Definition of pyruvate catabolism
As rules and steps, or see full text
Rules
Overview: Pyruvate is a central metabolite, so GapMind represents transport only.
- all: pyruvate-transport
- pyruvate-transport:
Steps
actP: large subunit of pyruvate transporter (actP-like)
- UniProt sequence A0A1N7U9G2: SubName: Full=Acetate permease {ECO:0000313|EMBL:AIB35691.1}; SubName: Full=Actetate permease {ECO:0000313|EMBL:ERH55332.1}; SubName: Full=Cation acetate symporter {ECO:0000313|EMBL:PRW83281.1}; SubName: Full=Cation/acetate symporter {ECO:0000313|EMBL:SFB56078.1};
- UniProt sequence G8AHY6: SubName: Full=Acetate transporter {ECO:0000313|EMBL:CCC96889.1};
- UniProt sequence A0A166PH03: SubName: Full=Cation acetate symporter {ECO:0000313|EMBL:KZN18898.1};
- UniProt sequence A0A165ZRB0: SubName: Full=Cation acetate symporter {ECO:0000313|EMBL:AMZ74981.1};
- Ignore hits to P32705 when looking for 'other' hits (Cation/acetate symporter ActP; Acetate permease; Acetate transporter ActP. Acetate/glyoxylate permease, ActP. acetate/glycolate:cation symporter. acetate/glycolate:cation symporter)
- UniProt sequence E4PHQ0: SubName: Full=Sodium: solute symporter family protein {ECO:0000313|EMBL:ADP97015.1};
- Curated sequence GFF346: actP-like component of D-alanine uptake system
- Comment: A group of heterodimeric pyruvate transporters. This is the actP-like large subunit. WCS417:GFF1743 = A0A1N7U9G2, azobra:AZOBR_RS02940 = G8AHY6, pseudo1_N1B4:Pf1N1B4_3673 = A0A166PH03, pseudo6_N2E2:Pf6N2E2_5849 = A0A165ZRB0, and psRCH2:Psest_0347 (GFF346) Closely related to E. coli actP = P32705, so ignore that. Added Marinobacter HP15_1251 (E4PHQ0) because it has a specific phenotype (if mild) and fills the gap. And it is closely related to the D-alanine uptake system , so ignore that.
- Total: 6 characterized proteins
yjcH: putative small subunit of pyruvate transporter (yjcH-like)
- Curated sequence GFF1742: required for pyruvate transport, with PS417_08865 (actP-like)
- Curated sequence AZOBR_RS02935: required for pyruvate transport, with AZOBR_RS02940
- Curated sequence Pf1N1B4_3672: required for pyruvate transport, with Pf1N1B4_3673 (actP-like)
- Curated sequence Pf6N2E2_5848: required for pyruvate transport, with Pf6N2E2_5849 (actP-like)
- Ignore hits to 18096 when looking for 'other' hits (DUF485 domain-containing inner membrane protein YjcH. required for glycolate transport, with actP)
- UniProt sequence E4PHQ1: SubName: Full=Membrane protein containing probable solute: sodium symporter, small subunit domain {ECO:0000313|EMBL:ADP97016.1};
- Curated sequence GFF345: small component of D-alanine uptake system, with Psest_0347 (actP-like)
- Comment: This is the yjcH-like small subunit. These are similar to E. coli b4068/yjcH/18096, involved in glycolate & acetate transport, so ignore that. Added Marinobacter HP15_1252 (E4PHQ1) because it has a specific phenotype (if mild) and fills the gap.
