As text, or see rules and steps
# GapMind represents succinate uptake only, as succinate is part of # central metabolism. Specifically, succinate can be consumed by the # TCA cycle enzymes succinate dehydrogenase, fumarase (forming # L-malate), and malate dehydrogenase (either decarboxylating, with # pyruvate as the product, or not, with oxalacetate with the product; # both compounds are central metabolic intermediates). It's also # possible that malate could be decarboxylated to lactate, as in # malolactic fermentation by lactic acid bacteria. # (Sodium-dependent dicarboxylate transporter SdcS (Q99SX1) was not originally included # because the description did not mention succinate specifically.) sdc succinate:Na+ symporter Sdc curated:TCDB::A4QAL6 curated:SwissProt::Q21339 curated:TCDB::Q2FFH9 curated:TCDB::Q65NC0 curated:TCDB::Q9KNE0 curated:SwissProt::Q99SX1 # Transporters were identified using # query: transporter:succinate succinate-transport: sdc # not initially included were AO356_18980, Q9I4F5, or Q01857. dctA succinate:H+ symporter DctA curated:CharProtDB::CH_014038 curated:TCDB::P96603 curated:TCDB::Q1J1H5 curated:TCDB::Q848I3 curated:reanno::pseudo5_N2C3_1:AO356_18980 curated:SwissProt::Q9I4F5 curated:TCDB::Q01857 succinate-transport: dctA # Ignore TCDB::A1JRS3 whose specificity seems to be unknown (although there is structural information) dauA succinate:H+ symporter DauA curated:SwissProt::P0AFR2 ignore:TCDB::A1JRS3 succinate-transport: dauA satP succinate:H+ symporter SatP curated:SwissProt::P0AC98 succinate-transport: satP # TRAP transporter DctQMP. # The P. aeruginosa system was not initially included (annotated as C4-dicarboxylate system; Q9HU16-8). # Similarly for the system from Shewanella loihica PV-4 or P. stutzeri RCH2 (just one component annotated). # The V. cholerae system is VC1927-VC1929 (PMID:22556361), but only the dctP # (Q9KQR9) component is curated; Q9KQS0 is dctQ; Q9KQS1 is dctM. # In Phaeobacter inhibens, the system is important for fumarate utilization: # PGA1_c20670 = dctQ = I7EY26, # PGA1_c20660 = dctM = I7DRS6, # PGA1_c20680 = dctP = I7END8. # Finally, ignore the system from S. amazonensis SB2B (Sama_2209:Sama_2211) # as we have no fitness data for succinate from this organism (but it does utilize succinate). dctQ succinate TRAP transporter, small permease component DctQ curated:SwissProt::O07837 curated:SwissProt::Q9HU17 curated:reanno::PV4:5208944 curated:reanno::psRCH2:GFF4196 uniprot:Q9KQS0 ignore:reanno::SB2B:6938089 uniprot:I7EY26 dctM succinate TRAP transporter, large permease protein DctM curated:SwissProt::O07838 curated:SwissProt::Q9HU16 curated:reanno::PV4:5208943 uniprot:Q9KQS1 ignore:reanno::SB2B:6938090 uniprot:I7DRS6 # B. subtilis DctB is similar to DctP but is probably involved in sensing, not transport, so is not included. # Q2IUT5 = RPB_3329, A3QCW5 = Shew_1446 = 5208945, and Q8ECK4 = SO_3134 were shown to bind succinate (PMC4310620). dctP succinate TRAP transporter, component DctP curated:SwissProt::P37735 curated:SwissProt::Q9HU18 curated:reanno::PV4:5208945 curated:SwissProt::Q9KQR9 ignore:reanno::SB2B:6938088 uniprot:I7END8 uniprot:Q2IUT5 uniprot:Q8ECK4 succinate-transport: dctQ dctM dctP # The TRAP system Dshi_1194:Dshi_1195 (A8LI82,A8LI83) is important for utilization of # succinate, fumarate, L-malate, and 2-oxoglutarate, # as is the related system HP15_723:HP15_722 (E4PQE4,E4PQE3). Dshi_1194 TRAP transporter for succinate, fumarate, L-malate, and 2-oxoglutarate, fused 4TM/12TM components uniprot:A8LI82 uniprot:E4PQE4 Dshi_1195 TRAP transporter for succinate, fumarate, L-malate, and 2-oxoglutarate, substrate-binding component uniprot:A8LI83 uniprot:E4PQE3 succinate-transport: Dshi_1194 Dshi_1195 # Ignore mitochondrial dicarboxylate:phosphate antiporters # Ignore antiporters dcuA/dcuB (i.e., fumarate:succinate antiport does not facilitate utilization of succinate) # Ignore antiporters ttdT/citT (i.e., tartarte:succinate antiport does not facilitate utilization of succinate) # Ignore mitochondrial succinate/fumarate antiporters # Ignore succinate dehydrogenase components # Ignore mitochondrial citrate/succinate antiporter # Ignore succinate exporter SucE1 / TMEM184B # Ignore succinate efflux transporter DcuC (although it acts as a succinate:proton symporter, # so maybe it could suffice) all: succinate-transport
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:
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