Rv2426c Family assigned · medium auto-curated

H37Rv Rv2426c · MTBC0 mtbc0_002583 · 291 aa · 2747576–2748451 (-) · RefSeq NP_216942.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationMoxR family ATPase
Revised (this work)MoxR family ATPase. Pfam: AAA_5 (PF07728.21), AAA (PF00004.36), AAA_2 (PF07724.21).

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

Curated reference (UniProt)

UniProt P71922 TrEMBL · unreviewed · Evidence at protein level
UniProt nameAAA+ ATPase domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred nameclpL
eggNOG descriptionassociated with various cellular activities
Orthologous groupCOG0714

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) pseudogene candidate

pN/pS 0.942 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 5 missense, 0 nonsense, 3 frameshift
Disruption 3 distinct premature-stop/frameshift site(s); most common in 14.10% of strains (20477) · clonal

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
AAA_5PF07728.21 6.7e-1146–194 AAA domain (dynein-related subfamily)
AAAPF00004.36 7.7e-1047–194 ATPase family associated with various cellular activities (AAA)
AAA_2PF07724.21 1.5e-0747–190 AAA domain (Cdc48 subfamily)

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

Closest characterised functional partner: proA (gamma-glutamyl phosphate reductase), high confidence from genomic context alone (score 826 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2425c hyp hypothetical protein 976 976 ctx neighborhood:882 cooccurence:771
Rv2427c proA gamma-glutamyl phosphate reductase 826 826 ctx neighborhood:817
Rv0368c hyp hypothetical protein 783 780 ctx cooccurence:752
Rv0373c carbon monoxyde dehydrogenase large subunit 621 604 ctx cooccurence:553
Rv2420c rsfS hyp hypothetical protein 592 591 ctx neighborhood:544
Rv2424c transposase 566 566 ctx neighborhood:561
Rv2417c DegV domain-containing protein 553 554 ctx neighborhood:544
Rv2418c octT hyp hypothetical protein 546 547 ctx neighborhood:544
Rv2421c nadD nicotinate-nucleotide adenylyltransferase 544 544 ctx neighborhood:544
Rv0369c membrane oxidoreductase 495 496 ctx cooccurence:434
Rv2435c cyclase 482 482 ctx neighborhood:482
Rv0375c carbon monoxyde dehydrogenase medium subunit 492 469 ctx cooccurence:403
Rv2427A oxyR Rv2427A, Pseudogene oxyR', inactivated by multiple mutations; identical to sequence in u16243 (see Deretic et al., 1995). 445 445 ctx neighborhood:445
Rv2332 mez malate oxidoreductase 425 426 coexpression:416
Rv2531c amino acid decarboxylase 438 414 experimental:405

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: hypothetical protein
  • MTBC0 PGAP product: MoxR family ATPase
  • Pfam (hmmscan --cut_ga): AAA_5 PF07728.21 (E=7e-11), AAA PF00004.36 (E=8e-10), AAA_2 PF07724.21 (E=1e-07)
  • (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_216942.1)
  • Domains: Pfam-A via hmmscan --cut_ga — AAA_5 (PF07728.21), AAA (PF00004.36), AAA_2 (PF07724.21)
  • 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 COG0714
  • Curated reference: UniProt P71922 (TrEMBL, unreviewed; 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 — 15 functional partner(s); context anchor proA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002583|Rv2426c|
MTVPARPTPLFADIADVSRRLAETGYLPDTATATAVFLADRLGKPLLVEGPAGVGKTELARAVAQATGSGLVRLQCYEGVDEARALYEWNHAKQILRIQAGSGDWEATKTDVFSEEFLLQRPLLTAIRRTEPTVLLIDETDKADIEIEGLLLEVLSDFAVTVPELGTLTATRAPFVLLTSNATRELSEALKRRCLYLHIDFPTPELERRILLSRVPELPEHFAEELVRIIGVLRGMQLKKVPSIAETIDWGRTVLALGLDTIDDAVVAATLGVVLKHQSDQQRATGELRLN