espD Resolved · medium auto-curated

H37Rv Rv3614c · MTBC0 mtbc0_003831 · 184 aa · 4077846–4078400 (-) · RefSeq NP_218131.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESX-1 secretion-associated protein EspD
MTBC0 PGAP re-annotationtype VII secretion system ESX-1 target EspD
Revised (this work)Type VII secretion system ESX-1 target EspD.

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

Curated reference (UniProt)

UniProt P9WJD5 SwissProt · reviewed · Evidence at protein level
UniProt nameESX-1 secretion-associated protein EspD
Curated functionRequired for ESX-1 function. Required for the maintenance of adequate cellular levels of both EspA and EspC. Facilitates EsxA secretion.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptioninterspecies interaction between organisms
Orthologous group2AVBJ
Gene Ontology (28) GO:0002790, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006810, GO:0008104, GO:0008150, GO:0009306, GO:0009987, GO:0015031, GO:0015833 +16 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 0.232 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 3 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

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

Closest characterised functional partner: espC (ESX-1 secretion-associated protein EspC), high confidence from genomic context alone (score 935 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3615c espC ESX-1 secretion-associated protein EspC 993 935 ctx neighborhood:558 coexpression:860 textmining:908
Rv3616c espA ESX-1 secretion-associated protein EspA 991 916 ctx neighborhood:423 coexpression:860 textmining:902
Rv3613c hyp hypothetical protein 912 912 ctx neighborhood:574 coexpression:802
Rv3612c hyp hypothetical protein 914 854 ctx neighborhood:480 coexpression:730 textmining:440
Rv3880c espL ESX-1 secretion-associated protein EspL 648 503 experimental:500
Rv3871 eccCb1 ESX-1 secretion system protein EccCb 416 166
Rv3870 eccCa1 ESX-1 secretion system protein EccCa 503 163 textmining:431
Rv3868 eccA1 ESX-1 secretion system protein EccA1 436 163
Rv3865 espF ESX-1 secretion-associated protein EspF 584 160 textmining:525
Rv3866 espG1 ESX-1 secretion-associated protein EspG 505 159 textmining:436
Rv3874 esxB ESAT-6-like protein EsxB 718 156 textmining:680
Rv3864 espE ESX-1 secretion-associated protein EspE 654 152 textmining:609
Rv3875 esxA ESAT-6 protein EsxA 766 123 textmining:744
Rv3824c papA1 acyltransferase 417 68 textmining:400
Rv3849 espR ESX-1 transcriptional regulator EspR 637 55 textmining:632

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-associated protein EspD
  • MTBC0 PGAP product: type VII secretion system ESX-1 target EspD
  • (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_218131.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 2AVBJ
  • Curated reference: UniProt P9WJD5 (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 — 21 functional partner(s); context anchor espC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003831|Rv3614c|espD
MDLPGNDFDSNDFDAVDLWGADGAEGWTADPIIGVGSAATPDTGPDLDNAHGQAETDTEQEIALFTVTNPPRTVSVSTLMDGRIDHVELSARVAWMSESQLASEILVIADLARQKAQSAQYAFILDRMSQQVDADEHRVALLRKTVGETWGLPSPEEAAAAEAEVFATRYSDDCPAPDDESDPW