mez Resolved · high auto-curated
H37Rv Rv2332 · MTBC0 mtbc0_002482 ·
548 aa · 2629857–2631503 (+) ·
RefSeq NP_216848.2
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | malate oxidoreductase |
|---|---|
| MTBC0 PGAP re-annotation | NAD-dependent malic enzyme |
| Revised (this work) | NAD-dependent malic enzyme. Pfam: malic (PF00390.25), Malic_M (PF03949.22). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WK25
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative malate oxidoreductase [NAD] |
| EC (curated) |
EC 1.1.1.38
|
UniProt still lists this protein as Putative malate oxidoreductase [NAD]; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | mez |
| eggNOG description | malic enzyme |
| Orthologous group | COG0281 |
| EC number |
EC 1.1.1.38, EC 4.1.1.101
|
| KEGG orthology |
K00027, K22212
|
| KEGG pathways |
map00620, map01120, map01200, map02020
|
| Gene Ontology (28) |
GO:0003674, GO:0003824, GO:0004470, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006082, GO:0006090, GO:0006108, GO:0008150 +16 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 | 0.544 · 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 |
|---|---|---|---|---|
malic | PF00390.25 | 4.0e-66 | 74–254 | Malic enzyme, N-terminal domain |
Malic_M | PF03949.22 | 6.9e-100 | 265–522 | Malic enzyme, NAD binding domain |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1240 mdh |
malate dehydrogenase | 978 | 947 | database:900 textmining:605 |
Rv1098c fum |
fumarate hydratase | 975 | 945 | coexpression:418 database:900 textmining:567 |
Rv1617 pykA |
pyruvate kinase | 975 | 939 | database:900 textmining:623 |
Rv2496c bkdB |
3-methyl-2-oxobutanoate dehydrogenase subunit beta | 947 | 925 | database:900 |
Rv2967c pca |
pyruvate carboxylase | 987 | 919 | database:900 textmining:848 |
Rv1837c glcB |
malate synthase | 940 | 907 | database:900 |
Rv2241 aceE |
pyruvate dehydrogenase E1 component | 937 | 907 | database:900 |
Rv2497c bkdA |
3-methyl-2-oxobutanoate dehydrogenase subunit alpha | 932 | 907 | database:900 |
Rv1127c ppdK |
pyruvate, phosphate dikinase PpdK | 917 | 906 | database:900 |
Rv2455c korA |
2-oxoglutarate oxidoreductase subunit KorA | 961 | 905 | database:900 textmining:615 |
Rv2852c mqo |
malate:quinone oxidoreductase | 917 | 904 | database:900 |
Rv1872c lldD2 |
L-lactate dehydrogenase | 915 | 903 | database:900 |
Rv0694 mftD |
mycofactocin system heme/flavin oxidoreductase MftD | 912 | 903 | database:900 |
Rv2454c korB |
2-oxoglutarate oxidoreductase subunit KorB | 935 | 900 | database:900 |
Rv3509c ilvX |
acetohydroxyacid synthase large subunit | 854 | 844 | 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 oxidoreductase
- MTBC0 PGAP product: NAD-dependent malic enzyme
- Pfam (hmmscan --cut_ga): malic PF00390.25 (E=4e-66), Malic_M PF03949.22 (E=7e-100)
- (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_216848.2)
- Domains: Pfam-A via hmmscan --cut_ga — malic (PF00390.25), Malic_M (PF03949.22)
- 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
COG0281 - Curated reference: UniProt P9WK25 (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 — 105 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002482|Rv2332|mez MSDARVPRIPAALSAPSLNRGVGFTHAQRRRLGLTGRLPSAVLTLDQQAERVWHQLQSLATDLGRNLLLEQLHYRHEVLYFKVLADHLPELMPVVYTPTVGEAIQRFSDEYRGQRGLFLSIDEPDEIEEAFNTLGLGPEDVDLIVCTDAEAILGIGDWGVGGIQIAVGKLALYTAGGGVDPRRCLAVSLDVGTDNEQLLADPFYLGNRHARRRGREYDEFVSRYIETAQRLFPRAILHFEDFGPANARKILDTYGTDYCVFNDDMQGTGAVVLAAVYSGLKVTGIPLRDQTIVVFGAGTAGMGIADQIRDAMVADGATLEQAVSQIWPIDRPGLLFDDMDDLRDFQVPYAKNRHQLGVAVGDRVGLSDAIKIASPTILLGCSTVYGAFTKEVVEAMTASCKHPMIFPLSNPTSRMEAIPADVLAWSNGRALLATGSPVAPVEFDETTYVIGQANNVLAFPGIGLGVIVAGARLITRRMLHAAAKAIAHQANPTNPGDSLLPDVQNLRAISTTVAEAVYRAAVQDGVASRTHDDVRQAIVDTMWLPAYD