- Total: 6 characterized proteins
cstA: large subunit of pyruvate transporter (CstA)
- UniProt sequence A0A0C4Y7X7: SubName: Full=Carbon starvation protein A {ECO:0000313|EMBL:AJG21527.1};
- Curated sequence P15078: Peptide transporter CstA; Carbon starvation protein A. carbon starvation protein A
- Curated sequence P39396: Pyruvate/proton symporter BtsT; Brenztraubensaure transporter; Pyruvate/H(+) symporter. pyruvate:H+ symporter. pyruvate:H+ symporter
- UniProt sequence A0A0N9VZ52: SubName: Full=Carbon starvation protein A {ECO:0000313|EMBL:ALI04206.1};
- Ignore hits to Q0P9Y2 when looking for 'other' hits (Peptide transporter CstA; Carbon starvation protein A. CstA of 703 aas and 18 putative TMSs. In C. jejuni, this protein plays a role in starvation responses and peptide uptake. A ΔcstA mutant has reduced use of di- and tri-peptides when used as nitrogen sources. The mutant also has reduced motility and agglutination and shows decreased host-pathogen relationships)
- Comment: E. coli cstA (P15078) was originally thought to be a peptide transporter, but is involved in pyruvate transport along with ybdD (PMID:29358499). The related protein btsT (P39396, formerly yjiY) is also a pyruvate transporter. And a similar protein from Cupriavidus basilensis, RR42_RS20515 = A0A0C4Y7X7, is important for pyruvate utilization. As is AO353_25255 (A0A0N9VZ52) from Pseudomonas fluorescens FW300-N2E3. CstA and RR42_RS20515 seem to operate together with ybdD or similar proteins, but purified BtsT is reported to transport pyruvate (PMID:29061664), so it may not require a ybdD-like component. It is not clear if AO353_25255 functions with a ybdD-like component: the downstream gene, AO353_25260, is ybdD-like and has subtle defects during growth on pyruvate. Q0P9Y2 (CSTA_CAMJE) was proposed to be a peptide transporter in Campylobacter jejuni, but is suspiciously similar to pyruvate transporters, so is ignored.
- Total: 4 characterized proteins
ybdD: small subunit of pyruvate transporter (YbdD)
- UniProt sequence P0AAS9: RecName: Full=Uncharacterized protein YbdD;
- Curated sequence RR42_RS20510: required for pyruvate transport, with cstA-like RR42_RS20515
- Comment: E. coli ybdD (P0AAS9) is involved in pyruvate transport with cstA (PMID:29358499). And a similar protein from Cupriavidus basilensis, RR42_RS20510, is important for pyruvate utilization.
- Total: 2 characterized proteins
SLC5A8: sodium-coupled pyruvate transporter
- Curated sequence Q3ZMH1: Sodium-coupled monocarboxylate transporter 1; Electrogenic sodium monocarboxylate cotransporter; zSMCTe; Sodium solute symporter family 5 member 8 protein; Solute carrier family 5 member 8. sodium-coupled monocarboxylate transporter 1. The high affinity (Km (lactate) = 0.2mM) electrogenic Na+ monocarboxylate (lactate, pyruvate, butyrate, nicotinate) transporter, SMCTe
- Curated sequence Q7T384: Sodium-coupled monocarboxylate transporter 2; Electroneutral sodium monocarboxylate cotransporter; zSMCTn; Low-affinity sodium-lactate cotransporter; Solute carrier family 5 member 12; zSLC5A12. sodium-coupled monocarboxylate transporter 2. The low affinity (Km (lactate) = 2mM) electroneutral Na+:monocarboxylate (lactate, pyruvate, butyrate, nicotinate) transporter, SMCTn
- Curated sequence Q8N695: Sodium-coupled monocarboxylate transporter 1; Apical iodide transporter; Electrogenic sodium monocarboxylate cotransporter; Sodium iodide-related cotransporter; Solute carrier family 5 member 8. Na+-dependent short chain fatty acid transporter SLC5A8 (tumor suppressor gene product, down-regulated in colon cancer) (substrates: lactate, pyruvate, acetate, propionate, butyrate (Km ≈1 mM)) [propionate:Na+ = 1:3] (Miyauchi et al., 2004). Pyroglutamate (5-oxoproline) is also transported in a Na+- coupled mechanism (Miyauchi et al., 2010). SMCT1 and SMCT2 may transport monocarboxylate drugs (e.g. nicotinate and its derivatives) across the intestinal brush boarder membrane
- Total: 3 characterized proteins
dctP: pyruvate TRAP transporter, substrate-binding component
- Curated sequence Q8YSQ6: Monocarboxylate 2-oxoacid-binding periplasmic protein all3028; Extracellular solute-binding protein; Extracytoplasmic solute receptor protein all3028; TRAP transporter monocarboxylate 2-oxoacid-binding subunit P. Extracellular solute-binding protein, component of The 2-oxo monocarboxylate transporter (Pernil et al., 2010). Transports pyruvate which is inhibited by various 2-ketoacids
- Curated sequence D5ALT6: TRAP dicarboxylate transporter, DctP-2 subunit, component of The 2-ketomonocarboxylate transporter (presented in order of affinity - 2-oxovalerate [highest affinity, KD=0.1 μM], 2-oxoisovalerate, 2-oxobutyrate, 2-oxoisocaproate, 2-oxo-3-methylvalerate, pyruvate [lowest affinity, KD=3 μM])
- Ignore hits to Q3J1R2 when looking for 'other' hits (Alpha-keto acid-binding periplasmic protein TakP; Extracytoplasmic solute receptor protein TakP; TRAP transporter alpha-keto acid-binding subunit P; TRAP-T family sorbitol/mannitol transporter, periplasmic binding protein, SmoM)
- UniProt sequence Q48AL6: SubName: Full=Extracellular solute-binding protein, family 7 {ECO:0000313|EMBL:AAZ28655.1};
- Comment: DctP from Nostoc, Rhodobacter; associated with dctQ and dctM. Similar to TakP (Q3J1R2), which is misannotated and not characterized. The related protein Q48AL6 = CPS_0129 was shown to bind calcium-pyruvate (PMC4310620).
