Definition of succinate catabolism
As rules and steps, or see full text
Rules
Overview: 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.
- all: succinate-transport
- succinate-transport:
Steps
sdc: succinate:Na+ symporter Sdc
- Curated sequence A4QAL6: The aerobic dicarboxylate (succinate (Km, 30 μM), fumarate (Km, 79
- Curated sequence Q21339: Sodium-dependent high-affinity dicarboxylate transporter 3; Na(+)/dicarboxylate cotransporter 3; NaDC-3; ceNaDC3. High affinity dicarboxylate:Na+ symporter, NaDC2 (INDY2) (relative affinities: fumarate > malate > α-ketoglutarate > maleate > succinate > lactate)
- Curated sequence Q2FFH9: The Na+ (or Li+):dicarboxylate (2:1) symporter, SdcS (catalyzes succinate:succinate antiport as well as electroneutral symport in reconstituted proteoliposomes
- Curated sequence Q65NC0: The Na+-coupled dicarboxylate (succinate; malate; fumarate) transporter, SdcL (transports aspartate, α-ketoglutarate and oxaloacetate with low affinity). Km for succinate, ~6
- Curated sequence Q9KNE0: Dicarboxylate (succinate, fumarate, malate) transporter, vcINDY
- Curated sequence Q99SX1: Sodium-dependent dicarboxylate transporter SdcS; Na(+)/dicarboxylate symporter
- Comment: (Sodium-dependent dicarboxylate transporter SdcS (Q99SX1) was not originally included because the description did not mention succinate specifically.)
- Total: 6 characterized proteins
dctA: succinate:H+ symporter DctA
- Curated sequence CH_014038: aerobic C4-dicarboxylate transport protein. Aerobic C4-dicarboxylate transport protein. Aerobic dicarboxylate transporter, DctA. Interacts with the DcuS sensor kinase. C4 dicarboxylate/orotate:H+ symporter. C4 dicarboxylate/orotate:H+ symporter
- Curated sequence P96603: The dicarboxylate (succinate, fumarate, malate and oxaloacetate):H+ symporter, DctA (probably 3H+ are transported per succinate taken up
- Curated sequence Q1J1H5: Fumarate:H+ symporter of 442 aas and 14 established TMSs, DctA. Responsible for the transport of dicarboxylates such as succinate, fumarate, and malate
- Curated sequence Q848I3: Organic acid uptake porter, DctA of 444 aas and 8 - 10 putative TMSs
- Curated sequence AO356_18980: sodium:C4-dicarboxylate symporter (dctA)
- Curated sequence Q9I4F5: C4-dicarboxylate transport protein 2
- Curated sequence Q01857: C4-dicarboxylate transporter (substrates: fumarate, D- and L-malate, succinate, succinamide, orotate, iticonate, mesaconate)
- Comment: not initially included were AO356_18980, Q9I4F5, or Q01857.
- Total: 7 characterized proteins
dauA: succinate:H+ symporter DauA
- Curated sequence P0AFR2: C4-dicarboxylic acid transporter DauA; Dicarboxylic acid uptake system A. Bicarbonate transporter, DauA (YchM). Also transports dicarboxylic acids including fumarate, aspartate and succinate, and is therefore designated the dicarboxylic acid uptake system A (DauA) (Karinou et al. 2013) It is the only succinate uptake porter at acidic pHs. The STAS domain forms a complex with the acyl carrier protein, ACP and malonyl-ACP, and the complex has been determined by x-ray crystallography (PDB# 3NY7). aerobic C4-dicarboxylate transporter DauA. aerobic C4-dicarboxylate transporter DauA
- Ignore hits to A1JRS3 when looking for 'other' hits (SulP homologue. The low resolution structure is available)
- Comment: Ignore TCDB::A1JRS3 whose specificity seems to be unknown (although there is structural information)
- Total: 1 characterized proteins
satP: succinate:H+ symporter SatP
- Curated sequence P0AC98: Succinate-acetate/proton symporter SatP; Succinate-acetate transporter protein. Acetate/succinate transporter, SatP or YaaH. acetate/succinate:H+ symporter. acetate/succinate:H+ symporter
- Total: 1 characterized proteins
dctQ: succinate TRAP transporter, small permease component DctQ
- Curated sequence O07837: C4-dicarboxylate TRAP transporter small permease protein DctQ. DctQ, component of Tripartite dicarboxylate:H+ symporter (substrates include: fumarate, D- and L-malate, succinate, succinamide, orotate, iticonate and mesaconate)
- Curated sequence Q9HU17: C4-dicarboxylate TRAP transporter small permease protein DctQ
- Curated sequence 5208944: dicarboxylate TRAP transporter (succinate, fumarate, L-malate, and alpha-ketoglutarate), small permease component
- Curated sequence GFF4196: C4-dicarboxylate transporter, DctQ subunit
- UniProt sequence Q9KQS0: RecName: Full=C4-dicarboxylate TRAP transporter small permease protein DctQ {ECO:0000305};
- Ignore hits to 6938089 when looking for 'other' hits (alpha-ketoglutarate TRAP transporter, small permease component)
- UniProt sequence I7EY26: SubName: Full=TRAP transporter, subunit DctQ {ECO:0000313|EMBL:AFO91752.1};
- Comment: 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).
