Pyrimidine base and nucleoside salvage

Recycling of preformed pyrimidine bases and ribonucleosides, taken up from the environment or released by RNA and nucleotide turnover, into UMP and CMP. Uracil is converted directly to UMP by uracil phosphoribosyltransferase with PRPP. Uridine and cytidine are phosphorylated by uridine-cytidine kinase to UMP and CMP; alternatively, cytidine is deaminated to uridine by cytidine deaminase, and the ribonucleosides are cleaved to their free bases either by a nucleoside hydrolase (fungi and protists) or by uridine phosphorylase (animals and bacteria). Cytosine is deaminated to uracil by cytosine deaminase, an enzyme present in fungi and bacteria but absent from animals; this is why the antifungal prodrug 5-fluorocytosine is selectively toxic to fungi. CMP made by salvage is phosphorylated to CDP by UMP/CMP kinase, and UMP joins the de novo product for conversion to UTP and CTP. The same enzymes act on some deoxyribonucleosides (deoxycytidine is phosphorylated or cleaved), but thymidine salvage requires thymidine kinase, which animals and many bacteria have and budding and fission yeasts lack. Uptake of pyrimidine bases and nucleosides by plasma-membrane permeases precedes the module.

MODULE:pyrimidine_salvageDRAFTMetabolic Pathwaymodules/pyrimidine_salvage.yaml

pyrimidine-containing compound salvageGO:0008655

YeastPathways:YEAST-RNT-SALV

salvage pathways of pyrimidine ribonucleotides (S. cerevisiae, SGD YeastPathways)

FUR1, URK1 (uridine and cytidine), CDD1, URH1 (uridine and cytidine), FCY1, URA6 (CMP kinase) and YNK1 (CDP kinase); the comment describes uptake by Fur4p, Fcy2p and Fui1p.

YeastPathways:YEAST-SALV-PYRMID-DNTP

salvage pathways of pyrimidine deoxyribonucleotides (S. cerevisiae, SGD YeastPathways)

Deoxycytidine phosphorylation (URK1), deamination (CDD1) and cleavage (URH1); deoxyuridine kinase, uridine/thymidine phosphorylase and thymidine kinase reactions are listed without genes because S. cerevisiae lacks them.

GO:0008655

pyrimidine-containing compound salvage

Module-level process term.

PMID:2189783

The FUR1 gene of Saccharomyces cerevisiae: cloning, structure and expression of wild-type and mutant alleles.

FUR1 encodes uracil phosphoribosyltransferase, converting uracil to UMP in the salvage pathway.

PMID:2169608

The URK1 gene of Saccharomyces cerevisiae encoding uridine kinase.

Identification of URK1 as the yeast uridine kinase gene.

PMID:10501935

New insights into the pyrimidine salvage pathway of Saccharomyces cerevisiae: requirement of six genes for cytidine metabolism.

CDD1 encodes cytidine deaminase; cytidine enters through Fcy2p, is cleaved to cytosine by Urh1p or phosphorylated to CMP by Urk1p, and cytosine deaminase (Fcy1p) is limiting for cytidine use as a UMP precursor.

PMID:12111094

The URH1 uridine ribohydrolase of Saccharomyces cerevisiae.

URH1 encodes a nucleoside hydrolase active on uridine, cytidine and deoxycytidine, related to protozoan inosine-uridine nucleoside hydrolases.

PMID:9000374

Characterization of the Saccharomyces cerevisiae FCY1 gene encoding cytosine deaminase and its homologue FCA1 of Candida albicans.

FCY1 disruption abolishes cytosine deaminase and confers 5-fluorocytosine resistance; Fcy1p resembles cytidine/CMP deaminases, not E. coli cytosine deaminase.

PMID:1333436

The adenylate kinase family in yeast: identification of URA6 as a multicopy suppressor of deficiency in major AMP kinase.

URA6 UMP kinase also phosphorylates CMP.

PMID:9485596

The ORF YBL042 of Saccharomyces cerevisiae encodes a uridine permease.

FUI1 (YBL042C) encodes the uridine permease (uptake, outside the module core).

