Rv0547c Family assigned · medium auto-curated

H37Rv Rv0547c · MTBC0 mtbc0_000576 · 294 aa · 641583–642467 (-) · RefSeq NP_215061.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)oxidoreductase
MTBC0 PGAP re-annotationSDR family oxidoreductase
Revised (this work)SDR family oxidoreductase. Pfam: adh_short (PF00106.32), 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 O06413 SwissProt · reviewed · Evidence at protein level
UniProt nameFatty acyl-CoA reductase Rv0547c
EC (curated) EC 1.2.1.-
Curated functionOxidoreductase that promotes the persistence of M.tuberculosis in host macrophages by reprogramming the fatty acid metabolism in host mitochondria. When localized in the host mitochondria, it potentially acts on unknown lipid substrates and converts them into products that directly or indirectly alter the lipid profile of the mitochondria. This change in lipid profile results in increased mitochondrial membrane fluidity, enhanced endogenous fatty acid oxidation and increased mitochondrial spare respiratory capacity. All these events eventually favor M.tuberculosis persistence in the host macro.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionBelongs to the short-chain dehydrogenases reductases (SDR) family
Orthologous groupCOG0300

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 0.724 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 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 1.1e-3741–233 short chain dehydrogenase
adh_short_C2PF13561.13 1.4e-2847–241 Enoyl-(Acyl carrier protein) reductase

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

Closest characterised functional partner: Rv0544c (transmembrane protein), high confidence from genomic context alone (score 716 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0544c transmembrane protein 715 716 ctx neighborhood:714
Rv0545c pitA low-affinity inorganic phosphate transporter 715 716 ctx neighborhood:714
Rv3485c short-chain type dehydrogenase/reductase 704 693 ctx cooccurence:651
Rv3740c diacyglycerol O-acyltransferase 669 669 ctx cooccurence:661
Rv3734c tgs2 diacyglycerol O-acyltransferase 666 667 ctx cooccurence:657
Rv0548c menB 1,4-dihydroxy-2-naphthoyl-CoA synthase 662 662 ctx neighborhood:657
Rv3480c diacyglycerol O-acyltransferase 658 659 ctx cooccurence:640
Rv0542c menE 2-succinylbenzoic acid--CoA ligase 662 653 ctx neighborhood:651
Rv0541c integral membrane protein 639 638 ctx neighborhood:635
Rv0551c fadD8 fatty-acid--CoA ligase FadD8 641 632 ctx neighborhood:630
Rv2285 diacylglycerol acyltransferase 631 632 ctx cooccurence:614
Rv0895 diacyglycerol O-acyltransferase 627 627 ctx cooccurence:617
Rv1714 oxidoreductase 624 615 ctx cooccurence:560
Rv0546c hyp hypothetical protein 597 597 ctx neighborhood:590
Rv3088 tgs4 diacyglycerol O-acyltransferase 571 572 ctx cooccurence:569

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: oxidoreductase
  • MTBC0 PGAP product: SDR family oxidoreductase
  • Pfam (hmmscan --cut_ga): adh_short PF00106.32 (E=1e-37), adh_short_C2 PF13561.13 (E=1e-28)
  • (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_215061.1)
  • Domains: Pfam-A via hmmscan --cut_ga — adh_short (PF00106.32), 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 COG0300
  • Curated reference: UniProt O06413 (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 — 38 functional partner(s); context anchor Rv0544c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000576|Rv0547c|
MSKRPLRWLTEQITLAGMRPPISPQLLINRPAMQPVDLTGKRILLTGASSGIGAAATKQFGLHRAVVVAVARRKDLLDAVADRITGDGGTAMSLPCDLSDMEAIDALVEDVEKRIGGIDILINNAGRSIRRPLAESLERWHDVERTMVLNYYAPLRLIRGLAPGMLERGDGHIINVATWGVLSEASPLFSVYNASKAALSAVSRIIETEWGSQGVHSTTLYYPLVATPMIAPTKAYDGLPALTAAEAAEWMVTAARTRPVRIAPRVAVAVNALDSIGPRWVNALMQRRNEQLNP