Definition of L-malate catabolism
As rules and steps, or see full text
Rules
Overview: Since L-malate is a TCA cycle intermediate, catabolic reactions are not represented in GapMind.
- all: L-malate-transport
- L-malate-transport:
- sdlC
- or dctA
- or maeN
- or dctM, dctP and dctQ
- or Dshi_1194 and Dshi_1195
- or mae1
- or mleP
- Comment: Transporters were identified using query: transporter:malate:L-malate:(S)-malate. (None of these transporters seem to be specific for D-malate, although E. coli can grow with D-malate as the sole source of carbon.) In B. subtilis, mleN (P54571) can contribute to growth on malate by a malate:lactate antiport mechanism (PMID:10903309), but it is not clear how this could be the sole malate uptake system for growth (no fixed carbon would be available for growth), so it was excluded.
Steps
sdlC: L-malate:Na+ symporter SdlC
- Curated sequence A4QAL6: The aerobic dicarboxylate (succinate (Km, 30 μM), fumarate (Km, 79
- Curated sequence CH_091173: tonoplast dicarboxylate transporter. Tonoplast dicarboxylate transporter; AttDT; Sodium-dicarboxylate cotransporter-like; AtSDAT; Vacuolar malate transporter. The tonoplast dicarboxylate (malate) transporter, AtDCT
- 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
- Total: 7 characterized proteins
dctA: L-malate:H+ symporter DctA
- Curated sequence P96603: The dicarboxylate (succinate, fumarate, malate and oxaloacetate):H+ symporter, DctA (probably 3H+ are transported per succinate taken up
- Curated sequence Q01857: C4-dicarboxylate transporter (substrates: fumarate, D- and L-malate, succinate, succinamide, orotate, iticonate, mesaconate)
- 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 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
- Total: 7 characterized proteins
maeN: malate transporter maeN
- Curated sequence O05256: Na(+)-malate symporter; Sodium-dependent malate transporter. Malate:Na+ symporter
- Curated sequence O07032: Malate:lactate antiporter (substrates include: S-lactate, R-lactate, S-malate and S-citramalate)
- Curated sequence P94363: L-malate/citrate:H+ symporter (electroneutral)
- Curated sequence Q53787: L-Malate permease
- Comment: This cluster seems to include both H+ and Na+ dependent malate transporters, as well as Lactococcus lactis mleP or maeP (O07032) which also exports lactate.
- Total: 4 characterized proteins
dctM: L-malate TRAP transporter, large permease component 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 5208943: dicarboxylate TRAP transporter (succinate, fumarate, L-malate, and alpha-ketoglutarate), large permease component
- Curated sequence Q9HU16: C4-dicarboxylate TRAP transporter large permease protein DctM
- UniProt sequence I7DRS6: SubName: Full=TRAP transporter, subunit DctM {ECO:0000313|EMBL:AFO91751.1};
- Ignore hits to 6938090 when looking for 'other' hits (alpha-ketoglutarate TRAP transporter, large permease component)
- Comment: 3-component TRAP transporter dctMPQ. In Phaeobacter inhibens, the system is important for L-malate utilization: PGA1_c20660 = dctM = I7DRS6; PGA1_c20680 = dctP = I7END8; PGA1_c20670 = dctQ = I7EY26. A very similar system is present in Shewanella amazonensis SB2B, which cannot grow on L-malate; it is still possible that this system transports L-malate, so it is marked ignore.
- Total: 4 characterized proteins
dctP: L-malate TRAP transporter, substrate-binding component DctP
- Curated sequence A3QCW5: C4-dicarboxylate-binding periplasmic protein DctP. dicarboxylate TRAP transporter (succinate, fumarate, L-malate, and alpha-ketoglutarate), solute receptor component
- 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 Q9KQR9: C4-dicarboxylate-binding periplasmic protein DctP
- Curated sequence Q9HU18: C4-dicarboxylate-binding periplasmic protein DctP
- UniProt sequence I7END8: SubName: Full=C4-dicarboxylate-binding periplasmic protein DctP {ECO:0000313|EMBL:AFO91753.1};
- Ignore hits to 6938088 when looking for 'other' hits (alpha-ketoglutarate TRAP transporter, solute receptor component)
- UniProt sequence Q9HVH5: SubName: Full=Probable c4-dicarboxylate-binding protein {ECO:0000313|EMBL:AAG08004.1};
- Curated sequence 5208945: C4-dicarboxylate-binding periplasmic protein DctP. dicarboxylate TRAP transporter (succinate, fumarate, L-malate, and alpha-ketoglutarate), solute receptor component
- Comment: Q9HVH5 = PA4616 is a malate-binding substrate-binding protein (PMC4310620)
- Total: 6 characterized proteins
dctQ: L-malate TRAP tranpsorter, 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 5208944: dicarboxylate TRAP transporter (succinate, fumarate, L-malate, and alpha-ketoglutarate), small permease component
- UniProt sequence I7EY26: SubName: Full=TRAP transporter, subunit DctQ {ECO:0000313|EMBL:AFO91752.1};
- Ignore hits to 6938089 when looking for 'other' hits (alpha-ketoglutarate TRAP transporter, small permease component)
- Total: 3 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
mae1: L-malate:H+ symporter Mae1
mleP: malate permease MleP
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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