eccD4 Family assigned · medium auto-curated

H37Rv Rv3448 · MTBC0 mtbc0_003667 · 467 aa · 3894237–3895640 (+) · RefSeq NP_217965.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESX-4 secretion system protein EccD4
MTBC0 PGAP re-annotationtype VII secretion system ESX-4 subunit EccD4
Revised (this work)Type VII secretion system ESX-4 subunit EccD4. Pfam: YukD (PF08817.17), EccD (PF19053.7).

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

Curated reference (UniProt)

UniProt P9WNQ1 SwissProt · reviewed · Inferred from homology
UniProt nameESX-4 secretion system protein eccD4

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred nameeccD
eggNOG descriptionWXG100 protein secretion system (Wss), protein YukD
Orthologous group28MNM
Gene Ontology (6) GO:0005575, 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 0.899 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 11 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
YukDPF08817.17 2.2e-209–83 WXG100 protein secretion system (Wss), protein YukD
EccDPF19053.7 1.3e-37118–462 EccD-like transmembrane domain

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

Closest characterised functional partner: eccC4 (ESX-4 secretion system protein EccC4), high confidence from genomic context alone (score 996 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3447c eccC4 ESX-4 secretion system protein EccC4 997 996 ctx neighborhood:778 cooccurence:758 coexpression:853 experimental:513 textmining:489
Rv3449 mycP4 membrane-anchored mycosin 995 987 ctx neighborhood:882 coexpression:850 textmining:645
Rv3446c hyp hypothetical protein 989 981 ctx neighborhood:778 cooccurence:428 coexpression:860 textmining:487
Rv1782 eccB5 ESX-5 type VII secretion system protein EccB5 937 930 ctx cooccurence:701 experimental:773
Rv3903c cpnT hyp hypothetical protein 921 920 ctx cooccurence:595 coexpression:805
Rv0283 eccB3 ESX-3 secretion system protein EccB3 917 907 ctx cooccurence:607 experimental:773
Rv1783 eccC5 ESX-5 type VII secretion system protein EccC5 882 870 ctx cooccurence:734 experimental:513
Rv0284 eccC3 ESX-3 secretion system protein EccC3 887 843 ctx cooccurence:681 experimental:513
Rv0292 eccE3 ESX-3 secretion system protein EccE 850 841 experimental:830
Rv2082 hyp hypothetical protein 831 832 ctx cooccurence:715 coexpression:432
Rv3894c eccC2 ESX-2 type VII secretion system protein EccC 921 827 ctx cooccurence:640 experimental:513 textmining:562
Rv3450c eccB4 ESX-4 secretion system protein EccB4 827 821 ctx cooccurence:770
Rv0603 hyp hypothetical protein 803 803 coexpression:803
Rv0602c tcrA two component DNA binding transcriptional regulator TcrA 802 802 coexpression:802
Rv0022c whiB5 transcriptional regulator WhiB5 799 799 coexpression:799

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 EccD4
  • MTBC0 PGAP product: type VII secretion system ESX-4 subunit EccD4
  • Pfam (hmmscan --cut_ga): YukD PF08817.17 (E=2e-20), EccD PF19053.7 (E=1e-37)
  • (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_217965.1)
  • Domains: Pfam-A via hmmscan --cut_ga — YukD (PF08817.17), EccD (PF19053.7)
  • 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 28MNM
  • Curated reference: UniProt P9WNQ1 (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 — 134 functional partner(s); context anchor eccC4
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003667|Rv3448|eccD4
MPTSDPGLRRVTVHAGAQAVDLTLPAAVPVATLIPSIVDILGDRGASPATAARYQLSALGAPALPNATTLAQCGIRDGAVLVLHKSSAQPPTPRCDDVAEAVAAALDTTARPQCQRTTRLSGALAASCITAGGGLMLVRNALGTNVTRYSDATAGVVAAAGLAALLFAVIACRTYRDPIAGLTLSVIATIFGAVAGLLAVPGVPGVHSVLVAAMAAAATSVLAMRITGCGGITLTAVACCAVVVAAATLVGAITAAPVPAIGSLATLASFGLLEVSARMAVLLAGLSPRLPPALNPDDADALPTTDRLTTRANRADAWLTSLLAAFAASATIGAIGTAVATHGIHRSSMGGIALAAVTGALLLLRARSADTRRSLVFAICGITTVATAFTVAADRALEHGPWIAALTAMLAAVAMFLGFVAPALSLSPVTYRTIELLECLALIAMVPLTAWLCGAYSAVRHLDLTWT