Rv3502c Resolved · high auto-curated

H37Rv Rv3502c · MTBC0 mtbc0_003717 · 317 aa · 3945669–3946622 (-) · RefSeq NP_218019.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)3-oxoacyl-ACP reductase
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 O53547 SwissProt · reviewed · Evidence at protein level
UniProt nameHydroxyacyl-CoA dehydrogenase ChsB1
EC (curated) EC 1.1.1.-
Curated functionA reversible dehydrogenase involved in cholesterol side-chain degradation. Catalyzes the oxidation of hydroxyl-cholesterol-CoA ester metabolic intermediate (22S)-HOCO-CoA (3-oxo-chol-4-ene-(22S)-hydroxy-24-oyl-CoA), the product of ChsH3, has no activity on (22R)-HOCO-CoA (the product of EchA19). Also acts on (3R)-hydroxyoctanoyl-CoA and 17-beta-hydroxyandrost-4-en-3-one, but not on 7-alpha-hydroxyandrost-4-en-3-one, uses NAD(+) but not NADP(+).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Q Secondary metabolites biosynthesis, transport and catabolism
Preferred namehsd4A
eggNOG descriptionBelongs to the short-chain dehydrogenases reductases (SDR) family
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
Gene Ontology (62) GO:0003674, GO:0003824, GO:0004303, GO:0005488, GO:0005515, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005777, GO:0006066, GO:0006629 +50 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 0.369 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 3 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 1.1e-3821–219 short chain dehydrogenase
KRPF08659.17 6.3e-1524–194 KR domain
adh_short_C2PF13561.13 2.5e-3127–263 Enoyl-(Acyl carrier protein) reductase

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

Closest characterised functional partner: Rv3538 (dehydrogenase), high confidence from genomic context alone (score 956 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3538 dehydrogenase 955 956 ctx fusion:900
Rv3389c htdY 3-hydroxyacyl-thioester dehydratase HtdY 947 947 ctx fusion:900
Rv3504 fadE26 acyl-CoA dehydrogenase FadE26 938 872 ctx neighborhood:736 textmining:541
Rv3505 fadE27 acyl-CoA dehydrogenase FadE27 860 843 ctx neighborhood:717
Rv2524c fas fatty acid synthase 826 800 coexpression:506 experimental:475
Rv3549c short-chain type dehydrogenase/reductase 774 774 ctx cooccurence:773
Rv3530c oxidoreductase 768 769 ctx cooccurence:766
Rv3506 fadD17 long-chain-fatty-acid--CoA ligase FadD17 784 753 ctx neighborhood:676
Rv3485c short-chain type dehydrogenase/reductase 751 751 ctx cooccurence:751
Rv3503c fdxD ferredoxin FdxD 726 726 ctx neighborhood:717
Rv1050 oxidoreductase 709 709 ctx cooccurence:702
Rv3492c Mce associated protein 701 700 ctx neighborhood:520
Rv3541c chsH1 hyp hypothetical protein 701 665 ctx cooccurence:512
Rv0765c oxidoreductase 645 646 ctx cooccurence:633
Rv3562 fadE31 acyl-CoA dehydrogenase FadE31 663 622 ctx cooccurence:422

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
  • MTBC0 PGAP product: 3-oxoacyl-ACP reductase
  • Pfam (hmmscan --cut_ga): adh_short PF00106.32 (E=1e-38), KR PF08659.17 (E=6e-15), adh_short_C2 PF13561.13 (E=3e-31)
  • (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_218019.1)
  • 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 O53547 (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 — 121 functional partner(s); context anchor Rv3538
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003717|Rv3502c|
MKLTESNRSPRTTNTTDLSGKVAVVTGAAAGLGRAEALGLARLGATVVVNDVASALDASDVVDEIGAAAADAGAKAVAVAGDISQRATADELLASAVGLGGLDIVVNNAGITRDRMLFNMSDEEWDAVIAVHLRGHFLLTRNAAAYWRDKAKDAEGGSVFGRLVNTSSEAGLVGPVGQANYAAAKAGITALTLSAARALGRYGVCANVICPRARTAMTADVFGAAPDVEAGQIDPLSPQHVVSLVQFLASPAAAEVNGQVFIVYGPQVTLVSPPHMERRFSADGTSWDPTELTATLRDYFAGRDPEQSFSATDLMRQ