phyA Resolved · high auto-curated

H37Rv Rv3397c · MTBC0 mtbc0_003610 · 302 aa · 3839529–3840437 (-) · RefSeq NP_217914.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)phytoene synthase
MTBC0 PGAP re-annotationpresqualene diphosphate synthase HpnD
Revised (this work)Presqualene diphosphate synthase HpnD. Pfam: SQS_PSY (PF00494.25).

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

Curated reference (UniProt)

UniProt P9WHP3 SwissProt · reviewed · Evidence at protein level
UniProt namePhytoene synthase
EC (curated) EC 2.5.1.-
Curated functionInvolved in the biosynthesis of carotenoids. Catalyzes the condensation of two molecules of geranylgeranyl diphosphate (GGPP) to give prephytoene diphosphate (PPPP) and the subsequent rearrangement of the cyclopropylcarbinyl intermediate to yield phytoene (By similarity).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred namecrtB
eggNOG descriptionPhytoene synthase
Orthologous groupCOG1562
EC number EC 2.5.1.32, EC 2.5.1.99
KEGG orthology K02291
KEGG pathways map00906, map01062, map01100, map01110
KEGG modules M00097
Gene Ontology (29) GO:0003674, GO:0003824, GO:0004337, GO:0004659, GO:0006629, GO:0006720, GO:0006721, GO:0008150, GO:0008152, GO:0008299, GO:0008610, GO:0009058 +17 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 0.892 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 5 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
SQS_PSYPF00494.25 6.0e-6216–268 Squalene/phytoene synthase

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

Closest characterised functional partner: idsA1 (multifunctional dimethylallyltransferase/geranyltranstransferase/farnesyltranstransferase), high confidence from genomic context alone (score 995 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3398c idsA1 multifunctional dimethylallyltransferase/geranyltranstransferase/farnesyltranstransferase 995 995 ctx neighborhood:741 coexpression:876 database:800
Rv2173 idsA2 geranylgeranyl pyrophosphate synthetase IdsA 954 886 database:800 textmining:620
Rv3399 S-adenosylmethionine-dependent methyltransferase 880 880 ctx neighborhood:508 coexpression:767
Rv0562 grcC1 polyprenyl-diphosphate synthase GrcC 903 864 database:800
Rv0989c grcC2 polyprenyl-diphosphate synthase GrcC 903 863 database:800
Rv3383c idsB polyprenyl synthetase IdsB 873 863 database:800
Rv3152 nuoH NADH-quinone oxidoreductase subunit H 859 851 database:844
Rv1814 erg3 membrane-bound C-5 sterol desaturase 877 840 experimental:785
Rv3396c guaA GMP synthase 792 793 ctx neighborhood:789
Rv2836c dinF DNA-damage-inducible protein DinF 790 777 coexpression:751
Rv1436 gap glyceraldehyde 3-phosphate dehydrogenase 793 771 coexpression:768
Rv3147 nuoC NADH-quinone oxidoreductase subunit C 795 765 database:727
Rv3153 nuoI NADH-quinone oxidoreductase subunit I 766 754 database:727
Rv3148 nuoD NADH-quinone oxidoreductase subunit D 756 740 database:727
Rv3146 nuoB NADH-quinone oxidoreductase subunit B 746 735 database:727

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: phytoene synthase
  • MTBC0 PGAP product: presqualene diphosphate synthase HpnD
  • Pfam (hmmscan --cut_ga): SQS_PSY PF00494.25 (E=6e-62)
  • (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_217914.1)
  • Domains: Pfam-A via hmmscan --cut_ga — SQS_PSY (PF00494.25)
  • 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 COG1562
  • Curated reference: UniProt P9WHP3 (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 — 116 functional partner(s); context anchor idsA1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003610|Rv3397c|phyA
MTEIEQAYRITESITRTAARNFYYGIRLLPREKRAALSAVYALGRRIDDVADGELAPETKITELDAIRKSLDNIDDSSDPVLVALADAARRFPVPIAMFAELIDGARMEIDWTGCRDFDELIVYCRRGAGTIGKLCLSIFGPVSTATSRYAEQLGIALQQTNILRDVREDFLNGRIYLPRDELDRLGVRLRLDDTGALDDPDGRLAALLRFSADRAADWYSLGLRLIPHLDRRSAACCAAMSGIYRRQLALIRASPAVVYDRRISLSGLKKAQVAAAALASSVTCGPAHGPLPADLGSHPSH