Rv3040c Resolved · medium auto-curated

H37Rv Rv3040c · MTBC0 mtbc0_003232 · 288 aa · 3421502–3422368 (-) · RefSeq NP_217556.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationNUDIX hydrolase
Revised (this work)NUDIX hydrolase.

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

Curated reference (UniProt)

UniProt O53287 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved protein

UniProt still lists this protein as Conserved protein; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
eggNOG descriptionNudix hydrolase
Orthologous groupCOG0494

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 0.7 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

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

Closest characterised functional partner: echA17 (enoyl-CoA hydratase EchA17), high confidence from genomic context alone (score 913 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3039c echA17 enoyl-CoA hydratase EchA17 913 913 ctx neighborhood:881
Rv3041c ABC transporter ATP-binding protein 905 905 ctx neighborhood:881
Rv3038c hyp hypothetical protein 878 879 ctx neighborhood:879
Rv3042c serB2 phosphoserine phosphatase SerB 872 872 ctx neighborhood:869
Rv3043c ctaD cytochrome C oxidase cytochrome 1 803 804 ctx neighborhood:803
Rv3036c TB22.2 hyp hypothetical protein 659 659 ctx neighborhood:647
Rv3677c beta lactamase 656 656 ctx cooccurence:445
Rv0331 dehydrogenase/reductase 651 636 database:583
Rv0737 transcriptional regulator 540 541 ctx cooccurence:534
Rv3680 anion transporter ATPase 522 505 ctx cooccurence:417
Rv3037c S-adenosylmethionine-dependent methyltransferase 491 492 ctx neighborhood:490
Rv3679 anion transporter ATPase 462 442
Rv3234c tgs3 diacyglycerol O-acyltransferase 438 439 ctx cooccurence:426
Rv3044 fecB FeIII-dicitrate-binding periplasmic lipoprotein 434 433 ctx neighborhood:425
Rv0998 acetyltransferase Pat 417 418 ctx cooccurence:413

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: NUDIX hydrolase
  • (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_217556.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 COG0494
  • Curated reference: UniProt O53287 (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 — 27 functional partner(s); context anchor echA17
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003232|Rv3040c|
MNSPREPLVPPPTPRPAATVMLVRDPDAGSASGLAVFLMRRHAAMDFAAGVMVFPGGGVDDRDRDADLGRLGAWAGPPPQWWAQRFGIEPDLAEALVCAAARETFEESGVLFAGPVDQDHSAPNSIVSDASVYGDARRALADRTLSFADFLQREKLVLRSDLLRPWANWVTPEAELTRRYDTYFFVGALPEGQRADGENTESDRAGWVLPADAIADFAAGRNFLLPPTWTQLDSLAGHTVADVLAVERQIVPVQPQLARNGDNWEIEFFDSDRYNQARRSGGSTGWPL