eccB4 Family assigned · medium auto-curated

H37Rv Rv3450c · MTBC0 mtbc0_003669 · 470 aa · 3896969–3898381 (-) · RefSeq NP_217967.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESX-4 secretion system protein EccB4
MTBC0 PGAP re-annotationtype VII secretion system ESX-4 subunit EccB4
Revised (this work)Type VII secretion system ESX-4 subunit EccB4. Pfam: T7SS_ESX1_EccB (PF05108.19).

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

Curated reference (UniProt)

UniProt P9WNR1 SwissProt · reviewed · Inferred from homology
UniProt nameESX-4 secretion system ATPase EccB4
EC (curated) EC 3.6.-.-
Curated functionAn ATPase (By similarity).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred nameeccB
eggNOG descriptionType VII secretion
Orthologous groupCOG3266
Gene Ontology (7) GO:0005575, GO:0005576, GO:0005618, GO:0005623, GO:0030312, 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 0.455 · purifying
Polymorphic sites (≥ 0.1% of strains) 7 synonymous, 8 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.15% of strains (224) · clonal

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_ESX1_EccBPF05108.19 1.7e-1595–468 Type VII secretion system ESX-1, transport TM domain B

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

Closest characterised functional partner: eccD4 (ESX-4 secretion system protein EccD4), high confidence from genomic context alone (score 821 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3448 eccD4 ESX-4 secretion system protein EccD4 827 821 ctx cooccurence:770
Rv3447c eccC4 ESX-4 secretion system protein EccC4 829 810 ctx cooccurence:725
Rv3657c membrane protein 802 802 coexpression:736
Rv3886c mycP2 membrane-anchored mycosin 788 771 ctx cooccurence:717
Rv3451 cut3 cutinase 770 770 ctx neighborhood:769
Rv1796 mycP5 membrane-anchored mycosin MycP 755 735 ctx cooccurence:675
Rv3871 eccCb1 ESX-1 secretion system protein EccCb 736 718 ctx cooccurence:575
Rv2474c hyp hypothetical protein 711 712 ctx cooccurence:710
Rv0358 hyp hypothetical protein 738 692 ctx cooccurence:688
Rv0284 eccC3 ESX-3 secretion system protein EccC3 711 678 ctx cooccurence:554
Rv3870 eccCa1 ESX-1 secretion system protein EccCa 699 672 ctx cooccurence:507
Rv1783 eccC5 ESX-5 type VII secretion system protein EccC5 677 641 ctx cooccurence:501
Rv2732c transmembrane protein 598 599 ctx cooccurence:596
Rv1682 hyp hypothetical protein 590 591 ctx cooccurence:582
Rv3256c hyp hypothetical protein 586 587 ctx cooccurence:584

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-4 secretion system protein EccB4
  • MTBC0 PGAP product: type VII secretion system ESX-4 subunit EccB4
  • Pfam (hmmscan --cut_ga): T7SS_ESX1_EccB PF05108.19 (E=2e-159)
  • (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_217967.1)
  • Domains: Pfam-A via hmmscan --cut_ga — T7SS_ESX1_EccB (PF05108.19)
  • 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 COG3266
  • Curated reference: UniProt P9WNR1 (SwissProt, reviewed; Inferred from homology)
  • 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 — 73 functional partner(s); context anchor eccD4
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003669|Rv3450c|eccB4
MPSPATTWLHVSGYRFLLRRIECALLFGDVCAATGALRARTTSLALGCVLAIVAAMGCAFVALLRPQSALGQAPIVMGRESGALYVRVDDVWHPVLNLASARLIAATNANPQPVSESELGHTKRGPLLGIPGAPQLLDQPLAGAESAWAICDSDNGGSTTVVVGPAEDSSAQVLTAEQMILVATESGSPTYLLYGGRRAVVDLADPAVVWALRLQGRVPHVVAQSLLNAVPEAPRITAPRIRGGGRASVGLPGFLVGGVVRITRASGDEYYVVLEDGVQRIGQVAADLLRFGDSQGSVNVPTVAPDVIRVAPIVNTLPVSAFPDRPPTPVDGSPGRAVTTLCVTWTPAQPGAARVAFLAGSGPPVPLGGVPVTLAQADGRGPALDAVYLPPGRSAYVAARSLSGGGTGTRYLVTDTGVRFAIHDDDVAHDLGLPTAAIPAPWPVLATLPSGPELSRANASVARDTVAPGP