Rv2170 Resolved · high auto-curated

H37Rv Rv2170 · MTBC0 mtbc0_002304 · 206 aa · 2458242–2458862 (+) · RefSeq NP_216686.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)GCN5-like N-acetyltransferase
MTBC0 PGAP re-annotationN-acetyltransferase
Revised (this work)N-acetyltransferase. Pfam: FR47 (PF08445.17), Acetyltransf_1 (PF00583.32), Acetyltransf_7 (PF13508.14).

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

Curated reference (UniProt)

UniProt O53504 SwissProt · reviewed · Evidence at protein level
UniProt nameGCN5-like protein acetyltransferase Rv2170
EC (curated) EC 2.3.1.-
Curated functionAcetyltransferase involved in the post-translational regulation of the central metabolic enzyme isocitrate dehydrogenase 1 (ICDH-1) through lysine acetylation. Catalyzes the acetylation of ICDH-1 at Lys-30 and Lys-129, using acetyl-CoA as a donor, leading to a reduction of ICDH-1 enzyme activity. Can also use propionyl-CoA and succinyl-CoA as donors. Cannot act on the isocitrate dehydrogenase 2 (ICDH-2). Might play a role in regulating the TCA cycle and methylcitrate cycle when M.tuberculosis utilizes fatty acid as carbon source..; FUNCTION: In addition, it can acetylate the amino group of iso.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
eggNOG descriptionAcetyltransferase (GNAT) family
Orthologous groupCOG0454

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 0.281 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 4 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)

PfamAccessioni-EvalueResiduesDescription
FR47PF08445.17 9.1e-07104–184 FR47-like protein
Acetyltransf_1PF00583.32 4.3e-05124–181 Acetyltransferase (GNAT) family
Acetyltransf_7PF13508.14 2.9e-06125–182 Acetyltransferase (GNAT) domain

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

Closest characterised functional partner: Rv2169c (transmembrane protein), high confidence from genomic context alone (score 776 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2169c transmembrane protein 776 776 ctx neighborhood:733
Rv2171 lppM lipoprotein LppM 775 776 ctx neighborhood:775
Rv3231c hyp hypothetical protein 770 771 ctx cooccurence:770
Rv3311 hyp hypothetical protein 763 763 ctx cooccurence:763
Rv2520c membrane protein 740 741 ctx cooccurence:740
Rv3212 hyp hypothetical protein 736 737 ctx cooccurence:735
Rv3605c hyp hypothetical protein 722 722 ctx cooccurence:722
Rv2179c 3'-5' exoribonuclease 715 716 ctx cooccurence:714
Rv3438 hyp hypothetical protein 712 712 ctx cooccurence:711
Rv1209 hyp hypothetical protein 700 700 ctx cooccurence:700
Rv2446c integral membrane protein 699 700 ctx cooccurence:699
Rv2980 hyp hypothetical protein 697 697 ctx cooccurence:697
Rv0948c chorismate mutase 695 695 ctx cooccurence:692
Rv3412 hyp hypothetical protein 686 686 ctx cooccurence:686
Rv2219 transmembrane protein 682 683 ctx cooccurence:681

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: GCN5-like N-acetyltransferase
  • MTBC0 PGAP product: N-acetyltransferase
  • Pfam (hmmscan --cut_ga): FR47 PF08445.17 (E=9e-07), Acetyltransf_1 PF00583.32 (E=4e-05), Acetyltransf_7 PF13508.14 (E=3e-06)
  • (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_216686.1)
  • Domains: Pfam-A via hmmscan --cut_ga — FR47 (PF08445.17), Acetyltransf_1 (PF00583.32), Acetyltransf_7 (PF13508.14)
  • 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 COG0454
  • Curated reference: UniProt O53504 (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 — 80 functional partner(s); context anchor Rv2169c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002304|Rv2170|
MAIFLIDLPPSDMERRLGDALTVYVDAMRYPRGTETLRAPMWLEHIRRRGWQAVAAVEVTAAEQAEAADTTALPSAAELSNAPMLGVAYGYPGAPGQWWQQQVVLGLQRSGFPRLAIARLMTSYFELTELHILPRAQGRGLGEALARRLLAGRDEDNVLLSTPETNGEDNRAWRLYRRLGFTDIIRGYHFAGDPRAFAILGRTLPL