eccC4 Family assigned · medium auto-curated

H37Rv Rv3447c · MTBC0 mtbc0_003666 · 1236 aa · 3890413–3894123 (-) · RefSeq NP_217964.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESX-4 secretion system protein EccC4
MTBC0 PGAP re-annotationtype VII secretion system ESX-4 FtsK/SpoIIIE family ATPase EccC4
Revised (this work)Type VII secretion system ESX-4 FtsK/SpoIIIE family ATPase EccC4. Pfam: FtsK_SpoIIIE (PF01580.25).

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

Curated reference (UniProt)

UniProt P9WNA7 SwissProt · reviewed · Inferred from homology
UniProt nameESX-4 secretion system protein EccC4

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category D Cell cycle control, cell division, chromosome partitioning
Preferred nameeccCa
eggNOG descriptionCOG1674 DNA segregation ATPase FtsK SpoIIIE and related proteins
Orthologous groupCOG1674
KEGG orthology K03466
Gene Ontology (6) GO:0005575, GO:0005623, GO:0005886, GO:0016020, 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) pseudogene candidate

pN/pS 0.744 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 17 synonymous, 33 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 2.26% of strains (3275) · 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
FtsK_SpoIIIEPF01580.25 7.9e-65721–967 FtsK/SpoIIIE family

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 996 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3448 eccD4 ESX-4 secretion system protein EccD4 997 996 ctx neighborhood:778 cooccurence:758 coexpression:853 experimental:513 textmining:489
Rv3446c hyp hypothetical protein 986 979 ctx neighborhood:881 coexpression:831
Rv3449 mycP4 membrane-anchored mycosin 967 965 ctx neighborhood:778 coexpression:807
Rv3445c esxU ESAT-6 like protein EsxU 946 939 ctx neighborhood:811 experimental:677
Rv0283 eccB3 ESX-3 secretion system protein EccB3 931 921 ctx cooccurence:553 experimental:824
Rv1782 eccB5 ESX-5 type VII secretion system protein EccB5 927 917 ctx cooccurence:515 experimental:824
Rv3444c esxT ESAT-6 like protein EsxT 876 863 ctx neighborhood:792
Rv1795 eccD5 ESX-5 type VII secretion system protein EccD 868 848 experimental:821
Rv0290 eccD3 ESX-3 secretion system protein EccD 849 828 experimental:821
Rv2891 hyp hypothetical protein 832 825 coexpression:823
Rv3450c eccB4 ESX-4 secretion system protein EccB4 829 810 ctx cooccurence:725
Rv3903c cpnT hyp hypothetical protein 792 764 coexpression:730
Rv0603 hyp hypothetical protein 738 738 coexpression:738
Rv0745 hyp hypothetical protein 735 735 coexpression:735
Rv3874 esxB ESAT-6-like protein EsxB 782 690 experimental:677

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 EccC4
  • MTBC0 PGAP product: type VII secretion system ESX-4 FtsK/SpoIIIE family ATPase EccC4
  • Pfam (hmmscan --cut_ga): FtsK_SpoIIIE PF01580.25 (E=8e-65)
  • (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_217964.1)
  • Domains: Pfam-A via hmmscan --cut_ga — FtsK_SpoIIIE (PF01580.25)
  • 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 COG1674
  • Curated reference: UniProt P9WNA7 (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 — 41 functional partner(s); context anchor eccD4
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003666|Rv3447c|eccC4
MNSGPACATADILVAPPPELRRSEPSSLLIRLLPVVMSVATVGVMVTVFLPGSPATRHPTFLAFPMMMLVSLVVTAVTGRGRRHVSGIHNDRVDYLGYLSVLRTSVTQTAAAQHVSLNWTHPDPATLWTLIGGPRMWERRPGAADFCRIRVGVGSAPLATRLVVGQLPPAQRADPVTRAALRCFLAAHATIADAPIAIPLRVGGPIAIDGDPTKVRGLLRAMICQLAVWHSPEELLIAGVVSDRNRAHWDWLKWLPHNQHPNACDALGPAPMVYSTLAEMQNALAATVLAHVVAIVDTAERGNGAITGVITIEVGARRDGAPPVVRCAGEVTALACPDQLEPQDALVCARRLAAHRVGHSGRTFIRGSGWAELVGIGDVAAFDPSTLWRNVNQHDRLRVPIGVTPDGTAVQLDIKEAAEQGMGPHGLCVGATGSGKSELLRTIALGMMARNSPEVLNLLLVDFKGGATFLDLAGAPHVAAVITNLAEEAPLVARMQDALAGEMSRRQQLLRMAGHLVSVTAYQRARQTGAQLPCLPILFIVVDEFSELLSQHPEFVDVFLAIGRVGRSLGMHLLLASQRLDEGRLRGLETHLSYRMCLKTWSASESRNVLGTQDAYQLPNTPGAGLLQTGTGELIRFQTAFVSGPLRRASPSAVHPVAPPSVRPFTTHAAAPVTAGPVGGTAEVPTPTVLHAVLDRLVGHGPAAHQVWLPPLDEPPMLGALLRDAEPAQAELAVPIGIVDRPFEQSRVPLTIDLSGAAGNVAVVGAPQTGKSTALRTLIMALAATHDAGRVQFYCLDFGGGALAQVDELPHVGAVAGRAQPQLASRMLAELESAVRFREAFFRDHGIDSVARYRQLRAKSAAESFADIFLVIDGWASLRQEFAALEESIVALAAQGLSFGVHVALSAARWAEIRPSLRDQIGSRIELRLADPADSELDRRQAQRVPVDRPGRGLSRDGMHMVIALPDLDGVALRRRSGDPVAPPIPLLPARVDYDSVVARAGDELGAHILLGLEERRGQPVAVDFGRHPHLLVLGDNECGKTAALRTLCREIVRTHTAARAQLLIVDFRHTLLDVIESEHMGGYVSSPAALGAKLSSLVDLLQARMPAPDVSQAQLRARSWWSGPDIYVVVDDYDLVAVSSGNPLMVLLEYLPHARDLGLHLVVARRSGGAARALFEPVLASLRDLGCRALLMSGRPDEGALFGSSRPMPLPPGRGILVTGAGDEQLVQVAWSPPP