Rv3600c Resolved · high auto-curated

H37Rv Rv3600c · MTBC0 mtbc0_003818 · 272 aa · 4066745–4067563 (-) · RefSeq NP_218117.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)type III pantothenate kinase
MTBC0 PGAP re-annotationtype III pantothenate kinase
Revised (this work)Type III pantothenate kinase. Pfam: Pan_kinase (PF03309.21).

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

Curated reference (UniProt)

UniProt P9WPA1 SwissProt · reviewed · Evidence at protein level
UniProt nameType III pantothenate kinase
EC (curated) EC 2.7.1.33
Curated functionCatalyzes the phosphorylation of pantothenate (Pan), the first step in CoA biosynthesis.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
Preferred namecoaX
eggNOG descriptionCatalyzes the phosphorylation of pantothenate (Pan), the first step in CoA biosynthesis
Orthologous groupCOG1521
EC number EC 2.7.1.33
KEGG orthology K03525
KEGG pathways map00770, map01100
KEGG modules M00120
Gene Ontology (6) GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944

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 0.121 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 2 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
Pan_kinasePF03309.21 1.6e-612–206 Type III pantothenate kinase

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

Closest characterised functional partner: panC (pantothenate synthetase), high confidence from genomic context alone (score 997 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3602c panC pantothenate synthetase 999 997 ctx neighborhood:882 coexpression:759 database:900 textmining:713
Rv3601c panD aspartate 1-decarboxylase 987 979 ctx neighborhood:882 coexpression:827 textmining:421
Rv1391 dfp bifunctional phosphopantothenoylcysteine decarboxylase/phosphopantothenate--cysteine ligase 935 926 database:900
Rv2965c kdtB phosphopantetheine adenylyltransferase 950 919 database:900 textmining:416
Rv1092c coaA pantothenate kinase 945 900 database:900 textmining:482
Rv3603c hyp hypothetical protein 986 897 ctx neighborhood:881 textmining:870
Rv3598c lysS lysine--tRNA ligase 958 800 ctx neighborhood:773 textmining:803
Rv3604c transmembrane protein 741 741 ctx neighborhood:740
Rv3597c lsr2 iron-regulated H-NS-like protein 703 703 ctx neighborhood:702
Rv3610c ftsH zinc metalloprotease FtsH 678 677 ctx neighborhood:657
Rv3609c folE GTP cyclohydrolase I 666 666 ctx neighborhood:661
Rv3608c folP1 dihydropteroate synthase 678 663 ctx neighborhood:661
Rv3607c folB dihydroneopterin aldolase 663 663 ctx neighborhood:661
Rv3605c hyp hypothetical protein 661 661 ctx neighborhood:661
Rv3606c folK 2-amino-4-hydroxy-6-hydroxymethyldihydropteridinepyrophosphokinase 596 597 ctx neighborhood:594

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: type III pantothenate kinase
  • MTBC0 PGAP product: type III pantothenate kinase
  • Pfam (hmmscan --cut_ga): Pan_kinase PF03309.21 (E=2e-61)
  • (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_218117.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Pan_kinase (PF03309.21)
  • 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 COG1521
  • Curated reference: UniProt P9WPA1 (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 — 26 functional partner(s); context anchor panC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003818|Rv3600c|
MLLAIDVRNTHTVVGLLSGMKEHAKVVQQWRIRTESEVTADELALTIDGLIGEDSERLTGTAALSTVPSVLHEVRIMLDQYWPSVPHVLIEPGVRTGIPLLVDNPKEVGADRIVNCLAAYDRFRKAAIVVDFGSSICVDVVSAKGEFLGGAIAPGVQVSSDAAAARSAALRRVELARPRSVVGKNTVECMQAGAVFGFAGLVDGLVGRIREDVSGFSVDHDVAIVATGHTAPLLLPELHTVDHYDQHLTLQGLRLVFERNLEVQRGRLKTAR