eccD3 Family assigned · medium auto-curated

H37Rv Rv0290 · MTBC0 mtbc0_000309 · 472 aa · 356377–357795 (+) · RefSeq NP_214804.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESX-3 secretion system protein EccD
MTBC0 PGAP re-annotationtype VII secretion system ESX-3 subunit EccD3
Revised (this work)Type VII secretion system ESX-3 subunit EccD3. 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 P9WNQ3 SwissProt · reviewed · Evidence at protein level
UniProt nameESX-3 secretion system protein EccD3
Curated functionPart of the ESX-3 specialized secretion system, which is important for iron and zinc uptake or homeostasis.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namesnm_2
eggNOG descriptionType VII secretion integral membrane protein EccD
Orthologous group2B6TZ
Gene Ontology (16) GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0005887, GO:0008150, GO:0016020, GO:0016021, GO:0030312, GO:0031224, GO:0031226, GO:0040007 +4 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 0.803 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 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
YukDPF08817.17 2.8e-168–90 WXG100 protein secretion system (Wss), protein YukD
EccDPF19053.7 1.3e-19130–469 EccD-like transmembrane 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 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0283 eccB3 ESX-3 secretion system protein EccB3 999 1000 ctx neighborhood:586 cooccurence:766 coexpression:703 experimental:997 textmining:970
Rv0284 eccC3 ESX-3 secretion system protein EccC3 999 1000 ctx neighborhood:669 cooccurence:657 coexpression:732 experimental:997 textmining:957
Rv0292 eccE3 ESX-3 secretion system protein EccE 999 1000 ctx neighborhood:882 coexpression:860 experimental:997 textmining:953
Rv0291 mycP3 membrane-anchored mycosin MycP 995 987 ctx neighborhood:882 coexpression:860 textmining:645
Rv0289 espG3 ESX-3 secretion-associated protein EspG3 996 969 ctx neighborhood:815 coexpression:841 textmining:878
Rv1782 eccB5 ESX-5 type VII secretion system protein EccB5 975 953 ctx cooccurence:590 experimental:882 textmining:498
Rv0286 PPE4 PPE family protein PPE4 936 898 ctx neighborhood:469 coexpression:815 textmining:405
Rv0287 esxG ESAT-6 like protein EsxG 951 885 ctx neighborhood:592 coexpression:730 textmining:594
Rv1783 eccC5 ESX-5 type VII secretion system protein EccC5 891 875 experimental:821
Rv3894c eccC2 ESX-2 type VII secretion system protein EccC 888 872 experimental:821
Rv0282 eccA3 ESX-3 secretion system protein EccA 943 835 ctx neighborhood:668 cooccurence:405 textmining:673
Rv3447c eccC4 ESX-4 secretion system protein EccC4 849 828 experimental:821
Rv0288 esxH ESAT-6-like protein EsxH 874 789 ctx neighborhood:658 coexpression:409 textmining:429
Rv3810 pirG cell surface protein 769 769 ctx cooccurence:766
Rv3707c hyp hypothetical protein 762 762 ctx cooccurence:761

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-3 secretion system protein EccD
  • MTBC0 PGAP product: type VII secretion system ESX-3 subunit EccD3
  • Pfam (hmmscan --cut_ga): YukD PF08817.17 (E=3e-16), EccD PF19053.7 (E=1e-19)
  • (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_214804.1)
  • 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 2B6TZ
  • Curated reference: UniProt P9WNQ3 (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 — 141 functional partner(s); context anchor eccB3
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000309|Rv0290|eccD3
MSGTVMQIVRVAILADSRLTEMALPAELPLREILPAVQRLVVPSAQNGDGGQADSGAAVQLSLAPVGGQPFSLDASLDTVGVVDGDLLVLQPVPAGPAAPGIVEDIADAAMIFSTSRLKPWGIAHIQRGALAAVIAVALLATGLTVTYRVATGVLAGLLAVAGIAVASALAGLLITIRSPRSGIALSIAALVPIGAALALAVPGKFGPAQVLLGAAGVAAWSLIALMIPSAERERVVAFFTAAAVVGASVALAAGAQLLWQLPLLSIGCGLIVAALLVTIQAAQLSALWARFPLPVIPAPGDPTPSAPPLRLLEDLPRRVRVSDAHQSGFIAAAVLLSVLGSVAIAVRPEALSVVGWYLVAATAAAATLRARVWDSAACKAWLLAQPYLVAGVLLVFYTATGRYVAAFGAVLVLAVLMLAWVVVALNPGIASPESYSLPLRRLLGLVAAGLDVSLIPVMAYLVGLFAWVLNR