mpa Resolved · high auto-curated

H37Rv Rv2115c · MTBC0 mtbc0_002247 · 609 aa · 2401724–2403553 (-) · RefSeq NP_216631.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)proteasome-associated ATPase
MTBC0 PGAP re-annotationproteasome ATPase
Revised (this work)Proteasome ATPase. Pfam: Prot_ATP_ID_OB_N (PF17758.8), Prot_ATP_ID_OB_C (PF16450.12), AAA (PF00004.36).

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

Curated reference (UniProt)

UniProt P9WQN5 SwissProt · reviewed · Evidence at protein level
UniProt nameProteasome-associated ATPase
Curated functionATPase which is responsible for recognizing, binding, unfolding and translocation of pupylated proteins into the bacterial 20S proteasome core particle. May be essential for opening the gate of the 20S proteasome via an interaction with its C-terminus, thereby allowing substrate entry and access to the site of proteolysis. Thus, the C-termini of the proteasomal ATPase may function like a 'key in a lock' to induce gate opening and therefore regulate proteolysis. Is required but not sufficient to confer resistance against the lethal effects of reactive nitrogen intermediates (RNI), antimicrobial.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category O Post-translational modification, protein turnover, chaperones
Preferred namearc
eggNOG descriptionATPase which is responsible for recognizing, binding, unfolding and translocation of pupylated proteins into the bacterial 20S proteasome core particle. May be essential for opening the gate of the 20S proteasome via an interaction with its C-terminus, thereby allowing substrate entry and access to the site of proteolysis. Thus, the C-termini of the proteasomal ATPase may function like a 'key in a lock' to induce gate opening and therefore regulate proteolysis
Orthologous groupCOG1222
KEGG orthology K13527
KEGG pathways map03050
KEGG modules M00342
Gene Ontology (85) GO:0000302, GO:0000502, GO:0003674, GO:0003824, GO:0005488, GO:0005515, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005886, GO:0006508 +73 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 0.217 · purifying
Polymorphic sites (≥ 0.1% of strains) 6 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
Prot_ATP_ID_OB_NPF17758.8 7.8e-24101–160 Proteasomal ATPase OB N-terminal domain
Prot_ATP_ID_OB_CPF16450.12 8.3e-18161–234 Proteasomal ATPase OB C-terminal domain
AAAPF00004.36 2.9e-37289–438 ATPase family associated with various cellular activities (AAA)

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

Closest characterised functional partner: prcA (proteasome subunit alpha), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2109c prcA proteasome subunit alpha 999 1000 ctx cooccurence:757 experimental:999 database:662 textmining:657
Rv2111c pup ubiquitin-like protein Pup 997 996 ctx cooccurence:764 experimental:982
Rv2110c prcB proteasome subunit beta 998 993 ctx cooccurence:764 experimental:898 database:662 textmining:805
Rv1334 mec [CysO 994 993 coexpression:463 experimental:918 database:844
Rv3696c glpK glycerol kinase 990 989 experimental:916 database:844
Rv3780 bpa hyp hypothetical protein 984 971 ctx cooccurence:724 database:900 textmining:466
Rv2097c pafA proteasome accessory factor PafA 984 835 ctx cooccurence:774 textmining:908
Rv2112c dop pup deamidase/depupylase 904 828 ctx cooccurence:774 textmining:465
Rv0983 pepD serine protease PepD 831 821 experimental:551 database:594
Rv1223 htrA serine protease HtrA 831 820 experimental:551 database:594
Rv3671c marP serine protease 824 813 experimental:551 database:594
Rv0125 pepA serine protease PepA 824 813 experimental:551 database:594
Rv1043c hyp hypothetical protein 824 813 experimental:551 database:594
Rv1488 hyp hypothetical protein 821 804 coexpression:779
Rv2867c GCN5-like N-acetyltransferase 789 790 coexpression:732

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: proteasome-associated ATPase
  • MTBC0 PGAP product: proteasome ATPase
  • Pfam (hmmscan --cut_ga): Prot_ATP_ID_OB_N PF17758.8 (E=8e-24), Prot_ATP_ID_OB_C PF16450.12 (E=8e-18), AAA PF00004.36 (E=3e-37)
  • (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_216631.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Prot_ATP_ID_OB_N (PF17758.8), Prot_ATP_ID_OB_C (PF16450.12), AAA (PF00004.36)
  • 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 COG1222
  • Curated reference: UniProt P9WQN5 (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 — 72 functional partner(s); context anchor prcA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002247|Rv2115c|mpa
MGESERSEAFGIPRDSPLSSGDAAELEQLRREAAVLREQLENAVGSHAPTRSARDIHQLEARIDSLAARNSKLMETLKEARQQLLALREEVDRLGQPPSGYGVLLATHDDDTVDVFTSGRKMRLTCSPNIDAASLKKGQTVRLNEALTVVEAGTFEAVGEISTLREILADGHRALVVGHADEERVVWLADPLIAEDLPDGLPEALNDDTRPRKLRPGDSLLVDTKAGYAFERIPKAEVEDLVLEEVPDVSYADIGGLSRQIEQIRDAVELPFLHKELYREYSLRPPKGVLLYGPPGCGKTLIAKAVANSLAKKMAEVRGDDAHEAKSYFLNIKGPELLNKFVGETERHIRLIFQRAREKASEGTPVIVFFDEMDSIFRTRGTGVSSDVETTVVPQLLSEIDGVEGLENVIVIGASNREDMIDPAILRPGRLDVKIKIERPDAEAAQDIYSKYLTEFLPVHADDLAEFDGDRSACIKAMIEKVVDRMYAEIDDNRFLEVTYANGDKEVMYFKDFNSGAMIQNVVDRAKKNAIKSVLETGQPGLRIQHLLDSIVDEFAENEDLPNTTNPDDWARISGKKGERIVYIRTLVTGKSSSASRAIDTESNLGQYL