Rv2005c Resolved · high auto-curated

H37Rv Rv2005c · MTBC0 mtbc0_002133 · 295 aa · 2274609–2275496 (-) · RefSeq NP_216521.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)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 P9WLN1 SwissProt · reviewed · Evidence at protein level
UniProt nameUniversal stress protein Rv2005c
Curated functionProbably involved in aminoglycosides resistance and virulence. Overexpression increases resistance to the aminoglycosides amikacin (AK) and kanamycin (KM).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category T Signal transduction mechanisms
eggNOG descriptionUniversal stress protein
Orthologous groupCOG0589
Gene Ontology (15) GO:0001666, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006950, GO:0008150, GO:0009628, GO:0016020, GO:0030312, GO:0036293, GO:0044464 +3 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 0.463 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 4 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 8.0e-29161–293 Universal stress protein family

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

Closest characterised functional partner: otsB1 (trehalose-6-phosphate phosphatase OtsB), high confidence from genomic context alone (score 894 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2004c hyp hypothetical protein 966 967 ctx neighborhood:771 coexpression:860
Rv2003c hyp hypothetical protein 911 912 ctx neighborhood:572 coexpression:802
Rv2006 otsB1 trehalose-6-phosphate phosphatase OtsB 893 894 ctx neighborhood:553 coexpression:772
Rv3133c devR two component transcriptional regulator DevR 866 849 coexpression:848
Rv2629 hyp hypothetical protein 846 847 coexpression:822
Rv3132c devS two component sensor histidine kinase DevS 850 838 coexpression:833
Rv0569 hyp hypothetical protein 819 819 coexpression:774
Rv2624c universal stress protein 802 803 coexpression:738
Rv1997 ctpF cation transporter ATPase F 829 802 coexpression:796
Rv0570 nrdZ vitamin B12-dependent ribonucleoside-diphosphate reductase 774 775 coexpression:774
Rv1736c narX nitrate reductase-like protein NarX 729 729 coexpression:729
Rv0571c hyp hypothetical protein 702 702 coexpression:624
Rv2029c pfkB 6-phosphofructokinase PfkB 656 657 coexpression:651
Rv2625c rip3 zinc metalloprotease Rip3 647 647 coexpression:553
Rv2623 TB31.7 universal stress protein 635 629 coexpression:615

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: universal stress protein
  • MTBC0 PGAP product: universal stress protein
  • Pfam (hmmscan --cut_ga): Usp PF00582.33 (E=8e-29)
  • (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_216521.1)
  • 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 P9WLN1 (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 — 32 functional partner(s); context anchor otsB1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002133|Rv2005c|
MSKPRKQHGVVVGVDGSLESDAAACWGATDAAMRNIPLTVVHVVNADVATWPPMPYPETWGVWQEDEGRQIVANAVKLAKEAVGADRKLSVKSELVFSTPVPTMVEISNEAEMVVLGSSGRGALARGLLGSVSSSLVRRAGCPVAVIHSDDAVIPDPQHAPVLVGIDGSPVSELATAVAFDEASRRGVELIAVHAWSDVEVVELPGLDFSAVQQEAELSLAERLAGWQERYPDVPVSRVVVCDRPARKLVQKSASAQLVVVGSHGRGGLTGMLLGSVSNAVLHAARVPVIVARQS