Rv2454c Family assigned · medium auto-curated

H37Rv Rv2454c · MTBC0 mtbc0_002613 · 373 aa · 2777873–2778994 (-) · RefSeq NP_216970.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)2-oxoglutarate oxidoreductase subunit KorB
MTBC0 PGAP re-annotation2-oxoacid:ferredoxin oxidoreductase subunit beta
Revised (this work)2-oxoacid:ferredoxin oxidoreductase subunit beta. Pfam: TPP_enzyme_C (PF02775.27).

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

Curated reference (UniProt)

UniProt O53181 SwissProt · reviewed · Evidence at protein level
UniProt name2-oxoglutarate oxidoreductase subunit KorB
EC (curated) EC 1.2.7.3
Curated functionComponent of KG oxidoreductase (KOR) that catalyzes the CoA-dependent oxidative decarboxylation of 2-oxoglutarate (alpha-ketoglutarate, KG) to succinyl-CoA. Methyl viologen can act as electron acceptor in vitro; the physiologic electron acceptor is unknown. Is involved in the alternative TCA pathway that functions concurrently with fatty acid beta-oxidation. Since a growing body of evidence indicates that lipids (for example cholesterol and fatty acids) are a predominant growth substrate for M.tuberculosis during infection, flux through KOR likely represents an important step in intermediary m.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namekorB
eggNOG descriptionferredoxin oxidoreductase
Orthologous groupCOG1013
EC number EC 1.2.7.11, EC 1.2.7.3
KEGG orthology K00175
KEGG pathways map00010, map00020, map00620, map00650, map00720, map01100, map01120, map01130, map01200
KEGG modules M00009, M00011, M00173, M00620
Gene Ontology (42) GO:0000287, GO:0003674, GO:0003824, GO:0005488, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006082, GO:0006091 +30 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 0.138 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 2 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
TPP_enzyme_CPF02775.27 4.0e-3088–235 Thiamine pyrophosphate enzyme, C-terminal TPP binding domain

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

Closest characterised functional partner: korA (2-oxoglutarate oxidoreductase subunit KorA), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2455c korA 2-oxoglutarate oxidoreductase subunit KorA 999 1000 ctx neighborhood:881 cooccurence:774 coexpression:989 experimental:999 database:900 textmining:932
Rv2453c mobA molybdenum cofactor guanylyltransferase 995 979 ctx neighborhood:881 coexpression:829 textmining:803
Rv0066c icd2 isocitrate dehydrogenase 946 944 coexpression:417 database:900
Rv0408 pta phosphate acetyltransferase 961 924 database:900 textmining:518
Rv1617 pykA pyruvate kinase 945 918 database:900
Rv0952 sucD succinyl-CoA ligase subunit alpha 945 916 database:900
Rv0951 sucC succinyl-CoA ligase subunit beta 944 912 database:900
Rv3667 acs acetyl-CoAsynthetase 921 909 database:900
Rv3509c ilvX acetohydroxyacid synthase large subunit 911 906 database:900
Rv3002c ilvN acetolactate synthase small subunit 905 906 database:900
Rv0889c citA citrate synthase 2 939 905 database:900
Rv0896 gltA2 citrate synthase 1 924 905 database:900
Rv1131 prpC methylcitrate synthase PrpC 913 905 database:900
Rv1820 ilvG acetolactate synthase large subunit IlvG 911 905 database:900
Rv3003c ilvB1 acetolactate synthase large subunit IlvB 910 905 database:900

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: 2-oxoglutarate oxidoreductase subunit KorB
  • MTBC0 PGAP product: 2-oxoacid:ferredoxin oxidoreductase subunit beta
  • Pfam (hmmscan --cut_ga): TPP_enzyme_C PF02775.27 (E=4e-30)
  • (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_216970.1)
  • Domains: Pfam-A via hmmscan --cut_ga — TPP_enzyme_C (PF02775.27)
  • 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 COG1013
  • Curated reference: UniProt O53181 (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 — 83 functional partner(s); context anchor korA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002613|Rv2454c|
MTRSGDEAQLMTGVTGDLAGTELGLTPSLTKNAGVPTTDQPQKGKDFTSDQEVRWCPGCGDYVILNTIRNFLPELGLRRENIVFISGIGCSSRFPYYLETYGFHSIHGRAPAIATGLALAREDLSVWVVTGDGDALSIGGNHLIHALRRNINVTILLFNNRIYGLTKGQYSPTSEVGKVTKSTPMGSLDHPFNPVSLALGAEATFVGRALDSDRNGLTEVLRAAAQHRGAALVEILQDCPIFNDGSFDALRKEGAEERVIKVRHGEPIVFGANGEYCVVKSGFGLEVAKTADVAIDEIIVHDAQVDDPAYAFALSRLSDQNLDHTVLGIFRHISRPTYDDAARSQVVAARNAAPSGTAALQSLLHGRDTWTVD