Rv3559c Family assigned · medium auto-curated

H37Rv Rv3559c · MTBC0 mtbc0_003776 · 262 aa · 4023324–4024112 (-) · RefSeq NP_218076.1

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), 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 I6YCF0 SwissProt · reviewed · Evidence at protein level
UniProt name(5R,7aS)-5-hydroxy-7a-methyl-1-oxo-2,3,5,6,7,7a-hexahydro-1H-indene-carboxyl-CoA reductase
EC (curated) EC 1.1.1.-
Curated functionInvolved in the final steps of cholesterol and steroid degradation. Probably catalyzes the oxidation of the 5-OH group of (5R,7aS)-5-hydroxy-7a-methyl-1-oxo-2,3,5,6,7,7a-hexahydro-1H-indene-carboxyl-CoA, leading to the formation of HIEC-CoA (Probable).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Q Secondary metabolites biosynthesis, transport and catabolism
eggNOG descriptionDehydrogenase
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 0.133 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 11 synonymous, 4 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 2.3e-5019–205 short chain dehydrogenase
KRPF08659.17 7.8e-1222–182 KR domain
adh_short_C2PF13561.13 2.6e-5826–257 Enoyl-(Acyl carrier protein) reductase

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

Closest characterised functional partner: fadE30 (acyl-CoA dehydrogenase FadE30), high confidence from genomic context alone (score 995 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3560c fadE30 acyl-CoA dehydrogenase FadE30 996 995 ctx neighborhood:882 cooccurence:425 coexpression:796 database:622
Rv3562 fadE31 acyl-CoA dehydrogenase FadE31 988 980 ctx neighborhood:788 cooccurence:505 coexpression:736 textmining:478
Rv2524c fas fatty acid synthase 981 979 coexpression:508 experimental:475 database:918
Rv3561 fadD3 fatty-acid--CoA ligase FadD3 969 969 ctx neighborhood:588 coexpression:815 database:500
Rv3564 fadE33 acyl-CoA dehydrogenase FadE33 954 953 ctx neighborhood:770 coexpression:710
Rv2243 fabD malonyl CoA-acyl carrier protein transacylase 945 943 database:900
Rv3552 CoA-transferase subunit beta 943 941 ctx cooccurence:709 coexpression:783
Rv3553 oxidoreductase 962 933 coexpression:813 database:500 textmining:462
Rv3563 fadE32 acyl-CoA dehydrogenase FadE32 961 929 ctx neighborhood:788 textmining:479
Rv0769 oxidoreductase 924 925 database:900
Rv3551 CoA-transferase subunit alpha 955 919 ctx cooccurence:706 coexpression:730 textmining:479
Rv1350 fabG2 3-oxoacyl-ACP reductase FabG 916 916 database:900
Rv0242c fabG4 3-oxoacyl-ACP reductase FabG 913 914 database:900
Rv0649 fabD2 malonyl CoA-acyl carrier protein transacylase 900 901 database:900
Rv3550 echA20 enoyl-CoA hydratase EchA20 942 894 ctx cooccurence:561 database:591 textmining:478

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=2e-50), KR PF08659.17 (E=8e-12), adh_short_C2 PF13561.13 (E=3e-58)
  • (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_218076.1)
  • 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 I6YCF0 (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 — 117 functional partner(s); context anchor fadE30
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003776|Rv3559c|
MNLSVAPKEIAGHGLLDGKVVVVTAAAGTGIGSATARRALAEGADVVISDHHERRLGETAAELSALGLGRVEHVVCDVTSTAQVDALIDSTTARMGRLDVLVNNAGLGGQTPVADMTDDEWDRVLDVSLTSVFRATRAALRYFRDAPHGGVIVNNASVLGWRAQHSQSHYAAAKAGVMALTRCSAIEAAEYGVRINAVSPSIARHKFLDKTASAELLDRLAAGEAFGRAAEPWEVAATIAFLASDYSSYLTGEVISVSCQHP