As text, or see rules and steps
# Pyruvate is a central metabolite, so GapMind represents transport only. # actP-yjcH is usually annotated as acetate permease and associated protein, but they are # often involved in pyruvate transport instead. # 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. actP large subunit of pyruvate transporter (actP-like) uniprot:A0A1N7U9G2 uniprot:G8AHY6 uniprot:A0A166PH03 uniprot:A0A165ZRB0 ignore:SwissProt::P32705 uniprot:E4PHQ0 curated:reanno::psRCH2:GFF346 # 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. yjcH putative small subunit of pyruvate transporter (yjcH-like) curated:reanno::WCS417:GFF1742 curated:reanno::azobra:AZOBR_RS02935 curated:reanno::pseudo1_N1B4:Pf1N1B4_3672 curated:reanno::pseudo6_N2E2:Pf6N2E2_5848 ignore:reanno::Keio:18096 uniprot:E4PHQ1 curated:reanno::psRCH2:GFF345 # Most of these transporters were identified using curated clusters and # query: transporter:pyruvate. ActP-yjcH and cstA-ybdD were identified from mutant fitness data. pyruvate-transport: yjcH actP # 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. cstA large subunit of pyruvate transporter (CstA) uniprot:A0A0C4Y7X7 curated:SwissProt::P15078 curated:SwissProt::P39396 uniprot:A0A0N9VZ52 ignore:SwissProt::Q0P9Y2 # 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. ybdD small subunit of pyruvate transporter (YbdD) uniprot:P0AAS9 curated:reanno::Cup4G11:RR42_RS20510 pyruvate-transport: cstA ybdD SLC5A8 sodium-coupled pyruvate transporter curated:SwissProt::Q3ZMH1 curated:SwissProt::Q7T384 curated:SwissProt::Q8N695 pyruvate-transport: SLC5A8 # 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). dctP pyruvate TRAP transporter, substrate-binding component curated:SwissProt::Q8YSQ6 curated:TCDB::D5ALT6 ignore:SwissProt::Q3J1R2 uniprot:Q48AL6 dctQ pyruvate TRAP transporter, small permease component curated:TCDB::D5ATK0 curated:TCDB::Q8YSQ8 dctM pyruvate TRAP transporter, large permease component curated:TCDB::D5ATK1 curated:TCDB::Q8YSQ7 pyruvate-transport: dctM dctP dctQ JEN1 pyruvate symporter JEN1 curated:CharProtDB::CH_091331 curated:CharProtDB::CH_123467 pyruvate-transport: JEN1 # formerly yjiY; cstA-like. # E. coli cstA (uniprot:P15078) might be a pyruvate transporter, so ignore btsT pyruvate symporter BtsT curated:SwissProt::P39396 ignore:SwissProt::P15078 pyruvate-transport: btsT # 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) mctC pyruvate symporter MctC curated:SwissProt::Q8NS49 pyruvate-transport: mctC MCT4 pyruvate symporter MCT4 (SLC16A3) curated:TCDB::O15427 pyruvate-transport: MCT4 # TCDB and SwissProt have slightly different sequences, include both mctP pyruvate permease MctP curated:TCDB::Q8VM88 curated:SwissProt::Q1M7A2 pyruvate-transport: mctP # Ignore various mitochondrial carriers and chloroplast transporters # This has weak evidence to be a pyruvate transporter, so ignore: # Acetate/haloacid transporter, Dehp2, with a possible atypical topology curated:TCDB::F8SVK1 all: pyruvate-transport
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 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