Function
Processes
Supplies ammonia to the coupled carbamoyl-phosphate synthetase domain.
The conserved six-reaction pathway that builds UMP from glutamine, hydrogencarbonate, ATP, aspartate, and PRPP, followed by phosphorylation of UMP to UTP and amination of UTP to CTP. Carbamoyl phosphate is formed first, followed by assembly and oxidation of the pyrimidine ring, attachment to phosphoribose, and decarboxylation to UMP. UMP kinase and nucleoside-diphosphate kinase then make UTP, and CTP synthase transfers the glutamine amide nitrogen to UTP to make CTP. Enzyme architecture varies: bacteria commonly use separate CarA, CarB, PyrB, PyrC, PyrE, and PyrF proteins, whereas animals fuse the first three activities in CAD and the final two activities in UMPS; fungi fuse the carbamoyl-phosphate synthetase and aspartate carbamoyltransferase in one protein that also carries an inactive dihydroorotase-like domain, and use separate dihydroorotase, orotate phosphoribosyltransferase and OMP decarboxylase proteins. These fusions do not change the chemical leaves represented by the module. Dihydroorotate oxidation has two implementations: membrane-associated quinone-dependent (class 2) enzymes, which in eukaryotes sit on the mitochondrial inner membrane and couple pyrimidine synthesis to respiration, and soluble fumarate-dependent (class 1A) enzymes, acquired by Saccharomyces yeasts from bacteria, which allow pyrimidine synthesis without oxygen. Bacteria phosphorylate UMP with a PyrH-type UMP kinase, eukaryotes with a UMP/CMP kinase of the adenylate kinase family.
All recommended fields populated.
✗ none found
No MODULE:de_novo_pyrimidine_synthesis deep-research report alongside the module YAML.
✓ every leaf node grounds to a representative protein.
✓ every declared conforms_to bundle matches its template motif.
33 gene-function check(s) reflected in core functions · 0 conflict(s) · 15 evidence or coverage gap(s) (55 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.
| Annoton | Participant | Function | Assessment |
|---|---|---|---|
| carbamoyl_phosphate_glutaminase_component | carA (Pseudomonas putida KT2440) UniProtKB:Q88DU5 Family Representative |
glutaminase activity GO:0004359 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| carbamoyl_phosphate_glutaminase_component | CAD (human) UniProtKB:P27708 Family Representative |
glutaminase activity GO:0004359 |
Annotation Supported
A retained annotation or curated replacement supports this function, but core_functions does not yet reflect it. |
| carbamoyl_phosphate_glutaminase_component | URA2 (Saccharomyces cerevisiae) UniProtKB:P07259 Family Representative |
glutaminase activity GO:0004359 |
Annotation Supported
A retained annotation or curated replacement supports this function, but core_functions does not yet reflect it. |
| carbamoyl_phosphate_glutaminase_component | ura1 (Schizosaccharomyces pombe) UniProtKB:Q09794 Family Representative |
glutaminase activity GO:0004359 |
Annotation Supported
A retained annotation or curated replacement supports this function, but core_functions does not yet reflect it. |
| carbamoyl_phosphate_synthetase_component | carB (Pseudomonas putida KT2440) UniProtKB:Q88DU6 Family Representative |
carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity GO:0004088 |
Contributes Only
The review records contribution to this activity, not independent enabling. Check whether the module participant should be a complex. |
| carbamoyl_phosphate_synthetase_component | CAD (human) UniProtKB:P27708 Family Representative |
carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity GO:0004088 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| carbamoyl_phosphate_synthetase_component | URA2 (Saccharomyces cerevisiae) UniProtKB:P07259 Family Representative |
carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity GO:0004088 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| carbamoyl_phosphate_synthetase_component | ura1 (Schizosaccharomyces pombe) UniProtKB:Q09794 Family Representative |
carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity GO:0004088 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| aspartate_carbamoyltransferase_activity | pyrB (Pseudomonas putida KT2440) UniProtKB:Q88D30 Family Representative |
aspartate carbamoyltransferase activity GO:0004070 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| aspartate_carbamoyltransferase_activity | CAD (human) UniProtKB:P27708 Family Representative |
aspartate carbamoyltransferase activity GO:0004070 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| aspartate_carbamoyltransferase_activity | URA2 (Saccharomyces cerevisiae) UniProtKB:P07259 Family Representative |
aspartate carbamoyltransferase activity GO:0004070 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| aspartate_carbamoyltransferase_activity | ura1 (Schizosaccharomyces pombe) UniProtKB:Q09794 Family Representative |
aspartate carbamoyltransferase activity GO:0004070 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| dihydroorotase_activity | pyrC (Pseudomonas putida KT2440) UniProtKB:Q88NW7 Family Representative |
dihydroorotase activity GO:0004151 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| dihydroorotase_activity | CAD (human) UniProtKB:P27708 Family Representative |
dihydroorotase activity GO:0004151 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| dihydroorotase_activity | URA4 (Saccharomyces cerevisiae) UniProtKB:P20051 Family Representative |
dihydroorotase activity GO:0004151 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| dihydroorotase_activity | ura2 (Schizosaccharomyces pombe) UniProtKB:Q9UTI0 Family Representative |
dihydroorotase activity GO:0004151 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| dihydroorotate_dehydrogenase_activity | pyrD (Pseudomonas putida KT2440) UniProtKB:Q88L40 Family Representative |
dihydroorotate dehydrogenase (quinone) activity GO:0106430 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| dihydroorotate_dehydrogenase_activity | DHODH (human) UniProtKB:Q02127 Family Representative |
dihydroorotate dehydrogenase (quinone) activity GO:0106430 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| dihydroorotate_dehydrogenase_activity | ura3 (Schizosaccharomyces pombe) UniProtKB:P32747 Family Representative |
dihydroorotate dehydrogenase (quinone) activity GO:0106430 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| dihydroorotate_dehydrogenase_fumarate_activity | URA1 (Saccharomyces cerevisiae) UniProtKB:P28272 Family Representative |
dihydroorotate dehydrogenase (fumarate) activity GO:1990663 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| orotate_phosphoribosyltransferase_activity | pyrE (Pseudomonas putida KT2440) UniProtKB:Q88C92 Family Representative |
orotate phosphoribosyltransferase activity GO:0004588 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| orotate_phosphoribosyltransferase_activity | UMPS (human) UniProtKB:P11172 Family Representative |
orotate phosphoribosyltransferase activity GO:0004588 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| orotate_phosphoribosyltransferase_activity | URA5 (Saccharomyces cerevisiae) UniProtKB:P13298 Family Representative |
orotate phosphoribosyltransferase activity GO:0004588 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| orotate_phosphoribosyltransferase_activity | URA10 (Saccharomyces cerevisiae) UniProtKB:P30402 Family Representative |
orotate phosphoribosyltransferase activity GO:0004588 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| orotate_phosphoribosyltransferase_activity | ura5 (Schizosaccharomyces pombe) UniProtKB:O94331 Family Representative |
orotate phosphoribosyltransferase activity GO:0004588 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| omp_decarboxylase_activity | pyrF (Pseudomonas putida KT2440) UniProtKB:Q88LW2 Family Representative |
orotidine-5'-phosphate decarboxylase activity GO:0004590 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| omp_decarboxylase_activity | UMPS (human) UniProtKB:P11172 Family Representative |
