Rv3189 Family assigned · medium auto-curated

H37Rv Rv3189 · MTBC0 mtbc0_003386 · 206 aa · 3576774–3577394 (+) · RefSeq NP_217705.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationRES family NAD+ phosphorylase
Revised (this work)RES family NAD+ phosphorylase. Pfam: RES (PF08808.18).

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

Curated reference (UniProt)

UniProt O53335 SwissProt · reviewed · Evidence at protein level
UniProt nameProbable NAD(+) phosphorylase Rv3189
EC (curated) EC 2.4.2.-
Curated functionProbable toxic component of a type II toxin-antitoxin (TA) system. Degrades NAD(+) by phosphorolysis. Neutralized by its cognate antitoxin Rv3188.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionRES domain
Orthologous group28VU7

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 1.849 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 4 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.19% of strains (274) · 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
RESPF08808.18 4.5e-1616–158 RES domain

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

Closest characterised functional partner: Rv3187 (Probable transposase; Rv3187, (MTV014.31), len: 328 aa. Probable IS6110 transposase. Identical to many other M. tuberculosis IS6110 transpos), medium confidence from genomic context alone (score 416 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3188 hyp hypothetical protein 976 888 ctx neighborhood:882 textmining:802
Rv3187 Probable transposase; Rv3187, (MTV014.31), len: 328 aa. Probable IS6110 transposase. Identical to many other M. tuberculosis IS6110 transpos 416 416 ctx neighborhood:414
Rv3186 Rv3186, (MTV014.30), len: 108 aa. Putative Transposase for IS6110 (fragment). Identical to many other M. tuberculosis IS6110 transposase sub 414 414 ctx neighborhood:414
Rv2035 hyp hypothetical protein 661 64 textmining:653
Rv0837c hyp hypothetical protein 526 59 textmining:517
Rv1989c mbcT hyp hypothetical protein 658 55 textmining:653
Rv2034 ArsR family HTH-type transcriptional repressor 528 55 textmining:522
Rv0836c hyp hypothetical protein 443 53 textmining:436
Rv1044 hyp hypothetical protein 446 52 textmining:440
Rv2865 relF antitoxin RelF 454 51 textmining:449
Rv2866 relG toxin RelG 516 50 textmining:512
Rv0549c vapC3 ribonuclease VapC3 440 50 textmining:435
Rv0550c vapB3 antitoxin VapB3 482 47 textmining:479
Rv1045 hyp hypothetical protein 440 47 textmining:437
Rv0918 hyp hypothetical protein 754 46 textmining:753

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: RES family NAD+ phosphorylase
  • Pfam (hmmscan --cut_ga): RES PF08808.18 (E=5e-16)
  • (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_217705.1)
  • Domains: Pfam-A via hmmscan --cut_ga — RES (PF08808.18)
  • 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 28VU7
  • Curated reference: UniProt O53335 (SwissProt, reviewed; 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 — 24 functional partner(s); context anchor Rv3187
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003386|Rv3189|
MKLADAIATAPRRTLKGTYWHQGPTRHPVTSCADPARGPGRYHRTGEPGVWYASNKEQGAWAELFRHFVDDGVDPFEVRRRVGRVAVTLQVLDLTDERTRSHLGVDETDLLSDDYTTTQAIAAARDANFDAVLAPAAALPGCQTLAVFVHALPNIEPERSEVRQPPPRLANLLPLIRPHEHMPDSVRRLLATLTRAGAEAIRRRRR