GapMind for catabolism of small carbon sources

 

Definition of L-alanine catabolism

As text, or see rules and steps

# GapMind describes L-alanine uptake only. No enzymatic steps are represented
# because L-alanine is a single transamination reaction
# away from pyruvate, which is a central metabolic intermediate.
# (L-alanine can also be converted to pyruvate by alanine dehydrogenase
# or by by alanine racemase and D-alanine dehydrogenase, metacyc:ALADEG-PWY).

# A sequence nearly identical to E. coli K-12's cycA (CYCA_ECOL6 / A0A0H2VDI7) is annotated as a D-alanine
#  transporter only, ignore.
# And add DL-alanine permease SERP2_LACLM / A2RI86.
# And add general amino-acid permease GAP1_YEAST / P19145, GAP2_CANAL / A0A1D8PK89.
cycA	L-alanine symporter CycA	curated:SwissProt::P0AAE0	curated:TCDB::F2HQ24	curated:TCDB::M1IW84	curated:TCDB::Q2VQZ4	curated:reanno::WCS417:GFF1065	curated:reanno::pseudo3_N2E3:AO353_16120	curated:reanno::pseudo5_N2C3_1:AO356_17670	ignore:SwissProt::A0A0H2VDI7	curated:SwissProt::A2RI86	curated:SwissProt::P19145	curated:SwissProt::A0A1D8PK89

# ABC transporters: there's BraCDEFG (P. aeruginosa), NatABCDE (Synechocystis), LivJFGHM (S. pneumoniae)
# Although TCDB suggests that LivJFGHM transports alanine and serine, this is not supported by PMID:19470745,
# so this was removed.
# Also, BraFG and NatAE are similar and were clustered together;
# clustering at 40% separates this into BraF/NatA and BraG/NatE (P21630/P73650).
# And an orthologous system to NatABCDE, TC 3.A.1.4.6, was missed initially
#
# Also, TC 3.A.1.4.3 from Rhizobium leguminosarum is described as BraCDEFG and as a L-alanine transporter.
# However, the substrate-binding protein BraC is not required for L-alanine uptake, so is another
# SBP is likely used.
#
# Also note: some components of the R. leguminosarum system are very similar to
# BraC (SMc01946) and BraDEFG (SMc01951:SMc01948) from S. meliloti, but some are quite distant.
# (In S. meliloti, these are important for utilization of some larger amino acids, and again,
# BraC does not seem to be the only SBP for this system.)

# braC and natB are quite distantly related and were not clustered, but both are SBP
braC	L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)	curated:SwissProt::P21175	curated:TCDB::Q55387	curated:TCDB::Q8YVY4

braD	L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)	curated:TCDB::P21627	curated:TCDB::P74318	curated:TCDB::Q8YXD0

braE	L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)	curated:TCDB::P21628	curated:TCDB::P74455	curated:TCDB::Q8YY08

braF	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)	curated:TCDB::P21629	curated:TCDB::Q55164	curated:TCDB::Q7A2H0

braG	L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)	curated:TCDB::P21630	curated:TCDB::P73650	curated:TCDB::Q8YT15

# Merge in TC 2.A.25.1.1 / P30144 (dagA from Alteromonas haloplanktis), which is similar but was
#   not included in the cluster because it is longer
alsT	L-alanine symporter AlsT/DagA	curated:SwissProt::P30145	curated:SwissProt::Q6LX42	curated:TCDB::Q45068	curated:TCDB::W0WFC6	curated:TCDB::P30144

SLC1A4	L-alanine symporter SLC1A4	curated:CharProtDB::CH_091534	curated:CharProtDB::CH_091706

SLC38A3	L-alanine symporter SLC38A3	curated:CharProtDB::CH_091437	curated:SwissProt::Q9EQ25

# Structural studies show these are related to TRIC transporters
TRIC	TRIC-type L-alanine transporter	curated:reanno::ANA3:7023996	curated:reanno::MR1:202450

AAP1	L-alanine permease AAP1	curated:CharProtDB::CH_091601

AAP24	L-alanine transporter AAP24	curated:TCDB::A4HUI4

snatA	L-alanine symporter SnatA	curated:TCDB::Q8J305

metP	sodium-dependent methionine/alanine transporter, large subunit MetP	curated:TCDB::Q8NRL8

metS	sodium-dependent methionine/alanine transporter, small subunit MetS	curated:TCDB::Q8NRL9

# Transporters were identified using curated clusters and
# query: transporter:L-alanine:alanine
alanine-transport: cycA
alanine-transport: braC braD braE braF braG
alanine-transport: alsT
alanine-transport: SLC1A4
alanine-transport: SLC38A3
alanine-transport: TRIC
alanine-transport: AAP1
alanine-transport: AAP24
alanine-transport: snatA
alanine-transport: metP metS

# Ignore LAT2_HUMAN / Q9UHI5 and related proteins, which are amino acid exchangers in animals.
# Ignore b2670 (ALAE_ECOLI) and related proteins, which are amino acid exporters.
# Ignore PA5152-PA5155, which probably transports D-alanine.
# Ignore D-alanyl carrier protein DCP (P39579).
# Ignore aspartate/alanine antiporter (Q8L3K8 or Q845W9).
# Ignore spore germination L-alanine receptor (P07869).
# Ignore likely efflux protein b4210 / YtfF.
# Ignore TC 2.A.21.4.1 / Q8VM88 which has far tighter affinity for lactate/pyruvate.

all: alanine-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:

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