As text, or see rules and steps
# Asparagine catabolism in GapMind is based on asparaginase, which forms ammonia and aspartate. # The asparaginase may be secreted or cytoplasmic. # Asparatate can be transaminated to oxaloacetate, which is an intermediate in central metabolism. # ABC transporters # AatJMPQ from Pseudomonas or BztBACD from Rhodobacter capsulatus import aspartate.steps:bztA bztB bztC bztD aatJ aatQ aatM aatP # Transporters were identified using # query: transporter:asparagine:L-asparagine asparagine-transport: aatJ aatQ aatM aatP asparagine-transport: bztA bztB bztC bztD # glnQP from Lactococcus lactis, TC 3.A.1.3.25 glnQ L-asparagine ABC transporter, ATPase component GlnQ curated:TCDB::Q9CES4 glnP L-asparagine ABC transporter, fused permease and substrate-binding components GlnP curated:TCDB::Q9CES5 asparagine-transport: glnQ glnP # AapJQMP from Rhizobium leguminosarum is described in glutamate.steps import glutamate.steps:aapJ aapQ aapM aapP asparagine-transport: aapJ aapQ aapM aapP # Other transporters ansP L-asparagine permease AnsP curated:SwissProt::P77610 curated:TCDB::P40812 asparagine-transport: ansP AGP1 L-asparagine permease AGP1 curated:CharProtDB::CH_091105 asparagine-transport: AGP1 yhiT probable L-asparagine transporter YhiT curated:TCDB::Q8ZLD2 asparagine-transport: yhiT agcS Probable asparagine:Na+ symporter AgcS curated:TCDB::W0WFC6 asparagine-transport: agcS # Ignored the export protein EamA # Ignored SLC38A3, which is a sodium/amino acid antiporter # Ignored gerBB (P39570), which is part of a receptor complex; it is not clear if it is # actually an amino acid transporter (see PMID:24488313) # Ignored the non-specific human permease SLC7A8 (TC 2.A.3.8.20) # Because many of the asparaginases are periplasmic, allow uptake of aspartate as well # (Also, some aspartate transporters probably transport asparagine as well.) import aspartate.steps:aspartate-transport # Isoaspartyl peptidases such as E. coli iaaA have this activity and are labeled heteromeric, # because the proenzyme is cleaved into two subunits; this need not be represented here. # TIGR00519 is not used because it hits GatD, a subunit of glutamyl-tRNA(Gln) amidotransferase ans asparaginase EC:3.5.1.1 EC:3.5.1.38 ignore_hmm:TIGR00519 all: ans aspartate-transport all: asparagine-transport ans
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:
Otherwise, a candidate is "medium confidence" if either:
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:
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