Rv2573 Resolved · high auto-curated

H37Rv Rv2573 · MTBC0 - · 246 aa · 2898043–2898783 (+) · RefSeq NP_217089.3

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)2-dehydropantoate 2-reductase
MTBC0 PGAP re-annotation
Revised (this work)2-dehydropantoate 2-reductase. Pfam: ApbA (PF02558.23), ApbA_C (PF08546.18).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P9WIL1 SwissProt · reviewed · Evidence at protein level
UniProt name2-dehydropantoate 2-reductase
EC (curated) EC 1.1.1.169
Curated functionCatalyzes the NADPH-dependent reduction of ketopantoate into pantoic acid.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred nameapbA_1
eggNOG descriptionCatalyzes the NADPH-dependent reduction of ketopantoate into pantoic acid
Orthologous groupCOG1893
EC number EC 1.1.1.169
KEGG orthology K00077
KEGG pathways map00770, map01100, map01110
KEGG modules M00119
Gene Ontology (57) GO:0003674, GO:0003824, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006082, GO:0006520, GO:0006573, GO:0006575, GO:0006732 +45 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 0.094 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 1 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
ApbAPF02558.23 5.1e-195–96 Ketopantoate reductase PanE/ApbA
ApbA_CPF08546.18 3.1e-21120–240 Ketopantoate reductase PanE/ApbA C terminal

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

Closest characterised functional partner: Rv2575 (membrane protein), high confidence from genomic context alone (score 812 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3602c panC pantothenate synthetase 933 913 database:900
Rv2225 panB 3-methyl-2-oxobutanoate hydroxymethyltransferase 930 908 database:900
Rv2575 membrane protein 811 812 ctx neighborhood:811
Rv2572c aspS aspartate--tRNA ligase 745 746 ctx neighborhood:745
Rv2574 hyp hypothetical protein 742 742 ctx neighborhood:703
Rv1000c hyp hypothetical protein 682 682 coexpression:682
Rv2687c antibiotic ABC transporter permease 438 438 ctx cooccurence:419
Rv0976c hyp hypothetical protein 430 430 coexpression:412
Rv1940 ribA1 riboflavin biosynthesis protein RibA 544 413 coexpression:413
Rv2686c antibiotic ABC transporter permease 410 411 ctx cooccurence:409
Rv1415 ribA2 bifunctional riboflavin biosynthesis GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase 518 408 coexpression:408
Rv2571c transmembrane protein 404 404 ctx neighborhood:400
Rv0630c recB exonuclease V subunit beta RecB 527 232 textmining:411
Rv2095c pafC proteasome accessory factor C 554 74 textmining:539
Rv1631 coaE dephospho-CoA kinase CoaE 713 73 textmining:703

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): 2-dehydropantoate 2-reductase
  • Pfam (hmmscan --cut_ga): ApbA PF02558.23 (E=5e-19), ApbA_C PF08546.18 (E=3e-21)
  • (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_217089.3)
  • Domains: Pfam-A via hmmscan --cut_ga — ApbA (PF02558.23), ApbA_C (PF08546.18)
  • 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 COG1893
  • Curated reference: UniProt P9WIL1 (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 — 18 functional partner(s); context anchor Rv2575
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2573|
MVPGPVHTSPREVAGPVDVLILAVKATQNDAARPWLTRLCDERTVVAVLQNGVEQVEQVQPHCPSSAVVPAIVWCSAETQPQGWVRLRGEAALVVPTGPAAEQFAGLLRGAGATVDCDPDFTTAAWRKLLVNALAGFMVLSGRRSAMFRRDDVAALSRRYVAECLAVARAEGARLDDDVVDEVVRLVRSAPQDMGTSMLADRAAHRPLEWDLRNGVIVRKARAHGLATPISDVLVPLLAAASDGPG