Rv0443 Resolved · high auto-curated

H37Rv Rv0443 · MTBC0 mtbc0_000465 · 171 aa · 535761–536276 (+) · RefSeq NP_214957.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationmycothiol transferase
Revised (this work)Mycothiol transferase. Pfam: MST (PF04978.18), DinB_2 (PF12867.13).

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

Curated reference (UniProt)

UniProt O53728 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 descriptionProtein of unknown function (DUF664)
Orthologous groupCOG2318

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 0.648 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 3 missense, 1 nonsense, 2 frameshift
Disruption 3 distinct premature-stop/frameshift site(s); most common in 2.97% of strains (4319) · 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
MSTPF04978.18 1.6e-3012–168 Mycothiol-S-transferase
DinB_2PF12867.13 7.4e-1416–163 DinB superfamily

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

Closest characterised functional partner: PPE10 (PPE family protein PPE10), medium confidence from genomic context alone (score 553 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0441c hyp hypothetical protein 615 615 ctx neighborhood:610
Rv0442c PPE10 PPE family protein PPE10 553 553 ctx neighborhood:553
Rv2466c hyp hypothetical protein 525 525 ctx cooccurence:521
Rv0801 hyp hypothetical protein 427 428 ctx cooccurence:407
Rv0959 hyp hypothetical protein 423 423 ctx cooccurence:422
Rv1082 mca mycothiol S-conjugate amidase 612 399

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: mycothiol transferase
  • Pfam (hmmscan --cut_ga): MST PF04978.18 (E=2e-30), DinB_2 PF12867.13 (E=7e-14)
  • (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_214957.1)
  • Domains: Pfam-A via hmmscan --cut_ga — MST (PF04978.18), DinB_2 (PF12867.13)
  • 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 COG2318
  • Curated reference: UniProt O53728 (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 — 6 functional partner(s); context anchor PPE10
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000465|Rv0443|
MASTDAAAQELLRDAFTRLIEHVDELTDGLTDQLACYRPTPSANSIAWLLWHSARVQDIQVAHVAGVEEVWTRDGWVDRFGLDLPRHDTGYGHRPEDVAKVRAPADLLSGYYHAVHKLTLEYIAGMTADELSRVVDTSWNPPVTVSARLVSIVDDCAQHLGQAAYLRGIAR