eccA5 Family assigned · medium auto-curated

H37Rv Rv1798 · MTBC0 mtbc0_001911 · 610 aa · 2054711–2056543 (+) · RefSeq NP_216314.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESX-5 type VII secretion system protein EccA
MTBC0 PGAP re-annotationtype VII secretion system ESX-5 AAA family ATPase EccA5
Revised (this work)Type VII secretion system ESX-5 AAA family ATPase EccA5. Pfam: T7SS_EccA1_N (PF21545.4), AAA_5 (PF07728.21), 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 P9WPI1 SwissProt · reviewed · Evidence at protein level
UniProt nameESX-5 secretion system protein EccA5
Curated functionPart of the ESX-5 specialized secretion system, which is responsible for the secretion of EsxN and a number of PE_PGRS and PPE proteins, including PPE41. EccA5 exhibits ATPase activity and may provide energy for the export of ESX-5 substrates (By similarity).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category O Post-translational modification, protein turnover, chaperones
Preferred nameeccA5
eggNOG descriptionType VII secretion
Orthologous groupCOG0457
Gene Ontology (6) GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944

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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 0 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 3.7e-9217–288 T7SS, ESX-1 secretion system protein EccA1, N-terminal domain
AAA_5PF07728.21 1.4e-06352–426 AAA domain (dynein-related subfamily)
AAAPF00004.36 8.4e-16354–486 ATPase family associated with various cellular activities (AAA)
AAA_lid_6PF17866.9 4.9e-07490–597 AAA lid domain

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

Closest characterised functional partner: mycP5 (membrane-anchored mycosin MycP), high confidence from genomic context alone (score 949 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1796 mycP5 membrane-anchored mycosin MycP 970 949 ctx neighborhood:780 coexpression:732 textmining:439
Rv1797 eccE5 ESX-5 type VII secretion system protein EccE 951 939 ctx neighborhood:781 coexpression:732
Rv1795 eccD5 ESX-5 type VII secretion system protein EccD 931 844 ctx neighborhood:780 textmining:579
Rv3887c eccD2 ESX-2 secretion system protein EccD 509 496 ctx cooccurence:493
Rv3805c aftB terminal beta-(1->2)-arabinofuranosyltransferase 474 474 coexpression:474
Rv0256c PPE2 PPE family protein PPE2 462 463 ctx cooccurence:461
Rv1794 espG5 hyp hypothetical protein 727 422 ctx neighborhood:415 textmining:547
Rv2574 hyp hypothetical protein 409 409 ctx cooccurence:409
Rv3895c eccB2 ESX-2 secretion system protein EccB 774 383 textmining:650
Rv3894c eccC2 ESX-2 type VII secretion system protein EccC 502 375
Rv1793 esxN ESAT-6 like protein EsxN 524 321
Rv3884c eccA2 ESX-2 secretion system protein EccA 428 284
Rv1782 eccB5 ESX-5 type VII secretion system protein EccB5 848 261 textmining:804
Rv1783 eccC5 ESX-5 type VII secretion system protein EccC5 595 209 textmining:510
Rv3883c mycP1 membrane-anchored mycosin 456 80 textmining:434

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-5 type VII secretion system protein EccA
  • MTBC0 PGAP product: type VII secretion system ESX-5 AAA family ATPase EccA5
  • Pfam (hmmscan --cut_ga): T7SS_EccA1_N PF21545.4 (E=4e-92), AAA_5 PF07728.21 (E=1e-06), AAA PF00004.36 (E=8e-16), AAA_lid_6 PF17866.9 (E=5e-07)
  • (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_216314.1)
  • Domains: Pfam-A via hmmscan --cut_ga — T7SS_EccA1_N (PF21545.4), AAA_5 (PF07728.21), 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 COG0457
  • Curated reference: UniProt P9WPI1 (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 mycP5
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001911|Rv1798|eccA5
MTRPQAAAEDARNAMVAGLLASGISVNGLQPSHNPQVAAQMFTTATRLDPKMCDAWLARLLAGDQSIEVLAGAWAAVRTFGWETRRLGVTDLQFRPEVSDGLFLRLAITSVDSLACAYAAVLAEAKRYQEAAELLDATDPRHPFDAELVSYVRGVLYFRTKRWPDVLAQFPEATQWRHPELKAAGAAMATTALASLGVFEEAFRRAQEAIEGDRVPGAANIALYTQGMCLRHVGREEEAVELLRRVYSRDAKFTPAREALDNPNFRLILTDPETIEARTDPWDPDSAPTRAQTEAARHAEMAAKYLAEGDAELNAMLGMEQAKKEIKLIKSTTKVNLARAKMGLPVPVTSRHTLLLGPPGTGKTSVARAFTKQLCGLTVLRKPLVVETSRTKLLGRYMADAEKNTEEMLEGALGGAVFFDEMHTLHEKGYSQGDPYGNAIINTLLLYMENHRDELVVFGAGYAKAMEKMLEVNQGLRRRFSTVIEFFSYTPQELIALTQLMGRENEDVITEEESQVLLPSYTKFYMEQSYSEDGDLIRGIDLLGNAGFVRNVVEKARDHRSFRLDDEDLDAVLASDLTEFSEDQLRRFKELTREDLAEGLRAAVAEKKTK