esxA Resolved · high auto-curated

H37Rv Rv3875 · MTBC0 - · 95 aa · 4352609–4352896 (+) · RefSeq YP_178023.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESAT-6 protein EsxA
MTBC0 PGAP re-annotation
Revised (this work)ESAT-6 protein EsxA. Pfam: WXG100 (PF06013.19).

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 P9WNK7 SwissProt · reviewed · Evidence at protein level
UniProt name6 kDa early secretory antigenic target
Curated functionA secreted protein that plays a number of roles in modulating the host's immune response to infection as well as being responsible for bacterial escape into the host cytoplasm. Acts as a strong host (human) T-cell antigen. Inhibits IL-12 p40 (IL12B) and TNF expression by infected host (mouse) macrophages, reduces the nitric oxide response by about 75%. In mice previously exposed to the bacterium, elicits high level of IFN-gamma production by T-cells upon subsequent challenge by M.tuberculosis, in the first phase of a protective immune response. Higher levels (1.6-3.3 uM) of recombinant protein.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred nameesxA
eggNOG descriptionBelongs to the WXG100 family
Orthologous groupCOG4842
KEGG orthology K14956
KEGG pathways map05152
Gene Ontology (72) GO:0002790, GO:0003674, GO:0005488, GO:0005515, GO:0005575, GO:0005576, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005886, GO:0006810 +60 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.

Domains (Pfam, hmmscan --cut_ga)

PfamAccessioni-EvalueResiduesDescription
WXG100PF06013.19 9.1e-185–87 Proteins of 100 residues with WXG

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

Closest characterised functional partner: esxB (ESAT-6-like protein EsxB), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3874 esxB ESAT-6-like protein EsxB 999 1000 ctx neighborhood:833 coexpression:853 experimental:999 textmining:997
Rv3877 eccD1 ESX-1 secretion system protein EccD1 971 893 ctx neighborhood:570 cooccurence:754 textmining:745
Rv3870 eccCa1 ESX-1 secretion system protein EccCa 946 857 ctx neighborhood:416 cooccurence:656 textmining:642
Rv3869 eccB1 ESX-1 secretion system protein EccB 900 822 ctx cooccurence:731 textmining:461
Rv2346c esxO ESAT-6 like protein EsxO 921 802 coexpression:802 textmining:621
Rv3620c esxW ESAT-6 like protein EsxW 924 800 coexpression:800 textmining:640
Rv1038c esxJ ESAT-6 like protein EsxJ 910 800 coexpression:800 textmining:569
Rv1197 esxK ESAT-6 like protein EsxK 903 800 coexpression:800 textmining:537
Rv1198 esxL ESAT-6 like protein EsxL 927 799 coexpression:799 textmining:652
Rv2347c esxP ESAT-6 like protein EsxP 930 798 coexpression:798 textmining:672
Rv1793 esxN ESAT-6 like protein EsxN 924 797 coexpression:797 textmining:645
Rv3871 eccCb1 ESX-1 secretion system protein EccCb 955 774 ctx cooccurence:537 textmining:810
Rv3882c eccE1 ESX-1 secretion system protein EccE1 869 771 ctx cooccurence:762 textmining:454
Rv3876 espI ESX-1 secretion-associated protein EspI 954 754 ctx neighborhood:592 textmining:822
Rv3619c esxV ESAT-6 like protein EsxV 908 748 coexpression:748 textmining:651

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): ESAT-6 protein EsxA
  • Pfam (hmmscan --cut_ga): WXG100 PF06013.19 (E=9e-18)
  • (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 YP_178023.1)
  • Domains: Pfam-A via hmmscan --cut_ga — WXG100 (PF06013.19)
  • 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 COG4842
  • Curated reference: UniProt P9WNK7 (SwissProt, reviewed; Evidence at protein level)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 111 functional partner(s); context anchor esxB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3875|esxA
MTEQQWNFAGIEAAASAIQGNVTSIHSLLDEGKQSLTKLAAAWGGSGSEAYQGVQQKWDATATELNNALQNLARTISEAGQAMASTEGNVTGMFA