kshB Family assigned · medium auto-curated
H37Rv Rv3571 · MTBC0 mtbc0_003790 ·
358 aa · 4036094–4037170 (+) ·
RefSeq NP_218088.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 3-ketosteroid-9-alpha-hydroxylase reductase subunit |
|---|---|
| MTBC0 PGAP re-annotation | 3-ketosteroid-9-alpha-hydroxylase reductase subunit |
| Revised (this work) | 3-ketosteroid-9-alpha-hydroxylase reductase subunit. 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 |
P9WJ93
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 3-ketosteroid-9-alpha-monooxygenase, ferredoxin reductase component |
| EC (curated) |
EC 1.14.15.30
|
| Curated function | Involved in the degradation of cholesterol. Catalyzes the introduction of a 9a-hydroxyl moiety into 1,4-androstadiene-3,17-dione (ADD) to yield the 9alpha-hydroxy-1,4-androstadiene-3,17-dione (9OHADD) intermediate which spontaneously form 3-hydroxy-9,10-seconandrost-1,3,5(10)-triene-9,17-dione (HSA) via the meta-cleavage of ring B with concomitant aromatization of ring A. KSH is also able to use 4-androstene-3,17-dione (AD), 3-oxo-23,24-bisnorcholesta-4-en-22-oate (4-BNC), 3-oxo-23,24-bisnorcholesta-1,4-dien-22-oate (1,4-BNC), 3-oxo-23,24-bisnorcholesta-4-en-22-oyl-coenzyme A thioester (4-BNC-. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | hmp |
| eggNOG description | COG1018 Flavodoxin reductases (ferredoxin-NADPH reductases) family 1 |
| Orthologous group | COG1018 |
| EC number |
EC 1.14.13.142
|
| KEGG orthology |
K15983
|
| KEGG pathways |
map00984, map01100, map01120
|
| Gene Ontology (77) |
GO:0000166, GO:0001666, GO:0003674, GO:0003824, GO:0004497, GO:0005488, GO:0006066, GO:0006629, GO:0006643, GO:0006664, GO:0006706, GO:0006707 +65 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 | 0.276 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
FAD_binding_6 | PF00970.31 | 6.6e-08 | 47–121 | Oxidoreductase FAD-binding domain |
NAD_binding_1 | PF00175.27 | 2.6e-12 | 132–229 | Oxidoreductase NAD-binding domain |
Fer2 | PF00111.33 | 3.6e-16 | 274–348 | 2Fe-2S iron-sulfur cluster binding domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: kshA (3-ketosteroid-9-alpha-monooxygenase oxygenase subunit), high confidence from genomic context alone (score 959 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3526 kshA |
3-ketosteroid-9-alpha-monooxygenase oxygenase subunit | 998 | 959 ctx | cooccurence:450 database:900 textmining:964 |
Rv3537 kstD |
3-oxosteroid 1-dehydrogenase | 992 | 936 | database:900 textmining:895 |
Rv3568c hsaC |
extradiol dioxygenase | 977 | 887 ctx | neighborhood:765 cooccurence:484 textmining:811 |
Rv3570c hsaA |
flavin-dependent monooxygenase oxygenase subunit HsaA | 945 | 880 ctx | neighborhood:772 cooccurence:472 textmining:563 |
Rv3572 hyp |
hypothetical protein | 857 | 857 ctx | neighborhood:855 |
Rv1465 |
nitrogen fixation related protein | 868 | 849 | database:621 |
Rv3025c iscS |
cysteine desulfurase | 854 | 834 | experimental:422 database:621 |
Rv3569c hsaD |
4,5-9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate hydrolase | 939 | 831 ctx | neighborhood:765 textmining:657 |
Rv3567c hsaB |
flavin-dependent monooxygenase reductase subunit HsaB | 927 | 795 ctx | neighborhood:758 textmining:662 |
Rv1175c fadH |
NADPH dependent 2,4-dienoyl-CoA reductase FadH | 837 | 777 | experimental:430 database:568 |
Rv0886 fprB |
ferredoxin/ferredoxin--NADP reductase | 866 | 773 | experimental:430 database:568 textmining:436 |
Rv3106 fprA |
NADPH-ferredoxin reductase FprA | 778 | 752 | experimental:430 database:568 |
Rv3858c gltD |
glutamate synthase small subunit | 777 | 751 | experimental:430 database:568 |
Rv3153 nuoI |
NADH-quinone oxidoreductase subunit I | 784 | 750 | experimental:700 |
Rv2940c mas |
multifunctional mycocerosic acid 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: 3-ketosteroid-9-alpha-hydroxylase reductase subunit
- MTBC0 PGAP product: 3-ketosteroid-9-alpha-hydroxylase reductase subunit
- Pfam (hmmscan --cut_ga): FAD_binding_6 PF00970.31 (E=7e-08), NAD_binding_1 PF00175.27 (E=3e-12), Fer2 PF00111.33 (E=4e-16)
- (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_218088.1)
- 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 P9WJ93 (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 —
130 functional partner(s); context anchor
kshA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003790|Rv3571|kshB MTEAIGDEPLGDHVLELQIAEVVDETDEARSLVFAVPDGSDDPEIPPRRLRYAPGQFLTLRVPSERTGSVARCYSLCSSPYTDDALAVTVKRTADGYASNWLCDHAQVGMRIHVLAPSGNFVPTTLDADFLLLAAGSGITPIMSICKSALAEGGGQVTLLYANRDDRSVIFGDALRELAAKYPDRLTVLHWLESLQGLPSASALAKLVAPYTDRPVFICGPGPFMQAARDALAALKVPAQQVHIEVFKSLESDPFAAVKVDDSGDEAPATAVVELDGQTHTVSWPRTAKLLDVLLAAGLDAPFSCREGHCGACACTLRAGKVNMGVNDVLEQQDLDEGLILACQSRPESDSVEVTYDE