orotidine-5'-phosphate decarboxylase activity GO:0004590 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| omp_decarboxylase_activity | URA3 (Saccharomyces cerevisiae) UniProtKB:P03962 Family Representative |
orotidine-5'-phosphate decarboxylase activity GO:0004590 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| omp_decarboxylase_activity | ura4 (Schizosaccharomyces pombe) UniProtKB:P14965 Family Representative |
orotidine-5'-phosphate decarboxylase activity GO:0004590 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| eukaryotic_ump_kinase_activity | URA6 (Saccharomyces cerevisiae) UniProtKB:P15700 Family Representative |
UMP kinase activity GO:0033862 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| eukaryotic_ump_kinase_activity | ura6 (Schizosaccharomyces pombe) UniProtKB:O59771 Family Representative |
UMP kinase activity GO:0033862 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| eukaryotic_ump_kinase_activity | CMPK1 (human) UniProtKB:P30085 Family Representative |
UMP kinase activity GO:0033862 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| pyrH_ump_kinase_activity | pyrH (Escherichia coli K-12) UniProtKB:P0A7E9 Family Representative |
UMP kinase activity GO:0033862 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| udp_ndp_kinase_activity | YNK1 (Saccharomyces cerevisiae) UniProtKB:P36010 Family Representative |
nucleoside diphosphate kinase activity GO:0004550 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| udp_ndp_kinase_activity | ndk1 (Schizosaccharomyces pombe) UniProtKB:P49740 Family Representative |
nucleoside diphosphate kinase activity GO:0004550 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| udp_ndp_kinase_activity | NME1 (human) UniProtKB:P15531 Family Representative |
nucleoside diphosphate kinase activity GO:0004550 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| ctp_synthase_activity | URA7 (Saccharomyces cerevisiae) UniProtKB:P28274 Family Representative |
CTP synthase activity GO:0003883 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| ctp_synthase_activity | URA8 (Saccharomyces cerevisiae) UniProtKB:P38627 Family Representative |
CTP synthase activity GO:0003883 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| ctp_synthase_activity | ura7 (Schizosaccharomyces pombe) UniProtKB:O42644 Family Representative |
CTP synthase activity GO:0003883 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| ctp_synthase_activity | CTPS1 (human) UniProtKB:P17812 Family Representative |
CTP synthase activity GO:0003883 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| ctp_synthase_activity | pyrG (Escherichia coli K-12) UniProtKB:P0A7E5 Family Representative |
CTP synthase activity GO:0003883 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| carbamoyl_phosphate_glutaminase_component | carbamoyl-phosphate synthase small-chain domain family InterPro:IPR006274 Family |
glutaminase activity GO:0004359 |
Family Review Missing
No supported structured family review is available for InterPro:IPR006274. |
| carbamoyl_phosphate_synthetase_component | carbamoyl-phosphate synthase large-chain domain family InterPro:IPR006275 Family |
carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity GO:0004088 |
Family Review Missing
No supported structured family review is available for InterPro:IPR006275. |
| aspartate_carbamoyltransferase_activity | aspartate carbamoyltransferase domain family InterPro:IPR002082 Family |
aspartate carbamoyltransferase activity GO:0004070 |
Family Review Missing
No supported structured family review is available for InterPro:IPR002082. |
| dihydroorotase_activity | dihydroorotase catalytic domain family InterPro:IPR002195 Family |
dihydroorotase activity GO:0004151 |
Family Review Missing
No supported structured family review is available for InterPro:IPR002195. |
| dihydroorotate_dehydrogenase_activity | class 2 dihydroorotate dehydrogenase family PANTHER:PTHR48109:SF4 Family |
dihydroorotate dehydrogenase (quinone) activity GO:0106430 |
Family Supported
