Definition of thymidine catabolism
As rules and steps, or see full text
Rules
Overview: Thymidine degradation in GapMind is based on thymidine phoshorylase (EC 2.4.2.4), which yields 2-deoxyribose-1-phosphate and thymine. The catabolism of thymine is not represented, as it may be excreted.
- all: thymidine-transport, deoA, deoB, deoC and acetaldehyde-degradation
- Comment: After the phosphorylase deoA forms deoxyribose 1-phosphate, a phosphopentomutase forms deoxyribose-5-phosphate, and an aldolase yields glyceraldehyde 3-phosphate (an intermediate in glycolysis) and acetaldehyde.
- acetaldehyde-degradation:
- ald-dh-CoA
- or adh and acs
- or adh, ackA and pta
- Comment: Acetaldehyde can be oxidized to acetyl-CoA, or oxidized to acetate and activated to acetyl-CoA by either acetyl-CoA synthetase (acs) or by acetate kinase (ackA) and phosphate acetyltransferase (pta).
- thymidine-transport:
- nupG
- or Slc29a1
- or nupC
- or Slc28a3
- Comment: Transporters were identified using query: transporter:thymidine:deoxythymidine
Steps
nupG: thymidine permease NupG/XapB
- Curated sequence CH_088596: nucleoside permease nupG. Nucleoside permease NupG; Nucleoside-transport system protein NupG. Nucleoside porter, NupG. nucleoside:H+ symporter NupG. nucleoside:H+ symporter NupG
- Curated sequence P45562: Xanthosine permease; Xanthosine transporter. Xanthosine porter, XapB. xanthosine:H+ symporter XapB. xanthosine:H+ symporter XapB
- Total: 2 characterized proteins
Slc29a1: thymidine transporter Slc29a1
- Curated sequence O54698: Equilibrative nucleoside transporter 1; Equilibrative nitrobenzylmercaptopurine riboside-sensitive nucleoside transporter; Equilibrative NBMPR-sensitive nucleoside transporter; Nucleoside transporter, es-type; Solute carrier family 29 member 1. Equilibrative high affinity nucleoside transporter (nitrobenzyl-thioinosine-sensitive) (transports thymidine, adenosine, cytosine, and guanosine; inosine and hypoxanthine are poorly transported)
- Total: 1 characterized proteins
nupC: thymidine permease NupC
- Curated sequence P0AFF2: Nucleoside permease NupC; Nucleoside-transport system protein NupC. Pyrimidine nucleoside:H+ symporter, NupC (Craig et al. 1994; Patching et al. 2005). Wild-type NupC had an apparent affinity for uridine of 22.2 +/- 3.7 muM and an apparent binding affinity of 1.8-2.6 mM, and various mutants with alterred properties were isolated and characterized (Sun et al. 2017). ADP-glucose is also a substrate of this system. nucleoside:H+ symporter NupC. nucleoside:H+ symporter NupC
- Ignore hits to P39141 when looking for 'other' hits (Nucleoside permease NupC. Pyrimidine-specific nucleoside:H+ symporter, NupC)
- UniProt sequence A0KU05: RecName: Full=Nucleoside permease {ECO:0000256|RuleBase:RU362018}; Flags: Precursor;
- Ignore hits to Q9KPL5 when looking for 'other' hits (Concentrative nucleoside transporter, CNT, of 418 aas and 12 TMSs. A repeat-swapped model of VcCNT predicts that nucleoside transport occurs via a mechanism involving an elevator-like substrate binding domain movement across the membrane)
- Ignore hits to P33021 when looking for 'other' hits (Putative nucleoside permease NupX. Nucleoside permease NupX. putative nucleoside transporter)
- Comment: A nupC-like protein from Shewanella sp. ANA-3 (Shewana3_1039, A0KU05) is important for utilization of thymidine and other nucleosides. A similar protein from V. cholerae (Q9KPL5) binds uridine and 2'-deoxyuridine and is likely to be a thymidine transporter as well, but this is not proven. The nupC protein from B. subtilis (P39141) was shown to be a uridine transporter (PMID:8550462) and is suspected to be a thymidine transporter as well, so it is ignored. The specificity of E. coli nupX (P33021, also known as yeiJ) seems to be unknown.
