GapMind for catabolism of small carbon sources

 

Definition of pyruvate catabolism

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

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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:

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:

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