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
Links
Downloads
Related tools
About GapMind
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 the paper from 2019 on GapMind for amino acid biosynthesis, the paper from 2022 on GapMind for carbon sources, or view the source code.
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