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:
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