Rv3369 Family assigned · medium auto-curated

H37Rv Rv3369 · MTBC0 - · 144 aa · 3780978–3781412 (+) · RefSeq NP_217886.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Contains PNPOx_N (PF01243.28) domain(s); putative function inferred from the domain architecture.

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).

Curated reference (UniProt)

UniProt O50398 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 S Function unknown
eggNOG descriptionPyridoxamine 5'-phosphate oxidase
Orthologous groupCOG3871

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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 0 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.24% of strains (355) · clonal

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)

PfamAccessioni-EvalueResiduesDescription
PNPOx_NPF01243.28 1.8e-1813–140 Pyridoxamine 5'-phosphate oxidase

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

Closest characterised functional partner: Rv3368c (oxidoreductase), medium confidence from genomic context alone (score 578 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3368c oxidoreductase 578 578 ctx neighborhood:573
Rv2216 epimerase family protein 515 516 coexpression:512
Rv1001 arcA arginine deiminase 443 443 coexpression:443
Rv1770 hyp hypothetical protein 434 435 ctx cooccurence:431
Rv2946c pks1 polyketide synthase 426 427
Rv3072c hyp hypothetical protein 426 426 ctx cooccurence:423
Rv2323c hyp hypothetical protein 418 418 coexpression:416
Rv1043c hyp hypothetical protein 408 409
Rv2043c pncA pyrazinamidase/nicotinamidase PncA 408 408 coexpression:408
Rv1015c rplY 50S ribosomal protein L25/general stress protein Ctc 407 408 coexpression:408
Rv1364c sigma factor regulatory protein 401 402 coexpression:402
Rv1155 pyridoxine/pyridoxamine 5'-phosphate oxidase 846 251 textmining:804
Rv1636 TB15.3 iron-regulated universal stress protein 757 249 textmining:690
Rv1875 hyp hypothetical protein 839 217 textmining:803
Rv0121c hyp hypothetical protein 893 215 textmining:870

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
  • Pfam (hmmscan --cut_ga): PNPOx_N PF01243.28 (E=2e-18)
  • (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_217886.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PNPOx_N (PF01243.28)
  • 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 COG3871
  • Curated reference: UniProt O50398 (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 — 29 functional partner(s); context anchor Rv3368c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3369|
MWAGYRWAMSVELTQEVSARLTSDLYGWLTTVARSGQPVPRLVWFYFDGTDLTVYSMPQAAKVAHITAHPQVSLNLDSDGNGAGIIVVGGTAAVVATDVDCRDDAPYWAKYREDAAKFGLTEAIAAYSTRLKITPTRVWTTPTG