pptT Resolved · high auto-curated

H37Rv Rv2794c · MTBC0 mtbc0_002973 · 227 aa · 3125672–3126355 (-) · RefSeq NP_217310.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)4'-phosphopantetheinyl transferase
MTBC0 PGAP re-annotation4'-phosphopantetheinyl transferase
Revised (this work)4'-phosphopantetheinyl transferase. Pfam: 4PPT_N (PF17837.7), ACPS (PF01648.26).

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

Curated reference (UniProt)

UniProt O33336 SwissProt · reviewed · Evidence at protein level
UniProt name4'-phosphopantetheinyl transferase PptT
EC (curated) EC 2.7.8.7
Curated functionTransfers the 4'-phosphopantetheine moiety from coenzyme A to a Ser of acyl-carrier-protein. Involved in post-translational modification of various type-I polyketide synthases required for the formation of both mycolic acids and lipid virulence factors. Acts on Pks13, Mas, PpsA, PpsB, PpsC and PpsD. Also acts on AcpM, the meromycolate extension acyl carrier protein. In addition, is involved in the activation of the acyl carrier protein MbtL and the nonribosomal peptides synthases MbtB and MbtE, which are involved in the biosynthesis of the siderophore mycobactin..; FUNCTION: Required for the r.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
Preferred namepptA
eggNOG descriptionBelongs to the P-Pant transferase superfamily
Orthologous groupCOG2977

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 0.188 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 15 synonymous, 8 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
4PPT_NPF17837.7 4.2e-2636–102 4'-phosphopantetheinyl transferase N-terminal domain
ACPSPF01648.26 2.4e-12110–186 4'-phosphopantetheinyl transferase superfamily

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

Closest characterised functional partner: truB (tRNA pseudouridine synthase B), high confidence from genomic context alone (score 906 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2795c hyp hypothetical protein 992 946 ctx neighborhood:882 textmining:870
Rv2793c truB tRNA pseudouridine synthase B 906 906 ctx neighborhood:882
Rv2383c mbtB phenyloxazoline synthase 953 895 ctx neighborhood:544 coexpression:780 textmining:578
Rv2790c ltp1 lipid-transfer protein 721 716 ctx neighborhood:712
Rv3800c pks13 polyketide synthase 932 713 coexpression:462 textmining:775
Rv2789c fadE21 acyl-CoA dehydrogenase FadE21 710 710 ctx neighborhood:697
Rv2384 mbtA 2,3-dihydroxybenzoate-AMP ligase 785 708 coexpression:684
Rv2799 membrane protein 692 692 ctx neighborhood:691
Rv1888A Rv1888A, len: 57 aa. Conserved hypothetical protein. Possibly continuation of Rv1889c, part of large family of Mycobacterium tuberculosis pr 557 557 ctx cooccurence:556
Rv2797c hyp hypothetical protein 547 546 ctx neighborhood:542
Rv2798c hyp hypothetical protein 545 545 ctx neighborhood:542
Rv2796c lppV lipoprotein LppV 545 544 ctx neighborhood:542
Rv2792c resolvase 490 490 ctx neighborhood:474
Rv2791c tnpB transposase 490 490 ctx neighborhood:474
Rv0101 nrp peptide synthetase Nrp 538 482 coexpression:412

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: 4'-phosphopantetheinyl transferase
  • MTBC0 PGAP product: 4'-phosphopantetheinyl transferase
  • Pfam (hmmscan --cut_ga): 4PPT_N PF17837.7 (E=4e-26), ACPS PF01648.26 (E=2e-12)
  • (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_217310.1)
  • Domains: Pfam-A via hmmscan --cut_ga — 4PPT_N (PF17837.7), ACPS (PF01648.26)
  • 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 COG2977
  • Curated reference: UniProt O33336 (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 — 55 functional partner(s); context anchor truB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002973|Rv2794c|pptT
MTVGTLVASVLPATVFEDLAYAELYSDPPGLTPLPEEAPLIARSVAKRRNEFITVRHCARIALDQLGVPPAPILKGDKGEPCWPDGVVGSLTHCAGYRGAVVGRRDAVRSVGIDAEPHDVLPNGVLDAISLPAERADMPRTMPAALHWDRILFCAKEATYKAWFPLTKRWLGFEDAHITFETDSTGWTGRFVSRILIDGSTLSGPPLTTLRGRWSVERGLVLTAIVL