Definition of L-alanine catabolism
As rules and steps, or see full text
Rules
Overview: 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, link).
- all: alanine-transport
- alanine-transport:
Steps
cycA: L-alanine symporter CycA
- Curated sequence P0AAE0: D-serine/D-alanine/glycine transporter. D-Serine/D-alanine/glycine/D-cycloserine:H+ symporter. D-serine/alanine/glycine/:H+symporter. D-serine/alanine/glycine/:H+symporter
- Curated sequence F2HQ24: Serine transporter, SerP2 or YdgB, of 459 aas and 12 TMSs (Trip et al. 2013). Transports L-alanine (Km = 20 μM), D-alanine (Km = 38 μM), L-serine, D-serine (Km = 356 μM) and glycine (Noens and Lolkema 2015). The encoding gene is adjacent to the one encoding SerP1 (TC# 2.A.3.1.21)
- Curated sequence M1IW84: D-serine/L-alanine/D-alanine/glycine/D-cycloserine uptake porter of 556 aas, CycA
- Curated sequence Q2VQZ4: Arbuscular mycorrhizal fungal proline:H+ symporter, AAP1 (binds and probably transports nonpolar, hydrophobic amino acids)
- Curated sequence GFF1065: L-alanine and D-alanine permease
- Curated sequence AO353_16120: D-alanine and L-alanine transporter
- Curated sequence AO356_17670: L-alanine and D-alanine permease
- Ignore hits to A0A0H2VDI7 when looking for 'other' hits (D-serine/D-alanine/glycine transporter)
- Curated sequence A2RI86: DL-alanine permease SerP2
- Curated sequence P19145: general amino-acid permease GAP1. General amino-acid permease GAP1. General amino acid permease (all L-amino acids and some D-amino acids as well as β-alanine, polyamines and GABA)
- Curated sequence A0A1D8PK89: General amino-acid permease GAP2. General amino and permease and transceptor, GAP2. Transports all amino acids including citruline and eight tested toxic amino acid derivatives
- Comment: 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.
- Total: 10 characterized proteins
braC: L-alanine/L-serine/L-threonine ABC transporter, substrate binding protein (BraC/NatB)
- Curated sequence P21175: Leucine-, isoleucine-, valine-, threonine-, and alanine-binding protein; LIVAT-BP; Leu/Ile/Val/Thr/Ala-binding protein. Leucine-, isoleucine-, valine-, threonine-, and alanine-binding protein, component of Branched chain amino acid uptake transporter. Transports alanine
- Curated sequence Q55387: NatB aka SLR0559, component of Leucine/proline/alanine/serine/glycine (and possibly histidine) porter, NatABCDE
- Curated sequence Q8YVY4: NatB, component of The neutral amino acid permease, N-1 (transports pro, phe, leu, gly, ala, ser, gln and his, but gln and his are not transported via NatB)
- Comment: braC and natB are quite distantly related and were not clustered, but both are SBP
- Total: 3 characterized proteins
braD: L-alanine/L-serine/L-threonine ABC transporter, permease component 1 (BraD/NatD)
- Curated sequence P21627: High-affinity branched-chain amino acid transport system permease protein BraD, component of Branched chain amino acid uptake transporter. Transports alanine
- Curated sequence P74318: NatD aka LivH aka SLR0949, component of Leucine/proline/alanine/serine/glycine (and possibly histidine) porter, NatABCDE
- Curated sequence Q8YXD0: NatD, component of The neutral amino acid permease, N-1 (transports pro, phe, leu, gly, ala, ser, gln and his, but gln and his are not transported via NatB)
- Total: 3 characterized proteins
braE: L-alanine/L-serine/L-threonine ABC transporter, permease component 2 (BraE/NatC)
- Curated sequence P21628: High-affinity branched-chain amino acid transport system permease protein BraE, component of Branched chain amino acid uptake transporter. Transports alanine
- Curated sequence P74455: NatC aka SLL0146, component of Leucine/proline/alanine/serine/glycine (and possibly histidine) porter, NatABCDE
- Curated sequence Q8YY08: NatC, component of The neutral amino acid permease, N-1 (transports pro, phe, leu, gly, ala, ser, gln and his, but gln and his are not transported via NatB)
- Total: 3 characterized proteins
braF: L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 1 (BraF/NatA)
- Curated sequence P21629: High-affinity branched-chain amino acid transport ATP-binding protein BraF, component of Branched chain amino acid uptake transporter. Transports alanine
- Curated sequence Q55164: NatA aka BRAF aka SLR0467, component of Leucine/proline/alanine/serine/glycine (and possibly histidine) porter, NatABCDE
- Curated sequence Q7A2H0: NatA, component of The neutral amino acid permease, N-1 (transports pro, phe, leu, gly, ala, ser, gln and his, but gln and his are not transported via NatB)
- Total: 3 characterized proteins
braG: L-alanine/L-serine/L-threonine ABC transporter, ATP-binding component 2 (BraG/NatE)
- Curated sequence P21630: High-affinity branched-chain amino acid transport ATP-binding protein BraG, component of Branched chain amino acid uptake transporter. Transports alanine
- Curated sequence P73650: NatE aka LivF aka SLR1881, component of Leucine/proline/alanine/serine/glycine (and possibly histidine) porter, NatABCDE
- Curated sequence Q8YT15: NatE, component of The neutral amino acid permease, N-1 (transports pro, phe, leu, gly, ala, ser, gln and his, but gln and his are not transported via NatB)
