Rv0976c Family assigned · medium auto-curated

H37Rv Rv0976c · MTBC0 mtbc0_001042 · 560 aa · 1095708–1097390 (-) · RefSeq NP_215491.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationacyclic terpene utilization AtuA family protein
Revised (this work)Acyclic terpene utilization AtuA family protein. Pfam: AtuA (PF07287.18), AtuA_ferredoxin (PF23544.2).

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

Curated reference (UniProt)

UniProt O86320 TrEMBL · unreviewed · Predicted
UniProt nameExopolyphosphatase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
eggNOG descriptionAcyclic terpene utilisation family protein AtuA
Orthologous groupCOG3185

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 0.98 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 8 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.26% of strains (373) · 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
AtuAPF07287.18 2.8e-1551–415 Acyclic terpene utilisation family protein AtuA
AtuA_ferredoxinPF23544.2 2.7e-16456–553 AtuA ferredoxin-like domain

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

Closest characterised functional partner: accD2 (acetyl-/propionyl-CoA carboxylase subunit beta), high confidence from genomic context alone (score 992 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0974c accD2 acetyl-/propionyl-CoA carboxylase subunit beta 992 992 ctx neighborhood:881 coexpression:907
Rv0975c fadE13 acyl-CoA dehydrogenase FadE13 986 986 ctx neighborhood:881 coexpression:859
Rv0973c accA2 acetyl/propionyl-CoA carboxylase subuit alpha 984 983 ctx neighborhood:881 coexpression:832
Rv0972c fadE12 acyl-CoA dehydrogenase fadE12 961 960 ctx neighborhood:881 cooccurence:487
Rv0971c echA7 enoyl-CoA hydratase EchA7 912 908 ctx neighborhood:881
Rv0036c hyp hypothetical protein 700 701 ctx cooccurence:628
Rv0981 mprA two-component response regulator MrpA 548 548 ctx neighborhood:544
Rv0979A rpmF 50S ribosomal protein L32 544 544 ctx neighborhood:544
Rv2502c accD1 acetyl-/propionyl-CoA carboxylase subunit beta 544 516 coexpression:454
Rv0977 PE_PGRS16 PE-PGRS family protein PE_PGRS16 502 502 ctx neighborhood:502
Rv2247 accD6 acetyl-/propionyl-CoA carboxylase subunit beta 506 476 coexpression:446
Rv3280 accD5 propionyl-CoA carboxylase subunit beta 506 476 coexpression:446
Rv3799c accD4 propionyl-CoA carboxylase subunit beta AccD 506 476 coexpression:446
Rv0939 bifunctional 2-hydroxyhepta-2,4-diene-1,7-dioate isomerase/cyclase/dehydrase 593 454
Rv2912c TetR family HTH-type transcriptional regulator 455 446

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: acyclic terpene utilization AtuA family protein
  • Pfam (hmmscan --cut_ga): AtuA PF07287.18 (E=3e-155), AtuA_ferredoxin PF23544.2 (E=3e-16)
  • (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_215491.1)
  • Domains: Pfam-A via hmmscan --cut_ga — AtuA (PF07287.18), AtuA_ferredoxin (PF23544.2)
  • 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 COG3185
  • Curated reference: UniProt O86320 (TrEMBL, unreviewed; Predicted)
  • 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 — 34 functional partner(s); context anchor accD2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001042|Rv0976c|
MRIGNCSGFYGDRLSAMREMLTGGELDYLTGDYLAELTMLILGRDRMKNPDRGYAKTFLAQLEDCLGLAHDRGVRIVTNAGGLNPAGLANAVRALAARLGIPAQVAHVEGDDLQPRAAELGLGTPLTANAYLGAWGIVDCFERGADVVVTGRVTDASVVVGAAAAHFGWGRTDYHRLAGAVVAGHVIECGVQATGGNYAFFTEIGDLTHAGFPLAEIAADGSSVITKHHGTGGLVSVDTITAQLLYEITGARYANPDVTARMDSVELSPDGPDRVRISGVIGEPPPPTYKVSLNSIGGFRNAMTFVLTGLDIDAKADLVRRQLEAALTVKPAELQWTLARTDHPDADTEETASALLTCVARDPDPANVGRQFSSAAVELALASYPGFTATAPPGDGQVYGVFTPGYVDAGKVAHIAVHADGTRTEIPCATETLELAPAHPPALPDPLPAGPTRRVPLGLIAGARSGDKGGSANVGVWVRTDEQWRWLAHTLTVELLKELLPETAGLVVTRHVLPNLRALNFVIEAILGQGVAYQARFDPQAKGLGEWLRSRHVEIPETLL