esxU Resolved · high auto-curated

H37Rv Rv3445c · MTBC0 mtbc0_003664 · 105 aa · 3888832–3889149 (-) · RefSeq NP_217962.2

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESAT-6 like protein EsxU
MTBC0 PGAP re-annotationtype VII secretion system ESX-4 protein EsxU
Revised (this work)Type VII secretion system ESX-4 protein EsxU. Pfam: WXG100 (PF06013.19).

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

Curated reference (UniProt)

UniProt I6Y3I6 SwissProt · reviewed · Evidence at protein level
UniProt nameESAT-6-like protein EsxU

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred nameesxU
eggNOG descriptionBelongs to the WXG100 family
Orthologous groupCOG4842

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 0.338 · purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 2 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
WXG100PF06013.19 1.2e-137–91 Proteins of 100 residues with WXG

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

Closest characterised functional partner: esxT (ESAT-6 like protein EsxT), high confidence from genomic context alone (score 974 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3444c esxT ESAT-6 like protein EsxT 998 974 ctx neighborhood:857 coexpression:827 textmining:948
Rv3447c eccC4 ESX-4 secretion system protein EccC4 946 939 ctx neighborhood:811 experimental:677
Rv3446c hyp hypothetical protein 861 822 ctx neighborhood:811
Rv3871 eccCb1 ESX-1 secretion system protein EccCb 828 822 experimental:815
Rv3448 eccD4 ESX-4 secretion system protein EccD4 815 789 ctx neighborhood:733
Rv3449 mycP4 membrane-anchored mycosin 900 766 ctx neighborhood:733 textmining:592
Rv3903c cpnT hyp hypothetical protein 736 737 coexpression:732
Rv3894c eccC2 ESX-2 type VII secretion system protein EccC 791 705 experimental:677
Rv1783 eccC5 ESX-5 type VII secretion system protein EccC5 732 698 experimental:677
Rv0284 eccC3 ESX-3 secretion system protein EccC3 731 696 experimental:677
Rv3443c rplM 50S ribosomal protein L13 523 523 ctx neighborhood:520
Rv3442c rpsI 30S ribosomal protein S9 522 523 ctx neighborhood:520
Rv3441c mrsA phosphoglucosamine mutase 406 406 ctx neighborhood:402
Rv0287 esxG ESAT-6 like protein EsxG 628 392 textmining:414
Rv3020c esxS ESAT-6 like protein EsxS 467 390

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: ESAT-6 like protein EsxU
  • MTBC0 PGAP product: type VII secretion system ESX-4 protein EsxU
  • Pfam (hmmscan --cut_ga): WXG100 PF06013.19 (E=1e-13)
  • (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_217962.2)
  • 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 I6Y3I6 (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 — 28 functional partner(s); context anchor esxT
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003664|Rv3445c|esxU
MSTPNTLNADFDLMRSVAGITDARNEEIRAMLQAFIGRMSGVPPSVWGGLAAARFQDVVDRWNAESTRLYHVLHAIADTIRHNEAALREAGQIHARHIAAAGGDL