eccA3 Resolved · high auto-curated

H37Rv Rv0282 · MTBC0 - · 631 aa · 342130–344025 (+) · RefSeq NP_214796.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESX-3 secretion system protein EccA
MTBC0 PGAP re-annotation
Revised (this work)ESX-3 secretion system protein EccA. 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.

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P9WPI3 SwissProt · reviewed · Evidence at protein level
UniProt nameESX-3 secretion system protein EccA3
Curated functionPart of the ESX-3 specialized secretion system, which is important for iron and zinc uptake or homeostasis. EccA3 exhibits ATPase activity and may provide energy for the export of ESX-3 substrates (By similarity).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category O Post-translational modification, protein turnover, chaperones
Preferred nameeccA3
eggNOG descriptionsecretion
Orthologous groupCOG0464
Gene Ontology (51) GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006873, GO:0006875, GO:0006879, GO:0006950, GO:0007154 +39 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 0.257 · purifying
Polymorphic sites (≥ 0.1% of strains) 8 synonymous, 6 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 9.1e-9043–316 T7SS, ESX-1 secretion system protein EccA1, N-terminal domain
Mg_chelatasePF01078.28 1.5e-04370–405 Magnesium chelatase, subunit ChlI
AAAPF00004.36 2.4e-18382–513 ATPase family associated with various cellular activities (AAA)
AAA_lid_6PF17866.9 1.0e-15517–617 AAA lid domain

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

Closest characterised functional partner: eccB3 (ESX-3 secretion system protein EccB3), high confidence from genomic context alone (score 986 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0283 eccB3 ESX-3 secretion system protein EccB3 995 986 ctx neighborhood:882 coexpression:860 textmining:690
Rv0284 eccC3 ESX-3 secretion system protein EccC3 994 984 ctx neighborhood:881 coexpression:848 textmining:670
Rv0281 S-adenosylmethionine-dependent methyltransferase 916 907 ctx neighborhood:499 coexpression:798
Rv0286 PPE4 PPE family protein PPE4 929 895 ctx neighborhood:801 coexpression:494
Rv0285 PE5 PE family protein PE5 894 882 ctx neighborhood:882
Rv0289 espG3 ESX-3 secretion-associated protein EspG3 915 845 ctx neighborhood:767 textmining:473
Rv0280 PPE3 PPE family protein PPE3 876 845 ctx neighborhood:416 coexpression:746
Rv0290 eccD3 ESX-3 secretion system protein EccD 943 835 ctx neighborhood:668 cooccurence:405 textmining:673
Rv0291 mycP3 membrane-anchored mycosin MycP 926 832 ctx neighborhood:581 coexpression:515 textmining:578
Rv3696c glpK glycerol kinase 744 745 database:606
Rv2109c prcA proteasome subunit alpha 756 742 experimental:406 database:537
Rv2110c prcB proteasome subunit beta 755 741 experimental:406 database:537
Rv1348 irtA iron ABC transporter ATP-binding protein/permease IrtA 855 716 database:528 textmining:511
Rv2115c mpa proteasome-associated ATPase 697 698 database:566
Rv1334 mec [CysO 705 687 database:502

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): ESX-3 secretion system protein EccA
  • Pfam (hmmscan --cut_ga): T7SS_EccA1_N PF21545.4 (E=9e-90), Mg_chelatase PF01078.28 (E=1e-04), AAA PF00004.36 (E=2e-18), AAA_lid_6 PF17866.9 (E=1e-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_214796.1)
  • 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 P9WPI3 (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 — 135 functional partner(s); context anchor eccB3
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0282|eccA3
MAGVGEGDSGGVERDDIGMVAASPVASRVNGKVDADVVGRFATCCRALGIAVYQRKRPPDLAAARSGFAALTRVAHDQCDAWTGLAAAGDQSIGVLEAASRTATTAGVLQRQVELADNALGFLYDTGLYLRFRATGPDDFHLAYAAALASTGGPEEFAKANHVVSGITERRAGWRAARWLAVVINYRAERWSDVVKLLTPMVNDPDLDEAFSHAAKITLGTALARLGMFAPALSYLEEPDGPVAVAAVDGALAKALVLRAHVDEESASEVLQDLYAAHPENEQVEQALSDTSFGIVTTTAGRIEARTDPWDPATEPGAEDFVDPAAHERKAALLHEAELQLAEFIGLDEVKRQVSRLKSSVAMELVRKQRGLTVAQRTHHLVFAGPPGTGKTTIARVVAKIYCGLGLLKRENIREVHRADLIGQHIGETEAKTNAIIDSALDGVLFLDEAYALVATGAKNDFGLVAIDTLLARMENDRDRLVVIIAGYRADLDKFLDTNEGLRSRFTRNIDFPSYTSHELVEIAHKMAEQRDSVFEQSALHDLEALFAKLAAESTPDTNGISRRSLDIAGNGRFVRNIVERSEEEREFRLDHSEHAGSGEFSDEELMTITADDVGRSVEPLLRGLGLSVRA