- Total: 3 characterized proteins
alsT: L-alanine symporter AlsT/DagA
- Curated sequence P30145: Sodium/proton-dependent alanine carrier protein. Alanine:Na+ (or H+) symporter
- Curated sequence Q6LX42: Sodium/alanine symporter AgcS; Alanine permease. Alanine:Na+ symporter, AgcS
- Curated sequence Q45068: Amino-acid carrier protein, AlsT
- Curated sequence W0WFC6: Probable Glycine/alanine/asparagine/glutamine uptake porter, AgcS
- Curated sequence P30144: Alanine (or glycine):Na+ symporter
- Comment: 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
- Total: 5 characterized proteins
SLC1A4: L-alanine symporter SLC1A4
- Curated sequence CH_091534: neutral amino acid transporter A. Neutral amino acid transporter A; Alanine/serine/cysteine/threonine transporter 1; ASCT-1; SATT; Solute carrier family 1 member 4. Neutral amino acid (alanine, serine, cysteine, threonine):Na+ symporter. Also transports homocysteine (Jiang et al., 2007). AscT1 is the Syncytin-1 (Q9UQF0) receptor. Syncytin-1, of 538 aas with 4-7 TMSs, is a viral fusion protein and is involved in the development of multiple sclerosis (Antony et al. 2007). Mutation causes nuerological problems including global developmental delay, severe progressive microcephaly, seizures, spasticity and thin corpus callosum (CC)
- Curated sequence CH_091706: neutral amino acid transporter B(0). Neutral amino acid transporter B(0); ATB(0); ASC-like Na(+)-dependent neutral amino acid transporter ASCT2; Insulin-activated amino acid transporter; Sodium-dependent neutral amino acid transporter type 2; Solute carrier family 1 member 5. Insulin-activated, Na+-dependet amino acid (serine, alanine, glutamate, glutamine and other neutral amino acids):amino acid antiporter (Ndaru et al. 2019). Also transports homocysteine
- Total: 2 characterized proteins
SLC38A3: L-alanine symporter SLC38A3
- Curated sequence CH_091437: sodium-coupled neutral amino acid transporter 3. Sodium-coupled neutral amino acid transporter 3; N-system amino acid transporter 1; Na(+)-coupled neutral amino acid transporter 3; Solute carrier family 38 member 3; System N amino acid transporter 1. System N1, SNAT3 [glutamine/histidine/asparagine/alanine]:[Na+ + H+] sym/antiporter (1 aa + 2 Na+ cotransported against 1 H+ antiported out) (probable orthologue of mNAT). Li+ can substitute for Na+; system N1 can function bidirectionally. SNAT3 is a primarily a glutamine transporter required for amino acid homeostasis. Loss cannot be compensated, suggesting that this transporter is a major route of glutamine transport in the liver, brain, and kidney
- Curated sequence Q9EQ25: Sodium-coupled neutral amino acid transporter 4; Amino acid transporter A3; Na(+)-coupled neutral amino acid transporter 4; Solute carrier family 38 member 4; System A amino acid transporter 3. sodium-coupled neutral amino acid transporter 4. The Na-dependent alanine/α-(methylamino) isobutyric acid-transporting system A, ATA3 or SNAT4
- Total: 2 characterized proteins
TRIC: TRIC-type L-alanine transporter
- Curated sequence 7023996: putative transporter, required for glycine and L-alanine utilization
- Curated sequence 202450: putative transporter, required for L-alanine utilization
- Comment: Structural studies show these are related to TRIC transporters
- Total: 2 characterized proteins
AAP1: L-alanine permease AAP1
- Curated sequence CH_091601: amino acid transporter. Amino acid permease 1; Amino acid transporter AAP1; Neutral amino acid transporter II. General amino acid permease 1, AAP1 (transports most neutral and acidic amino acids but not aspartate or the basic amino acids). amino acid permease 1
- Total: 1 characterized proteins
AAP24: L-alanine transporter AAP24
- Curated sequence A4HUI4: Proline/alanine transporter of 488 aas and 10 TMSs, AAP24. The first 18 amino acids of the negatively charged N-terminal LdAAP24 tail are required for alanine transport and may facilitate the electrostatic interactions of the entire negatively charged N-terminal tail with the positively charged internal loops in the transmembrane domain
- Total: 1 characterized proteins
snatA: L-alanine symporter SnatA
- Curated sequence Q8J305: The SnatA carrier. Transports glycine, L-alanine, L-serine, L-threonine and a variety of neutral L-amino acids
- Total: 1 characterized proteins
metP: sodium-dependent methionine/alanine transporter, large subunit MetP
- Curated sequence Q8NRL8: Transporter, component of The methionine/alanine uptake porter, MetPS (Trotschel et al., 2008) (MetP is the transporter; MetS is an essential auxiliary subunit)
- Total: 1 characterized proteins
metS: sodium-dependent methionine/alanine transporter, small subunit MetS
- Curated sequence Q8NRL9: Putative uncharacterized protein Cgl1029 (Putative secreted protein), component of The methionine/alanine uptake porter, MetPS (Trotschel et al., 2008) (MetP is the transporter; MetS is an essential auxiliary subunit)
- Total: 1 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:
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