Rv0756c Still unknown · low auto-curated

H37Rv Rv0756c · MTBC0 mtbc0_000805 · 241 aa · 855166–855891 (-) · RefSeq NP_215270.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical 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 P71813 TrEMBL · unreviewed · Evidence at protein level
UniProt nameUncharacterized protein

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

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2AG2I

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 0.233 · purifying
Polymorphic sites (≥ 0.1% of strains) 16 synonymous, 10 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: phoP (two component system response transcriptional positive regulator PhoP), high confidence from genomic context alone (score 774 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0757 phoP two component system response transcriptional positive regulator PhoP 783 774 ctx neighborhood:773
Rv0758 phoR two component system response sensor kinase PhoR 747 736 ctx neighborhood:733
Rv1125 hyp hypothetical protein 731 731 ctx cooccurence:731
Rv1274 lprB lipoprotein LprB 716 714 ctx cooccurence:711
Rv3906c hyp hypothetical protein 714 713 ctx cooccurence:708
Rv0383c ttfA hyp hypothetical protein 701 701 ctx cooccurence:701
Rv1275 lprC lipoprotein LprC 697 698 ctx cooccurence:695
Rv2342 hyp hypothetical protein 688 689 ctx cooccurence:685
Rv2876 transmembrane protein 671 671 ctx cooccurence:664
Rv3810 pirG cell surface protein 682 670 ctx cooccurence:669
Rv0466 hyp hypothetical protein 670 670 ctx cooccurence:669
Rv0513 transmembrane protein 663 663 ctx cooccurence:661
Rv3244c lpqB lipoprotein LpqB 662 663 ctx cooccurence:661
Rv3035 hyp hypothetical protein 657 658 ctx cooccurence:649
Rv1598c hyp hypothetical protein 657 657 ctx cooccurence:653

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: 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_215270.1)
  • 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 2AG2I
  • Curated reference: UniProt P71813 (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)
  • Model confidence: ESMFold per-residue pLDDT (mean 89.1, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 102 functional partner(s); context anchor phoP
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000805|Rv0756c|
MNLGQTLVGIATWPARAGLAAADTGLNMAGAAVDMAKQALGDAGGASGSTSMANMLGIDDTIARANRLARLLDDDMPLGRAIAPNGPMDRMLRPGGVVDLLTQPGGLLDRLTAEGGAMQRALQPGGLADQLLAEDGLIERVLSEDGLADRLLAEGGLIDKITAKDGPLEQLADVADTLARLTPGMEALEPAIATLQDAVIALTMVVNPLSSIAERIPLPGRRPARRSSSRSVRSQRVVDSE