eccA1 Family assigned · medium auto-curated

H37Rv Rv3868 · MTBC0 mtbc0_004101 · 573 aa · 4367471–4369192 (+) · RefSeq NP_218385.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESX-1 secretion system protein EccA1
MTBC0 PGAP re-annotationtype VII secretion system ESX-1 AAA family ATPase EccA1
Revised (this work)Type VII secretion system ESX-1 AAA family ATPase EccA1. Pfam: T7SS_EccA1_N (PF21545.4), Mg_chelatase (PF01078.28), 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 P9WPH9 SwissProt · reviewed · Evidence at protein level
UniProt nameESX-1 secretion system protein EccA1
Curated functionPart of the ESX-1 specialized secretion system, which delivers several virulence factors to host cells during infection, including the key virulence factors EsxA (ESAT-6) and EsxB (CFP-10). EccA1 exhibits ATPase activity and may provide energy for the export of ESX-1 substrates.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category O Post-translational modification, protein turnover, chaperones
Preferred nameeccA1
eggNOG descriptionEccA1 exhibits ATPase activity and may provide energy for the export of ESX-1 substrates
Orthologous groupCOG0464
Gene Ontology (22) GO:0003674, GO:0003824, GO:0005575, GO:0005623, GO:0005886, GO:0008150, GO:0016020, GO:0016462, GO:0016787, GO:0016817, GO:0016818, GO:0016887 +10 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 0.236 · purifying
Polymorphic sites (≥ 0.1% of strains) 7 synonymous, 5 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
T7SS_EccA1_NPF21545.4 3.3e-962–272 T7SS, ESX-1 secretion system protein EccA1, N-terminal domain
Mg_chelatasePF01078.28 7.3e-05315–369 Magnesium chelatase, subunit ChlI
AAAPF00004.36 5.5e-22330–464 ATPase family associated with various cellular activities (AAA)
AAA_lid_6PF17866.9 3.5e-12467–564 AAA lid domain

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

Closest characterised functional partner: espH (ESX-1 secretion-associated protein EspH), high confidence from genomic context alone (score 964 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3867 espH ESX-1 secretion-associated protein EspH 981 964 ctx neighborhood:801 coexpression:827 textmining:490
Rv3866 espG1 ESX-1 secretion-associated protein EspG 973 936 ctx neighborhood:825 coexpression:651 textmining:609
Rv3870 eccCa1 ESX-1 secretion system protein EccCa 969 920 ctx neighborhood:881 textmining:639
Rv3869 eccB1 ESX-1 secretion system protein EccB 957 905 ctx neighborhood:881 textmining:575
Rv3865 espF ESX-1 secretion-associated protein EspF 938 833 ctx neighborhood:825 textmining:650
Rv3871 eccCb1 ESX-1 secretion system protein EccCb 909 808 ctx neighborhood:771 textmining:549
Rv2109c prcA proteasome subunit alpha 760 746 experimental:406 database:537
Rv3696c glpK glycerol kinase 746 746 database:606
Rv2110c prcB proteasome subunit beta 756 742 experimental:406 database:537
Rv1334 mec [CysO 752 737 database:502
Rv2115c mpa proteasome-associated ATPase 710 710 database:566
Rv3873 PPE68 PPE family protein PPE68 798 709 ctx neighborhood:628
Rv0194 multidrug ABC transporter ATPase/permease 683 664 database:528
Rv2299c htpG chaperone protein HtpG 690 663 database:604
Rv1272c drug ABC transporter ATP-binding protein 683 663 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-1 secretion system protein EccA1
  • MTBC0 PGAP product: type VII secretion system ESX-1 AAA family ATPase EccA1
  • Pfam (hmmscan --cut_ga): T7SS_EccA1_N PF21545.4 (E=3e-96), Mg_chelatase PF01078.28 (E=7e-05), AAA PF00004.36 (E=6e-22), AAA_lid_6 PF17866.9 (E=4e-12)
  • (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_218385.1)
  • Domains: Pfam-A via hmmscan --cut_ga — T7SS_EccA1_N (PF21545.4), Mg_chelatase (PF01078.28), 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 P9WPH9 (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 — 130 functional partner(s); context anchor espH
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004101|Rv3868|eccA1
MTDRLASLFESAVSMLPMSEARSLDLFTEITNYDESACDAWIGRIRCGDTDRVTLFRAWYSRRNFGQLSGSVQISMSTLNARIAIGGLYGDITYPVTSPLAITMGFAACEAAQGNYADAMEALEAAPVAGSEHLVAWMKAVVYGAAERWTDVIDQVKSAGKWPDKFLAGAAGVAHGVAAANLALFTEAERRLTEANDSPAGEACARAIAWYLAMARRSQGNESAAVALLEWLQTTHPEPKVAAALKDPSYRLKTTTAEQIASRADPWDPGSVVTDNSGRERLLAEAQAELDRQIGLTRVKNQIERYRAATLMARVRAAKGMKVAQPSKHMIFTGPPGTGKTTIARVVANILAGLGVIAEPKLVETSRKDFVAEYEGQSAVKTAKTIDQALGGVLFIDEAYALVQERDGRTDPFGQEALDTLLARMENDRDRLVVIIAGYSSDIDRLLETNEGLRSRFATRIEFDTYSPEELLEIANVIAAADDSALTAEAAENFLQAAKQLEQRMLRGRRALDVAGNGRYARQLVEASEQCRDMRLAQVLDIDTLDEDRLREINGSDMAEAIAAVHAHLNMRE