Family review supports GO:0106430 for PANTHER:PTHR48109:SF4. Class 2 only. This is the function of the module's quinone_dhodh_variant, which uses the base family id with GO:0106430 as required function. That restriction is needed because the base family also contains the soluble class 1 enzymes. S. pombe ura3 activity depends on an intact respiratory chain, which fits a quinone acceptor. |
| dihydroorotate_dehydrogenase_fumarate_activity | class 1A (fumarate) dihydroorotate dehydrogenases PANTHER:PTHR48109:SF1 Family |
dihydroorotate dehydrogenase (fumarate) activity GO:1990663 |
Family Supported
Family review supports GO:1990663 for PANTHER:PTHR48109:SF1. Only class 1A members of SF1, such as S. cerevisiae URA1 and Lactococcus PyrDA. This is the function of the module's fumarate_dhodh_variant, which selects SF1 with no required_function. SF1 also holds 93 reviewed class 1B NAD(+)-type PyrDB catalytic subunits, so an SF1 selector on its own over-includes. See the member exception. |
| orotate_phosphoribosyltransferase_activity | orotate phosphoribosyltransferase domain family InterPro:IPR023031 Family |
orotate phosphoribosyltransferase activity GO:0004588 |
Family Review Missing
No supported structured family review is available for InterPro:IPR023031. |
| omp_decarboxylase_activity | OMP decarboxylase domain family InterPro:IPR014732 Family |
orotidine-5'-phosphate decarboxylase activity GO:0004590 |
Family Review Missing
No supported structured family review is available for InterPro:IPR014732. |
| eukaryotic_ump_kinase_activity | eukaryotic UMP/CMP kinases PANTHER:PTHR23359:SF206 Family |
UMP kinase activity GO:0033862 |
Family Supported
Family review supports GO:0033862 for PANTHER:PTHR23359:SF206. Eukaryotic UMP/CMP kinases only. PAINT places the term at PTN000599579 (Eukaryota), whose recipients include URA6, S. pombe ura6, CMPK1 and Arabidopsis UMK1, UMK2 and UMK3. This is the module's function for eukaryotic_ump_kinase_activity, which selects the three subfamilies listed here with representatives URA6, ura6 and CMPK1. The annoton has no required_function, so it is the subfamily list that keeps the selector off the adenylate kinases; a base-family selector would take in every adenylate kinase. SF206 also holds the bacterial adenylate kinases, which do not inherit the term (see the member exception); bacteria make UDP with PyrH (PTHR42833). Human AK9 (SF148) also inherits from PTN000599579 but was not assessed here. |
| eukaryotic_ump_kinase_activity | eukaryotic UMP/CMP kinases PANTHER:PTHR23359:SF171 Family |
UMP kinase activity GO:0033862 |
Family Supported
Family review supports GO:0033862 for PANTHER:PTHR23359:SF171. Eukaryotic UMP/CMP kinases only. PAINT places the term at PTN000599579 (Eukaryota), whose recipients include URA6, S. pombe ura6, CMPK1 and Arabidopsis UMK1, UMK2 and UMK3. This is the module's function for eukaryotic_ump_kinase_activity, which selects the three subfamilies listed here with representatives URA6, ura6 and CMPK1. The annoton has no required_function, so it is the subfamily list that keeps the selector off the adenylate kinases; a base-family selector would take in every adenylate kinase. SF206 also holds the bacterial adenylate kinases, which do not inherit the term (see the member exception); bacteria make UDP with PyrH (PTHR42833). Human AK9 (SF148) also inherits from PTN000599579 but was not assessed here. |
| eukaryotic_ump_kinase_activity | eukaryotic UMP/CMP kinases PANTHER:PTHR23359:SF246 Family |
UMP kinase activity GO:0033862 |
Family Supported
Family review supports GO:0033862 for PANTHER:PTHR23359:SF246. Eukaryotic UMP/CMP kinases only. PAINT places the term at PTN000599579 (Eukaryota), whose recipients include URA6, S. pombe ura6, CMPK1 and Arabidopsis UMK1, UMK2 and UMK3. This is the module's function for eukaryotic_ump_kinase_activity, which selects the three subfamilies listed here with representatives URA6, ura6 and CMPK1. The annoton has no required_function, so it is the subfamily list that keeps the selector off the adenylate kinases; a base-family selector would take in every adenylate kinase. SF206 also holds the bacterial adenylate kinases, which do not inherit the term (see the member exception); bacteria make UDP with PyrH (PTHR42833). Human AK9 (SF148) also inherits from PTN000599579 but was not assessed here. |
