Finding step dapA for L-lysine biosynthesis in Methanothermobacter thermautotrophicus Delta H
Classification of gap: spurious
Rationale: Although dapA was not found in the annotated proteins, it was found when analyzing the six-frame translation of the genome. This often indicates an error in the genome sequence.
No candidates for dapA: 4-hydroxy-tetrahydrodipicolinate synthase
GapMind classifies a step as low confidence even if it does not find any candidates. You can still try to find candidates by using Curated BLAST (which searches the 6-frame translation) or by text search of the annotations (which may indicate weak homology, under 30% identity or 50% coverage, that GapMind does not consider). See the links below.
Definition of step dapA
- Curated proteins or TIGRFams with EC 4.3.3.7 (search)
- Curated proteins or TIGRFams with EC 4.2.1.52 (search)
- Ignore hits to Q3MFY8 when looking for 'other' hits (4-hydroxy-tetrahydrodipicolinate synthase (EC 4.3.3.7))
- Ignore hits to Q3M723 when looking for 'other' hits (4-hydroxy-tetrahydrodipicolinate reductase (EC 1.17.1.8))
- Ignore hits to A9CGZ4 when looking for 'other' hits (4-hydroxy-tetrahydrodipicolinate synthase (EC 4.3.3.7))
- Ignore hits to A9CHR2 when looking for 'other' hits (4-hydroxy-tetrahydrodipicolinate synthase (EC 4.3.3.7))
- Ignore hits to A9CL94 when looking for 'other' hits (4-hydroxy-tetrahydrodipicolinate synthase (EC 4.3.3.7))
- Ignore hits to A9CL97 when looking for 'other' hits (4-hydroxy-tetrahydrodipicolinate synthase (EC 4.3.3.7))
- Ignore hits to Q7D0E8 when looking for 'other' hits (4-hydroxy-tetrahydrodipicolinate synthase (EC 4.3.3.7))
- Ignore hits to Q7D313 when looking for 'other' hits (4-hydroxy-tetrahydrodipicolinate synthase (EC 4.3.3.7))
- Ignore hits to Q8A3Z0 when looking for 'other' hits (4-hydroxy-tetrahydrodipicolinate synthase (EC 4.3.3.7))
- Comment: Q3MFY8, Q3M723, and many proteins form Agrobacterium tumefaciens are misannotated in BRENDA, and are ignored. (The reference for those points at gene 1133062 = Atu1024 as the synthase instead, and states that the other Agrobacterium dapA-like proteins lack this activity, see PMID:24677246.) Q8A3Z0 is annotated as this in BRENDA, but the cited paper does not demonstrate this activity, and another protein (BT0895) appears to be the major dapA in Bacteroides thetaiotaomicron, (it is essentail), so Q8A3Z0 is ignored.
Or cluster all characterized dapA proteins
This GapMind analysis is from Apr 10 2024. The underlying query database was built on Apr 09 2024.
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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