PMID:23670538

Nucleotide degradation and ribose salvage in yeast.

Urh1 releases ribose from pyrimidine nucleosides during starvation; pnp1 urh1 double mutants fail to salvage nucleotides.

PMID:14500848

Reconstitution of an efficient thymidine salvage pathway in Saccharomyces cerevisiae.

Thymidine salvage in budding yeast requires expression of a heterologous nucleoside kinase and nucleoside transporter.

PMID:15157888

In vivo labeling of fission yeast DNA with thymidine and thymidine analogs.

Yeasts neither take up exogenous thymidine efficiently nor phosphorylate it; fission yeast needs human ENT1 and herpes simplex virus thymidine kinase to incorporate thymidine.

PMID:5729618

Thymidine kinase: evidence for its absence from Neurospora crassa and some other micro-organisms, and the relevance of this to the specific labelling of deoxyribonucleic acid.

Classic evidence that thymidine kinase is absent from several fungi.

10Nodes

7Parts

1Variant Sets

2Variants

8Annotons

6Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:pyrimidine_salvage 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.

Function consistency and core coverage

14 gene-function check(s) reflected in core functions · 0 conflict(s) · 13 evidence or coverage gap(s) (31 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
uracil_prt_activity	FUR1 (Saccharomyces cerevisiae) UniProtKB:P18562 Family Representative	uracil phosphoribosyltransferase activity GO:0004845	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
uracil_prt_activity	SPAC1B3.01c (Schizosaccharomyces pombe) UniProtKB:O13867 Family Representative	uracil phosphoribosyltransferase activity GO:0004845	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
uracil_prt_activity	upp (Escherichia coli K-12) UniProtKB:P0A8F0 Family Representative	uracil phosphoribosyltransferase activity GO:0004845	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
uridine_kinase_activity	URK1 (Saccharomyces cerevisiae) UniProtKB:P27515 Family Representative	uridine kinase activity GO:0004849	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
uridine_kinase_activity	urk1 (Schizosaccharomyces pombe) UniProtKB:O74427 Family Representative	uridine kinase activity GO:0004849	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
uridine_kinase_activity	UCK2 (human) UniProtKB:Q9BZX2 Family Representative	uridine kinase activity GO:0004849	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
uridine_kinase_activity	udk (Escherichia coli K-12) UniProtKB:P0A8F4 Family Representative	uridine kinase activity GO:0004849	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
cytidine_deaminase_activity	CDD1 (Saccharomyces cerevisiae) UniProtKB:Q06549 Family Representative	cytidine deaminase activity GO:0004126	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cytidine_deaminase_activity	cdd1 (Schizosaccharomyces pombe) UniProtKB:Q09190 Family Representative	cytidine deaminase activity GO:0004126	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cytidine_deaminase_activity	CDA (human) UniProtKB:P32320 Family Representative	cytidine deaminase activity GO:0004126	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cytidine_deaminase_activity	cdd (Escherichia coli K-12) UniProtKB:P0ABF6 Family Representative	cytidine deaminase activity GO:0004126	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
uridine_nucleosidase_activity	URH1 (Saccharomyces cerevisiae) UniProtKB:Q04179 Family Representative	uridine nucleosidase activity GO:0045437	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
uridine_nucleosidase_activity	urh1 (Schizosaccharomyces pombe) UniProtKB:Q9P6J4 Family Representative	uridine nucleosidase activity GO:0045437	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
uridine_nucleosidase_activity	urh2 (Schizosaccharomyces pombe) UniProtKB:Q10314 Family Representative	uridine nucleosidase activity GO:0045437	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
uridine_phosphorylase_activity	UPP1 (human) UniProtKB:Q16831 Family Representative	uridine phosphorylase activity GO:0004850	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
uridine_phosphorylase_activity	udp (Escherichia coli K-12) UniProtKB:P12758 Family Representative	uridine phosphorylase activity GO:0004850	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
