Rv2971 Resolved · high auto-curated

H37Rv Rv2971 · MTBC0 mtbc0_003156 · 282 aa · 3347276–3348124 (+) · RefSeq NP_217487.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)oxidoreductase
MTBC0 PGAP re-annotationaldo/keto reductase
Revised (this work)Aldo/keto reductase. Pfam: Aldo_ket_red (PF00248.28).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WQA5 SwissProt · reviewed · Evidence at protein level
UniProt nameAldo-keto reductase Rv2971
EC (curated) EC 1.1.1.-
Curated functionCatalyzes the NADPH-dependent reduction of dicarbonyls. Exhibits narrow substrate specificity, with preferential activity against the dicarbonyl substrates methylglyoxal and phenylglyoxal. May play an important role in the detoxification of methylglyoxal.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namedkgA
eggNOG descriptionaldo keto reductase
Orthologous groupCOG0656
EC number EC 1.1.1.346
KEGG orthology K06221
Gene Ontology (10) GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0008150, GO:0016020, GO:0030312, GO:0040007, 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 1.024 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 3 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)

PfamAccessioni-EvalueResiduesDescription
Aldo_ket_redPF00248.28 1.1e-4429–265 Aldo/keto reductase family

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: lipN (lipase/esterase LipN), high confidence from genomic context alone (score 729 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2970A hyp hypothetical protein 889 889 ctx neighborhood:881
Rv3280 accD5 propionyl-CoA carboxylase subunit beta 750 741 coexpression:741
Rv2970c lipN lipase/esterase LipN 734 729 ctx neighborhood:713
Rv2124c metH methionine synthase 745 713 database:630
Rv2969c hyp hypothetical protein 704 705 ctx neighborhood:525 coexpression:404
Rv2298 oxidoreductase 652 606 coexpression:419
Rv2968c integral membrane protein 528 528 ctx neighborhood:521
Rv2006 otsB1 trehalose-6-phosphate phosphatase OtsB 534 508 coexpression:505
Rv0432 sodC superoxide dismutase 534 505 coexpression:449
Rv2940c mas multifunctional mycocerosic acid synthase 625 502 coexpression:418
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 684 494 coexpression:408 textmining:402
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 618 494 coexpression:408
Rv2048c pks12 polyketide synthase 618 494 coexpression:408
Rv1527c pks5 polyketide synthase 618 493 coexpression:407
Rv3372 otsB2 trehalose 6-phosphate phosphatase 514 486 coexpression:486

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: oxidoreductase
  • MTBC0 PGAP product: aldo/keto reductase
  • Pfam (hmmscan --cut_ga): Aldo_ket_red PF00248.28 (E=1e-44)
  • (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_217487.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Aldo_ket_red (PF00248.28)
  • 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 COG0656
  • Curated reference: UniProt P9WQA5 (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 — 43 functional partner(s); context anchor lipN
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003156|Rv2971|
MTGESGAAAAPSITLNDEHTMPVLGLGVAELSDDETERAVSAALEIGCRLIDTAYAYGNEAAVGRAIAASGVAREELFVTTKLATPDQGFTRSQEACRASLDRLGLDYVDLYLIHWPAPPVGKYVDAWGGMIQSRGEGHARSIGVSNFTAEHIENLIDLTFVTPAVNQIELHPLLNQDELRKANAQHTVVTQSYCPLALGRLLDNPTVTSIASEYVKTPAQVLLRWNLQLGNAVVVRSARPERIASNFDVFDFELAAEHMDALGGLNDGTRVREDPLTYAGT