As text, or see rules and steps
# Citrate is utilized via ATP-citrate lyase (metacyc:PWY-6038) or # by oxidation to 2-oxoglutarate (part of the the TCA cycle, # metacyc:TCA). 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. # Heteromeric transporters: E.coli FecBCDE and C. glutamicum TctABC. fecB ferric citrate ABC transporter, substrate-binding component FecB curated:SwissProt::P15028 fecC ferric citrate ABC transporter, permease component 1 (FecC) curated:SwissProt::P15030 fecD ferric citrate ABC transporter, permease component 2 (FecD) curated:CharProtDB::CH_004160 fecE ferric citrate ABC transporter, ATPase component FecE curated:CharProtDB::CH_088321 # Transporters were identified using # query: transporter:citric:citrate citrate-transport: fecB fecC fecD fecE # 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 tctA citrate/Na+ symporter, large transmembrane component TctA curated:TCDB::S5Y5N9 curated:TCDB::Q9FA44 curated:reanno::Dino:3609738 uniprot:E4PJQ9 tctB citrate/Na+ symporter, small transmembrane component TctB curated:TCDB::S5XH28 curated:TCDB::Q9FA45 curated:reanno::Dino:3609739 uniprot:E4PJR0 tctC citrate/Na+ symporter, substrate-binding component TctC curated:TCDB::S5XTE7 curated:TCDB::Q9FA46 curated:reanno::Dino:3609740 uniprot:E4PJR1 citrate-transport: tctA tctB tctC # Homomeric transporters: SLC13A5 citrate:Na+ symporter curated:CharProtDB::CH_091173 curated:SwissProt::Q86YT5 curated:SwissProt::Q8CJ44 curated:TCDB::Q13183 citrate-transport: SLC13A5 citA citrate:H+ symporter CitA curated:CharProtDB::CH_014606 curated:SwissProt::P0A2G3 curated:TCDB::P16482 citrate-transport: citA cimH citrate:H+ symporter CimH curated:TCDB::P94363 citrate-transport: cimH citW citrate exchange transporter CitW (with lactate or acetate) curated:BRENDA::Q8VS41 curated:TCDB::P21608 citrate-transport: citW cit1 citrate:H+ symporter Cit1 curated:TCDB::Q6D017 citrate-transport: cit1 citT citrate:succinate antiporter CitT curated:SwissProt::P0AE74 citrate-transport: citT # (Some of these were missed by the query, probably because the substrate field in TCDB mentions the cation only) citM citrate:cation:H+ symporter CitM curated:SwissProt::P55069 curated:TCDB::A4QA05 curated:TCDB::P42308 curated:TCDB::Q9S242 curated:TCDB::Q8DUC7 citrate-transport: citM citS citrate:Na+ symporter CitS curated:TCDB::P31602 citrate-transport: citS # Ignored metazoan or mitochondrial citric acid carrier proteins # Ignored plant citric acid efflux proteins # Ignored outer membrane ferric citrate porins (fecA) # Ignored vcINDY, reported to have low affinity for citrate # Citrate lyase has 3 subunits citDEF; activity also requires acetylation by # citrate lyase synthetase (citC); this is not represented here. citD citrate lyase, acyl carrier component CitD curated:metacyc::MONOMER-17000 curated:metacyc::ACPSUB-MONOMER citE citrate lyase, citryl-ACP lyase component CitE curated:BRENDA::Q037K5 curated:SwissProt::P0A9I1 curated:metacyc::MONOMER-16999 citF citrate lyase, citrate-ACP transferase component CitF curated:SwissProt::P75726 # 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. all: citrate-transport citD citE citF # Some similar sequences are annotated as aconitase but without the EC number acn aconitase EC:4.2.1.3 ignore_other:aconitase # Eukaryotic icd is heteromeric, but the regulatory subunits are similar to the # enzymatic subunits, so this is not represented here icd isocitrate dehydrogenase EC:1.1.1.41 EC:1.1.1.42 EC:1.1.1.286 # Or, citrate is isomerized to isocitrate by acn and oxidized to 2-oxoglutarate by icd. all: citrate-transport acn icd
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