Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | malate dehydrogenase |
|---|
| MTBC0 PGAP re-annotation | malate dehydrogenase |
|---|
| Revised (this work) | Malate dehydrogenase. Pfam: Ldh_1_N (PF00056.30), Ldh_1_C (PF02866.24). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WK13
SwissProt · reviewed
· Evidence at protein level
|
|---|
| UniProt name | Malate dehydrogenase |
|---|
| EC (curated) |
EC 1.1.1.37
|
|---|
| Curated function | Catalyzes the reversible oxidation of malate to oxaloacetate. |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|
| Preferred name | mdh |
|---|
| eggNOG description | Catalyzes the reversible oxidation of malate to oxaloacetate |
|---|
| Orthologous group | COG0039 |
|---|
| EC number |
EC 1.1.1.37
|
|---|
| KEGG orthology |
K00024
|
|---|
| KEGG pathways |
map00020, map00270, map00620, map00630, map00680, map00710, map00720, map01100, map01110, map01120, map01130, map01200
|
|---|
| KEGG modules |
M00009, M00011, M00012, M00168, M00173, M00346, M00374, M00620, M00740
|
|---|
| Gene Ontology (65) |
GO:0003674, GO:0003824, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0005975, GO:0006082, GO:0006091 +53 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 |
0.349 · purifying
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
5 synonymous, 5 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 |
|---|
Ldh_1_N | PF00056.30 |
1.3e-29 | 7–150 |
lactate/malate dehydrogenase, NAD binding domain |
Ldh_1_C | PF02866.24 |
2.7e-41 | 157–323 |
lactate/malate dehydrogenase, alpha/beta C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv0889c citA |
citrate synthase 2 |
992 |
979 |
coexpression:650 experimental:423 database:900 textmining:672 |
Rv0896 gltA2 |
citrate synthase 1 |
991 |
979 |
coexpression:658 experimental:423 database:900 textmining:613 |
Rv1131 prpC |
methylcitrate synthase PrpC |
989 |
979 |
coexpression:648 experimental:423 database:900 textmining:515 |
Rv1098c fum |
fumarate hydratase |
982 |
957 |
coexpression:491 database:900 textmining:617 |
Rv2332 mez |
malate oxidoreductase |
978 |
947 |
database:900 textmining:605 |
Rv2967c pca |
pyruvate carboxylase |
978 |
926 |
database:900 textmining:726 |
Rv1837c glcB |
malate synthase |
954 |
924 |
database:900 textmining:433 |
Rv2852c mqo |
malate:quinone oxidoreductase |
962 |
913 |
database:900 textmining:586 |
Rv0211 pckA |
phosphoenolpyruvate carboxykinase |
953 |
903 |
database:900 textmining:539 |
Rv3339c icd1 |
isocitrate dehydrogenase |
931 |
895 |
coexpression:794 experimental:428 |
Rv0066c icd2 |
isocitrate dehydrogenase |
934 |
870 |
coexpression:859 textmining:517 |
Rv1659 argH |
argininosuccinate lyase |
860 |
851 |
database:800 |
Rv0777 purB |
adenylosuccinate lyase PurB |
862 |
838 |
database:800 |
Rv0234c gabD1 |
succinate-semialdehyde dehydrogenase |
839 |
829 |
database:800 |
Rv1731 gabD2 |
succinate-semialdehyde dehydrogenase |
839 |
829 |
database:800 |
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 dehydrogenase
- MTBC0 PGAP product: malate dehydrogenase
- Pfam (hmmscan --cut_ga): Ldh_1_N PF00056.30 (E=1e-29), Ldh_1_C PF02866.24 (E=3e-41)
- (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_215756.1)
- Domains: Pfam-A via hmmscan --cut_ga — Ldh_1_N (PF00056.30), Ldh_1_C (PF02866.24)
- 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
COG0039
- Curated reference: UniProt
P9WK13
(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 —
185 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001329|Rv1240|mdh
MSASPLKVAVTGAAGQIGYSLLFRLASGSLLGPDRPIELRLLEIEPALQALEGVVMELDDCAFPLLSGVEIGSDPQKIFDGVSLALLVGARPRGAGMERSDLLEANGAIFTAQGKALNAVAADDVRVGVTGNPANTNALIAMTNAPDIPRERFSALTRLDHNRAISQLAAKTGAAVTDIKKMTIWGNHSATQYPDLFHAEVAGKNAAEVVNDQAWIEDEFIPTVAKRGAAIIDARGASSAASAASATIDAARDWLLGTPADDWVSMAVVSDGSYGVPEGLISSFPVTTKGGNWTIVSGLEIDEFSRGRIDKSTAELADERSAVTELGLI
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