Rv0122 Still unknown · low

H37Rv Rv0122 · MTBC0 mtbc0_000133 · 122 aa · 148657–149025 (+) · RefSeq NP_214636.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Conserved hypothetical protein; no Pfam domain above threshold. Foldseek gives a suggestive but non-significant fold similarity to a ribonuclease (prob 0.98, E=5e-2, TM=0.61) with weaker hits to HigBA-type toxin-antitoxin RNases: a possible RNase/toxin-like fold, not conclusive.

Curated reference (UniProt)

UniProt O07172 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 group296XN

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 0.671 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 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 58.7 (low). Low-confidence model: the fold may be unreliable, so treat these structural hits with caution.

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
3u97-assembly1_A 0.98 0.61 5.0e-02 3u97-assembly1_A 1.1 Angstrom-resolution crystal structure of the Brucella abortus ribonuclease toxin, BrnT
7snx-assembly1_A 0.44 0.56 5.0e-01 7snx-assembly1_A 1.70A Resolution Structure of NanoBiT Complementation Reporter Complex of LgBit and SmBiT Subunits
5jaa-assembly1_D 0.38 0.55 8.3e-01 5jaa-assembly1_D Crystal structure of the HigBA2 toxin-antitoxin complex
5m4y-assembly3_F 0.38 0.67 7.8e-01 5m4y-assembly3_F Crystal structure of the Sec3/Sso2 complex at 2.20 angstrom resolution
7sny-assembly1_A 0.35 0.52 5.0e-01 7sny-assembly1_A 2.10A Resolution Structure of NanoBiT Complementation Reporter Large Subunit LgBiT
7sns-assembly2_B 0.35 0.53 5.3e-01 7sns-assembly2_B 1.55A Resolution Structure of NanoLuc Luciferase
5ibo-assembly2_B 0.33 0.54 7.8e-01 5ibo-assembly2_B 1.95A resolution structure of NanoLuc luciferase
5lg4-assembly1_C 0.33 0.67 1.1e+00 5lg4-assembly1_C Crystal structure of the Sec3/Sso2 complex at 2.9 angstrom resolution

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

Closest characterised functional partner: PE_PGRS2 (PE-PGRS family protein PE_PGRS2), medium confidence from genomic context alone (score 405 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0123 hyp hypothetical protein 887 887 ctx neighborhood:882
Rv0121c hyp hypothetical protein 533 533 ctx neighborhood:532
Rv0124 PE_PGRS2 PE-PGRS family protein PE_PGRS2 406 405 ctx neighborhood:405

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

  • MTBC0 PGAP product: 'hypothetical protein'
  • Pfam: no domain above threshold
  • Foldseek on the ESMFold model: suggestive, non-significant similarity to a ribonuclease (3U97) and HigBA-type TA RNases

ESM Atlas signal (exploratory)

Ancestral protein hash 5135771dde1bc60ea490cc21e09cb3a3 · 10 ESM-space neighbours (max similarity 0.867). SAE features are orienting indices, not validated domains.

#IndexActivationInterpretation
110268 1.26 RNase domains and signal peptides
25823 0.69 Basic–aromatic ligand-binding cores
32522 0.61 Arg/Lys-rich N-terminal nucleic-acid-binding patch
411814 0.56 Bacterial disordered N-terminal tails
58753 0.54 Basic C-terminal RNA-binding tails
612874 0.48 C-terminal assembly region
712227 0.48 Tryptophan residue detector
81645 0.42 Exposed interaction-processing loop motif

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_214636.1)
  • 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 296XN
  • Curated reference: UniProt O07172 (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 58.7, low)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 3 functional partner(s); context anchor PE_PGRS2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000133|Rv0122|
MAGSVSAAAGIGWVGLNVTETNRDQCYRVERTTVDALTHPEYRVHTRGVQRVRVTRNARKHRVSKHRIVAAMRHCGVPVIQEDGSLYYQGRDTSGRLTEVVAVEADDGDLIITHAMPKEWKR