idsA1 Resolved · high auto-curated

H37Rv Rv3398c · MTBC0 - · 359 aa · 3815027–3816106 (-) · RefSeq YP_177970.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)multifunctional dimethylallyltransferase/geranyltranstransferase/farnesyltranstransferase
MTBC0 PGAP re-annotation
Revised (this work)Multifunctional dimethylallyltransferase/geranyltranstransferase/farnesyltranstransferase. Pfam: polyprenyl_synt (PF00348.23).

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 P9WKH1 SwissProt · reviewed · Evidence at protein level
UniProt name(2E,6E)-farnesyl diphosphate synthase
EC (curated) EC 2.5.1.10
Curated functionCatalyzes the condensation of isopentenyl pyrophosphate (IPP) with geranyl diphosphate (GPP) to yield (2E,6E)-farnesyl diphosphate (E,E-FPP). May be used for squalene and possibly sterol biosynthesis.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred nameidsA1
eggNOG descriptionBelongs to the FPP GGPP synthase family
Orthologous groupCOG0142
EC number EC 2.5.1.1, EC 2.5.1.10, EC 2.5.1.29
KEGG orthology K13787, K13789
KEGG pathways map00900, map01100, map01110, map01130
KEGG modules M00364, M00365, M00366
Gene Ontology (43) GO:0000287, GO:0003674, GO:0003824, GO:0004161, GO:0004659, GO:0005488, GO:0005506, GO:0006629, GO:0006644, GO:0006720, GO:0006721, GO:0006793 +31 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 0.098 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 7 synonymous, 2 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.19% of strains (282) · 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
polyprenyl_syntPF00348.23 7.9e-5670–292 Polyprenyl synthetase

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

Closest characterised functional partner: phyA (phytoene synthase), high confidence from genomic context alone (score 995 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3397c phyA phytoene synthase 995 995 ctx neighborhood:741 coexpression:876 database:800
Rv1086 (2Z,6E)-farnesyl diphosphate synthase 980 966 ctx cooccurence:644 database:900 textmining:462
Rv0989c grcC2 polyprenyl-diphosphate synthase GrcC 948 926 database:900
Rv0562 grcC1 polyprenyl-diphosphate synthase GrcC 948 925 database:900
Rv2173 idsA2 geranylgeranyl pyrophosphate synthetase IdsA 943 916 database:900
Rv3383c idsB polyprenyl synthetase IdsB 930 916 database:900
Rv1745c idi isopentenyl-diphosphate delta-isomerase 951 911 database:900 textmining:478
Rv3382c lytB1 4-hydroxy-3-methylbut-2-enyl diphosphate reductase 968 906 database:900 textmining:675
Rv1110 lytB2 4-hydroxy-3-methylbut-2-enyl diphosphate reductase 964 906 database:900 textmining:641
Rv3399 S-adenosylmethionine-dependent methyltransferase 789 789 ctx neighborhood:567 coexpression:458
Rv3396c guaA GMP synthase 788 778 ctx neighborhood:686
Rv2361c uppS decaprenyl diphosphate synthase 880 653 ctx cooccurence:622 textmining:669
Rv2752c rnj ribonuclease J 527 528 coexpression:512
Rv2337c hyp hypothetical protein 518 510 database:419
Rv0721 rpsE 30S ribosomal protein S5 500 500 coexpression:414

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): multifunctional dimethylallyltransferase/geranyltranstransferase/farnesyltranstransferase
  • Pfam (hmmscan --cut_ga): polyprenyl_synt PF00348.23 (E=8e-56)
  • (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 YP_177970.1)
  • Domains: Pfam-A via hmmscan --cut_ga — polyprenyl_synt (PF00348.23)
  • 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 COG0142
  • Curated reference: UniProt P9WKH1 (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 — 42 functional partner(s); context anchor phyA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3398c|idsA1
MRGTDEKYGLPPQPDSDRMTRRTLPVLGLAHELITPTLRQMADRLDPHMRPVVSYHLGWSDERGRPVNNNCGKAIRPALVFVAAEAAGADPHSAIPGAVSVELVHNFSLVHDDLMDRDEHRRHRPTVWALWGDAMALLAGDAMLSLAHEVLLDCDSPHVGAALRAISEATRELIRGQAADTAFESRTDVALDECLKMAEGKTAALMAASAEVGALLAGAPRSVREALVAYGRHIGLAFQLVDDLLGIWGRPEITGKPVYSDLRSRKKTLPVTWTVAHGGSAGRRLAAWLVDETGSQTASDDELAAVAELIECGGGRRWASAEARRHVTQGIDMVARIGIPDRPAAELQDLAHYIVDRQA