cytosine_deaminase_activity	FCY1 (Saccharomyces cerevisiae) UniProtKB:Q12178 Family Representative	cytosine deaminase activity GO:0004131	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cytosine_deaminase_activity	fcy1 (Schizosaccharomyces pombe) UniProtKB:O59834 Family Representative	cytosine deaminase activity GO:0004131	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cmp_kinase_activity	URA6 (Saccharomyces cerevisiae) UniProtKB:P15700 Family Representative	CMP kinase activity GO:0036430	Function Unreviewed No retained annotation or core molecular function supports this GO assertion. Missing or broader evidence is a coverage gap, not proof the activity is absent.
cmp_kinase_activity	ura6 (Schizosaccharomyces pombe) UniProtKB:O59771 Family Representative	CMP kinase activity GO:0036430	Function Unreviewed No retained annotation or core molecular function supports this GO assertion. Missing or broader evidence is a coverage gap, not proof the activity is absent.
cmp_kinase_activity	CMPK1 (human) UniProtKB:P30085 Family Representative	CMP kinase activity GO:0036430	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
thymidine_kinase_activity	TK1 (human) UniProtKB:P04183 Family Representative	thymidine kinase activity GO:0004797	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
thymidine_kinase_activity	tdk (Escherichia coli K-12) UniProtKB:P23331 Family Representative	thymidine kinase activity GO:0004797	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
uracil_prt_activity	Upp-type uracil phosphoribosyltransferases Family	uracil phosphoribosyltransferase activity GO:0004845	Family Id Missing The family has no identifier linking it to a curated family review.
uridine_kinase_activity	uridine-cytidine kinases (Udk/UCK) PANTHER:PTHR10285 Family	uridine kinase activity GO:0004849	Family Scope Restricted GO:0004849 is SUBFAMILY_ONLY; this family grounding does not establish the allowed subfamily scope. UCK subfamilies only. The pyrimidine_salvage module selects the base family for this activity, which also takes in the NRKs, PanK and YFH7.
cytidine_deaminase_activity	cytidine deaminases PANTHER:PTHR11644:SF2 Family	cytidine deaminase activity GO:0004126	Family Supported Family review supports GO:0004126 for PANTHER:PTHR11644:SF2. Cytidine deaminases (SF2: human CDA, S. cerevisiae CDD1, S. pombe pcd1, fly CG8353), as pyrimidine_salvage selects. SF28 is not characterized.
uridine_nucleosidase_activity	inosine-uridine preferring nucleoside hydrolases (Urh1 subfamily) PANTHER:PTHR12304:SF4 Family	uridine nucleosidase activity GO:0045437	Family Supported Family review supports GO:0045437 for PANTHER:PTHR12304:SF4. Uridine nucleosidase activity in SF4 (selected by pyrimidine_salvage), the plant URH subfamilies and RihC.
uridine_phosphorylase_activity	uridine phosphorylases PANTHER:PTHR43691 Family	uridine phosphorylase activity GO:0004850	Family Scope Restricted GO:0004850 is SUBFAMILY_ONLY; this family grounding does not establish the allowed subfamily scope. Asserted by pyrimidine_salvage and pyrimidine_nucleotide_catabolism; accepted by UPP1 and UPP2.
cytosine_deaminase_activity	fungal cytidine-deaminase-fold cytosine deaminases PANTHER:PTHR11079 Family	cytosine deaminase activity GO:0004131	Family Function Unreviewed Family review leaves GO:0004131 UNRESOLVED. The pyrimidine_salvage module selects the base family for the fungal cytosine deaminases. These do not form one subfamily: S. cerevisiae FCY1 is in SF190, but S. pombe SPCC965.14c is in SF149 with the TAD2/ADAT2 tRNA deaminases, including S. pombe tad2 itself. No subfamily scope is therefore safe; the term holds for FCY1 and SPCC965.14c by their reviews.
cmp_kinase_activity	eukaryotic UMP/CMP kinases PANTHER:PTHR23359:SF206 Family	CMP kinase activity GO:0036430	Family Supported Family review supports GO:0036430 for PANTHER:PTHR23359:SF206. This is the function the pyrimidine_salvage module's cmp_kinase_activity annoton asserts for URA6, ura6 and CMPK1 through PTHR23359:SF206, this assessment's applicable subfamily. CMP phosphorylation is a property of the UMP/CMP kinases, but the evidence for yeast URA6 conflicts. Schricker et al. report significant CMP phosphorylation. Jong et al. list UMP and dUMP as the main acceptors and do not include CMP among the minor ones. The URA6 gene review keeps CMP-related terms as non-core. PAINT asserts no CMP kinase activity term. The scope is the eukaryotic UMP/CMP kinases of SF206, minus the bacterial Adk members.
thymidine_kinase_activity	TK1-type thymidine kinases PANTHER:PTHR11441 Family	thymidine kinase activity GO:0004797	Family Supported Family review supports GO:0004797 FAMILY_WIDE. Asserted by pyrimidine_salvage for human TK1 and E. coli Tdk. No member gene review exists in this repository.

