Rv3553 Resolved · high auto-curated

H37Rv Rv3553 · MTBC0 mtbc0_003770 · 355 aa · 4015298–4016365 (+) · RefSeq NP_218070.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)oxidoreductase
MTBC0 PGAP re-annotationnitronate monooxygenase
Revised (this work)Nitronate monooxygenase. Pfam: IMPDH (PF00478.32), NMO (PF03060.22), FMN_dh (PF01070.25).

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

Curated reference (UniProt)

UniProt P71847 SwissProt · reviewed · Evidence at protein level
UniProt name(3aS,4S,5R,7aS)-5-hydroxy-7a-methyl-1-oxo-octahydro-1H-indene-4-carboxyl-CoA dehydrogenase
EC (curated) EC 1.3.1.-
Curated functionInvolved in the final steps of cholesterol and steroid degradation. Probably catalyzes the introduction of a double bound into the C ring of 5OH-HIC-CoA, leading to the formation of (5R,7aS)-5-hydroxy-7a-methyl-1-oxo-3,5,6,7-tetrahydro-2H-indene-4-carboxyl-CoA (Probable).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namefabK
eggNOG description2-nitropropane dioxygenase
Orthologous groupCOG2070
EC number EC 1.13.12.16
KEGG orthology K00459
KEGG pathways map00910
Gene Ontology (148) GO:0000166, GO:0001775, GO:0002252, GO:0002263, GO:0002274, GO:0002275, GO:0002283, GO:0002366, GO:0002376, GO:0002443, GO:0002444, GO:0002446 +136 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 0.186 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 1 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
IMPDHPF00478.32 9.8e-102–205 IMP dehydrogenase / GMP reductase domain
NMOPF03060.22 5.1e-1035–341 Nitronate monooxygenase
FMN_dhPF01070.25 3.1e-06111–200 FMN-dependent dehydrogenase

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

Closest characterised functional partner: Rv3551 (CoA-transferase subunit alpha), high confidence from genomic context alone (score 981 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3551 CoA-transferase subunit alpha 996 981 ctx neighborhood:773 cooccurence:454 coexpression:860 textmining:803
Rv3552 CoA-transferase subunit beta 980 981 ctx neighborhood:773 cooccurence:446 coexpression:860
Rv3550 echA20 enoyl-CoA hydratase EchA20 988 979 ctx neighborhood:773 coexpression:864 textmining:472
Rv3549c short-chain type dehydrogenase/reductase 982 955 ctx neighborhood:713 coexpression:815 textmining:625
Rv3559c oxidoreductase 962 933 coexpression:813 database:500 textmining:462
Rv3548c short-chain type dehydrogenase/reductase 979 895 ctx neighborhood:449 coexpression:751 textmining:812
Rv3562 fadE31 acyl-CoA dehydrogenase FadE31 843 836 coexpression:737
Rv3560c fadE30 acyl-CoA dehydrogenase FadE30 914 825 coexpression:751 textmining:532
Rv3563 fadE32 acyl-CoA dehydrogenase FadE32 912 813 coexpression:736 textmining:552
Rv3561 fadD3 fatty-acid--CoA ligase FadD3 909 808 coexpression:805 textmining:547
Rv3554 fdxB electron transfer protein FdxB 798 780 ctx neighborhood:779
Rv2524c fas fatty acid synthase 780 746 coexpression:710
Rv0243 fadA2 acetyl-CoA acetyltransferase FadA 534 534 database:500
Rv1074c fadA3 beta-ketoacyl CoA thiolase FadA 528 528 database:500
Rv3541c chsH1 hyp hypothetical protein 526 527 ctx cooccurence:504

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: nitronate monooxygenase
  • Pfam (hmmscan --cut_ga): IMPDH PF00478.32 (E=1e-09), NMO PF03060.22 (E=5e-103), FMN_dh PF01070.25 (E=3e-06)
  • (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_218070.1)
  • Domains: Pfam-A via hmmscan --cut_ga — IMPDH (PF00478.32), NMO (PF03060.22), FMN_dh (PF01070.25)
  • 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 COG2070
  • Curated reference: UniProt P71847 (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 — 42 functional partner(s); context anchor Rv3551
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003770|Rv3553|
MRLRTPLTELIGIEHPVVQTGMGWVAGARLVSATANAGGLGILASATMTLDELAAAITKVKAVTDKPFGVNIRADAADAGDRVELMIREGVRVASFALAPKQQLIARLKEAGAVVIPSIGAAKHARKVAAWGADAMIVQGGEGGGHTGPVATTLLLPSVLDAVAGTGIPVIAAGGFFDGRGLAAALCYGAAGVAMGTRFLLTSDSTVPDAVKRRYLQAGLDGTVVTTRVDGMPHRVLRTELVEKLESGSRARGFAAALRNAGKFRRMSQMTWRSMIRDGLTMRHGKELTWSQVLMAANTPMLLKAGLVDGNTEAGVLASGQVAGILDDLPSCKELIESIVLDAITHLQTASALVE