Rv1228a Still unknown · low auto-curated

H37Rv Rv1228a · MTBC0 - · 57 aa · 1371529–1371702 (+) · RefSeq YP_009030032.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Conserved hypothetical; no reliable functional assignment. A Foldseek hit resembles 6jqy-assembly1_A Crystal structure of N-terminal domain, but that function is encoded elsewhere in the genome (vapb46 = Rv3385c) -- treated as a paralogue-of-fold artefact, not propagated.

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

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

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionAntitoxin Phd_YefM, type II toxin-antitoxin system
Orthologous group29UVB

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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 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).

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 79.3 (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
6jqy-assembly1_A 1.00 0.90 5.9e-03 sig 6jqy-assembly1_A Crystal structure of N-terminal domain of VapB46 antitoxin from Mycobacterium tuberculosis
2odk-assembly2_D 1.00 0.81 7.4e-02 2odk-assembly2_D Putative prevent-host-death protein from Nitrosomonas europaea
4zm2-assembly1_B 0.99 0.67 4.3e-02 4zm2-assembly1_B Antitoxin Phd from phage P1 in complex with its operator DNA inverted repeat in a monoclinic space group
4zm2-assembly2_D 0.99 0.67 4.6e-02 4zm2-assembly2_D Antitoxin Phd from phage P1 in complex with its operator DNA inverted repeat in a monoclinic space group
4zlx-assembly1_B 0.99 0.66 4.6e-02 4zlx-assembly1_B N-terminal DNA binding domain of the antitoxin Phd from phage P1
3hs2-assembly4_H 0.99 0.66 4.3e-02 3hs2-assembly4_H Crystal structure of PHD truncated to residue 57 in an orthorhombic space group
3hs2-assembly1_B 0.99 0.67 5.2e-02 3hs2-assembly1_B Crystal structure of PHD truncated to residue 57 in an orthorhombic space group
3k33-assembly1_B-2 0.98 0.66 6.9e-02 3k33-assembly1_B-2 Crystal structure of the Phd-Doc complex

Evidence

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
  • Foldseek best: 6jqy-assembly1_A Crystal structure of N-terminal domain of VapB46 antitoxin from (prob 1.00, E=6e-03, TM=0.90)
  • (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 YP_009030032.1)
  • 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 29UVB
  • 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 79.3, confident)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv1228a|
MYSGAMKSISVGELRQNPAPMIADLERGEPYALTRHNHRIGTIIPAVSSATLIPRKA