Gene-review completeness (16/23 grounded genes reviewed)

15 complete review(s) · 7 with deep research · 7 missing review · 9 reviewed but lacking deep research

Gene	Review	Complete	Deep research
CDA P32320	✓	✓	✗
CDD1 Q06549	✓	✓	✓
FCY1 Q12178	✓	✓	✓
FUR1 P18562	✓	✓	✓
TK1 (human) P04183	✗	—	—
upp (Escherichia coli K-12) P0A8F0	✗	—	—
udk (Escherichia coli K-12) P0A8F4	✗	—	—
cdd (Escherichia coli K-12) P0ABF6	✗	—	—
udp (Escherichia coli K-12) P12758	✗	—	—
tdk (Escherichia coli K-12) P23331	✗	—	—
CMPK1 (human) P30085	✗	—	—
pcd1 Q09190	✓	✓	✗
SPAC17G8.02 Q10314	✓	✓	✗
SPAC1B3.01c O13867	✓	✓	✗
SPBC1683.06c Q9P6J4	✓	✓	✗
SPCC965.14c O59834	✓	✓	✗
UCK2 Q9BZX2	✓	21/23	✓
UPP1 Q16831	✓	✓	✗
ura6 O59771	✓	✓	✗
URA6 P15700	✓	✓	✓
URH1 Q04179	✓	✓	✓
urk1 O74427	✓	✓	✗
URK1 P27515	✓	✓	✓

Tree

Pyrimidine base and nucleoside salvageMetabolic Pathwaypyrimidine_salvage

Parts
1. 1. uracil phosphoribosylation
2. uracil + PRPP to UMP + PPiReactionuracil_prt_step
  
  Annotons
  - Uracil phosphoribosyltransferase Family: Upp-type uracil phosphoribosyltransferases
3. 2. uridine and cytidine phosphorylation
4. uridine/cytidine + ATP (or GTP) to UMP/CMPReactionuridine_cytidine_kinase_step
  
  Annotons
  - Uridine-cytidine kinase Family: uridine-cytidine kinases (Udk/UCK)
5. 3. cytidine deamination
6. cytidine + H2O to uridine + NH3Reactioncytidine_deamination_step
  
  Annotons
  - Cytidine deaminase Family: cytidine deaminases
7. 4. nucleoside cleavage to free bases
8. uridine/cytidine to uracil/cytosineReactionnucleoside_cleavage
  
  Variants
  1. Nucleoside cleavage chemistry by hydrolysis (nucleoside hydrolase) versus phosphorolysis (uridine phosphorylase) (One Or More)
    
    Pyrimidine nucleoside hydrolase (fungi, protists)Reactionnucleoside_hydrolase_variant
    
    Annotons
    
    Uridine-cytidine nucleoside hydrolase (Urh1) Family: inosine-uridine preferring nucleoside hydrolases (Urh1 subfamily)
    
    Uridine phosphorylase (animals, bacteria)Reactionuridine_phosphorylase_variant
    
    Annotons
    
    Uridine phosphorylase Family: uridine phosphorylases
9. 5. cytosine deamination (fungi and bacteria) optional
10. cytosine + H2O to uracil + NH3Reactioncytosine_deamination_step
  
