fabG4 Resolved · high auto-curated

H37Rv Rv0242c · MTBC0 mtbc0_000258 · 454 aa · 291046–292410 (-) · RefSeq NP_214756.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)3-oxoacyl-ACP reductase FabG
MTBC0 PGAP re-annotation3-oxoacyl-ACP reductase
Revised (this work)3-oxoacyl-ACP reductase. Pfam: adh_short (PF00106.32), KR (PF08659.17), adh_short_C2 (PF13561.13).

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

Curated reference (UniProt)

UniProt I6Y778 SwissProt · reviewed · Evidence at protein level
UniProt name3-oxoacyl-[acyl-carrier-protein] reductase [NADH]
EC (curated) EC 1.1.1.212
Curated functionCatalyzes the NADH-dependent reduction of beta-ketoacyl derivatives. Can accept the beta-oxo fatty acyl group covalently linked with CoA or ACP for catalysis. Highly specific for NADH. Could be involved in fatty acid biosynthesis (Probable).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Q Secondary metabolites biosynthesis, transport and catabolism
Preferred namefabG
eggNOG descriptionCatalyzes the first of the two reduction steps in the elongation cycle of fatty acid synthesis
Orthologous groupCOG1028
EC number EC 1.1.1.100
KEGG orthology K00059
KEGG pathways map00061, map00333, map00780, map01040, map01100, map01130, map01212
KEGG modules M00083, M00572

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 0.223 · purifying
Polymorphic sites (≥ 0.1% of strains) 10 synonymous, 6 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
adh_shortPF00106.32 5.7e-45214–401 short chain dehydrogenase
KRPF08659.17 2.0e-13216–373 KR domain
adh_short_C2PF13561.13 2.3e-47220–447 Enoyl-(Acyl carrier protein) reductase

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

Closest characterised functional partner: htdX (3-hydroxyacyl-thioester dehydratase HtdX), high confidence from genomic context alone (score 997 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0241c htdX 3-hydroxyacyl-thioester dehydratase HtdX 998 997 ctx neighborhood:879 cooccurence:768 coexpression:853 textmining:449
Rv0243 fadA2 acetyl-CoA acetyltransferase FadA 992 992 ctx neighborhood:773 cooccurence:740 coexpression:863
Rv2524c fas fatty acid synthase 981 979 coexpression:508 experimental:475 database:918
Rv2243 fabD malonyl CoA-acyl carrier protein transacylase 960 959 database:900
Rv3389c htdY 3-hydroxyacyl-thioester dehydratase HtdY 951 931 ctx fusion:900
Rv3538 dehydrogenase 931 931 ctx fusion:899
Rv3559c oxidoreductase 913 914 database:900
Rv0769 oxidoreductase 913 914 database:900
Rv1350 fabG2 3-oxoacyl-ACP reductase FabG 918 913 database:900
Rv0649 fabD2 malonyl CoA-acyl carrier protein transacylase 900 900 database:900
Rv0148 short-chain type dehydrogenase/reductase 899 899 ctx fusion:899
Rv3085 sadH oxidoreductase SadH 680 681 ctx cooccurence:672
Rv1543 oxidoreductase 612 598 ctx cooccurence:540
Rv3140 fadE23 acyl-CoA dehydrogenase FadE23 590 556
Rv1937 oxygenase 591 543

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: 3-oxoacyl-ACP reductase FabG
  • MTBC0 PGAP product: 3-oxoacyl-ACP reductase
  • Pfam (hmmscan --cut_ga): adh_short PF00106.32 (E=6e-45), KR PF08659.17 (E=2e-13), adh_short_C2 PF13561.13 (E=2e-47)
  • (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_214756.1)
  • Domains: Pfam-A via hmmscan --cut_ga — adh_short (PF00106.32), KR (PF08659.17), adh_short_C2 (PF13561.13)
  • 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 COG1028
  • Curated reference: UniProt I6Y778 (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 — 111 functional partner(s); context anchor htdX
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000258|Rv0242c|fabG4
MAPKRSSDLFSQVVNSGPGSFLARQLGVPQPETLRRYRAGEPPLTGSLLIGGAGRVVEPLRAALEKDYDLVGNNLGGRWADSFGGLVFDATGITEPAGLKGLHEFFTPVLRNLGRCGRVVVVGGTPEAAASTNERIAQRALEGFTRSLGKELRRGATTALVYLSPDAKPAATGLESTMRFLLSAKSAYVDGQVFSVGADDSTPPADWEKPLDGKVAIVTGAARGIGATIAEVFARDGAHVVAIDVESAAENLAETASKVGGTALWLDVTADDAVDKISEHLRDHHGGKADILVNNAGITRDKLLANMDDARWDAVLAVNLLAPLRLTEGLVGNGSIGEGGRVIGLSSIAGIAGNRGQTNYATTKAGMIGITQALAPGLAAKGITINAVAPGFIETQMTAAIPLATREVGRRLNSLLQGGQPVDVAEAIAYFASPASNAVTGNVIRVCGQAMIGA