eis Resolved · high auto-curated

H37Rv Rv2416c · MTBC0 - · 402 aa · 2714124–2715332 (-) · RefSeq NP_216932.2

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)enhanced intracellular survival protein
MTBC0 PGAP re-annotation
Revised (this work)Enhanced intracellular survival protein. Pfam: Acetyltransf_9 (PF13527.14), Acetyltransf_17 (PF17668.8), SCP2_2 (PF13530.12).

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 P9WFK7 SwissProt · reviewed · Evidence at protein level
UniProt nameN-acetyltransferase Eis
EC (curated) EC 2.3.1.-
Curated functionEffector that is released into the host cell and affects host immune responses; it negatively modulates inflammation, macrophage autophagy, and cell death through redox-dependent signaling. Acts as an acetyltransferase. Acetylates 'Lys-55' of dual-specificity protein phosphatase 16 (DUSP16)/mitogen-activated protein kinase phosphatase-7 (MKP-7), a JNK-specific phosphatase; this leads to the inhibition of JNK-dependent autophagy, phagosome maturation, and ROS (reactive oxygen species) generation for enhanced intracellular survival of M.tuberculosis. Inhibits Con A-mediated T-cell proliferation .

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred nameeis
eggNOG descriptionN-acetyltransferase Eis
Orthologous groupCOG4552
Gene Ontology (89) GO:0003674, GO:0003824, GO:0005488, GO:0005515, GO:0008080, GO:0008150, GO:0008152, GO:0009056, GO:0009605, GO:0009607, GO:0009987, GO:0010941 +77 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 2.505 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 7 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.37% of strains (540) · 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
Acetyltransf_9PF13527.14 1.4e-269–134 Acetyltransferase (GNAT) domain
Acetyltransf_17PF17668.8 1.4e-18188–298 Acetyltransferase (GNAT) domain
SCP2_2PF13530.12 2.4e-15301–395 Sterol carrier protein domain

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

Closest characterised functional partner: Rv3737 (transmembrane protein), medium confidence from genomic context alone (score 541 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2415c hyp hypothetical protein 865 865 ctx neighborhood:429 coexpression:774
Rv1258c tap multidrug-efflux transporter 898 845 coexpression:845
Rv1988 erm(37) 23S rRNA (adenine(2058)-N(6))-methyltransferase Erm(37) 832 805 coexpression:805
Rv3737 transmembrane protein 540 541 ctx cooccurence:475
Rv3365c hyp hypothetical protein 521 521 ctx cooccurence:518
Rv2417c DegV domain-containing protein 691 499 ctx neighborhood:494 textmining:410
Rv1226c transmembrane protein 471 472 ctx cooccurence:470
Rv2709 transmembrane protein 442 442 ctx cooccurence:442
Rv1249c membrane protein 439 440 ctx cooccurence:438
Rv2414c hyp hypothetical protein 427 426 ctx neighborhood:418
Rv2725c hflX GTP-binding protein HflX 414 415 coexpression:415
Rv3882c eccE1 ESX-1 secretion system protein EccE1 411 411 ctx cooccurence:411
Rv1171 hyp hypothetical protein 410 410 ctx cooccurence:403
Rv0801 hyp hypothetical protein 407 407 ctx cooccurence:407
Rv0977 PE_PGRS16 PE-PGRS family protein PE_PGRS16 401 401 ctx cooccurence:401

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): enhanced intracellular survival protein
  • Pfam (hmmscan --cut_ga): Acetyltransf_9 PF13527.14 (E=1e-26), Acetyltransf_17 PF17668.8 (E=1e-18), SCP2_2 PF13530.12 (E=2e-15)
  • (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_216932.2)
  • Domains: Pfam-A via hmmscan --cut_ga — Acetyltransf_9 (PF13527.14), Acetyltransf_17 (PF17668.8), SCP2_2 (PF13530.12)
  • 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 COG4552
  • Curated reference: UniProt P9WFK7 (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 Rv3737
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2416c|eis
MTVTLCSPTEDDWPGMFLLAAASFTDFIGPESATAWRTLVPTDGAVVVRDGAGPGSEVVGMALYMDLRLTVPGEVVLPTAGLSFVAVAPTHRRRGLLRAMCAELHRRIADSGYPVAALHASEGGIYGRFGYGPATTLHELTVDRRFARFHADAPGGGLGGSSVRLVRPTEHRGEFEAIYERWRQQVPGGLLRPQVLWDELLAECKAAPGGDRESFALLHPDGYALYRVDRTDLKLARVSELRAVTADAHCALWRALIGLDSMERISIITHPQDPLPHLLTDTRLARTTWRQDGLWLRIMNVPAALEARGYAHEVGEFSTVLEVSDGGRFALKIGDGRARCTPTDAAAEIEMDRDVLGSLYLGAHRASTLAAANRLRTKDSQLLRRLDAAFASDVPVQTAFEF