  Annotons
  - Cytosine deaminase (fungal CDA-fold type) Family: fungal cytidine-deaminase-fold cytosine deaminases
11. 6. CMP phosphorylation
12. CMP + ATP to CDP + ADPReactioncmp_kinase_step
  
  Annotons
  - UMP/CMP kinase (CMP reaction) Family: eukaryotic UMP/CMP kinases
13. 7. thymidine phosphorylation (absent from yeasts) optional
14. thymidine + ATP to dTMP + ADPReactionthymidine_kinase_step
  
  Annotons
  - Thymidine kinase (TK1 type) Family: TK1-type thymidine kinases

Details

Context

FungiNCBITaxon:4751

cytosolGO:0005829

Pyrimidine base and nucleoside salvageMetabolic Pathwaypyrimidine_salvage

pyrimidine-containing compound salvageGO:0008655

Context

FungiNCBITaxon:4751

cytosolGO:0005829

NEW module from the YeastPathways crosswalk (YEAST-RNT-SALV, YEAST-SALV-PYRMID-DNTP) and the PomBase model 69a0c46f00003691, scoped to fungal pyrimidine base/nucleoside salvage with animal and bacterial alternatives as variants. All YeastCyc catalysts (FUR1, URK1, CDD1, URH1, FCY1, URA6, YNK1) are correct; the CDP-to-CTP step (YNK1) is the NDP kinase step of de_novo_pyrimidine_synthesis and is not repeated. The defining realisation caveats are absences: S. cerevisiae and S. pombe have no thymidine kinase, uridine/thymidine phosphorylase or deoxyuridine kinase (the gene-less THYKI-RXN, THYM-PHOSPH-RXN, URA-PHOSPH-RXN and DURIDKI-RXN of YEAST-SALV-PYRMID-DNTP; no S288C or S. pombe UniProt protein carries EC 2.7.1.21, 2.4.2.3 or 2.4.2.4, checked 2026-10-06), so the thymidine kinase part is optional and has only animal/bacterial exemplars; deoxyuridine cannot replace uracil for ura- yeast. Deoxycytidine is handled by URK1 and URH1 (PMID:12111094). GO-CAM disagreements: FCY1 carries the obsolete GO:0102480 and URA6 the obsolete GO:0004127; URK1 cytidine phosphorylation uses GO:0004849 rather than GO:0043771. In the PomBase model, uracil phosphoribosyltransferase activity is asserted for three proteins: Q9HE15 (SPAC1399.04c, a UPRT domain protein classified by PANTHER as a uridine kinase-family member), O13867 (SPAC1B3.01c) and urg2 (Q9US43, a plastid-type UPRT, PTHR32315:SF4); only O13867, annotated part_of uracil salvage, is used as an exemplar, and the PomBase cytidine kinase SPAC227.14 (Q9UTC5) is noted but not used. The PomBase S. pombe fcy1 (O59834) is classified by PANTHER in the TAD2 subfamily; it is retained as an exemplar because PomBase asserts cytosine deaminase activity. Uptake permeases (FUR4 uracil, FUI1 uridine, FCY2 purine-cytosine) are transport steps outside the enzymatic core, as are the 5'-nucleotidases and the pyrimidine catabolism activities of the PomBase model (pyrimidine_nucleotide_catabolism). Downstream, UMP and CDP join de_novo_pyrimidine_synthesis (UTP/CTP) and dntp_de_novo_synthesis.

Connections

cytidine_deamination_step -> uridine_cytidine_kinase_step Provides Input For

Uridine from cytidine deamination is phosphorylated to UMP.

cytidine_deamination_step -> nucleoside_cleavage Provides Input For

Uridine from cytidine deamination can be cleaved to uracil.

nucleoside_cleavage -> uracil_prt_step Provides Input For

Uracil released by nucleoside cleavage is converted to UMP.

nucleoside_cleavage -> cytosine_deamination_step Provides Input For

Cytosine released from cytidine is deaminated to uracil.

cytosine_deamination_step -> uracil_prt_step Provides Input For

Uracil from cytosine deamination is converted to UMP.

uridine_cytidine_kinase_step -> cmp_kinase_step Provides Input For

CMP from cytidine phosphorylation is phosphorylated to CDP.

