panC Resolved · high auto-curated

H37Rv Rv3602c · MTBC0 mtbc0_003820 · 309 aa · 4067985–4068914 (-) · RefSeq NP_218119.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)pantothenate synthetase
MTBC0 PGAP re-annotationpantoate--beta-alanine ligase
Revised (this work)Pantoate--beta-alanine ligase. Pfam: Pantoate_ligase (PF02569.22).

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

Curated reference (UniProt)

UniProt P9WIL5 SwissProt · reviewed · Evidence at protein level
UniProt namePantothenate synthetase
EC (curated) EC 6.3.2.1
Curated functionCatalyzes the condensation of pantoate with beta-alanine in an ATP-dependent reaction via a pantoyl-adenylate intermediate.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred namepanC
eggNOG descriptionCatalyzes the condensation of pantoate with beta-alanine in an ATP-dependent reaction via a pantoyl-adenylate intermediate
Orthologous groupCOG0414
EC number EC 6.3.2.1
KEGG orthology K01918
KEGG pathways map00410, map00770, map01100, map01110
KEGG modules M00119
Gene Ontology (84) GO:0000166, GO:0000287, GO:0001505, GO:0003674, GO:0003824, GO:0004592, GO:0005488, GO:0005524, GO:0005575, GO:0005622, GO:0005623, GO:0005737 +72 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 0.096 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 1 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
Pantoate_ligasePF02569.22 7.0e-9418–283 Pantoate-beta-alanine ligase

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

Closest characterised functional partner: panD (aspartate 1-decarboxylase), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3601c panD aspartate 1-decarboxylase 999 1000 ctx neighborhood:882 cooccurence:678 coexpression:967 database:900 textmining:942
Rv3600c coaX type III pantothenate kinase 999 997 ctx neighborhood:882 coexpression:759 database:900 textmining:713
Rv2225 panB 3-methyl-2-oxobutanoate hydroxymethyltransferase 999 995 ctx fusion:811 cooccurence:774 coexpression:859 textmining:917
Rv3603c hyp hypothetical protein 997 986 ctx neighborhood:881 fusion:795 cooccurence:471 textmining:806
Rv3432c gadB glutamate decarboxylase GadB 946 943 coexpression:421 database:900
Rv2573 2-dehydropantoate 2-reductase 933 913 database:900
Rv1712 cmk cytidylate kinase 908 908 ctx fusion:900
Rv3293 pcd piperideine-6-carboxylic acid dehydrogenase 905 901 database:900
Rv1092c coaA pantothenate kinase 963 900 database:900 textmining:650
Rv2589 gabT 4-aminobutyrate aminotransferase 905 900 database:900
Rv0223c aldehyde dehydrogenase 904 900 database:900
Rv0147 aldehyde dehydrogenase 903 900 database:900
Rv0768 aldA aldehyde dehydrogenase AldA 903 900 database:900
Rv1391 dfp bifunctional phosphopantothenoylcysteine decarboxylase/phosphopantothenate--cysteine ligase 927 866 database:800 textmining:480
Rv3598c lysS lysine--tRNA ligase 881 787 ctx neighborhood:773 textmining:465

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: pantothenate synthetase
  • MTBC0 PGAP product: pantoate--beta-alanine ligase
  • Pfam (hmmscan --cut_ga): Pantoate_ligase PF02569.22 (E=7e-94)
  • (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_218119.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Pantoate_ligase (PF02569.22)
  • 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 COG0414
  • Curated reference: UniProt P9WIL5 (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 — 52 functional partner(s); context anchor panD
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003820|Rv3602c|panC
MTIPAFHPGELNVYSAPGDVADVSRALRLTGRRVMLVPTMGALHEGHLALVRAAKRVPGSVVVVSIFVNPMQFGAGEDLDAYPRTPDDDLAQLRAEGVEIAFTPTTAAMYPDGLRTTVQPGPLAAELEGGPRPTHFAGVLTVVLKLLQIVRPDRVFFGEKDYQQLVLIRQLVADFNLDVAVVGVPTVREADGLAMSSRNRYLDPAQRAAAVALSAALTAAAHAATAGAQAALDAARAVLDAAPGVAVDYLELRDIGLGPMPLNGSGRLLVAARLGTTRLLDNIAIEIGTFAGTDRPDGYRAILESHWRN