iniA Resolved · high auto-curated

H37Rv Rv0342 · MTBC0 - · 640 aa · 410838–412760 (+) · RefSeq NP_214856.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)isoniazid inductible protein IniA
MTBC0 PGAP re-annotation
Revised (this work)Isoniazid inductible protein IniA. Pfam: Dynamin_N (PF00350.30).

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 P9WJ99 SwissProt · reviewed · Evidence at protein level
UniProt nameIsoniazid-induced protein IniA
Curated functionParticipates in the development of tolerance to both isoniazid and ethambutol. May function through a MDR-pump like mechanism, although it does not appear to directly transport isoniazid from the cell.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred nameiniA
eggNOG descriptionDynamin family
Orthologous groupCOG0699
Gene Ontology (17) GO:0003674, GO:0005215, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006810, GO:0008150, GO:0015562, GO:0016020, GO:0022857, GO:0030312 +5 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 0.631 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 9 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.33% of strains (485) · 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
Dynamin_NPF00350.30 3.0e-0973–220 Dynamin family

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

Closest characterised functional partner: iniC (iIsoniazid inductible protein IniC), high confidence from genomic context alone (score 989 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0343 iniC iIsoniazid inductible protein IniC 988 989 ctx neighborhood:780 cooccurence:774 coexpression:788
Rv0341 iniB isoniazid inducible protein IniB 954 952 ctx neighborhood:651 coexpression:839
Rv0339c iniR transcriptional regulator 837 837 ctx cooccurence:774
Rv0312 hyp hypothetical protein 806 795 ctx cooccurence:607 database:411
Rv2264c hyp hypothetical protein 798 786 ctx cooccurence:587 database:411
Rv3835 hyp hypothetical protein 679 679 ctx cooccurence:678
Rv1853 ureD urease accessory protein UreD 656 656 ctx cooccurence:656
Rv3459c rpsK 30S ribosomal protein S11 654 654 database:609
Rv0563 htpX protease HtpX 666 647 database:643
Rv1977 hyp hypothetical protein 664 644 database:643
Rv1845c blaR sensor-transducer protein BlaR 663 644 database:643
Rv3077 hydrolase 634 635 database:517
Rv2006 otsB1 trehalose-6-phosphate phosphatase OtsB 630 631 database:587
Rv3372 otsB2 trehalose 6-phosphate phosphatase 629 630 database:587
Rv2843 hyp hypothetical protein 620 620 ctx cooccurence:620

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): isoniazid inductible protein IniA
  • Pfam (hmmscan --cut_ga): Dynamin_N PF00350.30 (E=3e-09)
  • (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_214856.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Dynamin_N (PF00350.30)
  • 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 COG0699
  • Curated reference: UniProt P9WJ99 (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 — 69 functional partner(s); context anchor iniC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0342|iniA
MVPAGLCAYRDLRRKRARKWGDTVTQPDDPRRVGVIVELIDHTIAIAKLNERGDLVQRLTRARQRITDPQVRVVIAGLLKQGKSQLLNSLLNLPAARVGDDEATVVITVVSYSAQPSARLVLAAGPDGTTAAVDIPVDDISTDVRRAPHAGGREVLRVEVGAPSPLLRGGLAFIDTPGVGGLGQPHLSATLGLLPEADAVLVVSDTSQEFTEPEMWFVRQAHQICPVGAVVATKTDLYPRWREIVNANAAHLQRARVPMPIIAVSSLLRSHAVTLNDKELNEESNFPAIVKFLSEQVLSRATERVRAGVLGEIRSATEQLAVSLGSELSVVNDPNLRDRLASDLERRKREAQQAVQQTALWQQVLGDGFNDLTADVDHDLRTRFRTVTEDAERQIDSCDPTAHWAEIGNDVENAIATAVGDNFVWAYQRSEALADDVARSFADAGLDSVLSAELSPHVMGTDFGRLKALGRMESKPLRRGHKMIIGMRGSYGGVVMIGMLSSVVGLGLFNPLSVGAGLILGRMAYKEDKQNRLLRVRSEAKANVRRFVDDISFVVSKQSRDRLKMIQRLLRDHYREIAEEITRSLTESLQATIAAAQVAETERDNRIRELQRQLGILSQVNDNLAGLEPTLTPRASLGRA