Definition of citrate catabolism
As rules and steps, or see full text
Rules
Overview: Citrate is utilized via ATP-citrate lyase (link) or by oxidation to 2-oxoglutarate (part of the the TCA cycle, link). MetaCyc does not explicitly represent the TCA cycle as a means for catabolizing citrate, but it is expected to function under respiratory conditions. Fitness data confirms that in diverse bacteria, ATP-citrate lyase is not necessary for aerobic utilization of citrate.
- all:
- citrate-transport, citD, citE and citF
- or citrate-transport, acn and icd
- Comment: ATP-citrate lyase (citDEF) produces oxaloacetate (a central metabolite) and acetate. Because this is often a fermentative pathway, the acetate may be excreted, so activation to acetyl-CoA is not represented. Or, citrate is isomerized to isocitrate by acn and oxidized to 2-oxoglutarate by icd.
- citrate-transport:
Steps
fecB: ferric citrate ABC transporter, substrate-binding component FecB
- Curated sequence P15028: Fe(3+) dicitrate-binding periplasmic protein; Iron(III) dicitrate-binding periplasmic protein. FecB aka B4290, component of Iron (Fe3+) or ferric-dicitrate porter. ferric citrate ABC transporter periplasmic binding protein (EC 7.2.2.18). ferric citrate ABC transporter periplasmic binding protein (EC 7.2.2.18)
- Total: 1 characterized proteins
fecC: ferric citrate ABC transporter, permease component 1 (FecC)
- Curated sequence P15030: Fe(3+) dicitrate transport system permease protein FecC; Iron(III) dicitrate transport system permease protein FecC. FecC aka B4289, component of Iron (Fe3+) or ferric-dicitrate porter. ferric citrate ABC transporter membrane subunit FecC (EC 7.2.2.18). ferric citrate ABC transporter membrane subunit FecC (EC 7.2.2.18)
- Total: 1 characterized proteins
fecD: ferric citrate ABC transporter, permease component 2 (FecD)
- Curated sequence CH_004160: iron(III) dicitrate transport system permease protein FecD. Fe(3+) dicitrate transport system permease protein FecD; Iron(III) dicitrate transport system permease protein FecD. FecD aka B4288, component of Iron (Fe3+) or ferric-dicitrate porter. ferric citrate ABC transporter membrane subunit FecD (EC 7.2.2.18). ferric citrate ABC transporter membrane subunit FecD (EC 7.2.2.18)
- Total: 1 characterized proteins
fecE: ferric citrate ABC transporter, ATPase component FecE
- Curated sequence CH_088321: iron(III) dicitrate transport ATP-binding protein FecE. Fe(3+) dicitrate transport ATP-binding protein FecE; Iron(III) dicitrate transport ATP-binding protein FecE. Fe(3+) dicitrate transport ATP-binding protein FecE, component of Iron (Fe3+) or ferric-dicitrate porter. ferric citrate ABC transporter ATP binding subunit (EC 7.2.2.18). ferric citrate ABC transporter ATP binding subunit (EC 7.2.2.18)
- Total: 1 characterized proteins
tctA: citrate/Na+ symporter, large transmembrane component TctA
- Curated sequence S5Y5N9: Citrate uptake transporter, membrane subunit, component of Pmf-dependent citrate uptake porter, TctABC
- Curated sequence Q9FA44: TctA, component of The tricarboxylate transporter, TctABC
- Curated sequence 3609738: Tricarboxylate transport membrane protein TctA
- UniProt sequence E4PJQ9: SubName: Full=Tricarboxylic transport TctA {ECO:0000313|EMBL:ADP98423.1};
- Comment: TctABC is also studied in S. typhimurium and D. shibae but was missed by the query. Fitness data confirms that HP15_2659:HP15_2661 (E4PJQ9,E4PJR0,E4PJR1) in Marinobacter adhaerens are tctABC
- Total: 4 characterized proteins
tctB: citrate/Na+ symporter, small transmembrane component TctB
- Curated sequence S5XH28: Citrate uptake transporter, membrane subunit, component of Pmf-dependent citrate uptake porter, TctABC
- Curated sequence Q9FA45: TctB aka STM2787, component of The tricarboxylate transporter, TctABC
- Curated sequence 3609739: Tricarboxylate transport protein TctB
- UniProt sequence E4PJR0: SubName: Full=Tricarboxylic transport membrane protein {ECO:0000313|EMBL:ADP98424.1};
- Total: 4 characterized proteins
tctC: citrate/Na+ symporter, substrate-binding component TctC
- Curated sequence S5XTE7: Citrate uptake transporter, substrate binding protein, component of Pmf-dependent citrate uptake porter, TctABC
- Curated sequence Q9FA46: TctC aka STM2786, component of The tricarboxylate transporter, TctABC
- Curated sequence 3609740: Tricarboxylate transport protein TctC
- UniProt sequence E4PJR1: SubName: Full=Tricarboxylic transport TctC {ECO:0000313|EMBL:ADP98425.1};