- Total: 2 characterized proteins
Slc28a3: thymidine:Na+ symporter SLC28A3
- Curated sequence Q9UA35: Broadly selective nucleoside:Na+ cotransporter, hfCNT (transports uridine, thymidine, inosine, 3'-azido-3'deoxythymidine, 2'3'dideoxycytidine, and 2'3'dideoxyinosine) (Na+/uridine = 2)
- Total: 1 characterized proteins
deoA: thymidine phosphorylase DeoA
- Curated proteins or TIGRFams with EC 2.4.2.2
- Curated proteins or TIGRFams with EC 2.4.2.4
- Ignore hits to P19663 when looking for 'other' hits (Thymidine phosphorylase; TdRPase; EC 2.4.2.4)
- Ignore hits to items matching 2.4.2.3 when looking for 'other' hits
- Comment: P19663 is ignored because it is a sequence fragment. Many uridine phosphorylases (EC 2.4.2.3) are also deoxyuridine phosphorylases and thymidine phosphyrylases, so hits to these are ignored.
- Total: 3 HMMs and 14 characterized proteins
deoB: phosphopentomutase
deoC: deoxyribose-5-phosphate aldolase
ald-dh-CoA: acetaldehyde dehydrogenase, acylating
- Curated proteins or TIGRFams with EC 1.2.1.10
- Ignore hits to items matching 1.1.1.1 when looking for 'other' hits
- Ignore hits to items matching 1.1.1.71 when looking for 'other' hits
- Ignore hits to items matching 1.2.1.57 when looking for 'other' hits
- Ignore hits to Q2XQZ7 when looking for 'other' hits (4-hydroxy-2-oxovalerate aldolase (EC 4.1.3.39))
- Comment: Many enzymes are multifunctional alcohol/acetaldehyde dehydrogenases, and many close homologs have just one annotation. EC 1.2.1.57 is acylating butanal dehydrogenase, which may also act on acetaldehyde. Q2XQZ7 is probably misannotated.
- Total: 2 HMMs and 20 characterized proteins
adh: acetaldehyde dehydrogenase (not acylating)
acs: acetyl-CoA synthetase, AMP-forming
ackA: acetate kinase
pta: phosphate acetyltransferase
- Curated proteins or TIGRFams with EC 2.3.1.8
- Ignore hits to P32796 when looking for 'other' hits (carnitine O-acetyltransferase (EC 2.3.1.7); phosphate acetyltransferase (EC 2.3.1.8). Carnitine O-acetyltransferase, mitochondrial; Carnitine acetylase; EC 2.3.1.7)
- Comment: BRENDA misannotates yeast's carnitine acetyltransferase with EC 2.3.1.8
- Total: 1 HMMs and 18 characterized proteins
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Each pathway is defined by a set of rules based on individual steps or genes. Candidates for each step are identified by using
ublast (a fast alternative to protein BLAST)
against a database of manually-curated proteins (most of which are experimentally characterized) or by using
HMMer with enzyme models (usually from
TIGRFam). Ublast hits may be split across two different proteins.
A candidate for a step is "high confidence" if either:
- ublast finds a hit to a characterized protein at above 40% identity and 80% coverage, and bits >= other bits+10.
- (Hits to curated proteins without experimental data as to their function are never considered high confidence.)
- HMMer finds a hit with 80% coverage of the model, and either other identity < 40 or other coverage < 0.75.
where "other" refers to the best ublast hit to a sequence that is not annotated as performing this step (and is not "ignored").
Otherwise, a candidate is "medium confidence" if either:
- ublast finds a hit at above 40% identity and 70% coverage (ignoring otherBits).
- ublast finds a hit at above 30% identity and 80% coverage, and bits >= other bits.
- HMMer finds a hit (regardless of coverage or other bits).
Other blast hits with at least 50% coverage are "low confidence."
Steps with no high- or medium-confidence candidates may be considered "gaps."
For the typical bacterium that can make all 20 amino acids, there are 1-2 gaps in amino acid biosynthesis pathways.
For diverse bacteria and archaea that can utilize a carbon source, there is a complete
high-confidence catabolic pathway (including a transporter) just 38% of the time, and
there is a complete medium-confidence pathway 63% of the time.
Gaps may be due to:
- our ignorance of proteins' functions,
- omissions in the gene models,
- frame-shift errors in the genome sequence, or
- the organism lacks the pathway.
GapMind relies on the predicted proteins in the genome and does not search the six-frame translation. In most cases, you can search the six-frame translation by clicking on links to Curated BLAST for each step definition (in the per-step page).
For more information, see:
If you notice any errors or omissions in the step descriptions, or any questionable results, please let us know
by Morgan Price, Arkin group, Lawrence Berkeley National Laboratory