Rv3230c Resolved · high auto-curated

H37Rv Rv3230c · MTBC0 mtbc0_003439 · 380 aa · 3629254–3630396 (-) · RefSeq NP_217747.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)stearoyl-CoA 9-desaturase electron transfer protein
MTBC0 PGAP re-annotationNADPH oxidoreductase
Revised (this work)NADPH oxidoreductase. Pfam: FAD_binding_6 (PF00970.31), NAD_binding_1 (PF00175.27), Fer2 (PF00111.33).

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

Curated reference (UniProt)

UniProt P9WNE9 SwissProt · reviewed · Evidence at protein level
UniProt nameNADPH oxidoreductase
EC (curated) EC 1.-.-.-
Curated functionIs likely involved in the aerobic desaturation system responsible for the synthesis of oleic acid from stearoyl-CoA; oleic acid is a precursor of mycobacterial membrane phospholipids and triglycerides. Is the electron transfer partner for the stearoyl-CoA 9-desaturase DesA3. Catalyzes electron transfer reaction between NADPH and the diiron center of DesA3. Cannot use NADH.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
eggNOG descriptionOxidoreductase FAD-binding domain
Orthologous groupCOG1018
Gene Ontology (23) GO:0000166, GO:0003674, GO:0003824, GO:0005488, GO:0006091, GO:0008150, GO:0008152, GO:0009055, GO:0009987, GO:0016491, GO:0022900, GO:0036094 +11 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 0.36 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 5 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
FAD_binding_6PF00970.31 1.1e-0888–161 Oxidoreductase FAD-binding domain
NAD_binding_1PF00175.27 2.4e-08173–267 Oxidoreductase NAD-binding domain
Fer2PF00111.33 6.2e-11305–372 2Fe-2S iron-sulfur cluster binding domain

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

Closest characterised functional partner: desA3 (stearoyl-CoA 9-desaturase), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3229c desA3 stearoyl-CoA 9-desaturase 999 1000 ctx neighborhood:788 fusion:794 cooccurence:766 coexpression:824 database:900 textmining:700
Rv0824c desA1 acyl-ACP desaturase DesA 931 928 database:900
Rv1094 desA2 acyl-ACP desaturase DesA 930 927 database:900
Rv1465 nitrogen fixation related protein 869 850 database:621
Rv3025c iscS cysteine desulfurase 855 834 experimental:422 database:621
Rv1175c fadH NADPH dependent 2,4-dienoyl-CoA reductase FadH 862 812 experimental:430 database:568
Rv0886 fprB ferredoxin/ferredoxin--NADP reductase 867 775 experimental:430 database:568 textmining:436
Rv3231c hyp hypothetical protein 952 769 ctx neighborhood:768 textmining:803
Rv3858c gltD glutamate synthase small subunit 778 752 experimental:430 database:568
Rv3153 nuoI NADH-quinone oxidoreductase subunit I 786 751 experimental:700
Rv3106 fprA NADPH-ferredoxin reductase FprA 777 751 experimental:430 database:568
Rv3148 nuoD NADH-quinone oxidoreductase subunit D 749 733 experimental:702
Rv2940c mas multifunctional mycocerosic acid synthase 808 731 experimental:703
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 808 731 experimental:703
Rv2048c pks12 polyketide synthase 808 731 experimental:703

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: stearoyl-CoA 9-desaturase electron transfer protein
  • MTBC0 PGAP product: NADPH oxidoreductase
  • Pfam (hmmscan --cut_ga): FAD_binding_6 PF00970.31 (E=1e-08), NAD_binding_1 PF00175.27 (E=2e-08), Fer2 PF00111.33 (E=6e-11)
  • (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_217747.1)
  • Domains: Pfam-A via hmmscan --cut_ga — FAD_binding_6 (PF00970.31), NAD_binding_1 (PF00175.27), Fer2 (PF00111.33)
  • 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 COG1018
  • Curated reference: UniProt P9WNE9 (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 — 108 functional partner(s); context anchor desA3
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003439|Rv3230c|
MSKKHTTLNASIIDTRRPTVAGADRHPGWHALRKIAARITTPLLPDDYLHLANPLWSARELRGRILGVRRETEDSATLFIKPGWGFSFDYQPGQYIGIGLLVDGRWRWRSYSLTSSPAASGSARMVTVTVKAMPEGFLSTHLVAGVKPGTIVRLAAPQGNFVLPDPAPPLILFLTAGSGITPVMSMLRTLVRRNQITDVVHLHSAPTAADVMFGAELAALAADHPGYRLSVRETRAQGRLDLTRIGQQVPDWRERQTWACGPEGVLNQADKVWSSAGASDRLHLERFAVSKTAPAGAGGTVTFARSGKSVAADAATSLMDAGEGAGVQLPFGCRMGICQSCVVDLVEGHVRDLRTGQRHEPGTRVQTCVSAASGDCVLDI