Rv1249c Still unknown · low auto-curated

H37Rv Rv1249c · MTBC0 mtbc0_001338 · 262 aa · 1401638–1402426 (-) · RefSeq NP_215765.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)membrane protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Conserved hypothetical protein; no recognised domain. Function unknown.

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

Curated reference (UniProt)

UniProt O50464 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible membrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG description5-oxoprolinase (ATP-hydrolyzing) activity
Orthologous groupCOG1540

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 0.521 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 8 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: kgd (multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase), high confidence from genomic context alone (score 749 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0264c hyp hypothetical protein 814 778 coexpression:760
Rv1248c kgd multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase 749 749 ctx neighborhood:747
Rv0263c hyp hypothetical protein 791 746 coexpression:725
Rv1245c short-chain type dehydrogenase/reductase 684 684 ctx neighborhood:602
Rv1188 proline dehydrogenase 612 612 coexpression:612
Rv1171 hyp hypothetical protein 609 609 ctx cooccurence:605
Rv0048c membrane protein 582 583 ctx cooccurence:579
Rv3667 acs acetyl-CoAsynthetase 560 561 coexpression:561
Rv1250 MFS-type drug transporter 518 518 ctx neighborhood:513
Rv2923c hyp hypothetical protein 491 491 ctx cooccurence:414
Rv2852c mqo malate:quinone oxidoreductase 484 484 coexpression:418
Rv2560 hyp hypothetical protein 471 471 ctx cooccurence:466
Rv3063 cstA carbon starvation protein A 469 470 coexpression:460
Rv0889c citA citrate synthase 2 464 464 coexpression:462
Rv0896 gltA2 citrate synthase 1 463 464 coexpression:462

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: membrane protein
  • MTBC0 PGAP product: hypothetical protein
  • (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_215765.1)
  • 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 COG1540
  • Curated reference: UniProt O50464 (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 — 38 functional partner(s); context anchor kgd
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001338|Rv1249c|
MSARRIRSWKRFDNRSANAAEPDPQLAGTGGRPKVSTRALAQVIERSSRIQGPAAQAYVARLRRAHPGASPAKIVAKLEKRFLSVVTASGAAVGAAATLPGIGTLAAWFAAAGEVVVFLEATALFVLALASVHAIPLDHRERRRALVLAVLVGDNTTAVADLLGPGRTSGGWVSETMASLPLPAISSLNSRMLKYVVKRFALKRGALMFGKLVPMGIGAIIGAIGNRLVGKKLVRNARSAFGTPPARWPVTLHVLPTVRDAS