eccCa1 Family assigned · medium auto-curated

H37Rv Rv3870 · MTBC0 mtbc0_004103 · 747 aa · 4370638–4372881 (+) · RefSeq NP_218387.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESX-1 secretion system protein EccCa
MTBC0 PGAP re-annotationtype VII secretion system ESX-1 FtsK/SpoIIIE family ATPase EccCa1
Revised (this work)Type VII secretion system ESX-1 FtsK/SpoIIIE family ATPase EccCa1. 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 P9WNB3 SwissProt · reviewed · Evidence at protein level
UniProt nameESX-1 secretion system protein EccCa1
Curated functionPart of the ESX-1 specialized secretion system, which delivers several virulence factors to host cells during infection, including the key virulence factors EsxA (ESAT-6) and EsxB (CFP-10).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category D Cell cycle control, cell division, chromosome partitioning
Preferred nameeccCa
eggNOG descriptionFtsK/SpoIIIE family
Orthologous groupCOG1674
KEGG orthology K03466
Gene Ontology (57) GO:0002790, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006810, GO:0008104, GO:0008150, GO:0009306, GO:0009405, GO:0009605, GO:0009607 +45 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 0.277 · purifying
Polymorphic sites (≥ 0.1% of strains) 16 synonymous, 13 missense, 0 nonsense, 3 frameshift
Disruption 3 distinct premature-stop/frameshift site(s); most common in 0.40% of strains (575) · 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 2.7e-53430–637 FtsK/SpoIIIE family

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

Closest characterised functional partner: eccCb1 (ESX-1 secretion system protein EccCb), high confidence from genomic context alone (score 998 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3871 eccCb1 ESX-1 secretion system protein EccCb 998 998 ctx neighborhood:771 fusion:899 coexpression:860
Rv3869 eccB1 ESX-1 secretion system protein EccB 997 992 ctx neighborhood:881 cooccurence:766 coexpression:651 textmining:657
Rv3868 eccA1 ESX-1 secretion system protein EccA1 969 920 ctx neighborhood:881 textmining:639
Rv3877 eccD1 ESX-1 secretion system protein EccD1 974 867 ctx cooccurence:733 textmining:815
Rv3875 esxA ESAT-6 protein EsxA 946 857 ctx neighborhood:416 cooccurence:656 textmining:642
Rv3865 espF ESX-1 secretion-associated protein EspF 832 833 ctx neighborhood:825
Rv3866 espG1 ESX-1 secretion-associated protein EspG 885 832 ctx neighborhood:825
Rv3867 espH ESX-1 secretion-associated protein EspH 870 831 ctx neighborhood:801
Rv3874 esxB ESAT-6-like protein EsxB 937 821 ctx neighborhood:580 experimental:585 textmining:664
Rv3882c eccE1 ESX-1 secretion system protein EccE1 926 805 ctx cooccurence:699 textmining:640
Rv2553c mltG membrane protein 776 777 coexpression:731
Rv3864 espE ESX-1 secretion-associated protein EspE 814 724 ctx neighborhood:524
Rv2542 hyp hypothetical protein 804 721 ctx cooccurence:720
Rv3448 eccD4 ESX-4 secretion system protein EccD4 705 693 ctx cooccurence:498
Rv3873 PPE68 PPE family protein PPE68 705 691 ctx neighborhood:672

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-1 secretion system protein EccCa
  • MTBC0 PGAP product: type VII secretion system ESX-1 FtsK/SpoIIIE family ATPase EccCa1
  • Pfam (hmmscan --cut_ga): FtsK_SpoIIIE PF01580.25 (E=3e-53)
  • (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_218387.1)
  • 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 P9WNB3 (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 — 38 functional partner(s); context anchor eccCb1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004103|Rv3870|eccCa1
MTTKKFTPTITRGPRLTPGEISLTPPDDLGIDIPPSGVQKILPYVMGGAMLGMIAIMVAGGTRQLSPYMLMMPLMMIVMMVGGLAGSTGGGGKKVPEINADRKEYLRYLAGLRTRVTSSATSQVAFFSYHAPHPEDLLSIVGTQRQWSRPANADFYAATRIGIGDQPAVDRLLKPAVGGELAAASAAPQPFLEPVSHMWVVKFLRTHGLIHDCPKLLQLRTFPTIAIGGDLAGAAGLMTAMICHLAVFHPPDLLQIRVLTEEPDDPDWSWLKWLPHVQHQTETDAAGSTRLIFTRQEGLSDLAARGPHAPDSLPGGPYVVVVDLTGGKAGFPPDGRAGVTVITLGNHRGSAYRIRVHEDGTADDRLPNQSFRQVTSVTDRMSPQQASRIARKLAGWSITGTILDKTSRVQKKVATDWHQLVGAQSVEEITPSRWRMYTDTDRDRLKIPFGHELKTGNVMYLDIKEGAEFGAGPHGMLIGTTGSGKSEFLRTLILSLVAMTHPDQVNLLLTDFKGGSTFLGMEKLPHTAAVVTNMAEEAELVSRMGEVLTGELDRRQSILRQAGMKVGAAGALSGVAEYEKYRERGADLPPLPTLFVVVDEFAELLQSHPDFIGLFDRICRVGRSLRVHLLLATQSLQTGGVRIDKLEPNLTYRIALRTTSSHESKAVIGTPEAQYITNKESGVGFLRVGMEDPVKFSTFYISGPYMPPAAGVETNGEAGGPGQQTTRQAARIHRFTAAPVLEEAPTP