eccA2 Family assigned · medium auto-curated

H37Rv Rv3884c · MTBC0 mtbc0_004118 · 619 aa · 4389225–4391084 (-) · RefSeq NP_218401.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESX-2 secretion system protein EccA
MTBC0 PGAP re-annotationtype VII secretion system ESX-2 AAA family ATPase EccA2
Revised (this work)Type VII secretion system ESX-2 AAA family ATPase EccA2. Pfam: T7SS_EccA1_N (PF21545.4), AAA (PF00004.36), AAA_lid_6 (PF17866.9).

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

Curated reference (UniProt)

UniProt P9WPH7 SwissProt · reviewed · Evidence at protein level
UniProt nameESX-2 secretion system protein EccA2
Curated functionShows ATPase activity. Could provide energy for export of ESX-2 substrates (By similarity).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category O Post-translational modification, protein turnover, chaperones
eggNOG descriptionType VII secretion
Orthologous groupCOG0464

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 1.439 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 12 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 5.93% of strains (8604) · 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
T7SS_EccA1_NPF21545.4 6.7e-2732–204 T7SS, ESX-1 secretion system protein EccA1, N-terminal domain
AAAPF00004.36 2.3e-18369–504 ATPase family associated with various cellular activities (AAA)
AAA_lid_6PF17866.9 4.1e-15507–607 AAA lid domain

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

Closest characterised functional partner: eccE2 (ESX-2 secretion system protein EccE), high confidence from genomic context alone (score 954 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3885c eccE2 ESX-2 secretion system protein EccE 954 954 ctx neighborhood:794 coexpression:788
Rv3887c eccD2 ESX-2 secretion system protein EccD 916 899 ctx neighborhood:794 cooccurence:519
Rv3888c membrane protein 876 850 ctx neighborhood:794
Rv3886c mycP2 membrane-anchored mycosin 845 835 ctx neighborhood:794
Rv3696c glpK glycerol kinase 752 752 database:606
Rv3883c mycP1 membrane-anchored mycosin 912 742 ctx neighborhood:728 textmining:673
Rv3882c eccE1 ESX-1 secretion system protein EccE1 801 739 ctx neighborhood:731
Rv2109c prcA proteasome subunit alpha 754 739 experimental:406 database:537
Rv2110c prcB proteasome subunit beta 754 739 experimental:406 database:537
Rv2115c mpa proteasome-associated ATPase 697 698 database:566
Rv1334 mec [CysO 705 687 database:502
Rv1273c drug ABC transporter ATP-binding protein 686 666 database:528
Rv1272c drug ABC transporter ATP-binding protein 686 666 database:528
Rv2299c htpG chaperone protein HtpG 691 664 database:604
Rv1348 irtA iron ABC transporter ATP-binding protein/permease IrtA 705 663 database:528

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: ESX-2 secretion system protein EccA
  • MTBC0 PGAP product: type VII secretion system ESX-2 AAA family ATPase EccA2
  • Pfam (hmmscan --cut_ga): T7SS_EccA1_N PF21545.4 (E=7e-27), AAA PF00004.36 (E=2e-18), AAA_lid_6 PF17866.9 (E=4e-15)
  • (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_218401.1)
  • Domains: Pfam-A via hmmscan --cut_ga — T7SS_EccA1_N (PF21545.4), AAA (PF00004.36), AAA_lid_6 (PF17866.9)
  • 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 COG0464
  • Curated reference: UniProt P9WPH7 (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 — 122 functional partner(s); context anchor eccE2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004118|Rv3884c|eccA2
MSRMVDTMGDLLTARRHFDRAMTIKNGQGCVAALPEFVAATEADPSMADAWLGRIACGDRDLASLKQLNAHSEWLHRETTRIGRTLAAEVQLGPSIGITVTDASQVGLALSSALTIAGEYAKADALLANRELLDSWRNYQWHQLARAFLMYVTQRWPDVLSTAAEDLPPQAIVMPAVTASICALAAHAAAHLGQGRVALDWLDRVDVIGHSRSSGRFGADVLTAAIGPADIPLLVADLAYVRGMVYRQLHEEDKAQIWLSKATINGVLTDAAKEALADPNLRLIVTDERTIASRSDRWDASTAKSRDQLDDDNAAQRRGELLAEGRELLAKQVGLAAVKQAVSALEDQLEVRMMRLEHGLPVEGQTNHMLLVGPPGTGKTTTAEALGKIYAGMGIVRHPEIREVRRSDFCGHYIGESGPKTNELIEKSLGRIIFMDEFYSLIERHQDGTPDMIGMEAVNQLLVQLETHRFDFCFIGAGYEDQVDEFLTVNPGLAGRFNRKLRFESYSPVEIVEIGHRYATPRASQLDDAAREVFLDAVTTIRNYTTPSGQHGIDAMQNGRFARNVIERAEGFRDTRVVAQKRAGQPVSVQDLQIITATDIDAAIRSVCSDNRDMAAIVW