TB15.3 Resolved · high auto-curated

H37Rv Rv1636 · MTBC0 mtbc0_001744 · 146 aa · 1854415–1854855 (+) · RefSeq NP_216152.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)iron-regulated universal stress protein
MTBC0 PGAP re-annotationuniversal stress protein
Revised (this work)Universal stress protein. Pfam: Usp (PF00582.33).

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

Curated reference (UniProt)

UniProt P9WFC9 SwissProt · reviewed · Evidence at protein level
UniProt nameUniversal stress protein Rv1636

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category T Signal transduction mechanisms
Preferred nameuspA3
eggNOG descriptionUniversal stress protein
Orthologous groupCOG0589
Gene Ontology (12) GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0008150, GO:0016020, GO:0030312, GO:0042221, GO:0044464, GO:0046677, GO:0050896, GO:0071944

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, 1 missense, 0 nonsense, 0 frameshift

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
UspPF00582.33 1.7e-274–144 Universal stress protein family

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

Closest characterised functional partner: Rv1635c (mannosyltransferase), medium confidence from genomic context alone (score 619 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0951 sucC succinyl-CoA ligase subunit beta 687 688 coexpression:687
Rv1635c mannosyltransferase 618 619 ctx neighborhood:617
Rv1318c adenylate cyclase 551 548 ctx cooccurence:548
Rv1319c adenylate cyclase 544 541 ctx cooccurence:541
Rv1320c adenylate cyclase 541 524 ctx cooccurence:523
Rv3645 transmembrane protein 529 522 ctx cooccurence:514
Rv3584 lpqE lipoprotein LpqE 448 449
Rv3718c hyp hypothetical protein 446 446 ctx cooccurence:443
Rv1316c ogt methylated-DNA--protein-cysteine methyltransferase 427 428 coexpression:419
Rv0655 mkl ABC transporter ATP-binding protein 422 423 ctx cooccurence:412
Rv3314c deoA thymidine phosphorylase 412 413 coexpression:410
Rv3241c raiA hyp hypothetical protein 407 380
Rv0079 hyp hypothetical protein 400 372
Rv1240 mdh malate dehydrogenase 499 295
Rv3369 hyp hypothetical protein 757 249 textmining:690

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: iron-regulated universal stress protein
  • MTBC0 PGAP product: universal stress protein
  • Pfam (hmmscan --cut_ga): Usp PF00582.33 (E=2e-27)
  • (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_216152.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Usp (PF00582.33)
  • 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 COG0589
  • Curated reference: UniProt P9WFC9 (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 — 35 functional partner(s); context anchor Rv1635c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001744|Rv1636|TB15.3
MSAYKTVVVGTDGSDSSMRAVDRAAQIAGADAKLIIASAYLPQHEDARAADILKDESYKVTGTAPIYEILHDAKERAHNAGAKNVEERPIVGAPVDALVNLADEEKADLLVVGNVGLSTIAGRLLGSVPANVSRRAKVDVLIVHTT