Finding step argA for L-proline biosynthesis in Paucidesulfovibrio gracilis DSM 16080
3 candidates for argA: N-acylglutamate synthase
Confidence: high confidence medium confidence low confidence
? – known gap: despite the lack of a good candidate for this step, this organism (or a related organism) performs the pathway
GapMind searches the predicted proteins for candidates by using ublast (a fast alternative to protein BLAST) to find similarities to characterized proteins or by using HMMer to find similarities to enzyme models (usually from TIGRFams). For alignments to characterized proteins (from ublast), scores of 44 bits correspond to an expectation value (E) of about 0.001.
Definition of step argA
- Curated proteins or TIGRFams with EC 2.3.1.1 (search)
- Curated proteins matching N-succinylglutamate synthase
- UniProt sequence Q8A1A5_BACTN: RecName: Full=GNAT family N-acetyltransferase {ECO:0008006|Google:ProtNLM};
- UniProt sequence L0G3H4_ECHVK: SubName: Full=Acetyltransferase, N-acetylglutamate synthase {ECO:0000313|EMBL:AGA80057.1};
- Curated sequence A0A0H2X8L7: acetylglutamate kinase (EC 2.7.2.8)
- Curated sequence Q8P8J6: acetylglutamate kinase (EC 2.7.2.8)
- Ignore hits to G6759-MONOMER when looking for 'other' hits (L-amino acid N-acyltransferase MnaT; L-methionine N-acyltransferase; L-methionine sulfoximine/L-methionine sulfone N-acetyltransferase; L-phenylglycine N-acetyltransferase; EC 2.3.1.-. L-amino acid N-acyltransferase (EC 2.3.1.1). L-amino acid N-acyltransferase (EC 2.3.1.1))
- Ignore hits to items matching EC 2.3.1.35 when looking for 'other' hits
- Ignore hits to CH_123299 when looking for 'other' hits (arginine biosynthetic enzyme activities)
- Curated sequence CH_122594: glutamate N-acetyltransferase (Eurofung)
- Ignore hits to Q9I3W7 when looking for 'other' hits (amino-acid N-acetyltransferase (EC 2.3.1.1))
- Ignore hits to Q8P8J6 when looking for 'other' hits (acetylglutamate kinase (EC 2.7.2.8))
- Predicted: UniProt sequence A0A127FCT3: RecName: Full=DUF1611 domain-containing protein {ECO:0008006|Google:ProtNLM};
- Comment: Bacteroidetes have a divergent N-acylglutamate synthase, see BT3761 (Q8A1A5_BACTN) or Echvi_3845 (L0G3H4_ECHVK). Bacteroides use succinylated intermediates (PMID:16704984), so their proteins are probably N-succinylglutamate synthases. (These enzymes are also known as argA2, see PMC9026213.) Q8P8J6 is annotated as argB in BRENDA, but it is also argA (a fusion protein). N515DRAFT_3768 (A0A1I2DIM7) is similar to ArgAB fusion proteins and mutants are rescued by arginine. It is not clear if mnaT (link) would acetylate arginine, so it is ignored. Some EC 2.3.1.35 enzymes are probably dedicated for converting N-acetylornithine back to ornithine, while others are bifunctional for N-acetylglutamate formation as well (argJ); so similarity to this EC number is inconclusive. For some CharProtDB entries it is unclear if they have this activity or not, while others are labeled with this function but without the EC number. Q9I3W7 is annotated as this in BRENDA but we did not find experimental evidence of its activity on glutamate, so it is ignored. In Steroidobacter denitrificans, argA is missing but the arginine synthesis cluster includes a potential N-acetyltransferase ACG33_RS14135 (A0A127FCT3). Homologs of this protein are conserved in the cluster, and it is never found together with argA; it is distantly related to D-glutamate acetyltransferase dgcN (formerly DUF1611, see PMC10030869).
Or cluster all characterized argA proteins
This GapMind analysis is from Jul 25 2024. The underlying query database was built on Jul 25 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