Part 1: uracil phosphoribosylation

uracil + PRPP to UMP + PPiReactionuracil_prt_step

Annotons

Uracil phosphoribosyltransferase

uracil_prt_activity

Participant: Family: Upp-type uracil phosphoribosyltransferases

Family:

Upp-type uracil phosphoribosyltransferases No single PANTHER family covers the fungal and bacterial enzymes (FUR1 is unclassified, E. coli Upp is in PTHR32315:SF4), so no family id is asserted.

Representative Members: FUR1 (Saccharomyces cerevisiae)UniProtKB:P18562 SPAC1B3.01c (Schizosaccharomyces pombe)UniProtKB:O13867 upp (Escherichia coli K-12)UniProtKB:P0A8F0

Function

uracil phosphoribosyltransferase activityGO:0004845

Substrates: uracil PRPP

Products: UMP diphosphate

Single step from uracil to UMP; target of 5-fluorouracil activation, so fur1 mutants are 5-FU resistant.

Part 2: uridine and cytidine phosphorylation

uridine/cytidine + ATP (or GTP) to UMP/CMPReactionuridine_cytidine_kinase_step

Annotons

Uridine-cytidine kinase

uridine_kinase_activity

Participant: Family: uridine-cytidine kinases (Udk/UCK)

Family:

uridine-cytidine kinases (Udk/UCK)PANTHER:PTHR10285

Representative Members: URK1 (Saccharomyces cerevisiae)UniProtKB:P27515 urk1 (Schizosaccharomyces pombe)UniProtKB:O74427 UCK2 (human)UniProtKB:Q9BZX2 udk (Escherichia coli K-12)UniProtKB:P0A8F4

Function

uridine kinase activityGO:0004849

Substrates: uridine (also cytidine) ATP or GTP

Products: UMP (or CMP) ADP or GDP

Salvages uridine and cytidine directly to the monophosphates; in yeast also the route for deoxycytidine.

Part 3: cytidine deamination

cytidine + H2O to uridine + NH3Reactioncytidine_deamination_step

Annotons

Cytidine deaminase

cytidine_deaminase_activity

Participant: Family: cytidine deaminases

Family:

cytidine deaminasesPANTHER:PTHR11644:SF2

Representative Members: CDD1 (Saccharomyces cerevisiae)UniProtKB:Q06549 cdd1 (Schizosaccharomyces pombe)UniProtKB:Q09190 CDA (human)UniProtKB:P32320 cdd (Escherichia coli K-12)UniProtKB:P0ABF6

Function

cytidine deaminase activityGO:0004126

Substrates: cytidine (or 2'-deoxycytidine) water

Products: uridine (or 2'-deoxyuridine) ammonia

Converts cytidine to uridine. In yeast it is not the limiting route for cytidine use (PMID:10501935), and its in vivo role on deoxycytidine is doubtful.

Part 4: nucleoside cleavage to free bases

uridine/cytidine to uracil/cytosineReactionnucleoside_cleavage

Variant set: Nucleoside cleavage chemistry by hydrolysis (nucleoside hydrolase) versus phosphorolysis (uridine phosphorylase) (One Or More)

Pyrimidine nucleoside hydrolase (fungi, protists)Reactionnucleoside_hydrolase_variant

Annotons

Uridine-cytidine nucleoside hydrolase (Urh1)

uridine_nucleosidase_activity

Participant: Family: inosine-uridine preferring nucleoside hydrolases (Urh1 subfamily)

Family:

inosine-uridine preferring nucleoside hydrolases (Urh1 subfamily)PANTHER:PTHR12304:SF4

Representative Members: URH1 (Saccharomyces cerevisiae)UniProtKB:Q04179 urh1 (Schizosaccharomyces pombe)UniProtKB:Q9P6J4 urh2 (Schizosaccharomyces pombe)UniProtKB:Q10314

Function

uridine nucleosidase activityGO:0045437

Substrates: uridine (also cytidine, deoxycytidine) water

Products: uracil (or cytosine) D-ribose (or 2-deoxy-D-ribose)

Hydrolyses pyrimidine ribonucleosides to the free bases and ribose, which is recycled through the pentose phosphate pathway (PMID:23670538). Yeasts have no uridine phosphorylase (no EC 2.4.2.3 protein in S. cerevisiae or S. pombe UniProt).

