Rv0836c Family assigned · low auto-curated · to review

H37Rv Rv0836c · MTBC0 - · 217 aa · 932279–932932 (-) · RefSeq NP_215351.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)No Pfam domain above threshold; Foldseek indicates a fold similar to 8an5-assembly1_B MenAT1 toxin-antitoxin complex (rv0078a-rv0078b) from Mycobacte (prob 1.00, TM 0.48). Structure-based, putative.

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed (flagged for human review).

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt O53848 TrEMBL · unreviewed · Predicted
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)

COG category S Function unknown
eggNOG descriptionProtein conserved in bacteria
Orthologous groupCOG4849

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 0.346 · purifying
Polymorphic sites (≥ 0.1% of strains) 2 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).

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 89.7 (confident). A confident model makes the fold comparison meaningful.

Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.

TargetProbTME-valueDescription
8an5-assembly1_B 1.00 0.48 3.6e-04 sig 8an5-assembly1_B MenAT1 toxin-antitoxin complex (rv0078a-rv0078b) from Mycobacterium tuberculosis H37Rv
6y8q-assembly3_C 0.57 0.33 5.6e-02 6y8q-assembly3_C AbiEi antitoxin from Streptococcus agalactiae
6y8q-assembly4_D 0.10 0.34 1.6e+00 6y8q-assembly4_D AbiEi antitoxin from Streptococcus agalactiae
6ojk-assembly1_A 0.08 0.56 8.2e+00 6ojk-assembly1_A Structure of YePL2A K291W in Complex with Tetragalacturonic Acid
2hz8-assembly1_A 0.08 0.39 4.2e+00 2hz8-assembly1_A QM/MM structure refined from NMR-structure of a single chain diiron protein
6ojl-assembly1_A 0.08 0.56 8.7e+00 6ojl-assembly1_A Structure of YePL2A R194K in Complex with Pentagalacturonic Acid
8wwm-assembly1_R 0.07 0.22 1.4e+00 8wwm-assembly1_R MCH-MCHR1-Gi complex, L2 state
5uho-assembly1_D 0.06 0.33 3.0e+00 5uho-assembly1_D Crystal structure of the core catalytic domain of human O-GlcNAcase complexed with PUGNAc

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

Closest characterised functional partner: PE_PGRS28 (PE-PGRS family protein PE_PGRS28), high confidence from genomic context alone (score 747 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0837c hyp hypothetical protein 997 989 ctx neighborhood:754 cooccurence:774 coexpression:815 textmining:758
Rv1452c PE_PGRS28 PE-PGRS family protein PE_PGRS28 747 747 ctx cooccurence:747
Rv0355c PPE8 PPE family protein PPE8 747 747 ctx cooccurence:747
Rv1004c membrane protein 746 747 ctx cooccurence:746
Rv3350c PPE56 PPE family protein PPE56 746 746 ctx cooccurence:745
Rv3347c PPE55 PPE family protein PPE55 745 745 ctx cooccurence:744
Rv2490c PE_PGRS43 PE-PGRS family protein PE_PGRS43 741 741 ctx cooccurence:741
Rv0304c PPE5 PPE family protein PPE5 740 741 ctx cooccurence:740
Rv1917c PPE34 PPE family protein PPE34 736 737 ctx cooccurence:736
Rv2209 integral membrane protein 733 734 ctx cooccurence:733
Rv1651c PE_PGRS30 PE-PGRS family protein PE_PGRS30 731 731 ctx cooccurence:731
Rv3343c PPE54 PPE family protein PPE54 729 729 ctx cooccurence:729
Rv2082 hyp hypothetical protein 726 727 ctx cooccurence:724
Rv0872c PE_PGRS15 PE-PGRS family protein PE_PGRS15 717 717 ctx cooccurence:717
Rv1753c PPE24 PPE family protein PPE24 705 705 ctx cooccurence:705

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
  • Foldseek best: 8an5-assembly1_B MenAT1 toxin-antitoxin complex (rv0078a-rv0078b) from Mycobacte (prob 1.00, E=4e-04, TM=0.48)
  • (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_215351.1)
  • 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 COG4849
  • Curated reference: UniProt O53848 (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)
  • Model confidence: ESMFold per-residue pLDDT (mean 89.7, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 94 functional partner(s); context anchor PE_PGRS28
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0836c|
MLVGAQCRDLLHWRFCRGVPPRATNDTDIAGTLNNWDHFEAIRATFRALGSTGHRFLIADRAVDALPFGEVESPTGTTRHPPGNQLMNVHGCTDAYLRADVLPLPGGLTVHLPQPPNYAVLKLHAWLDRSADHDYKDGPDLALVVHWYAGDLDRLYAKPDQWALRRHDFDLRTAAAALLGHDMRASVSAPEAAVLATRATQADHDLLAQHFAVGRPG