- Total: 6 characterized proteins
dctM: succinate TRAP transporter, large permease protein DctM
- Curated sequence O07838: C4-dicarboxylate TRAP transporter large permease protein DctM. DctM, component of Tripartite dicarboxylate:H+ symporter (substrates include: fumarate, D- and L-malate, succinate, succinamide, orotate, iticonate and mesaconate)
- Curated sequence Q9HU16: C4-dicarboxylate TRAP transporter large permease protein DctM
- Curated sequence 5208943: dicarboxylate TRAP transporter (succinate, fumarate, L-malate, and alpha-ketoglutarate), large permease component
- UniProt sequence Q9KQS1: RecName: Full=C4-dicarboxylate TRAP transporter large permease protein DctM {ECO:0000305};
- Ignore hits to 6938090 when looking for 'other' hits (alpha-ketoglutarate TRAP transporter, large permease component)
- UniProt sequence I7DRS6: SubName: Full=TRAP transporter, subunit DctM {ECO:0000313|EMBL:AFO91751.1};
- Total: 5 characterized proteins
dctP: succinate TRAP transporter, component DctP
- Curated sequence P37735: C4-dicarboxylate-binding periplasmic protein DctP. DctP, component of Tripartite dicarboxylate:H+ symporter (substrates include: fumarate, D- and L-malate, succinate, succinamide, orotate, iticonate and mesaconate)
- Curated sequence Q9HU18: C4-dicarboxylate-binding periplasmic protein DctP
- Curated sequence 5208945: C4-dicarboxylate-binding periplasmic protein DctP. dicarboxylate TRAP transporter (succinate, fumarate, L-malate, and alpha-ketoglutarate), solute receptor component
- Curated sequence Q9KQR9: C4-dicarboxylate-binding periplasmic protein DctP
- Ignore hits to 6938088 when looking for 'other' hits (alpha-ketoglutarate TRAP transporter, solute receptor component)
- UniProt sequence I7END8: SubName: Full=C4-dicarboxylate-binding periplasmic protein DctP {ECO:0000313|EMBL:AFO91753.1};
- UniProt sequence Q2IUT5: SubName: Full=TRAP dicarboxylate transporter DctP subunit {ECO:0000313|EMBL:ABD08025.1}; Flags: Precursor;
- UniProt sequence Q8ECK4: SubName: Full=TRAP-type C4-dicarboxylate:H+ symport system substrate-binding component DctP {ECO:0000313|EMBL:AAN56138.1};
- Comment: 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).
- Total: 7 characterized proteins
Dshi_1194: TRAP transporter for succinate, fumarate, L-malate, and 2-oxoglutarate, fused 4TM/12TM components
- UniProt sequence A8LI82: SubName: Full=TRAP transporter {ECO:0000313|EMBL:ABV92936.1};
- UniProt sequence E4PQE4: SubName: Full=TRAP transporter, 4TM/12TM fusion protein {ECO:0000313|EMBL:ADP96487.1};
- Comment: 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).
- Total: 2 characterized proteins
Dshi_1195: TRAP transporter for succinate, fumarate, L-malate, and 2-oxoglutarate, substrate-binding component
- UniProt sequence A8LI83: SubName: Full=TRAP transporter solute receptor {ECO:0000313|EMBL:ABV92937.1};
- UniProt sequence E4PQE3: SubName: Full=Immunogenic protein {ECO:0000313|EMBL:ADP96486.1};
- Total: 2 characterized proteins
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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