Uridine phosphorylase (animals, bacteria)Reactionuridine_phosphorylase_variant

Annotons

Uridine phosphorylase

uridine_phosphorylase_activity

Participant: Family: uridine phosphorylases

Family:

uridine phosphorylasesPANTHER:PTHR43691

Representative Members: UPP1 (human)UniProtKB:Q16831 udp (Escherichia coli K-12)UniProtKB:P12758

Function

uridine phosphorylase activityGO:0004850

Substrates: uridine phosphate

Products: uracil alpha-D-ribose 1-phosphate

Phosphorolytic alternative; in animals it mainly serves catabolism (pyrimidine_nucleotide_catabolism).

Part 5: cytosine deamination (fungi and bacteria) (optional)

cytosine + H2O to uracil + NH3Reactioncytosine_deamination_step

Annotons

Cytosine deaminase (fungal CDA-fold type)

cytosine_deaminase_activity

Participant: Family: fungal cytidine-deaminase-fold cytosine deaminases

Family:

fungal cytidine-deaminase-fold cytosine deaminasesPANTHER:PTHR11079 Broad CDA-fold deaminase family (also containing tRNA adenosine deaminases); the leaf function restricts it to cytosine deaminases. Bacterial CodA is an unrelated amidohydrolase (PTHR32027) and is not an exemplar here.

Representative Members: FCY1 (Saccharomyces cerevisiae)UniProtKB:Q12178 fcy1 (Schizosaccharomyces pombe)UniProtKB:O59834

Function

cytosine deaminase activityGO:0004131

Substrates: cytosine water

Products: uracil ammonia

Converts cytosine (and cytidine-derived cytosine) to uracil for FUR1; the limiting step for cytidine use in yeast (PMID:10501935). Absent from animals, which is the basis of 5-fluorocytosine selectivity. Optional because animals lack it.

Part 6: CMP phosphorylation

CMP + ATP to CDP + ADPReactioncmp_kinase_step

Annotons

UMP/CMP kinase (CMP reaction)

cmp_kinase_activity

Participant: Family: eukaryotic UMP/CMP kinases

Family:

eukaryotic UMP/CMP kinases

Representative Members: URA6 (Saccharomyces cerevisiae)UniProtKB:P15700 ura6 (Schizosaccharomyces pombe)UniProtKB:O59771 CMPK1 (human)UniProtKB:P30085

Function

CMP kinase activityGO:0036430

Substrates: CMP ATP

Products: CDP ADP

Converts salvaged CMP to CDP, which NDP kinase (YNK1) phosphorylates to CTP. The same protein is the UMP kinase of de_novo_pyrimidine_synthesis.

Part 7: thymidine phosphorylation (absent from yeasts) (optional)

thymidine + ATP to dTMP + ADPReactionthymidine_kinase_step

Not realised in S. cerevisiae or S. pombe, which lack thymidine kinase and cannot salvage exogenous thymidine (PMID:15157888, PMID:14500848); dTMP comes only from thymidylate synthase (dntp_de_novo_synthesis).

Annotons

Thymidine kinase (TK1 type)

thymidine_kinase_activity

Participant: Family: TK1-type thymidine kinases

Family:

TK1-type thymidine kinasesPANTHER:PTHR11441

Representative Members: TK1 (human)UniProtKB:P04183 tdk (Escherichia coli K-12)UniProtKB:P23331

Function

thymidine kinase activityGO:0004797

Substrates: thymidine (also 2'-deoxyuridine) ATP

Products: dTMP (or dUMP) ADP

Cytosolic thymidine salvage in animals and bacteria. Its absence in yeasts is why yeast DNA cannot be labelled with thymidine or BrdU without a heterologous kinase; the mitochondrial TK2 of animals is in mitochondrial_dntp_supply.