Rv0396 Still unknown · low auto-curated

H37Rv Rv0396 · MTBC0 mtbc0_000415 · 130 aa · 478714–479106 (+) · RefSeq NP_214910.1

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. Foldseek best (non-significant) hit: 5qhm-assembly1_A PanDDA analysis group deposition of models with model (prob 0.66, TM 0.69).

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

Curated reference (UniProt)

UniProt P95204 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)

Orthologous group2BWWP

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, 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 77.4 (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
5qhm-assembly1_A 0.66 0.69 6.7e-01 5qhm-assembly1_A PanDDA analysis group deposition of models with modelled events (e.g. bound ligands) -- Crystal Structure of human FAM83B in complex with OX-145
4urj-assembly1_A 0.63 0.52 3.1e-01 4urj-assembly1_A Crystal structure of human BJ-TSA-9
4urj-assembly2_C 0.44 0.49 4.0e-01 4urj-assembly2_C Crystal structure of human BJ-TSA-9
5lzk-assembly1_A 0.35 0.46 3.5e-01 5lzk-assembly1_A Structure of the domain of unknown function DUF1669 from human FAM83B
3k6l-assembly3_C 0.04 0.23 2.0e+00 3k6l-assembly3_C The structure of E.coli peptide deformylase (PDF) in complex with peptidomimetic ligand BB2827
3vqx-assembly1_A 0.04 0.32 7.1e+00 3vqx-assembly1_A Crystal structure of the catalytic domain of pyrrolysyl-tRNA synthetase in triclinic crystal form
2q7e-assembly1_A-2 0.04 0.31 5.5e+00 2q7e-assembly1_A-2 The structure of pyrrolysyl-tRNA synthetase bound to an ATP analogue
8ifj-assembly4_H 0.03 0.23 4.0e+00 8ifj-assembly4_H Crystal structure of pyrrolysyl-tRNA synthetase from methanogenic archaeon ISO4-G1

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv0395 hyp hypothetical protein 889 889 ctx neighborhood:882
Rv0397 hyp hypothetical protein 619 619 ctx neighborhood:615
Rv0394c hyp hypothetical protein 598 598 ctx neighborhood:596

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
  • Foldseek best: 5qhm-assembly1_A PanDDA analysis group deposition of models with modelled events (prob 0.66, E=7e-01, TM=0.69)
  • (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_214910.1)
  • 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 2BWWP
  • Curated reference: UniProt P95204 (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 77.4, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 3 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000415|Rv0396|
MRALGWLREDRKPLLNAKLLVLGHLALNVYDPDNGYGEEVLDFEPRTVWWGSANWTVRAGSHLEVGFACDDPTLVEEATAFVADVIAFSEPIDTTCAGPEPNLVQVEFDDAAMAEAMEEMAEPDDDGEDW