Definition of L-serine catabolism
As rules and steps, or see full text
Rules
Overview: L-serine degradation in GapMind is based on the MetaCyc pathway (link)
- all: serine-transport and serine-ammonia-lyase
- Comment: Serine ammonia-lyase converts serine to pyruvate and ammonia via 2-aminoprop-2-enoate and 2-iminopropanoate.
- serine-ammonia-lyase:
- serine-transport:
Steps
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
Ac3H11_2396: L-tyrosine ABC transporter, substrate-binding component component
- UniProt sequence A0A165KTD4: SubName: Full=Branched chain amino acid ABC transporter substrate-binding protein {ECO:0000313|EMBL:KZT16064.1};
- Comment: A 5-part ABC transporter for serine and other amino acids was identified in Acidovorax sp. GW101-3H11. It is related to branched-amino-acid transporters. The substrate-binding component (Ac3H11_2396) is not nearby but is cofit.
- Total: 1 characterized proteins
Ac3H11_1695: L-tyrosine ABC transporter, permease component 1
Ac3H11_1694: L-tyrosine ABC transporter, permease component 2
Ac3H11_1693: L-tyrosine ABC transporter, ATPase component 1
Ac3H11_1692: L-tyrosine ABC transporter, ATPase component 2
serP: L-serine permease SerP
- Curated sequence A2RI87: Serine permease SerP1
- 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 F2HQ25: Serine uptake transporter, SerP1, of 259 aas and 12 TMSs (Trip et al. 2013). L-serine is the highest affinity substrate (Km = 18 μM), but SerP1 also transports L-threonine and L-cysteine (Km values = 20 - 40 μM)
- Ignore hits to A2RI86 when looking for 'other' hits (DL-alanine permease SerP2)
- Ignore hits to P0AAE0 when looking for 'other' hits (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)
- Ignore hits to A0A0H2VDI7 when looking for 'other' hits (D-serine/D-alanine/glycine transporter)
- Comment: This cluster also includes cycA (P0AAE0 or A0A0H2VDI7), but that may only transport D-serine. A close homolog of SerP2, A2RI87, is annotated as a D,L-alanine permease and is reported to have weak affinity for L-serine (see SwissProt); it is also marked ignore.
- Total: 3 characterized proteins
dlsT: L-serine transporter DlsT
sdaC: L-serine transporter:H+ symporter sdaC
- Curated sequence P0AAD6: Serine transporter. Serine permease. serine:H+ symporter SdaC. serine:H+ symporter SdaC
- Curated sequence P0AAD8: Threonine/serine transporter TdcC; H(+)/threonine-serine symporter. Threonine/Serine permease. threonine/serine:H+ symporter. threonine/serine:H+ symporter
- Total: 2 characterized proteins
AAP1: L-serine transporter 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
sstT: L-serine:Na+ symporter SstT
- Curated sequence P0AGE4: Serine/threonine transporter SstT; Na(+)/serine-threonine symporter. Serine/threonine:Na+ symporter, SstT. serine/threonine:Na+ symporter
- Total: 1 characterized proteins
snatA: L-serine transporter
- 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
sdaB: L-serine ammonia-lyase
sdhA: FeS-containing L-serine dehydratase, alpha subunit
- UniProt sequence P33073: RecName: Full=L-serine dehydratase, alpha chain; Short=SDH; EC=4.3.1.17; AltName: Full=L-serine deaminase; Short=L-SD;
- Ignore hits to items matching 4.3.1.17 when looking for 'other' hits
- Comment: Heteromeric iron-cluster-containing form
- Total: 1 characterized proteins
sdhB: FeS-containing L-serine dehydratase, beta subunit
- UniProt sequence P33074: RecName: Full=L-serine dehydratase, beta chain; Short=SDH; EC=4.3.1.17; AltName: Full=L-serine deaminase; Short=L-SD;
- Ignore hits to items matching 4.3.1.17 when looking for 'other' hits
- 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 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