| pyrH_ump_kinase_activity | PyrH-type UMP kinases PANTHER:PTHR42833 Family |
UMP kinase activity GO:0033862 |
Family Supported
Family review supports GO:0033862 FAMILY_WIDE. This is the module's function for the bacterial PyrH variant. It holds for the bacterial and plastid members. The MosB caveat is in the coherence reason; MosB is not a PAINT recipient. |
| udp_ndp_kinase_activity | nucleoside-diphosphate kinases (NDK/NME) PANTHER:PTHR11349 Family |
nucleoside diphosphate kinase activity GO:0004550 |
Family Function Unreviewed
Family review leaves GO:0004550 UNRESOLVED. Awd and classical NDKs catalyze nucleoside-diphosphate phosphorylation; the Awd killer-of-prune mutation changes protein stability without abolishing catalytic efficiency (PMID:1320004). The classification also includes NDK-like/domain-containing branches for which this source does not resolve a complete active-site and biochemical boundary. Awd activity is supported, but an unconditional grant to all classified NDK-like proteins remains unresolved. Notch regulation and other Awd-specific pathways are not universal NDK functions. |
| ctp_synthase_activity | CTP synthases (PyrG/CTPS/URA7) PANTHER:PTHR11550 Family |
CTP synthase activity GO:0003883 |
Family Supported
Family review supports GO:0003883 FAMILY_WIDE. This is the module's function for ctp_synthase_activity. It holds for all members, and the two yeast isozymes overlap in function. |
25 complete review(s) · 19 with deep research · 4 missing review · 10 reviewed but lacking deep research
| Gene | Review | Complete | Deep research |
|---|---|---|---|
| CAD P27708 | ✓ | 70/84 | ✗ |
| carA Q88DU5 | ✓ | ✓ | ✓ |
| carB Q88DU6 | ✓ | ✓ | ✓ |
| CTPS1 P17812 | ✓ | 53/54 | ✗ |
| DHODH Q02127 | ✓ | 25/26 | ✓ |
| ndk1 P49740 | ✓ | ✓ | ✗ |
| pyrG (Escherichia coli K-12) P0A7E5 | ✗ | — | — |
| pyrH (Escherichia coli K-12) P0A7E9 | ✗ | — | — |
| NME1 (human) P15531 | ✗ | — | — |
| CMPK1 (human) P30085 | ✗ | — | — |
| pyrB Q88D30 | ✓ | ✓ | ✓ |
| pyrC Q88NW7 | ✓ | ✓ | ✓ |
| pyrD Q88L40 | ✓ | ✓ | ✓ |
| pyrE Q88C92 | ✓ | ✓ | ✓ |
| pyrF Q88LW2 | ✓ | ✓ | ✓ |
| UMPS P11172 | ✓ | ✓ | ✗ |
| URA1 P28272 | ✓ | ✓ | ✓ |
| ura1 Q09794 | ✓ | ✓ | ✗ |
| URA10 P30402 | ✓ | ✓ | ✓ |
| URA2 P07259 | ✓ | ✓ | ✓ |
| ura2 Q9UTI0 | ✓ | ✓ | ✗ |
| URA3 P03962 | ✓ | ✓ | ✓ |
| ura3 P32747 | ✓ | ✓ | ✗ |
| ura4 P14965 | ✓ | ✓ | ✗ |
| URA4 P20051 | ✓ | ✓ | ✓ |
| ura5 O94331 | ✓ | ✓ | ✗ |
| URA5 P13298 | ✓ | ✓ | ✓ |
| ura6 O59771 | ✓ | ✓ | ✗ |
| URA6 P15700 | ✓ | ✓ | ✓ |
| ura7 O42644 | ✓ | ✓ | ✓ |
| URA7 P28274 | ✓ | ✓ | ✓ |
| URA8 P38627 | ✓ | 29/30 | ✓ |
| YNK1 P36010 | ✓ | ✓ | ✓ |
ALIGN with the YeastPathways crosswalk (PWY-5686-1, PYRIMID-RNTSYN-PWY, PWY0-162, PWY-7176). The six chemical leaves are conserved despite taxon-specific protein architecture: bacteria commonly use separate CarA/CarB/PyrB/PyrC/PyrE/PyrF chains, animals fuse the first three activities in CAD and the last two in UMPS, and fungi use a CPSase-ATCase fusion (S. cerevisiae URA2, S. pombe ura1) whose dihydroorotase-like domain is inactive (PMID:2679804), plus separate URA4/ura2 dihydroorotase, URA5+URA10/ura5 OPRTase and URA3/ura4 ODCase. Fungal gene names are not orthologous between the two yeasts (S. cerevisiae URA1 = DHODH but S. pombe ura1 = CPSase-ATCase). Dihydroorotate oxidation is modelled as two variants: class 2 quinone DHODH (bacteria, animals, S. pombe ura3 in mitochondria) and the class 1A fumarate DHODH of S. cerevisiae URA1, which is cytosolic and of bacterial origin (PMID:1409592, PMID:15014982). The UMP to UTP and CTP steps (URA6, YNK1, URA7/URA8) were added as part 7 per the crosswalk; bacterial PyrH and eukaryotic UMP/CMP kinases are unrelated families and are modelled as variants. YeastCyc corrections: CPA1/CPA2 