istB Family assigned · medium auto-curated

H37Rv Rv3427c · MTBC0 mtbc0_003642 · 251 aa · 3869323–3870078 (-) · RefSeq NP_217944.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transposase
MTBC0 PGAP re-annotationIS21-like element ISMt2 family helper ATPase IstB
Revised (this work)IS21-like element ISMt2 family helper ATPase IstB. Pfam: IstB_IS21 (PF01695.24), Bac_DnaA (PF00308.25), AAA (PF00004.36).

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

Curated reference (UniProt)

UniProt Q50701 SwissProt · reviewed · Inferred from homology
UniProt namePutative ATP-binding protein Rv3427c in insertion sequence

UniProt still lists this protein as Putative ATP-binding protein Rv3427c in insertion sequence; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
eggNOG descriptionIstB-like ATP binding protein
Orthologous groupCOG1484
Gene Ontology (35) GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005886, GO:0006139, GO:0006259, GO:0006260, GO:0006261, GO:0006271, GO:0006725, GO:0006807 +23 more

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, 4 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (181) · 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
IstB_IS21PF01695.24 3.3e-5012–245 IstB-like ATP binding protein
Bac_DnaAPF00308.25 1.2e-0771–208 Bacterial DnaA ATPAse domain
AAAPF00004.36 3.2e-04104–204 ATPase family associated with various cellular activities (AAA)

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

Closest characterised functional partner: Rv3428c (transposase), high confidence from genomic context alone (score 900 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3428c transposase 986 900 ctx neighborhood:547 cooccurence:774 textmining:875
Rv0058 dnaB replicative DNA helicase 815 798 experimental:773
Rv2943 insertion sequence element IS1533 transposase 790 783 ctx cooccurence:762
Rv2943A transposase 773 773 ctx cooccurence:772
Rv0071 maturase 590 587 ctx cooccurence:585
Rv3637 Possible transposase; Rv3637, (MTCY15C10.15c), len: 166 aa. Possible transposase. C-terminal end highly similar to Q9RLQ9|ISTA putative tran 600 585 ctx cooccurence:546
Rv3127 hyp hypothetical protein 663 71 textmining:653
Rv1756c Putative transposase; Rv1756c, (MTCY28.22c), len: 328 aa. Putative Transposase subunit for IS6110. Identical to many other M. tuberculosis I 452 65 textmining:439
Rv3048c nrdF2 ribonucleoside-diphosphate reductase subunit beta NrdF2 804 49 textmining:803
Rv3193c transmembrane protein 658 47 textmining:656
Rv3231c hyp hypothetical protein 536 47 textmining:534
Rv3128c Rv3128c, (MTCY164.38c), len: 337 aa. Conserved hypothetical protein, similar to other conserved hypothetical proteins. This ORF corresponds 870 46 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

  • Legacy H37Rv annotation: transposase
  • MTBC0 PGAP product: IS21-like element ISMt2 family helper ATPase IstB
  • Pfam (hmmscan --cut_ga): IstB_IS21 PF01695.24 (E=3e-50), Bac_DnaA PF00308.25 (E=1e-07), AAA PF00004.36 (E=3e-04)
  • (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_217944.1)
  • Domains: Pfam-A via hmmscan --cut_ga — IstB_IS21 (PF01695.24), Bac_DnaA (PF00308.25), AAA (PF00004.36)
  • 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 COG1484
  • Curated reference: UniProt Q50701 (SwissProt, reviewed; Inferred from homology)
  • 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 — 12 functional partner(s); context anchor Rv3428c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003642|Rv3427c|istB
MSICDPALRNALRTLKLSGMLDTLDARLAQTRNGDLGHLEFLQALREDEIARRESAALTRRLRRAKFEAQATFEDFDFTANPKLPGAMLRDLAALRWLDAGESVILHGPVGVGKTHVAQALVHAVARRGGDVRFAKTSRMLSDLAGGHADRSWGQRIREYTKPLVLILDDFAMREHTAMHADDLYELISDRAITGKPLILTSNRAPNNWYGLFPNPVVAESLLDRLINTSHQILMDGPSYRPRKRPGRTTS