- Total: 4 characterized proteins
SLC13A5: citrate:Na+ symporter
- 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 Q86YT5: Solute carrier family 13 member 5; Na(+)/citrate cotransporter; NaCT; Sodium-coupled citrate transporter; Sodium-dependent citrate transporter. Na+-coupled citrate transporter (NaCT) (Km=20 μM) (also may transport dicarboxylates and other tricarboxylates with lower affinity) (Inoue et al., 2002b; Bergeron et al. 2013). Na+:citrate = 3-4:1 (Bergeron et al. 2013). Na+:citrate = 3-4:1
- Curated sequence Q8CJ44: Solute carrier family 13 member 5; Na(+)/citrate cotransporter; NaCT; Sodium-coupled citrate transporter; Sodium-dependent citrate transporter
- Curated sequence Q13183: Solute carrier family 13 member 2 (Na /di- and tricarboxylate cotransporter 1) (NaDC-1) (Renal sodium/dicarboxylate cotransporter)
- Total: 4 characterized proteins
citA: citrate:H+ symporter CitA
- Curated sequence CH_014606: citrate transporter
- Curated sequence P0A2G3: Citrate-proton symporter; Citrate carrier protein; Citrate transporter; Citrate utilization determinant; Citrate utilization protein A. The citrate/tricarballylate:H+ symporter (CitA or TcuC); probably orthologous to 2.A.1.6.1
- Curated sequence P16482: Citrate:H+ symporter
- Total: 3 characterized proteins
cimH: citrate:H+ symporter CimH
citW: citrate exchange transporter CitW (with lactate or acetate)
- Curated sequence Q8VS41: citrate lyase holo-[acyl-carrier protein] synthase (EC 2.7.7.61). Citrate:acetate antiporter, CitW
- Curated sequence P21608: Electrogenic citrate:L-lactate exchanger, CitP or CitN
- Total: 2 characterized proteins
cit1: citrate:H+ symporter Cit1
citT: citrate:succinate antiporter CitT
- Curated sequence P0AE74: Citrate/succinate antiporter; Citrate carrier; Citrate transporter. Citrate:succinate antiporter. citrate:succinate antiporter. citrate:succinate antiporter
- Total: 1 characterized proteins
citM: citrate:cation:H+ symporter CitM
- Curated sequence P55069: Mg(2+)/citrate complex secondary transporter. [Citrate or D-isocitrate]•M2+ (Mg2+ preferring):H+ symporter, CitM (transports Mg2+, Mn2+, Ni2+, Co2+ & Zn2+)
- Curated sequence A4QA05: Citrate-inducible divalent cation:citrate uptake transporter, CitH
- Curated sequence P42308: [Citrate]•M2+ (Ca2+ preferring):H+ symporter, CitH (transports Ca2+, Ba2+ & Sr2+)
- Curated sequence Q9S242: Citrate-M2+ (Fe3+ preferring): H+ symporter, Cit (transports Fe3+, Ca2+, Pb2+, Ba2+ and Mn2+, but not Mg2+, Ni2+ or Co2+)
- Curated sequence Q8DUC7: Citrate•Me2+ (Fe2+/Mn2+ preferring):H+ symporter, CitM
- Comment: (Some of these were missed by the query, probably because the substrate field in TCDB mentions the cation only)
- Total: 5 characterized proteins
citS: citrate:Na+ symporter CitS
citD: citrate lyase, acyl carrier component CitD
- Curated sequence MONOMER-17000: citrate lyase γ subunit
- Curated sequence ACPSUB-MONOMER: citrate lyase gamma chain. Citrate lyase acyl carrier protein; Citrate lyase gamma chain. citrate lyase acyl carrier protein. citrate lyase acyl carrier protein
- Comment: Citrate lyase has 3 subunits citDEF; activity also requires acetylation by citrate lyase synthetase (citC); this is not represented here.
- Total: 2 characterized proteins
citE: citrate lyase, citryl-ACP lyase component CitE
- Curated sequence Q037K5: citrate (pro-3S)-lyase (EC 4.1.3.6)
- Curated sequence P0A9I1: Citrate lyase subunit beta; Citrase beta chain; Citrate (pro-3S)-lyase subunit beta; Citryl-CoA lyase subunit; EC 4.1.3.6; EC 4.1.3.34. citrate lyase β subunit
- Curated sequence MONOMER-16999: citrate lyase β subunit (EC 4.1.3.34)
- Total: 3 characterized proteins
citF: citrate lyase, citrate-ACP transferase component CitF
- Curated sequence P75726: Citrate lyase alpha chain; Citrase alpha chain; Citrate (pro-3S)-lyase alpha chain; Citrate CoA-transferase subunit; EC 4.1.3.6; EC 2.8.3.10. citrate lyase α subunit
- Total: 1 characterized proteins
acn: aconitase
icd: isocitrate dehydrogenase
- Curated proteins or TIGRFams with EC 1.1.1.41
- Curated proteins or TIGRFams with EC 1.1.1.42
- Curated proteins or TIGRFams with EC 1.1.1.286
- Comment: Eukaryotic icd is heteromeric, but the regulatory subunits are similar to the enzymatic subunits, so this is not represented here
- Total: 4 HMMs and 74 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 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