Definition of 2-oxoglutarate (alpha-ketoglutarate) catabolism

GapMind for catabolism of small carbon sources

Definition of 2-oxoglutarate (alpha-ketoglutarate) catabolism

# Since 2-oxoglutarate (also known as alpha-ketoglutarate) is a TCA cycle intermediate,
# GapMind represents uptake only.

# HSERO_RS16820 (D8J257) is similar and is important for 2-oxoglutarate utilization.
# uniprot:Q52000 is a dicarboxylate transporter and could be active on 2-oxoglutarate as well, so is ignored.
kgtP	2-oxoglutarate:H+ symporter KgtP	curated:SwissProt::P0AEX3	curated:reanno::pseudo3_N2E3:AO353_03810	curated:reanno::pseudo5_N2C3_1:AO356_17790	uniprot:D8J257	ignore:TCDB::Q52000

# Transporters were identified using
# query: transporter:2-ketoglutarate:alpha-ketoglutarate:ketoglutarate:2-oxoglutarate:oxoglutarate
2-oxoglutarate-transport: kgtP

csbX	2-oxoglutarate permease csbX	curated:TCDB::O05390
2-oxoglutarate-transport: csbX

# Besides the system in Shewanellas, a similar system in Phaeobacter inhibens is important for
# 2-oxoglutarate utilization: DctP = PGA1_c20680 = I7END8; DctQ = PGA1_c20670 = I7EY26; DctM = PGA1_c20660 = I7DRS6.
# And for various related dctP-like components, it's not clear if alpha-ketoglutarate is a substrate or not,
# so they are ignored.
dctP	2-oxoglutarate TRAP transporter, solute receptor component DctP	curated:reanno::SB2B:6938088	curated:SwissProt::A3QCW5	uniprot:I7END8	ignore:SwissProt::Q9KQR9	ignore:SwissProt::Q9HU18	ignore:SwissProt::P37735

dctQ	2-oxoglutarate TRAP transporter, small permease component DctQ	curated:reanno::SB2B:6938089	curated:reanno::PV4:5208944	uniprot:I7EY26

# O07838 and Q9HU16 are reported to transport various dicarboxylates, and transport of
# 2-oxoglutarate does not seem to have been tested, so they are marked ignore.
dctM	2-oxoglutarate TRAP transporter, large permease component DctM	curated:reanno::SB2B:6938090	curated:reanno::PV4:5208943	uniprot:I7DRS6	ignore:SwissProt::O07838	ignore:SwissProt::Q9HU16

2-oxoglutarate-transport: dctP dctQ dctM

Psest_0084	2-oxoglutarate TRAP transporter, fused 4TM/12TM components	curated:reanno::psRCH2:GFF84	uniprot:A8LI82	uniprot:E4PQE4

Psest_0085	2-oxoglutarate TRAP transporter, solute receptor component	curated:reanno::psRCH2:GFF85	uniprot:A8LI83	uniprot:E4PQE3

2-oxoglutarate-transport: Psest_0084 Psest_0085

import succinate.steps:Dshi_1194 Dshi_1195 # TRAP dicarboxylate transporter
2-oxoglutarate-transport: Dshi_1194 Dshi_1195

# Eukaryotic antiporters and related carrier proteins were ignored
# SdcL from Bacillus (TC 2.A.47.1.13) might be a low-affinity 2-oxoglutarate transporter; ignored

all: 2-oxoglutarate-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:

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 preprint 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

GapMind for catabolism of small carbon sources