Definition of 2'-deoxyinosine catabolism
As rules and steps, or see full text
Rules
Overview: In the known pathway for deoxyinosine utilization, a phosphorylase forms deoxyribose 1-phosphate, phosphopentomutase forms deoxyribose 5-phosphate, and an aldolase produces 3-phosphoglycerate (an intermediate in glycolysis) and acetaldehyde (link). MetaCyc also describes a purine deoxyribonucleosidase (EC 3.2.2.M2), yielding deoxyribose, but this enzyme has not been linked to sequence, so it is not included in GapMind. This reaction might also occur non-specifically via ribonucleosidases. The fitness data for Paraburkholderia bryophila 376MFSha3.1 does suggest cytoplasmic hydrolysis of purine deoxynucleosides, but did not identify the deoxyribonucleosidase.
- all: deoxyinosine-transport, deoD, deoB, deoC and acetaldehyde-degradation
- 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).
- deoxyinosine-transport:
Steps
nupC: deoxyinosine:H+ symporter NupC
- Curated sequence O25792: Nucleoside 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
- Curated sequence P42312: Purine nucleoside transport protein NupG. The purine nucleoside uptake transporter NupG (YxjA)
- Curated sequence Q9KPL5: 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: These proteins are reported to transport inosine, and likely transport deoxyinosine as well. The specificity of E. coli nupX (P33021, also known as yeiJ) seems to be unknown.
- Total: 4 characterized proteins
nupG: deoxyinosine 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
- Comment: These two proteins are reported to transport inosine and (deoxy)thymidine, and probably tranpsort deoxyinosine as well.
- Total: 2 characterized proteins
H281DRAFT_01115: deoxynucleoside transporter, permease component 1
- Curated sequence H281DRAFT_01115: deoxynucleoside transporter, permease component 1
- Comment: In Paraburkholderia bryophila 376MFSha3.1, H281DRAFT_01115-01112 is a 4-component ABC transporter that is important for deoxyinosine utilization.
- Total: 1 characterized proteins
H281DRAFT_01114: deoxynucleoside transporter, substrate-binding component
H281DRAFT_01113: deoxynucleoside transporter, ATPase component
H281DRAFT_01112: deoxynucleoside transporter, permease component 2
nupA: deoxyinosine ABC transporter, ATPase component
- Curated sequence A2RKA7: Purine/cytidine ABC transporter ATP-binding protein, component of General nucleoside uptake porter, NupABC/BmpA (transports all common nucleosides as well as 5-fluorocytidine, inosine, deoxyuridine and xanthosine) (Martinussen et al., 2010) (Most similar to 3.A.1.2.12). NupA is 506aas with two ABC (C) domains. NupB has 8 predicted TMSs, NupC has 9 or 10 predicted TMSs in a 4 + 1 (or 2) + 4 arrangement
- Curated sequence Q8DU37: RnsB, component of The (deoxy)ribonucleoside permease; probably takes up all deoxy- and ribonucleosides (cytidine, uridine, adenosine and toxic analogues, fluorocytidine and fluorouridine tested), but not ribose or nucleobases
- Comment: In Lactococcus lactis, a 4-component ABC transporter is active on deoxyinosine A related system, RnsBCDA from Streptococcus mutans, also probably transports deoxyinosine
- Total: 2 characterized proteins
nupB: deoxyinosine ABC transporter, permease component 1
- Curated sequence A2RKA6: Purine/cytidine ABC transporter permease protein, component of General nucleoside uptake porter, NupABC/BmpA (transports all common nucleosides as well as 5-fluorocytidine, inosine, deoxyuridine and xanthosine) (Martinussen et al., 2010) (Most similar to 3.A.1.2.12). NupA is 506aas with two ABC (C) domains. NupB has 8 predicted TMSs, NupC has 9 or 10 predicted TMSs in a 4 + 1 (or 2) + 4 arrangement
- Curated sequence Q8DU38: RnsC, component of The (deoxy)ribonucleoside permease; probably takes up all deoxy- and ribonucleosides (cytidine, uridine, adenosine and toxic analogues, fluorocytidine and fluorouridine tested), but not ribose or nucleobases
- Total: 2 characterized proteins
nupC': deoxyinosine ABC transporter, permease component 2
- Curated sequence A2RKA5: Purine/cytidine ABC transporter permease protein, component of General nucleoside uptake porter, NupABC/BmpA (transports all common nucleosides as well as 5-fluorocytidine, inosine, deoxyuridine and xanthosine) (Martinussen et al., 2010) (Most similar to 3.A.1.2.12). NupA is 506aas with two ABC (C) domains. NupB has 8 predicted TMSs, NupC has 9 or 10 predicted TMSs in a 4 + 1 (or 2) + 4 arrangement
- Curated sequence Q8DU39: RnsD, component of The (deoxy)ribonucleoside permease; probably takes up all deoxy- and ribonucleosides (cytidine, uridine, adenosine and toxic analogues, fluorocytidine and fluorouridine tested), but not ribose or nucleobases
- Total: 2 characterized proteins
bmpA: deoxyinosine ABC transporter, substrate-binding component
- Curated sequence D2BKA1: Basic membrane lipoprotein, component of General nucleoside uptake porter, NupABC/BmpA (transports all common nucleosides as well as 5-fluorocytidine, inosine, deoxyuridine and xanthosine) (Martinussen et al., 2010) (Most similar to 3.A.1.2.12). NupA is 506aas with two ABC (C) domains. NupB has 8 predicted TMSs, NupC has 9 or 10 predicted TMSs in a 4 + 1 (or 2) + 4 arrangement
- Curated sequence Q8DU36: RnsA, component of The (deoxy)ribonucleoside permease; probably takes up all deoxy- and ribonucleosides (cytidine, uridine, adenosine and toxic analogues, fluorocytidine and fluorouridine tested), but not ribose or nucleobases
- Total: 2 characterized proteins
deoD: deoxyinosine phosphorylase
- Curated proteins or TIGRFams with EC 2.4.2.1
- Ignore hits to items matching 2.4.2.15 when looking for 'other' hits
- Comment: The phosphorylase produces 2-deoxy-alpha-D-ribose 1-phosphate (2.4.2.1 includes activity on purine nucleosides and deoxynucleosides) Ignore hits to guanosine phosphorylase (EC 2.4.2.15), which is a quite similar reaction
- Total: 5 HMMs and 26 characterized proteins
deoB: phosphopentomutase
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
deoC: deoxyribose-5-phosphate aldolase
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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