lldD2 Resolved · high auto-curated
H37Rv Rv1872c · MTBC0 mtbc0_001985 ·
414 aa · 2139946–2141190 (-) ·
RefSeq NP_216388.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | L-lactate dehydrogenase |
|---|---|
| MTBC0 PGAP re-annotation | quinone-dependent L-lactate dehydrogenase |
| Revised (this work) | Quinone-dependent L-lactate dehydrogenase. Pfam: FMN_dh (PF01070.25). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WND5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative L-lactate dehydrogenase |
| EC (curated) |
EC 1.1.-.-
|
UniProt still lists this protein as Putative L-lactate dehydrogenase; 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 | lldD2 |
| eggNOG description | Dehydrogenase |
| Orthologous group | COG1304 |
| EC number |
EC 1.1.2.3, EC 1.1.3.15
|
| KEGG orthology |
K00101, K00104
|
| KEGG pathways |
map00620, map00630, map01100, map01110, map01120, map01130
|
| Gene Ontology (8) |
GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0016020, GO:0030312, GO:0044464, GO:0071944
|
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 | 0.592 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 8 synonymous, 13 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 |
|---|---|---|---|---|
FMN_dh | PF01070.25 | 3.2e-126 | 44–402 | FMN-dependent dehydrogenase |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1871c hyp |
hypothetical protein | 965 | 964 ctx | neighborhood:750 coexpression:862 |
Rv1617 pykA |
pyruvate kinase | 938 | 932 | database:900 |
Rv0694 mftD |
mycofactocin system heme/flavin oxidoreductase MftD | 936 | 920 | database:900 |
Rv2967c pca |
pyruvate carboxylase | 911 | 906 | database:900 |
Rv2455c korA |
2-oxoglutarate oxidoreductase subunit KorA | 929 | 904 | database:900 |
Rv2332 mez |
malate oxidoreductase | 915 | 903 | database:900 |
Rv2497c bkdA |
3-methyl-2-oxobutanoate dehydrogenase subunit alpha | 906 | 903 | database:900 |
Rv2454c korB |
2-oxoglutarate oxidoreductase subunit KorB | 910 | 902 | database:900 |
Rv2241 aceE |
pyruvate dehydrogenase E1 component | 910 | 901 | database:900 |
Rv2496c bkdB |
3-methyl-2-oxobutanoate dehydrogenase subunit beta | 904 | 901 | database:900 |
Rv1127c ppdK |
pyruvate, phosphate dikinase PpdK | 906 | 900 | database:900 |
Rv3003c ilvB1 |
acetolactate synthase large subunit IlvB | 904 | 899 | database:893 |
Rv3509c ilvX |
acetohydroxyacid synthase large subunit | 904 | 899 | database:893 |
Rv1820 ilvG |
acetolactate synthase large subunit IlvG | 904 | 899 | database:893 |
Rv3470c ilvB2 |
acetolactate synthase large subunit | 911 | 898 | database:893 |
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: L-lactate dehydrogenase
- MTBC0 PGAP product: quinone-dependent L-lactate dehydrogenase
- Pfam (hmmscan --cut_ga): FMN_dh PF01070.25 (E=3e-126)
- (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_216388.1)
- Domains: Pfam-A via hmmscan --cut_ga — FMN_dh (PF01070.25)
- 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
COG1304 - Curated reference: UniProt P9WND5 (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 — 141 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001985|Rv1872c|lldD2 MAVNRRVPRVRDLAPLLQFNRPQFDTSKRRLGAALTIQDLRRIAKRRTPRAAFDYADGAAEDELSIARARQGFRDIEFHPTILRDVTTVCAGWNVLGQPTVLPFGIAPTGFTRLMHTEGEIAGARAAAAAGIPFSLSTLATCAIEDLVIAVPQGRKWFQLYMWRDRDRSMALVRRAAAAGFDTMLVTVDVPVAGARLRDVRNGMSIPPALTLRTVLDAMGHPRWWFDLLTTEPLAFASLDRWPGTVGEYLNTVFDPSLTFDDLAWIKSQWPGKLVVKGIQTLDDARAVVDRGVDGIVLSNHGGRQLDRAPVPFHLLPHVARELGKHTEILVDTGIMSGADIVAAIALGARCTLIGRAYLYGLMAGGEAGVNRAIEILQTGVIRTMRLLGVTCLEELSPRHVTQLRRLGPIGAPT