrolase_activity
Participant: Family: cupin ureidoglycine aminohydrolase
Family:
cupin ureidoglycine aminohydrolasePANTHER:PTHR34571
Representative Members: UGLYAH (Arabidopsis thaliana)UniProtKB:Q8GXV5 allE (Escherichia coli K-12)UniProtKB:P75713
Required Function:
ureidoglycine aminohydrolase activityGO:0071522

Function

ureidoglycine aminohydrolase activityGO:0071522
Substrates: (S)-2-ureidoglycine water
Products: (S)-ureidoglycolate ammonium

Locations

endoplasmic reticulumGO:0005783

ER-resident in plants (PMID:21482173).

Part 4: ureidoglycolate breakdown to glyoxylate
(S)-ureidoglycolate to glyoxylateReactionureidoglycolate_breakdown_step
Variant set: Ureidoglycolate breakdown routes by route variant (Exactly One)
Ureidoglycolate lyase (urea-releasing; fungi, many bacteria)Reactionureidoglycolate_lyase_route

Annotons

Ureidoglycolate lyase (DAL3/AllA)
ureidoglycolate_lyase_activity
Participant: Family: cupin ureidoglycolate lyase
Family:
cupin ureidoglycolate lyasePANTHER:PTHR21221:SF1
Representative Members: DAL3 (S. cerevisiae)UniProtKB:P32459 dal1 (S. pombe, SPAC19G12.04)UniProtKB:O13843 allA (Escherichia coli K-12)UniProtKB:P77731
Required Function:
ureidoglycolate lyase activityGO:0050385

Function

ureidoglycolate lyase activityGO:0050385
Substrates: (S)-ureidoglycolate
Products: glyoxylate urea

Locations

cytosolGO:0005829

Releases the second urea; in S. cerevisiae both ureas then go to DUR1,2.

Ureidoglycolate amidohydrolase (ammonium-releasing, no urea; plants)Reactionureidoglycolate_amidohydrolase_route

Annotons

Ureidoglycolate amidohydrolase (UAH)
ureidoglycolate_amidohydrolase_activity
Participant: Family: M20-peptidase-like ureidoglycolate amidohydrolase
Family:
M20-peptidase-like ureidoglycolate amidohydrolasePANTHER:PTHR32494 Same PANTHER family as plant AAH.
Representative Members: UAH (Arabidopsis thaliana)UniProtKB:Q8VXY9
Required Function:
ureidoglycolate hydrolase activityGO:0004848

Function

ureidoglycolate hydrolase activityGO:0004848
Substrates: (S)-ureidoglycolate water
Products: glyoxylate ammonium (2) CO2

Locations

endoplasmic reticulumGO:0005783

Combined with AAH and UGLYAH this releases all four ring nitrogens as ammonium with no urea (PMID:21482173).

Part 5: urea cleavage to ammonium and CO2 (optional)

Required whenever allantoicase or ureidoglycolate lyase release urea. A plant-type route through AAH, UGLYAH and UAH makes no urea.

urea to 2 NH4+ + CO2Reactionurea_cleavage_step
urea catabolic processGO:0043419
Variant set: Urea cleavage enzymes by enzyme family / lineage (Exactly One)
Nickel urease (one step; most fungi, plants, many bacteria)Reactionurease_route

Fungal and plant ureases are single chains; bacterial ureases have two or three subunits. Nickel insertion needs the UreD/UreF/UreG accessory proteins, which are modelled in urease_biogenesis_urea_hydrolysis.

Annotons

Urease (single-chain fungal/plant type)
urease_activity
Participant: Family: urease
Family:
ureasePANTHER:PTHR33569
Representative Members: ure2 (S. pombe, SPAC1952.11c)UniProtKB:O00084
Required Function:
urease activityGO:0009039

Function

urease activityGO:0009039
Substrates: urea water
Products: ammonium (2) CO2

Locations

cytosolGO:0005829
Urea amidolyase (urea carboxylase + allophanate hydrolase; Saccharomycetes)Metabolic Pathwayurea_amidolyase_route

ATP- and biotin-dependent two-step cleavage. In Saccharomycetes both activities are domains of one polypeptide (DUR1,2); some other fungi, green algae and bacteria have separate urea carboxylase and allophanate hydrolase proteins (PMID:21447149).

Connections

Part 1: urea carboxylation
urea + HCO3- + ATP to allophanate + ADP + PiReactionurea_carboxylase_step

Annotons

Urea carboxylase domain of urea amidolyase (DUR1,2)
urea_carboxylase_activity
Participant: Family: urea amidolyase
Family:
urea amidolyasePANTHER:PTHR18866:SF128
Representative Members: DUR1,2 (S. cerevisiae)UniProtKB:P32528
Required Function:
urea carboxylase activityGO:0004847

Function

urea carboxylase activityGO:0004847
Substrates: urea hydrogencarbonate ATP (biotin cofactor)
Products: urea-1-carboxylate (allophanate) ADP phosphate

Locations

cytosolGO:0005829
Part 2: allophanate hydrolysis
allophanate to 2 NH4+ + 2 CO2Reactionallophanate_hydrolase_step

Annotons

Allophanate hydrolase domain of urea amidolyase (DUR1,2)
allophanate_hydrolase_activity
Participant: Family: urea amidolyase
Family:
urea amidolyasePANTHER:PTHR18866:SF128
Representative Members: DUR1,2 (S. cerevisiae)UniProtKB:P32528
Required Function:
allophanate hydrolase activityGO:0004039

Function

allophanate hydrolase activityGO:0004039
Substrates: urea-1-carboxylate (allophanate) water
Products: ammonium (2) CO2 (2)

Locations

cytosolGO:0005829