- Total: 3 characterized proteins
dctQ: pyruvate TRAP transporter, small permease component
- Curated sequence D5ATK0: Tripartite ATP-independent periplasmic transporter, DctQ-2 component, component of The 2-ketomonocarboxylate transporter (presented in order of affinity - 2-oxovalerate [highest affinity, KD=0.1 μM], 2-oxoisovalerate, 2-oxobutyrate, 2-oxoisocaproate, 2-oxo-3-methylvalerate, pyruvate [lowest affinity, KD=3 μM])
- Curated sequence Q8YSQ8: Alr3026 protein, component of The 2-oxo monocarboxylate transporter (Pernil et al., 2010). Transports pyruvate which is inhibited by various 2-ketoacids
- Total: 2 characterized proteins
dctM: pyruvate TRAP transporter, large permease component
- Curated sequence D5ATK1: TRAP C4-dicarboxylate transport system permease, DctM-2 subunit, component of The 2-ketomonocarboxylate transporter (presented in order of affinity - 2-oxovalerate [highest affinity, KD=0.1 μM], 2-oxoisovalerate, 2-oxobutyrate, 2-oxoisocaproate, 2-oxo-3-methylvalerate, pyruvate [lowest affinity, KD=3 μM])
- Curated sequence Q8YSQ7: Alr3027 protein, component of The 2-oxo monocarboxylate transporter (Pernil et al., 2010). Transports pyruvate which is inhibited by various 2-ketoacids
- Total: 2 characterized proteins
JEN1: pyruvate symporter JEN1
- Curated sequence CH_091331: Carboxylic acid transporter protein homolog. The lactate/pyruvate:H+ symporter. Residues in the substrate translocation pathway have been reported (Soares-Silva et al., 2011). This systems and its orthologs in fungi have been reviewed
- Curated sequence CH_123467: lactate/pyruvate transporter
- Total: 2 characterized proteins
btsT: pyruvate symporter BtsT
- Curated sequence P39396: Pyruvate/proton symporter BtsT; Brenztraubensaure transporter; Pyruvate/H(+) symporter. pyruvate:H+ symporter. pyruvate:H+ symporter
- Ignore hits to P15078 when looking for 'other' hits (Peptide transporter CstA; Carbon starvation protein A. carbon starvation protein A)
- Comment: formerly yjiY; cstA-like. E. coli cstA (P15078) might be a pyruvate transporter, so ignore
- Total: 1 characterized proteins
mctC: pyruvate symporter MctC
- Curated sequence Q8NS49: Monocarboxylic acid transporter. Pyruvate/acetate/propionate: H+ symporter, MctC (DhlC; cg0953)
- Comment: Note this is related to actP, and was identified by genetics, and is adjacent to a small protein (cg0952) that could be the other subunit (it belongs to DUF485)
- Total: 1 characterized proteins
MCT4: pyruvate symporter MCT4 (SLC16A3)
- Curated sequence O15427: Plasma membrane proton-linked monocarboxylate transporter, MCT4 (SLC16A3). Catalyzes the rapid low affinity plasma membrane transport of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate
- Total: 1 characterized proteins
mctP: pyruvate permease MctP
- Curated sequence Q8VM88: The monocarboxylate uptake (H+ symport?) permease, MctP (transports lactate (Km = 4.4 μM), pyruvate (Km = 3.8), propionate, butyrate (butanoic acid), α-hydroxybutyrate, L- and D-alanine (Km = 0.5 mM), and possibly cysteine and histidine)
- Curated sequence Q1M7A2: Monocarboxylate transport permease protein
- Comment: TCDB and SwissProt have slightly different sequences, include both
- 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 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