Rv0358 Resolved · medium auto-curated

H37Rv Rv0358 · MTBC0 mtbc0_000378 · 215 aa · 440222–440869 (+) · RefSeq NP_214872.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationpeptidase M50
Revised (this work)Peptidase M50.

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

Curated reference (UniProt)

UniProt O06308 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 I Lipid transport and metabolism
eggNOG descriptionlipid kinase activity
Orthologous groupCOG1597

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 1.229 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 3 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: rip2 (zinc metalloprotease), high confidence from genomic context alone (score 850 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0359 rip2 zinc metalloprotease 850 850 ctx neighborhood:845
Rv0357c purA adenylosuccinate synthetase 923 785 ctx neighborhood:782 textmining:660
Rv3205c hyp hypothetical protein 781 781 ctx cooccurence:773
Rv3438 hyp hypothetical protein 785 774 ctx cooccurence:773
Rv2446c integral membrane protein 774 774 ctx cooccurence:774
Rv3217c integral membrane protein 774 774 ctx cooccurence:765
Rv2732c transmembrane protein 774 774 ctx cooccurence:773
Rv3850 hyp hypothetical protein 772 772 ctx cooccurence:771
Rv0556 transmembrane protein 772 772 ctx cooccurence:772
Rv0996 transmembrane protein 768 769 ctx cooccurence:768
Rv1109c hyp hypothetical protein 768 768 ctx cooccurence:768
Rv0863 hyp hypothetical protein 767 767 ctx cooccurence:766
Rv3212 hyp hypothetical protein 764 765 ctx cooccurence:764
Rv1083 hyp hypothetical protein 764 764 ctx cooccurence:764
Rv3311 hyp hypothetical protein 763 763 ctx cooccurence:762

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: peptidase M50
  • (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_214872.1)
  • 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 COG1597
  • Curated reference: UniProt O06308 (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 — 139 functional partner(s); context anchor rip2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000378|Rv0358|
MYTAENAPGVAVLLSGDADVPGPLTGLPTHQDNLDTVIGRYSRLIVVGADADLGAVLTRLLRTDRLDVEVGYVPRRRSPATRAYRLPAGRRAARRARCGVARRVPLIRDETGSVIVGRAQWLPAEEQALIHGEAVVDDTVLFDGDVAGVCIEPTLTLPGLRAAVDGAGKWRRWIGGRAAQLGTTGAAVLRDGVAAPRPVRRSTFYRNVEGWLLVR