bpa Resolved · high auto-curated

H37Rv Rv3780 · MTBC0 mtbc0_004008 · 178 aa · 4251110–4251646 (+) · RefSeq NP_218297.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationproteasome activator protein Bpa
Revised (this work)Proteasome activator protein Bpa. Pfam: BPA (PF10759.15).

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

Curated reference (UniProt)

UniProt P9WKX3 SwissProt · reviewed · Evidence at protein level
UniProt nameBacterial proteasome activator
Curated functionInteracts with the core proteasome alpha-subunit (PrcA) through its C-terminal hydrophobic-tyrosine-X motif (HbYX motif). Interaction of Bpa with the proteasome stimulates proteasomal peptidase and casein degradation activity, which suggests Bpa could play a role in the removal of non-native or damaged proteins by influencing the conformation of the proteasome complex upon interaction. Can inhibit degradation of Pup-tagged substrates in vitro by competing with Mpa for association with the proteasome.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namebpa
eggNOG descriptionInteracts with the core proteasome alpha-subunit (PrcA) through its C-terminal hydrophobic-tyrosine-X motif (HbYX motif). Interaction of Bpa with the proteasome stimulates proteosomal peptidase and casein degradation activity, which suggests Bpa could play a role in the removal of non-native or damaged proteins by influencing the conformation of the proteasome complex upon interaction
Orthologous group291ZT
Gene Ontology (62) GO:0000502, GO:0003674, GO:0005488, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005886, GO:0008150, GO:0009893, GO:0009894, GO:0009896 +50 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 0.33 · purifying
Polymorphic sites (≥ 0.1% of strains) 1 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
BPAPF10759.15 7.6e-7932–170 Bacterial proteasome activator

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

Closest characterised functional partner: prcA (proteasome subunit alpha), high confidence from genomic context alone (score 976 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2109c prcA proteasome subunit alpha 981 976 ctx cooccurence:766 experimental:900
Rv2115c mpa proteasome-associated ATPase 984 971 ctx cooccurence:724 database:900 textmining:466
Rv2110c prcB proteasome subunit beta 960 949 ctx cooccurence:754 experimental:800
Rv3781 rfbE O-antigen/lipopolysaccharide ABC transporter ATP-binding protein RfbE 964 884 ctx neighborhood:882 textmining:703
Rv3782 glfT1 galactofuranosyl transferase GlfT 943 884 ctx neighborhood:882 textmining:533
Rv3783 rfbD O-antigen/lipopolysaccharide ABC transporter permease RfbD 962 882 ctx neighborhood:881 textmining:694
Rv3779 transmembrane protein 897 882 ctx neighborhood:881
Rv2097c pafA proteasome accessory factor PafA 777 713 ctx cooccurence:709
Rv2112c dop pup deamidase/depupylase 786 687 ctx cooccurence:685
Rv2111c pup ubiquitin-like protein Pup 694 681 ctx cooccurence:679
Rv3778c aminotransferase 639 639 ctx neighborhood:636
Rv0738 hyp hypothetical protein 567 567 ctx cooccurence:566
Rv3660c ssd hyp hypothetical protein 539 539 ctx cooccurence:539
Rv3221A rshA anti-sigma factor RshA 538 539 ctx cooccurence:536
Rv3784 dTDP-glucose 4,6-dehydratase 473 473 ctx neighborhood:471

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: proteasome activator protein Bpa
  • Pfam (hmmscan --cut_ga): BPA PF10759.15 (E=8e-79)
  • (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_218297.1)
  • Domains: Pfam-A via hmmscan --cut_ga — BPA (PF10759.15)
  • 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 291ZT
  • Curated reference: UniProt P9WKX3 (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 — 22 functional partner(s); context anchor prcA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004008|Rv3780|bpa
MRKRMVIGLSTGSDDDDVEVIGGVDPRLIAVQENDSDESSLTDLVEQPAKVMRIGTMIKQLLEEVRAAPLDEASRNRLRDIHATSIRELEDGLAPELREELDRLTLPFNEDAVPSDAELRIAQAQLVGWLEGLFHGIQTALFAQQMAARAQLQQMRQGALPPGVGKSGQHGHGTGQYL