Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | malate synthase |
|---|
| MTBC0 PGAP re-annotation | malate synthase G |
|---|
| Revised (this work) | Malate synthase G. Pfam: MS_N (PF20656.3), MSG_insertion (PF20658.3), MS_TIM-barrel (PF01274.29), MS_C (PF20659.3). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WK17
SwissProt · reviewed
· Evidence at protein level
|
|---|
| UniProt name | Malate synthase G |
|---|
| EC (curated) |
EC 2.3.3.9
|
|---|
| Curated function | Involved in the glycolate utilization. Catalyzes the condensation and subsequent hydrolysis of acetyl-coenzyme A (acetyl-CoA) and glyoxylate to form malate and CoA. |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|
| Preferred name | glcB |
|---|
| eggNOG description | Involved in the glycolate utilization. Catalyzes the condensation and subsequent hydrolysis of acetyl-coenzyme A (acetyl-CoA) and glyoxylate to form malate and CoA |
|---|
| Orthologous group | COG2225 |
|---|
| EC number |
EC 2.3.3.9
|
|---|
| KEGG orthology |
K01638
|
|---|
| KEGG pathways |
map00620, map00630, map01100, map01110, map01120, map01200
|
|---|
| KEGG modules |
M00012
|
|---|
| Gene Ontology (92) |
GO:0000287, GO:0001968, GO:0003674, GO:0003824, GO:0004474, GO:0005488, GO:0005515, GO:0005575, GO:0005576, GO:0005618, GO:0005622, GO:0005623 +80 more
|
|---|
Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are
computed annotations, not manual curation; cross-check against the primary literature
before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS |
0.519 · relaxed/neutral
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
5 synonymous, 8 missense, 0 nonsense, 0 frameshift
|
|---|
pN/pS from segregating SNPs (singletons removed) normalised by possible sites.
Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene).
A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic
variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A
clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a
convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|
MS_N | PF20656.3 |
2.1e-21 | 16–75 |
Malate synthase, N-terminal domain |
MSG_insertion | PF20658.3 |
8.7e-29 | 160–234 |
Malate synthase G, alpha-beta insertion domain |
MS_TIM-barrel | PF01274.29 |
2.6e-71 | 336–580 |
Malate synthase, TIM barrel domain |
MS_C | PF20659.3 |
5.5e-27 | 593–697 |
Malate synthase, C-terminal |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv0467 icl1 |
isocitrate lyase |
999 |
992 |
coexpression:923 database:900 textmining:956 |
Rv1915 aceAa |
isocitrate lyase AceAa |
993 |
973 |
coexpression:696 database:900 textmining:757 |
Rv1916 aceAb |
isocitrate lyase AceAb |
994 |
969 |
coexpression:695 database:900 textmining:823 |
Rv3667 acs |
acetyl-CoAsynthetase |
975 |
968 |
coexpression:651 database:900 |
Rv0408 pta |
phosphate acetyltransferase |
986 |
966 |
coexpression:666 database:900 textmining:602 |
Rv0896 gltA2 |
citrate synthase 1 |
989 |
950 |
coexpression:452 database:900 textmining:793 |
Rv0889c citA |
citrate synthase 2 |
976 |
949 |
coexpression:440 database:900 textmining:565 |
Rv1131 prpC |
methylcitrate synthase PrpC |
981 |
948 |
coexpression:435 database:900 textmining:653 |
Rv1323 fadA4 |
acetyl-CoA acetyltransferase |
941 |
933 |
database:900 |
Rv1074c fadA3 |
beta-ketoacyl CoA thiolase FadA |
929 |
926 |
database:900 |
Rv0243 fadA2 |
acetyl-CoA acetyltransferase FadA |
928 |
925 |
database:900 |
Rv1240 mdh |
malate dehydrogenase |
954 |
924 |
database:900 textmining:433 |
Rv3546 fadA5 |
acetyl-CoA acetyltransferase FadA |
927 |
924 |
database:900 |
Rv0914c |
lipid carrier protein or keto acyl-CoA thiolase |
927 |
924 |
database:900 |
Rv0859 fadA |
acyltransferase |
927 |
924 |
database:900 |
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression,
experimental, database, text-mining) into a 0–1000 score. The ctx
badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion,
phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an
unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not
depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with
the operon context and the primary literature before assigning a function.
Evidence
- Legacy H37Rv annotation: malate synthase
- MTBC0 PGAP product: malate synthase G
- Pfam (hmmscan --cut_ga): MS_N PF20656.3 (E=2e-21), MSG_insertion PF20658.3 (E=9e-29), MS_TIM-barrel PF01274.29 (E=3e-71), MS_C PF20659.3 (E=6e-27)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024),
An imputed ancestral reference genome for the MTBC,
doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_216353.1)
- Domains: Pfam-A via hmmscan --cut_ga — MS_N (PF20656.3), MSG_insertion (PF20658.3), MS_TIM-barrel (PF01274.29), MS_C (PF20659.3)
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
COG2225
- Curated reference: UniProt
P9WK17
(SwissProt, reviewed; Evidence at protein level)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of
145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
106 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001950|Rv1837c|glcB
MTDRVSVGNLRIARVLYDFVNNEALPGTDIDPDSFWAGVDKVVADLTPQNQALLNARDELQAQIDKWHRRRVIEPIDMDAYRQFLTEIGYLLPEPDDFTITTSGVDAEITTTAGPQLVVPVLNARFALNAANARWGSLYDALYGTDVIPETDGAEKGPTYNKVRGDKVIAYARKFLDDSVPLSSGSFGDATGFTVQDGQLVVALPDKSTGLANPGQFAGYTGAAESPTSVLLINHGLHIEILIDPESQVGTTDRAGVKDVILESAITTIMDFEDSVAAVDAADKVLGYRNWLGLNKGDLAAAVDKDGTAFLRVLNRDRNYTAPGGGQFTLPGRSLMFVRNVGHLMTNDAIVDTDGSEVFEGIMDALFTGLIAIHGLKASDVNGPLINSRTGSIYIVKPKMHGPAEVAFTCELFSRVEDVLGLPQNTMKIGIMDEERRTTVNLKACIKAAADRVVFINTGFLDRTGDEIHTSMEAGPMVRKGTMKSQPWILAYEDHNVDAGLAAGFSGRAQVGKGMWTMTELMADMVETKIAQPRAGASTAWVPSPTAATLHALHYHQVDVAAVQQGLAGKRRATIEQLLTIPLAKELAWAPDEIREEVDNNCQSILGYVVRWVDQGVGCSKVPDIHDVALMEDRATLRISSQLLANWLRHGVITSADVRASLERMAPLVDRQNAGDVAYRPMAPNFDDSIAFLAAQELILSGAQQPNGYTEPILHRRRREFKARAAEKPAPSDRAGDDAAR
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