Rv0121c Family assigned · medium

H37Rv Rv0121c · MTBC0 mtbc0_000132 · 144 aa · 148074–148508 (-) · RefSeq NP_214635.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationTIGR03668 family PPOX class F420-dependent oxidoreductase
Revised (this work)F420-dependent / PNPOx-class oxidoreductase (Pfam PNPOx_N PF01243; PGAP TIGR03668 PPOX-class F420-dependent oxidoreductase). Putative deazaflavin (F420)-dependent oxidoreductase, a redox chemistry characteristic of mycobacteria.

Curated reference (UniProt)

UniProt O07171 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 descriptionPFAM pyridoxamine 5'-phosphate
Orthologous groupCOG3576

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) pseudogene candidate

pN/pS 0.688 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 3 missense, 1 nonsense, 1 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 1.03% of strains (1500) · 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 1.2e-1610–142 Pyridoxamine 5'-phosphate oxidase

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

Closest characterised functional partner: fusA2 (elongation factor G), medium confidence from genomic context alone (score 630 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0120c fusA2 elongation factor G 629 630 ctx neighborhood:558
Rv3079c hyp hypothetical protein 612 597 ctx cooccurence:591
Rv1875 hyp hypothetical protein 940 559 ctx cooccurence:552 textmining:870
Rv0122 hyp hypothetical protein 533 533 ctx neighborhood:532
Rv0123 hyp hypothetical protein 533 533 ctx neighborhood:532
Rv2125 hyp hypothetical protein 511 511 coexpression:447
Rv0953c oxidoreductase 489 469 ctx cooccurence:466
Rv3463 hyp hypothetical protein 470 451 ctx cooccurence:448
Rv2714 hyp hypothetical protein 447 447 coexpression:447
Rv3072c hyp hypothetical protein 424 400
Rv1240 mdh malate dehydrogenase 400 400
Rv2161c hyp hypothetical protein 411 387
Rv1155 pyridoxine/pyridoxamine 5'-phosphate oxidase 894 219 textmining:870
Rv3369 hyp hypothetical protein 893 215 textmining:870
Rv0132c fgd2 F420-dependent glucose-6-phosphate dehydrogenase 423 192

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: 'TIGR03668 family PPOX class F420-dependent oxidoreductase'
  • Pfam: PNPOx_N PF01243 (E=1.2e-16)

ESM Atlas signal (exploratory)

Ancestral protein hash 449a9f213d8e03fddbfcfe1ab6b924bd · 10 ESM-space neighbours (max similarity 0.902). SAE features are orienting indices, not validated domains.

#IndexActivationInterpretation
18276 1.07 Acidic/His catalytic loops
23114 0.95 Active-site rim β-loop elements
3733 0.93 Aromatic cofactor-binding glycine loop
49248 0.79 Beta-sheet strand-turn motif
55217 0.77 Ligand-binding cleft rim module
67714 0.69 C-terminal cofactor-binding tails
737 0.53 Basic/aromatic ligand-binding patches
814850 0.51 Active site adjacent cofactor motifs

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_214635.1)
  • 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 COG3576
  • Curated reference: UniProt O07171 (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 — 20 functional partner(s); context anchor fusA2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000132|Rv0121c|
MGEFDPKLRFAQSPVARLATSTPDGTPHLVPVVFALGARRPAEATGADVIYTAVDAKRKTTQRLRRLANLEHNPRASVLVDSYADDWTQLWWVRADGVAAIHRDGEVMRAAYRLLRAKYAQYQSVPLNGPVIAIAVQRWASWHA