are listed for CARBPSYN-RXN in PWY-5686-1 but form the arginine-specific CPSase A (committed CPA1/CPA2 reviews) and are not exemplars here, although CPSase A carbamoyl phosphate can partly reach the pyrimidine pathway; PYRIMID-RNTSYN-PWY draws URA1 with the quinone-dependent reaction (EC 1.3.5.2) instead of the fumarate reaction; UDP kinase has no gene in YeastCyc (YNK1 added, as in the GO-CAM). GO-CAM disagreements: YeastPathways_PYRIMID-RNTSYN-PWY gives URA1 the generic GO:0004152 with no location, URA6 the obsolete GO:0004127 in several models, and labels the pathway GO:0006207 'de novo' pyrimidine nucleobase biosynthetic process although its products are nucleotides. The PomBase model 69a0c46f00003691 (listed in the crosswalk under pyrimidine_salvage) supplies the S. pombe exemplars. Carbamoyl phosphate also feeds arginine biosynthesis, so pathway assignment of bacterial CarA/CarB requires process context rather than reaction identity alone; pyrimidine CPS II must not be conflated with mitochondrial urea-cycle CPS1. PRPP supply (pentose_phosphate_pathway) is upstream and pyrimidine salvage (pyrimidine_salvage) and deoxynucleotide synthesis (dntp_de_novo_synthesis) are separate modules. Regulation (outside the core): UTP feedback-inhibits URA2 CPSase and Ppr1p senses dihydroorotate and orotate to activate later URA genes (PMID:9858611). Human disease and drug examples remain useful context: UMPS deficiency causes hereditary orotic aciduria, DHODH deficiency causes Miller syndrome, CAD deficiency causes a uridine-responsive developmental epileptic encephalopathy, and DHODH is targeted by leflunomide/teriflunomide. Pseudomonas PyrC' is a lineage-specific inactive dihydroorotase-like structural partner of PyrB and is not an additional dihydroorotase reaction leaf.
The glutaminase and ATP-dependent synthetase domains occur in separate CarA and CarB chains in many bacteria, in one CAD polypeptide in animals and in the CPSase-ATCase protein of fungi (URA2 / S. pombe ura1). Fungi have a second, arginine-specific carbamoyl-phosphate synthetase (CPA1/CPA2) that is not part of this module.
Supplies ammonia to the coupled carbamoyl-phosphate synthetase domain.
Uses channeled ammonia, hydrogencarbonate, and ATP to form carbamoyl phosphate.
Builds the first carbon-nitrogen framework of the pyrimidine ring. In P. putida, catalytic PyrB chains assemble with inactive PyrC' pseudoenzyme chains rather than PyrI regulatory subunits.
Closes the pyrimidine ring to form dihydroorotate. The dihydroorotase-like domain of fungal URA2 is catalytically inactive (PMID:2679804), so fungi need the separate URA4 enzyme.
Some yeasts (for example Lachancea kluyveri) carry both types (PMID:15014982). Class 1B NAD-dependent PyrDB-PyrK enzymes of some bacteria are not modelled.
Oxidizes dihydroorotate to orotate. Class-2 enzymes are membrane-associated: bacterial PyrD acts peripherally at the plasma membrane, whereas animal and most fungal DHODHs are anchored to the mitochondrial inner membrane and pass electrons to ubiquinone, making pyrimidine synthesis respiration-dependent.
Soluble FMN enzyme that uses fumarate instead of quinone, making pyrimidine synthesis independent of oxygen and the respiratory chain; it allows anaerobic growth of Saccharomyces yeasts (PMID:15014982).
Attaches the completed pyrimidine ring to phosphoribose.
Produces UMP, completing the de novo UMP pathway.
Downstream extension shared with pyrimidine salvage: UMP kinase, nucleoside-diphosphate kinase and CTP synthase. The UDP made here is also the ribonucleotide reductase substrate for dUTP/dTTP synthesis (dntp_de_novo_synthesis).
Also phosphorylates CMP and dCMP (salvage) and dUMP; the same protein serves pyrimidine_salvage.
Unrelated hexameric UMP kinase of bacteria and archaea (convergent with the eukaryotic enzyme).
Broad-specificity terminal phosphorylation of UDP.
The only de novo source of CTP; CTP is required for RNA, CDP-diacylglycerol phospholipid synthesis and dCTP formation. The enzyme forms filaments in many species.