espK Family assigned · medium auto-curated

H37Rv Rv3879c · MTBC0 - · 729 aa · 4357593–4359782 (-) · RefSeq NP_218396.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESX-1 secretion-associated protein EspK
MTBC0 PGAP re-annotation
Revised (this work)ESX-1 secretion-associated protein EspK. Pfam: EspK_C (PF27215.1).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P9WJC1 SwissProt · reviewed · Evidence at protein level
UniProt nameESX-1 secretion-associated protein EspK
Curated functionMay act as a chaperone that facilitates EspB secretion through an interaction with EccCb1.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred nameespK
eggNOG descriptiondomain protein
Orthologous groupCOG4932
Gene Ontology (11) GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0016020, GO:0044424, GO:0044444, 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 0.443 · purifying
Polymorphic sites (≥ 0.1% of strains) 14 synonymous, 17 missense, 0 nonsense, 10 frameshift
Disruption 10 distinct premature-stop/frameshift site(s); most common in 2.33% of strains (3385) · convergent

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
EspK_CPF27215.1 3.5e-108502–725 EspK C-terminal domain

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

Closest characterised functional partner: eccE1 (ESX-1 secretion system protein EccE1), high confidence from genomic context alone (score 825 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3881c espB ESX-1 secretion-associated protein EspB 989 912 experimental:900 textmining:886
Rv3882c eccE1 ESX-1 secretion system protein EccE1 937 825 ctx cooccurence:768 textmining:659
Rv3877 eccD1 ESX-1 secretion system protein EccD1 929 802 ctx cooccurence:768 textmining:657
Rv0341 iniB isoniazid inducible protein IniB 774 775 ctx cooccurence:774
Rv0355c PPE8 PPE family protein PPE8 773 773 ctx cooccurence:773
Rv3350c PPE56 PPE family protein PPE56 773 773 ctx cooccurence:773
Rv1004c membrane protein 773 773 ctx cooccurence:773
Rv3347c PPE55 PPE family protein PPE55 773 773 ctx cooccurence:773
Rv0304c PPE5 PPE family protein PPE5 773 773 ctx cooccurence:773
Rv1917c PPE34 PPE family protein PPE34 773 773 ctx cooccurence:773
Rv3864 espE ESX-1 secretion-associated protein EspE 830 772 ctx cooccurence:772
Rv3343c PPE54 PPE family protein PPE54 777 772 ctx cooccurence:772
Rv1651c PE_PGRS30 PE-PGRS family protein PE_PGRS30 772 772 ctx cooccurence:772
Rv2209 integral membrane protein 772 772 ctx cooccurence:772
Rv2490c PE_PGRS43 PE-PGRS family protein PE_PGRS43 772 772 ctx cooccurence:772

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): ESX-1 secretion-associated protein EspK
  • Pfam (hmmscan --cut_ga): EspK_C PF27215.1 (E=3e-108)
  • (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_218396.1)
  • Domains: Pfam-A via hmmscan --cut_ga — EspK_C (PF27215.1)
  • 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 COG4932
  • Curated reference: UniProt P9WJC1 (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 — 155 functional partner(s); context anchor eccE1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3879c|espK
MSITRPTGSYARQMLDPGGWVEADEDTFYDRAQEYSQVLQRVTDVLDTCRQQKGHVFEGGLWSGGAANAANGALGANINQLMTLQDYLATVITWHRHIAGLIEQAKSDIGNNVDGAQREIDILENDPSLDADERHTAINSLVTATHGANVSLVAETAERVLESKNWKPPKNALEDLLQQKSPPPPDVPTLVVPSPGTPGTPGTPITPGTPITPGTPITPIPGAPVTPITPTPGTPVTPVTPGKPVTPVTPVKPGTPGEPTPITPVTPPVAPATPATPATPVTPAPAPHPQPAPAPAPSPGPQPVTPATPGPSGPATPGTPGGEPAPHVKPAALAEQPGVPGQHAGGGTQSGPAHADESAASVTPAAASGVPGARAAAAAPSGTAVGAGARSSVGTAAASGAGSHAATGRAPVATSDKAAAPSTRAASARTAPPARPPSTDHIDKPDRSESADDGTPVSMIPVSAARAARDAATAAASARQRGRGDALRLARRIAAALNASDNNAGDYGFFWITAVTTDGSIVVANSYGLAYIPDGMELPNKVYLASADHAIPVDEIARCATYPVLAVQAWAAFHDMTLRAVIGTAEQLASSDPGVAKIVLEPDDIPESGKMTGRSRLEVVDPSAAAQLADTTDQRLLDLLPPAPVDVNPPGDERHMLWFELMKPMTSTATGREAAHLRAFRAYAAHSQEIALHQAHTATDAAVQRVAVADWLYWQYVTGLLDRALAAAC